acid-phosphatase and Bone-Neoplasms

In tumors characterized by a high osteotropism, such as multiple myeloma, the measurement of bone metabolism markers is helpful in monitoring both severity and prognosis of the skeletal disease. Here, we review the pathophysiology of these markers including tartrate resistant acid phosphatase (TRAcP), which appears highly specific and closely related to the extent of myeloma bone lesions.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Isoenzymes; Multiple Myeloma; Tartrate-Resistant Acid Phosphatase

The spread of cancer to bone is considered a terminal event. Two main types of bone metastasis can manifest, i.e. osteoblastic and osteolytic. Irrespective of metastatic type, uncoupled bone remodeling is always present and perpetuates a vicious cycle of excess bone resorption and destruction. Biochemical markers of bone metabolism are potentially useful to diagnose metastatic bone disease and to monitor treatment response in cancer patients. Tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) is a biochemical marker of osteoclast number and activity. Mounting evidence has demonstrated serum TRACP 5b as a useful marker of bone resorption and therefore bears clinical applicability in diagnosis and management of metabolic and pathologic bone diseases. Serum TRACP 5b is among one of the many bone resorption biochemical markers that have been studied to be a surrogate marker of bone metastasis in cancer patients. Its serum level may reflect the degree of lytic bone metastasis and, in turn, the tumor burden within the bone milieu. This review summarizes the development of specific immunoassays for serum TRACP 5b as well as current evidence for its exploitation as a biomarker for diagnosis, treatment response, and prognosis in various cancers with high incidence of bone metastasis including breast, prostate, lung, and multiple myeloma.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Immunoassay; Isoenzymes; Neoplasms; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Biomarkers; Bone Diseases, Metabolic; Bone Neoplasms; Bone Remodeling; Bone Resorption; Electrophoresis, Polyacrylamide Gel; Humans; Immunoprecipitation; Isoenzymes; Osteoclasts; Reference Values; Specimen Handling; Spectrophotometry; Tartrate-Resistant Acid Phosphatase

Bone turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Bone Remodeling; Collagen; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

To review the efficacy of the combination of the anti-androgen nilutamide (Anandron) plus orchidectomy in patients with stage D prostate cancer who had received no previous treatment.. The results of seven randomized double-blind trials were analysed. In these studies patients were followed up until progression of disease or withdrawal for other reasons. Bone pain, urinary symptoms, performance status, levels of prostatic acid phosphatase (PAP) and alkaline phosphatase (AP) were evaluated before treatment and after 1, 3, 6, 12 and 18 months of treatment. Bone scans and X-rays were taken every 6 months. The best objective response, the time of progression and the time of death were recorded. The changes from baseline in symptoms and levels of tumour markers at month six and the percentages of objective regressions in the two treatment groups were compared using the Cochran-Mantel-Haenszel test stratified by study. Peto's method was used for the analysis of time to progression and of survival.. Of the 1191 patients enrolled in all the original trials, 1056 were eligible. In the group of patients treated with nilutamide 50% had complete or partial regression of disease compared with 33% of those who were given a placebo (P < 0.001); bone pain and levels of PAP and AP were improved or returned to normal significantly more frequently (P < 0.01); the odds of disease progression were significantly reduced (odds ratio 0.84, P = 0.05); the odds of death from cancer and from other causes were reduced but the difference was not statistically significant.. The combination of nilutamide and orchidectomy has a beneficial effect on pain of metastatic origin, levels of tumour markers, the objective response of disease and the time to disease progression. This treatment combination might also improve survival.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Double-Blind Method; Humans; Imidazoles; Imidazolidines; Male; Odds Ratio; Orchiectomy; Prostate; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo-hormonal therapy produces more favorable results than hormonal treatment alone.

Topics: Acid Phosphatase; Androgens; Antineoplastic Agents; Bone Neoplasms; Cell Division; Diethylstilbestrol; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone

Topics: Acid Phosphatase; Adrenalectomy; Androgen Antagonists; Androgens; Antineoplastic Agents; Bone Neoplasms; Combined Modality Therapy; Drug Evaluation; Estrogens; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Bone and Bones; Bone Neoplasms; Humans; Kidney Neoplasms; Male; Prognosis; Prostate; Prostatic Neoplasms; Radionuclide Imaging; Testicular Neoplasms; Urinary Bladder Neoplasms

Topics: Acid Phosphatase; Antineoplastic Agents; Bone Neoplasms; Carcinoembryonic Antigen; Cisplatin; Clinical Trials as Topic; Creatine Kinase; Doxorubicin; Humans; Male; Prostatic Neoplasms

Topics: Acid Phosphatase; Biopsy; Biopsy, Needle; Bone Neoplasms; Clinical Enzyme Tests; Cytodiagnosis; Humans; Male; Mass Screening; Methods; Palpation; Prostatic Neoplasms; Radiography

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatic Neoplasms

This paper reports a case of carcinoma of the prostate in an 11-year-old boy. The clinical findings were characterized by a mass in the prostatic region, extensive osteoblastic bone metastasis, and normal serum acid phosphatase. Autopsy demonstrated an undifferentiated tumor, which probably originated from the outer gland of the prostate. Metastases to the bones, liver, lungs, and the lymph nodes were present. Light and electron microscopic studies revealed undifferentiated neoplastic cell, which is in contrast to the usual adenocarcinoma in older individuals. Histochemical examination failed to demonstrate acid phosphatase activity within the tumor cells. The authors considered that this tumor probably originated from immature basal cells of the prostatic gland. Review of the literature disclosed 15 cases of carcinoma of the prostate in individuals under 21 years of age. These cases were also characterized by an undifferentiated appearance of tumor cells and normal serum acid phosphatase level.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Carcinoma; Child; Child, Preschool; Humans; Infant; Male; Neoplasm Metastasis; Prostatic Neoplasms

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Aryl Hydrocarbon Hydroxylases; Bone Neoplasms; Clinical Enzyme Tests; gamma-Glutamyltransferase; Humans; Isoenzymes; Isomerases; Leucyl Aminopeptidase; Lipase; Liver Neoplasms; Lung Neoplasms; Male; Muramidase; Neoplasms; Nucleotidases; Oxidoreductases; Pancreatic Neoplasms; Prostatic Neoplasms; Sulfatases

Initial studies indicated that bone and cartilage, when treated with a hypertonic glutaraldehyde fixative for a short period, retained significant enzyme activity for histochemistry and also maintained excellent fine structure. We used 6% glutaraldehyde in 0.1 M cacodylate buffer, pH = 7.2, 4 degrees C to fix small pieces of bone or cartilage for three hours while the tissues were being constantly agitated. These samples were demineralized in 10% ethylene diamine tetraacetic acid, buffered to pH = 7.2 with 0.1 M Tris HC1, at 4 degrees C. The demineralized tissue was frozen and cryostat sections 32 microns thick were taken for incubation at 37 degrees C in various media for histochemistry. For electron microscopic localization of enzymes a heavy metal capturing method had to be used. For light microscopy, the azo dye methods were frequently used, but these were not usable for electron microscopy. Alkaline phosphatase was found on the outer surface of osteoblast and hypertrophic cartilage cell membranes. The only intracellular enzyme activity was found on the mitochondrial membranes of the osteoclast and only when the pH of the media was lowered from the optimum 9.5 to 8.5. Alkaline phosphatase was not found along the osteocyte or young cartilage cell membranes...

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Cartilage; Cartilage Diseases; Cell Membrane; Giant Cell Tumors; Golgi Apparatus; Histocytochemistry; Humans; Lysosomes; Mucolipidoses; Organoids; Osteoblasts; Osteoclasts; Osteocytes; Osteogenesis Imperfecta; Osteosarcoma; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Histocytochemistry; Humans; Hydronephrosis; Immunodiffusion; Lymphatic Metastasis; Male; Prostate; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Urination Disorders

Topics: Acid Phosphatase; Adenocarcinoma; Aniline Compounds; Bone Neoplasms; Cyclophosphamide; Evaluation Studies as Topic; Fluorouracil; Humans; Hypercalcemia; Hypophysectomy; Male; Mechlorethamine; Neoplasm Metastasis; Plicamycin; Prostatic Neoplasms

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Acid Phosphatase; Adrenal Gland Neoplasms; Alkaline Phosphatase; Amino Acids; Amylases; Bone Neoplasms; Breast Neoplasms; Carcinoid Tumor; Catecholamines; Chorionic Gonadotropin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Female; Glucose-6-Phosphate Isomerase; Humans; Hydroxyindoleacetic Acid; L-Lactate Dehydrogenase; Liver Neoplasms; Male; Neoplasms; Neoplasms, Nerve Tissue; Neuroblastoma; Nucleotidases; Pancreatic Neoplasms; Pheochromocytoma; Pregnancy; Prostatic Neoplasms; Trophoblastic Neoplasms; Vanilmandelic Acid

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Aminopeptidases; Bone Neoplasms; Breast Neoplasms; Cervix Uteri; Clinical Enzyme Tests; Diagnosis, Differential; Esterases; Female; Glucosephosphate Dehydrogenase; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hyperplasia; Microscopy, Fluorescence; Neoplasms; Nucleic Acids; Sex Chromatin; Uterine Cervical Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Marrow Diseases; Bone Neoplasms; Esterases; Glucosyltransferases; Glycogen; Histocytochemistry; Leukemia; Lipid Metabolism; Myeloproliferative Disorders; Peroxidases; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Biopsy; Bone Neoplasms; Citrates; Cytodiagnosis; Humans; L-Lactate Dehydrogenase; Lactates; Male; Neoplasm Metastasis; Prostatic Neoplasms; Strontium Isotopes; Urography

Topics: 17-Ketosteroids; Acid Phosphatase; Adrenal Cortex Hormones; Alkaline Phosphatase; Bone Neoplasms; Castration; Estrogens; Geriatrics; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Prostatic Neoplasms; Surgical Procedures, Operative; Urine

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Collagen; Collagen Type I; Disease-Free Survival; Female; Glycoproteins; Humans; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Prognosis; Survival Rate

Prostate specific antigen (PSA), prostatic acid phosphatase and alkaline phosphatase were analyzed in 2 large prospective multicenter and multinational trials to assess their correlation with time to progression and overall survival after hormonal therapy for metastatic carcinoma of the prostate.. A total of 868 patients who underwent medical or surgical castration was randomized to receive an oral antiandrogen (nilutamide) or placebo. The serum markers under study were measured at baseline and at 1, 3, 6 and every 6 months thereafter.. At baseline the strongest predictive factor was serum alkaline phosphatase. Patients with an alkaline phosphatase of 2 or less times normal lived almost twice as long as those with a level of more than 2 times normal (p < 0.0001). The longer survival was observed in patients whose PSA became normal 3 months after initiation of hormonal therapy compared to those whose PSA never reached normal (p < 0.0001).. Serum markers at baseline and during the few months after initiation of hormonal therapy can provide prognostic information for the clinical treatment of patients with metastatic carcinoma of the prostate. In addition, the PSA level at month 3 can serve as a surrogate end point in clinical trials.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Disease Progression; Disease-Free Survival; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Multivariate Analysis; Orchiectomy; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Time Factors

Androgen deprivation displays the mean therapy of advanced stage prostatic cancer. The development of hormone-resistant disease leads to a fatal tumor progression. High-dose fosfestrol (diethylstilbestrol disphosphate) has been suggested to circumvent hormone resistance and to induce a direct cytotoxic effect. Twenty-one patients with hormone-refractory prostate cancer were enrolled in a phase I trial of continuous infusion of high, daily escalating dose of fosfestrol. Fosfestrol was given in a 3.5 hr infusion in 0.9% normal saline at a starting dose of 1.5 g/d. The dose was increased daily in the same patient according to the following schedule: 1.5, 1.8, 2.4, 3.0, 3.6, 3.9, 4.5, 5.1 and 5.7 g/d. The duration of the infusion was prolonged to 7 or 10.5 hr, if a major side effect occurred. There was neither hematological nor cardiovascular toxicity. The main dose-limiting toxicities were nausea/vomiting in 17 patients, edema in 2 patients, and more than 5% weight gain in 3 patients. The planned maximal dose was reached in 10 patients during a 3.5 hr infusion, and in 3 additional patients, after infusion prolongation. Seven patients experienced a subjective improvement: Prostatic acid phosphatase and prostatic specific antigen decreased in 4 out of 11 and in 7 out of 12 patients, respectively. The suggested dose to phase II trial is 4 g/d in 3.5 hr infusion for a duration of up to 10 days.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Drug Resistance; Humans; Infusions, Intravenous; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Bone scintigraphy is often performed to assess the response to systemic therapy of bone metastasis from prostate cancer. We examined the changes in bone scintigraphic findings and the agreement with AIP, AcP, or other tumor markers measured in the follow-up of patients with known bone metastasis after hormonal therapy. Out of 32 patients, 22 (69%) showed improved scintigraphic findings on the first follow-up bone scintigraphy after hormonal therapy. However, 7 out of 22 patients who showed improvement on the first follow-up scintigraphy, deteriorated thereafter. Changes in the scintigraphic findings were closely correlated with those in the measured tumor markers except for patients with small bone metastasis. Though there were no significant differences in the agreement ratios of the 6 tumor markers evaluated, AIP might be a practical and acceptable indicator. Bone X-ray findings did not change at all in almost half of the cases though the scintigraphic findings showed improvement or deterioration.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Estrogens; Follow-Up Studies; Humans; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Radiography; Radioimmunoassay; Radionuclide Imaging; Seminal Plasma Proteins; Time Factors

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

Topics: Acid Phosphatase; Actuarial Analysis; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Combined Modality Therapy; Double-Blind Method; Follow-Up Studies; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Orchiectomy; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis

Hormone-refractory metastatic prostate cancer remains a therapeutic challenge. Cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), a drug combination that is active in solid tumors, was evaluated using specific response criteria.. Fifty-two eligible patients with measurable (19), evaluable (29), or bone scan only (4) metastatic prostate cancer were treated with cyclophosphamide, 100 mg/m2 every day by mouth, methotrexate, 15 mg/m2 intravenously weekly, and 5-fluorouracil, 300 mg/m2 intravenously weekly. Treatment was given continuously unless interrupted by toxicity or disease progression.. There were two partial responses (7%) among the evaluable patients. Six (32%) measurable patients and four (14%) evaluable patients had stable disease. Median time to progression was 3.2 months for measurable and 2.8 months for evaluable disease patients. Median survivals were 10.9 and 10.2 months, respectively. There was no difference between the two groups with regard to response rate or survival. Toxicity was acceptable and consisted primarily of myelosuppression.. CMF is minimally active in hormone-refractory metastatic prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Cyclophosphamide; Fluorouracil; Humans; Male; Methotrexate; Middle Aged; Prostatic Neoplasms; Remission Induction; Survival Rate

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Testosterone

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Diethylstilbestrol; Goserelin; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation

Response criteria and the reporting of results in clinical trials on drug therapy of stage D prostate cancer were evaluated by examination of studies listed in the Index Medicus 1980-1984. During this 5-year period, 70 studies (51 phase II and 16 phase III) were listed, comprising 3184 evaluable patients. Among 346 patients reported as having evaluable disease according to the WHO criteria, 198 had well-defined evaluable disease. A variety of response criteria were used, the NPCP criteria being the most frequent. Only three studies included solely patients with evaluable disease according to the WHO criteria. Reporting of results was often inadequate. The value of the most frequently used response parameters such as acid phosphatase, bone scan, per-rectal ultrasound, CT scan, bone pain and performance status is discussed. A system to standardise the reporting of results is proposed.

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Trials as Topic; Drug Evaluation; Humans; Liver Neoplasms; Male; Pain Management; Prognosis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Soft Tissue Neoplasms

During an 8-year period, 1,065 serum specimens were collected from 79 patients with prostate cancer of stages B2 to D1 (group I) and 51 patients with newly diagnosed stage D2 prostate cancer (group II) to evaluate statistically the relative reliability of elevated tumor-associated markers for progressive disease in prostate cancer. Forty of the group I patients and 21 of the group II patients presented a clinical progression of disease during follow-up. With the use of Gail's modification of Cox's regression model, serial acid phosphatase (AcP), total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), prostatic acid phosphatase (PAP), and prostate-specific antigen (PA) were analyzed. Results from group I patients revealed that only PA (P = .0002) and PAP (P = .0684) were prognostically important markers for detection of imminent disease progression. However, all markers were prognostically important in group II patients. Comparative studies indicated that PA (P = .0052) and PAP (P = .0359) were the more reliable markers for group I patients, whereas PA (P less than .0001), BAP (P = .0007), and PAP (P = .0206) were the more reliable markers for group II patients. Multivariate analyses revealed that, after adjustment for the effect of PA, no other marker was significantly related to the risk of progression. Elevated PA levels were predictive of increased risk 6 months before disease progression in group I patients only (P less than .0001). Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Bone and Bones; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation; Risk; Time Factors

Chronic administration of a depot form of D-Trp6 luteinizing hormone-releasing hormone (LH-RH), an LH-RH analogue (3 mg i.m. every 28 days for a mean period of 9.1 months), to 14 patients with locally extended or metastatic cancer of the prostate provided a good degree of disease control. After a slight and transient increase in gonadotropin secretion, the peptide induced a sharp and long-lasting inhibition of both gonadotropin and testosterone secretion, contemporaneously with clinical improvement and without any important side effects. These results are comparable to those recorded by others after daily administration of LH-RH analogues.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents; Bone Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Male; Prostate; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Eighty-seven previously untreated patients with clinical stage D2 (bone metastases) prostate cancer have received the combination therapy with a pure antiandrogen and an LHRH agonist (or orchiectomy) as first treatment in a multicentre study for up to 34 months (average = 16.2 months). A positive objective response assessed according to the criteria of the US NPCP has been observed in all cases. Pain disappeared in all patients within 1 month and performance become normal in all (including 2 bedridden patients) within 4 months. Progression of the disease after a period of remission has been observed in only 8 patients. Only one patient has died from prostate cancer while 3 have died from other causes. The probability of continuing response and survival at 2 years for the patients who receive the combination treatment (Kaplan-Meier's method) is 81 and 91%, respectively. By contrast, in the randomized group who had orchiectomy alone, 4 of 7 have died from prostate cancer (P less than 0.05 as compared to combination therapy). In addition to a marked improvement in the remission rate and survival, combination therapy maintains a good quality of life, hot flashes and a decrease or loss of libido being the only side-effects.

Topics: Acid Phosphatase; Anilides; Bone and Bones; Bone Neoplasms; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Testosterone

Response criteria for phase II and phase II trials of prostate carcinoma patients of the EORTC Genito Urinary-Group are described. These criteria, initially closely related to National Prostatic Cancer Project criteria, have gone through a development into the direction of more stringency. Admission of patients to phase II trials is now restricted to those showing objectively measurable lesions, excluding bone metastases. World Health Organization criteria are applied to these patients. For phase III trials, progression to Metastatic TNM system status, time to progression, and duration of survival are recommended as end points. Measurable marker lesions, as for phase II trials and subjective and nonspecific response criteria, are accepted as parameters for progression. Response usually is not evaluated in these studies. Based on recent literature and personal experiences, the author suggests that serum acid phosphatase (SPAP) and volume changes of the primary tumor can be used as indicators for response under certain conditions. There is obviously a great need for further development of objective response criteria for prostatic cancer patients.

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Trials as Topic; Humans; Male; Prostate; Prostatic Neoplasms; Ultrasonography

Evaluation of response to systemic therapy in metastatic prostate cancer is often difficult because of the infrequency of nonbony indicator lesions. The authors previously described a set of response criteria for Phase II and III studies which can be applied in patients with only bony disease. They have retrospectively evaluated response to Adriamycin (doxorubicin) and (5-fluorouracil) 5-FU in 38 patients with measurable soft tissue and visceral disease, using their response criteria for acid phosphatase and clinical status and standard definitions of response. No correlation was attempted for bone disease. Agreement between the results obtained with each system was good. Using this system of evaluating response, patients with metastatic prostate cancer with bone-dominant disease are eligible for Phase II and III studies.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Clinical Trials as Topic; Doxorubicin; Drug Evaluation; Fluorouracil; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Soft Tissue Neoplasms

Seventy-two patients with advanced prostatic carcinoma without previous endocrine therapy were treated with an oral nonsteroidal antiandrogen, flutamide. Sixty-three patients (87.5%) had a favorable response, and 9 patients showed no response. Flutamide appears to be a safe antiandrogen, usually effective in the management of patients with advanced prostatic cancer who have had no prior endocrine therapy.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Anilides; Bone Neoplasms; Clinical Trials as Topic; Flutamide; Humans; Hydronephrosis; Male; Middle Aged; Prostatic Neoplasms; Soft Tissue Neoplasms; Urination Disorders

Topics: Acid Phosphatase; Antineoplastic Agents; Bone Neoplasms; Carcinoembryonic Antigen; Cisplatin; Clinical Trials as Topic; Creatine Kinase; Doxorubicin; Humans; Male; Prostatic Neoplasms

The results of radiation therapy of patients with carcinoma of the prostate category T3-4NxMo are compared with those of the hormonal therapy and with those of hormonal therapy combined with external irradiation. The type of first indicators of existing or threatening metastases has been evaluated, their appearance after first treatment and the period between their appearance and the development of clinical metastases have been assessed. These data and perhaps the bone-marrow serum acid phosphatase levels prior to treatment might be helpful in the choice of treatment. As damage due to irradiation has become minimal, radiation therapy should be preferred in all patients prone to cardio-vascular accidents and in healthy men up to about 75 years.

Topics: Academies and Institutes; Acid Phosphatase; Age Factors; Aged; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Netherlands; Prostatic Neoplasms; Radiotherapy Dosage

Approximately, 90% of men with advanced prostate cancer will develop bone metastasis. However, there have been few reports about noninvasive biomarker to detect and predict clinical outcome of bone metastasis (BM) in prostate cancer patients.. We examined 1127 patients who underwent prostate biopsy from August 2012 to June 2017. We also investigated bone turnover markers such as bone-specific alkaline phosphatase, type I collagen cross-linked N-terminal telopeptide, C-terminal pyridinoline cross-linked telopeptide of type I collagen, and tartrate-resistant acid phosphatase type 5b (TRACP 5b).. A total of 282 patients were diagnosed as prostate cancer with complete clinical data, and 34 patients with bone metastasis. Multivariate analysis revealed C-terminal pyridinoline cross-linked telopeptide of type I collagen, tartrate-resistant acid phosphatase type 5b, and prostate-specific antigen (PSA) were independent biomarkers in detection of BM (p < 0.05, respectively). Furthermore, we developed predictive model formula based on tartrate-resistant acid phosphatase type 5b and PSA, for which the area under the curve was 0.95. In patients with bone metastasis, multivariate cox proportional hazards analysis revealed that this model was significantly associated with poor clinical outcome of cancer-specific survival (p < 0.05). In validation cohort with 137 patients, we also confirmed the utility of this model for diagnosis of BM (the area under the curve = 0.95).. Our developed formula of tartrate-resistant acid phosphatase type 5b in accordance with PSA may serve as the useful tool in diagnosis and prediction of clinical outcome for prostate cancer with bone metastasis.

Topics: Acid Phosphatase; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Collagen Type I; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase

Serum tartrate-resistant acid phosphatase 5b is well known to be increased in giant cell tumors of bone. However, there are only a few studies that analyzed the association with tartrate-resistant acid phosphatase 5b expression in those patients. Therefore, we analyzed the characteristics of patients with giant cell tumors of bone and high tartrate-resistant acid phosphatase 5b expression.. This retrospective study included 26 patients with giant cell tumors of bone. The correlation between tartrate-resistant acid phosphatase 5b before initial treatment and tumor volume was evaluated. Patients were divided into two groups according to tartrate-resistant acid phosphatase 5b level. Statistical analysis was performed between the two groups.. Tartrate-resistant acid phosphatase 5b was elevated in 17/26 patients, and the mean value was 852 mU/dL. There was no correlation with tumor volume (r = 0.034, P = 0.86). The mean age of 34.5 years in the HT group was significantly younger than the mean age of 47.4 years in the LT group (P = 0.040). Pathologically, 19/26 cases showed at least one focal area with features of typical giant cell tumor of bone. Although 11/18 patients in the LT group exhibited relatively noticeable secondary changes, all patients in the HT group exhibited typical features (P = 0.0074).. Tartrate-resistant acid phosphatase 5b levels were not elevated in some giant cell tumors of bone. This study suggested that tartrate-resistant acid phosphatase 5b may be elevated in younger patients and in cases with fewer pathological secondary changes, regardless of tumor volume.

Topics: Acid Phosphatase; Adult; Biomarkers; Bone Neoplasms; Giant Cell Tumor of Bone; Humans; Middle Aged; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Tumor Burden

Bone metastases often occur in the majority of patients with advanced cancer, such as prostate cancer, lung cancer and breast cancer. Serum tartrate-resistant acid phosphatase 5b (TRACP 5b), a novel bone resorption marker, has been used gradually in the clinics as a specific and sensitive marker of bone resorption for the early diagnosis of cancer patients with bone metastasis. Here, we reported that high concentrations of uric acid (UA) lead to decrease of TRACP 5b levels and determined whether TRACP 5b level was associated with UA in interference experiment.. A total of 77 patients with high concentrations of UA and 77 healthy subjects were tested to evaluate the differences in their TRACP 5b levels. Serial dilutions of UA were respectively spiked with a known concentration of TRACP 5b standard sample, then Serum TRACP 5b was detected by using bone TRAP® Assay. A correction equation was set to eliminate UA-derived TRACP 5b false-decrease. The effect of this correction was evaluated in high-UA individuals.. The average TRACP level of the high-UA individuals (1.47 ± 0.62 U/L) was significantly lower than that of the healthy subjects (2.62 ± 0.63 U/L) (t-test, p < 0.0001). The UA correction equation derived: ΔTRACP 5b = -1.9751lgΔUA + 3.7365 with an R2 = 0.98899. Application of the UA correction equation resulted in a statistically non-significant difference in TRACP 5b values between the healthy subjects and high-UA individuals (p = 0.24).. High UA concentrations can falsely decrease TRACP 5b levels due to a method-related systematic error. To avoid misdiagnoses or inappropriate therapeutic decisions, increased attention should be paid to UA interference, when TRACP 5b is used for early diagnosis of cancer patients with bone metastasis, evaluation of the aggressiveness of osteosarcoma or prediction of survival in prostate cancer and breast cancer with bone metastases.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Case-Control Studies; False Negative Reactions; Female; Humans; Immunoassay; Isoenzymes; Male; Middle Aged; Neoplasms; Tartrate-Resistant Acid Phosphatase; Uric Acid; Young Adult

Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Neoplasms; Bone Remodeling; Breast; Breast Neoplasms; Cell Communication; Cell Differentiation; Cell Line, Tumor; Female; Galectin 3; Humans; Isoenzymes; Male; Mice; Myosins; Neoplasm Metastasis; Osteoclasts; Prostatic Neoplasms; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Bone metastases develop in several malignancies (multiple myeloma, breast, prostate and lung carcinoma) and cause several complications. The aim of this study was to search for new biomarkers to use in monitoring of bone metastatic disease with the use of xMAP technology.. We assessed 62 oncological patients: 23 with no bone metastases, 28 with metastatic disease not having undergone therapy and 11 with metastatic disease treated by denosumab. Serum levels of dickkopf-related protein 1 (DKK1), growth differentiation factor-15 (GDF15), neuron-specific enolase (NSE), osteoprotegerin (OPG), osteonectin, periostin, tartrate-resistant acid phosphatase (TRAP5), tumor necrosis factor related weak inducer of apoptosis (TWEAK), chitinase-3-like protein 1 (YKL40), carboxy-terminal telopeptide (CTX) and procollagen type 1 N-terminal propeptide (PINP) were measured in each sample.. The following biomarkers were observed to have significantly higher levels in the groups of patients with metastases in comparison to metastasis-free patients: GDF15 (p<0.0001), osteonectin (p=0.0311), TRAP5 (p<0.0046), TWEAK (p<0.0343) and YKL40 (p<0.0034). The changes in DKK1, NSE, OPG and periostin were not significant.. We identified five new biomarkers: GDF15, osteonectin, TRAP5, TWEAK, and YKL40 as being promising markers for monitoring bone metastases.

Topics: Acid Phosphatase; Adipokines; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Chitinase-3-Like Protein 1; Colorectal Neoplasms; Cytokine TWEAK; Female; Growth Differentiation Factor 15; Humans; Isoenzymes; Lectins; Lung Neoplasms; Male; Middle Aged; Osteonectin; Pilot Projects; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factors

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Humans; Male; Mice; Mice, SCID; Osteoblasts; Osteoprotegerin; Prostatic Neoplasms; RANK Ligand; RNA, Small Interfering; Signal Transduction

To investigate the serum levels of N-terminal telopeptide of type I collagen (NTx) and tartrate-resistant acid phosphatase 5b (TRACP5b) in giant cell tumor of bone (GCT) patients and the clinical implications.. 56 GCT patients (29 males and 27 females, 15 to 60 years old with a median age of 28.0 years old) with clinicopathological characteristics of GCT were enrolled in the Department of Bone Cancer, the Affiliated Cancer Hospital of Xinjiang Medical University from October 2008 to October 2014. The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of NTx and TRACP5b in the patients.. Compared with 21 patients who had a GCT of < 5 cm, the serum levels of NTx and TRACP5b in the 35 patients with a GCT of ≥ 5 cm were significantly increased (p < 0.05). Compared with those GCT patients who had a grade I tumor, the levels of NTx and TRACP5b in grade II patients were not increased (p > 0.05), but the levels of NTx and TRACP5b were significantly increased in grade III patients (p < 0.05). Moreover, compared with the patients in histologic stage I, the levels of NTx and TRACP5b in stage II GCT patients were not increased (p > 0.05), whereas the levels in grade III patients were significantly increased (p < 0.05). In addition, the location of the tumor had a significant effect on the serum levels of NTx and TRACP5b (p < 0.05).. Our study suggests that serum NTx and TRACP5b are sensitive and simple biomarkers to indicate aberrant bone metabolism in GCT patients, and they may have a clinical significance in GCT diagnosis. Combined examination for both markers helps in the classification of clinicopathological stages of GCT patients and in the prognosis of the disease.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers, Tumor; Bone Neoplasms; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Middle Aged; Neoplasm Grading; Peptides; Predictive Value of Tests; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed; Tumor Burden; Young Adult

Diagnostic significance of estimation of the tartratresistent acid phosphatase (bone TRAP--5b) activity was studied for prognosis of occurrence of metastases in bones (MB) in patients with a renal-cell cancer (RCC). The risk of the MB occurrence was determined in patients after surgical treatment. A skeleton affection rate in patients, to whom zolendronic acid was prescribed, was trustworthy bigger, than such while conduction of treatment. So, application of bisphosphonates is recommended, in particular--zolendronic acid in dosage 4 mg every month under control of the bone TRAP--5b activity with objective of prophylaxis of the MB occurrence in patients, suffering RCC. But, we recommend for the MB diagnosis the method of determination of this marker activity as additional one while examining patients together with standard methods, including osteoscintigraphy, computer tomography.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bone Density Conservation Agents; Bone Neoplasms; Carcinoma, Renal Cell; Diphosphonates; Drug Administration Schedule; Female; Gene Expression; Humans; Imidazoles; Isoenzymes; Kidney Neoplasms; Male; Middle Aged; Radiography; Tartrate-Resistant Acid Phosphatase; Tomography, Emission-Computed; Treatment Outcome; Zoledronic Acid

Approximately 90 % of patients who die of prostate cancer (PCa) have bone metastases, often promoting osteoblastic lesions. We observed that 88 % of castration-resistant PCa (CRPC) bone metastases express prostatic acid phosphatase (PAP), a soluble secreted protein expressed by prostate epithelial cells in predominately osteoblastic (n = 18) or osteolytic (n = 15) lesions. Additionally, conditioned media (CM) of an osteoblastic PCa xenograft LuCaP 23.1 contained significant levels of PAP and promoted mineralization in mouse and human calvaria-derived cells (MC3T3-E1 and HCO). To demonstrate that PAP promotes mineralization, we stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. Furthermore, the mineralization promoted by LuCaP 23.1 CM was also blocked by phosphonic acid, suggesting PAP is responsible for the mineralization promoting activity of LuCaP 23.1. In addition, gene expression arrays comparing osteoblastic to osteolytic CRPC (n = 14) identified betacellulin (BTC) as a gene upregulated during the osteoblastic response in osteoblasts during new bone formation. Moreover, BTC levels were increased in bone marrow stromal cells in response to LuCaP 23.1 CM in vitro. Because new bone formation does occur in osteoblastic and can occur in osteolytic CRPC bone metastases, we confirmed by immunohistochemistry (n = 36) that BTC was highly expressed in osteoblasts involved in new bone formation occurring in both osteoblastic and osteolytic sites. These studies suggest a role for PAP in promoting the osteoblastic reaction in CRPC bone metastases and identify BTC as a novel downstream protein expressed in osteoblasts during new bone formation.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Cell Line, Tumor; Humans; Male; Mass Spectrometry; Osteoblasts; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; Tumor Microenvironment

We examined the effects of vitamin E supplementation (VES) on osteoclast (OC) resorbing activity and cytomorphometry in Walker 256/B tumor osteolytic rats. Twenty-four aged male rats were randomized into 3 groups: 6 were sham operated; 9 were injected in the right hind limb with Walker 256/B cells (W256 group); and 9 were injected as above and supplemented with VE (45mg/kg BW) (W256VE group). Twenty days later, bone mass (BV/TV) and some microarchitectural parameters were assessed. Some histodynamic parameters, cellular and nuclear form factors (FFC and FFN), and nuclear-cytoplasmic ratio (N/C) of OC were measured for each group. W256 group exhibited osteolytic lesions in the operated femora. Walker 256/B induced trabecular perforation and decreased BV/TV associated with significant increases in OC numbering (N.Oc/B.Ar and Oc.N/B.Pm) and activity (ES/BS and Oc.S/BS). While FFN remain unchanged, the FFC and N/C ratio increased in the W256 group. W256VE showed less osteolytic lesions. Moreover, disruption of bone microarchitecture and OC activity in W256VE group decreased. VES reduced the malignant Walker 256/B-induced enhanced OC resorbing activity with cytoinhibition rate reaching 41%. The protective effect of VE may be due to its modulation of OC cytomorphometry and subsequently their activity.

Topics: Acid Phosphatase; alpha-Tocopherol; Animals; Biomarkers; Bone Neoplasms; Bone Remodeling; Breast Neoplasms, Male; Dietary Supplements; Femur; Isoenzymes; Male; Osteoclasts; Osteolysis; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Time Factors; Vitamins

Giant cell tumor of bone is an osteolytic, usually benign, tumor characterized by the infiltration of osteoclast-like giant cells. The receptor activator of nuclear factor kappa-B ligand pathway has been shown to play a key role in the pathogenesis of giant cell tumor. Treatment for refractory, recurrent, or metastatic giant cell tumor remains challenging. A monoclonal antibody to receptor activator of nuclear factor kappa-B ligand, denosumab, offers promise in these patients. Tartrate-resistant acid phosphatase 5b, a bone resorption marker, is secreted from osteoclasts and this marker is reported to be high in patients with giant cell tumor of bone. We investigated the effects of denosumab and the usefulness of a tartrate-resistant acid phosphatase 5b as a monitoring marker in the management of a refractory giant cell tumor of bone.. A 41-year-old Japanese male with right ischiac pain was diagnosed with a giant cell tumor in his right ischium. Since the tumor extended to the acetabulum, there was a possibility that en bloc resection might significantly impair function of the hip joint and curettage could cause massive bleeding. Therefore, denosumab therapy (120 mg, administered 3 times every 4 weeks) was performed before radical surgery. The giant cell tumor of bone was treated with denosumab successfully. No adverse reaction was noted. Tartrate-resistant acid phosphatase 5b secretion was measured in the patient's serum to monitor the response to denosumab, and a rapid normalization of the marker was observed after the first denosumab administration.. This case suggests that denosumab therapy might be an option for treating refractory giant cell tumor of bone, and that tartrate-resistant acid phosphatase 5b might be an early marker with which to monitor the efficacy of denosumab therapy for refractory giant cell tumor.

Topics: Acid Phosphatase; Adult; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Denosumab; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

The relationship between biochemical markers of bone resorption (C-terminal telopeptide, deoxypyridinoline, tartrate-resistant acid phosphatase 5b) and osteosynthesis (bone alkaline phosphatase) and clinical manifestations of bone metastases were studied in 239 patients with breast cancer with and without signs of bone involvement. High levels of C-terminal telopeptide and bone alkaline phosphatase were associated with poor prognosis: more severe skeletal complications and lesser survival values. These biochemical markers can be used for prognosis and optimization of therapy for bone metastases in patients with breast cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Analysis of Variance; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoenzymes; Kaplan-Meier Estimate; Osteogenesis; Peptides; Prognosis; Radionuclide Imaging; Tartrate-Resistant Acid Phosphatase

To evaluate the relationship between IL-11 and bone metastasis in patients with breast cancer and explore the potential molecular mechanism, total serum samples were collected from 180 breast cancer patients and 20 women without breast cancer. The serum expression level of interleukin (IL)-11, connective tissue growth factor (CTGF), transforming growth factor-β, and Tracp5b was determined by enzyme-linked immunosorbent assay, and mRNA expression of IL-11 in fresh breast cancer tissue was determined by RT-PCR. Immunohistochemical staining was used to detect the expression of IL-11 and CTGF in breast cancer tissue, and Western blot was used to detect the expression of p-38, p-C-JUN, p-STAT3, and p-gp130 in fresh breast cancer tissue. DNA-binding activity of AP-1 was examined by electrophoretic mobility shift assay. Differences were statistically analyzed between the group with breast cancer metastatic to bone (MBC-B) and the group with only primary breast cancer (PBC). Serum level and mRNA expression of IL-11 in the MBC-B group were significantly higher than those in the PBC group. IL-11 immunohistochemical staining showed that the percentage of positively stained cells in the MBC-B group (57.5 %) was significantly higher than that in the PBC group (14.29 %). Western blot analysis showed higher expression of p-p38, p-C-JUN, p-STAT3, and p-gp130 in the MBC-B group than in the PBC group. DNA-binding activity of AP-1 was significantly higher in the MBC-B group than in the PBC group. These data suggest that IL-11 is associated with bone metastasis and may be of value for predicting bone metastasis from breast cancer.

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Breast Neoplasms; Connective Tissue Growth Factor; Cytokine Receptor gp130; Female; Humans; Interleukin-11; Isoenzymes; Middle Aged; Neoplasm Metastasis; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-jun; RNA, Messenger; STAT3 Transcription Factor; Tartrate-Resistant Acid Phosphatase; Transcription Factor AP-1; Transforming Growth Factor beta

We investigated the clinical significance of serum bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) and type I collagen carboxyterminal telopeptide (ICTP) as bone metabolic markers for bone metastasis (BM) screening in lung cancer patients.. Newly diagnosed advanced lung cancer patients with (N = 130) and without (N = 135) BM were enrolled in the study. Serum BAP, TRACP 5b and ICTP were measured before the treatment.. BAP, TRACP 5b and ICTP values were higher in patients with BM compared with patients without BM (all P < 0.0001). Area under ROC curve (AUC) of BAP, TRACP 5b and ICTP was 0.760, 0.753 and 0.835 (all P < 0.0001), respectively. The cut-off values for BAP, TRACP 5b and ICTP were 21.8 μg/l, 7.8 U/l and 8.8 μg/l, respectively. When TRACP 5b and ICTP were combined, AUC was elevated to 0.895 (P < 0.0001), and the cut-off values were TRACP 5b 7.6 U/l and ICTP 8.4 μg/l.. We conclude that serum BAP, TRACP 5b and ICTP may serve as useful tools for BM screening in lung cancer patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Collagen Type I; Female; Humans; Isoenzymes; Lung Neoplasms; Male; Middle Aged; Peptides; Tartrate-Resistant Acid Phosphatase; Young Adult

Osteochondromas and enchondromas are the most common tumors affecting the skeleton. Osteochondromas can occur as multiple lesions, such as those in patients with hereditary multiple exostoses. Unexpectedly, while studying the role of β-catenin in cartilage development, we found that its conditional deletion induces ectopic chondroma-like cartilage formation in mice. Postnatal ablation of β-catenin in cartilage induced lateral outgrowth of the growth plate within 2 weeks after ablation. The chondroma-like masses were present in the flanking periosteum by 5 weeks and persisted for more than 6 months after β-catenin ablation. These long-lasting ectopic masses rarely contained apoptotic cells. In good correlation, transplants of β-catenin-deficient chondrocytes into athymic mice persisted for a longer period of time and resisted replacement by bone compared to control wild-type chondrocytes. In contrast, a β-catenin signaling stimulator increased cell death in control chondrocytes. Immunohistochemical analysis revealed that the amount of detectable β-catenin in cartilage cells of osteochondromas obtained from hereditary multiple exostoses patients was much lower than that in hypertrophic chondrocytes in normal human growth plates. The findings in our study indicate that loss of β-catenin expression in chondrocytes induces periosteal chondroma-like masses and may be linked to, and cause, the persistence of cartilage caps in osteochondromas.

Topics: Acid Phosphatase; Animals; Apoptosis; beta Catenin; Bone Neoplasms; Cartilage; Cell Proliferation; Chondrocytes; Chondroma; Choristoma; Collagen Type II; Growth Plate; Humans; In Situ Nick-End Labeling; Indoles; Integrases; Isoenzymes; Mice; Osteochondroma; Oximes; Periosteum; Proliferating Cell Nuclear Antigen; Radiography; Ribs; Tamoxifen; Tartrate-Resistant Acid Phosphatase

A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases.. Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density.. Preventive dosing administration of sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels.. The findings suggest that sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.

Topics: Acid Phosphatase; Angiogenesis Inhibitors; Animals; Antigens, CD34; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Cell Line, Tumor; Drug Administration Schedule; Female; Humans; Immunohistochemistry; Indoles; Isoenzymes; Mice; Mice, Nude; Protein Kinase Inhibitors; Pyrroles; Sunitinib; Tartrate-Resistant Acid Phosphatase; Time Factors; Transfection; Tumor Burden; Xenograft Model Antitumor Assays

The aim of this study was to determine whether the ethanol extract of roasted licorice (rLE) could inhibit breast cancer-mediated bone destruction. rLE treatment reduced the viability of MDA-MB-231 human metastatic breast cancer cells but did not show any cytotoxicity in hFOB1.19 human osteoblastic cells and murine bone marrow-derived macrophages (BMMs). rLE inhibited expression and secretion of receptor activator of nuclear factor κB ligand (RANKL) as well as the mRNA and protein expression of cyclooxygenase-2 in osteoblastic cells exposed to the conditioned medium of breast cancer cells. rLE dramatically inhibited RANKL-induced osteoclastogenesis in BMMs, thereby reducing osteoclast-mediated pit formation. Moreover, treatment with licochalcone A and isoliquiritigenin as the active components, whose contents are increased by the roasting process, remarkably suppressed RANKL-induced osteoclast formation in BMMs, respectively. Furthermore, orally administered rLE substantially blocked tumor growth and bone destruction in mice inoculated with breast cancer cells in the tibiae. Serum levels of tartrate-resistant acid phosphatase and C-terminal cross-linking telopeptide of type I collagen and trabecular bone morphometric parameters were reversed to almost the same levels as the control mice by the rLE treatment. In conclusion, rLE may be a beneficial agent for preventing and treating bone destruction in patients with breast cancer.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Cell Line, Tumor; Chalcones; Cyclooxygenase 2; Female; Glycyrrhiza; Humans; Isoenzymes; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Neoplasm Metastasis; Osteoblasts; Osteoclasts; Plant Extracts; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Although increasing evidence suggests a critical role for platelet-derived growth factor (PDGF) receptor β (β-PDGFR) signaling in prostate cancer (PCa) progression, the precise roles of β-PDGFR and PDGF isoform-specific cell signaling have not been delineated. Recently, we identified the PDGF-D isoform as a ligand for β-PDGFR in PCa and showed that PDGF-D is activated by serine protease-mediated proteolytic removal of the CUB domain in a two-step process, yielding first a hemidimer (HD) and then a growth factor domain dimer. Herein, we demonstrate that the expression of PDGF-D in human PCa LNCaP cells leads to enhanced bone tumor growth and bone responses in immunodeficient mice. Histopathological analyses of bone tumors generated by PDGF-D-expressing LNCaP cells (LNCaP-PDGF-D) revealed osteolytic and osteoblastic responses similar to those observed in human PCa bone metastases. Importantly, we discovered a novel function of PDGF-D in the regulation of osteoclast differentiation, independent of the RANKL/RANK signaling axis. Although both PDGF-B and -D were able to activate β-PDGFR, only PDGF-D was able to induce osteoclastic differentiation in vitro, and upregulate the expression and nuclear translocation of nuclear factor of activated T cells 1, a master transcription factor for osteoclastogenesis. Taken together, these results reveal a new function of PDGF-D as a regulator of osteoclastic differentiation, an activity critical for the establishment of skeletal metastatic deposit in PCa patients.

Topics: Acid Phosphatase; Animals; Blotting, Western; Bone Neoplasms; Cell Differentiation; Cell Line; Cell Line, Tumor; Humans; Immunohistochemistry; Isoenzymes; Lymphokines; Male; Mice; Mice, SCID; Mutation; NIH 3T3 Cells; Osteoclasts; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; RANK Ligand; Receptor, Platelet-Derived Growth Factor beta; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Tibia

Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14+ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP+ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Giant Cell Tumor of Bone; Giant Cells; Growth Substances; Hepatocyte Growth Factor; Humans; Isoenzymes; Macrophage Colony-Stimulating Factor; Membrane Proteins; Monocytes; Osteoclasts; Placenta Growth Factor; Pregnancy Proteins; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor D

Diagnosis and follow-up of bone metastasis (BMet) in non-small cell lung cancer (NSCLC) patients usually rely on symptoms and image studies. A serum marker of bone resorption may improve the quality of treatment in such patients. Tartrate-resistant acid phosphatase 5b (TRACP5b) is a specific marker for osteoclasts and we proposed it can be used as a marker of BMet in NSCLC patients.. In November 2002 till August 2008 serum samples were obtained from 141 newly diagnosed stage IIIA, IIIB or IV NSCLC patients and 41 normal subjects. All patients received baseline bone scintinography examination and evaluation of clinical symptoms as a standard of BMet diagnosis. Patients were divided into 2 groups by having BMet (Group I, n = 72) or not (Group II, n = 69). An in-house immunoassay using a TRACP-specific monoclonal antibody, 14G6, was used to measure the serum TRACP5b activity at pH 6.1.. The mean serum TRACP5b activities of Group I, Group II and normal subjects were 3.50 ± 2.2 3U/l, 2.09 ± 0.72 U/l and 2.33 ± 0.52 U/l, respectively. After adjusting for age, stage, gender, and histology in a generalized linear model, Group I has significantly higher TRACP5b activity than Group II (p < 0.001). The receiver operating characteristic analysis established a cutoff value of 2.551 U/l to identify BMet in NSCLC patients with a sensitivity of 63.9% and a specificity of 76.8%. TRACP5b activity declined in patients who responded to treatment (p = 0.047), and elevated in patients who developed new BMet (p = 0.05).. Serum TRACP5b activity test is a potentially useful adjunct in diagnosing and monitoring BMet in NSCLC. Further study is warranted to establish its real value in diagnosis and monitoring of BMet in NSCLC patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Female; Follow-Up Studies; Humans; Isoenzymes; Lung Neoplasms; Male; Middle Aged; ROC Curve; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRAP) exists in human serum as two major isoforms, monomeric 5a and proteolytically processed enzymatically active 5b. The 5b isoform is secreted by osteoclasts and has recently been advocated as a serum marker for bone metastasis in breast cancer patients. The 5a isoform, on the other hand, is not bone-derived and has been proposed to be a marker of activated macrophages and chronic inflammation. In this study, expression of TRAP protein and enzymatic activity in bone metastases from different primary sites was examined. TRAP activity was high in bone metastases from prostate cancer, intermediate in breast cancer, and low in lung and kidney cancers. The partially purified TRAP from breast cancer bone metastasis samples exhibited the enzymatic characteristics of purple acid phosphatase. Both 5a and 5b isoforms were expressed in bone metastases of different histogenetic origins, i.e. prostate, breast, lung and kidney, and also a novel previously unreported 42 kDa variant of the TRAP 5a isoform was identified in bone metastases. This novel TRAP 5a isoform was absent in human bone, indicating that the 42 kDa variant is specific to metastatic cancer tissue. Immunohistochemistry revealed that metastatic cancer cells were the predominant source of TRAP 5a, whereas tumor-associated macrophages and occasionally multinucleated giant cells in the tumor stroma preferentially expressed the proteolytically processed TRAP 5b variant. Our results indicate the presence of a previously unstudied variant of monomeric TRAP 5a in cancer cells, which may have functional and diagnostic implications. Moreover, the presence of TRAP-positive macrophages in bone metastases could, together with cancer cells and osteoclasts, contribute to the elevated levels of serum TRAP activity observed in patients with bone metastases.

Topics: Acid Phosphatase; Bone Neoplasms; Breast Neoplasms; Humans; Immunohistochemistry; Isoenzymes; Stromal Cells; Tartrate-Resistant Acid Phosphatase

Vitamin D is considered as an important determinant of bone turnover as well as cancer growth. Using a murine model of bone metastasis, we investigated the effect of vitamin D deficiency on prostate cancer cell growth in bone.. Three-week-old male nude mice were fed either normal chow (control) or a diet deficient in vitamin D. The latter diet resulted in severe hypovitaminosis D within 6 weeks. At this point of time, 5 × 10(4)  cells of the prostate cancer cell line, PC-3, were injected either into the bone marrow (tibia) or subcutaneously into soft tissues. Osteoprotegerin (OPG) was co-administered in subgroups of mice to suppress bone remodeling. Osteolytic lesions were monitored by serial X-ray, while soft tissue tumor growth was measured by caliper. All tissues were analyzed by micro-CT and histology at endpoint.. Bone turnover was significantly accelerated in vitamin D deficient compared to vitamin D sufficient mice from week 6 onwards. Intra-tibially implanted PC-3 cells resulted in mixed osteolytic and osteosclerotic lesion. At endpoint, osteolytic and osteosclerotic lesion areas, total tumor area, and tumor mitotic activity were all significantly increased in vitamin D deficient mice compared to controls. Regardless of diet, OPG reduced bone turnover, total tumor, and osteosclerotic area as well as tumor mitotic activity, while promoting cell apoptosis. In contrast, vitamin D deficiency did not alter tumor growth in soft tissues.. Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Bone Remodeling; Calcitriol; Cell Line, Tumor; Histocytochemistry; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoprotegerin; Peptide Fragments; Procollagen; Prostatic Neoplasms; Specific Pathogen-Free Organisms; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed; Vitamin D; Vitamin D Deficiency

In recent years, oncolytic adenoviruses have shown some promise as a novel class of antitumor agents. However, their utility in targeting bone metastases is relatively less studied. We have examined whether the systemic therapy of oncolytic adenoviruses expressing the soluble form of transforming growth factor-β (TGFβ) receptor II fused with human immunoglobulin G1 can be developed for the treatment of established breast cancer bone metastases. MDA-MB-231-luc2 human breast cancer cells were injected in the left heart ventricle of nude mice to establish bone metastasis. Mice with hind limb tumors were administered (on days 8 and 11) oncolytic adenoviruses-Ad.sTβRFc or mhTERTAd.sTβRFc. Skeletal tumor growth was monitored weekly by bioluminescence imaging (BLI) and radiography. At the termination time on day 28, hind limb bones were analyzed for tumor burden, synchrotron micro-computed tomography, and osteoclast activation. Intravenous delivery of Ad.sTβRFc and mhTERTAd.sTβRFc induced significant inhibition of tumor growth, reduction of tumor burden, osteoclast activation, and increased animals' survival. Oncolytic adenoviruses were safer than dl309, a wild-type virus. A slight elevation of liver enzyme activity was observed after Ad.sTβRFc administration; this subsided with time. Based on these studies, we believe that Ad.sTβRFc and mhTERTAd.sTβRFc can be developed as a safe and effective approach for the treatment of established bone metastasis.

Topics: Acid Phosphatase; Adenoviridae; Animals; Bone Neoplasms; Breast Neoplasms; Female; Genetic Therapy; HEK293 Cells; Humans; Injections, Intravenous; Isoenzymes; Mice; Mice, Inbred BALB C; Mice, Nude; Oncolytic Virotherapy; Oncolytic Viruses; Osteoclasts; Protein Serine-Threonine Kinases; Radiography; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Synchrotrons; Tartrate-Resistant Acid Phosphatase; Tumor Burden; Virus Replication; Weight Loss; Xenograft Model Antitumor Assays

Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells. We demonstrate that PAP is strongly expressed in PCa bone metastases in 7/7 patients, while prostate-specific antigen (PSA) is only weakly expressed. The human PCa cell line VCaP secretes PAP and induces an osteoblastic reaction in bone similar to that seen in human PCa bone metastases. Coculture of MC3T3 mouse preosteoblast cells with VCaP cells induces MC3T3 cell growth and differentiation as measured by alkaline phosphatase secretion, and this effect is inhibited by addition of the PAP-inhibitor, l-tartrate. Taken together, these data indicate that PAP is expressed in PCa bone metastases and may play a causal role in the osteoblastic phase of the disease.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Osteoblasts; Osteogenesis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

The aim of the study was to test the bone resorption marker TRAcP 5b regarding its suitability for detection of bone metastases in breast cancer patients.. Serum samples from a total of 101 patients with histologically proven breast cancer and from 100 healthy probands were analyzed. The patients were divided into three groups: eight patients without osseous involvement, 65 patients with untreated bone metastases, 28 patients whose bone metastases were treated with bisphosphonate therapy.. The TRAcP 5b concentration was significantly higher in breast cancer patients compared to healthy probands. It was not possible to demonstrate a statistically significant difference in the TRAcP 5b concentration if osseous metastases in breast cancer patients were present or not.. Our research cannot support the claim that TRAcP 5b could be useful as a diagnostic tool for the detection of bone metastases in patients with breast cancer.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Female; Humans; Isoenzymes; Male; Middle Aged; Mucin-1; ROC Curve; Tartrate-Resistant Acid Phosphatase

To assess the diagnostic accuracy of serum bone turnover markers for detection of bone metastasis in patients with prostate cancer (PCa) and to assess the usefulness of these markers as predictors of mortality from PCa.. Serum total alkaline phosphatase, bone-specific alkaline phosphatase, carboxy-terminal pyridinoline cross-linked telopeptide parts of type-I collagen (1CTP), tartrate-resistant acid phosphatase type 5 b, and prostate-specific antigen (PSA) levels were measured in 222 patients (58 with bone metastasis, 57 with T2M0 PCa, 55 with T3M0 PCa, and 52 without PCa). Multivariate stepwise logistic regression analysis was used to identify independent predictors of bone metastasis. Correlation of serum marker levels with bone metastasis was assessed using receiver operating characteristics analysis. Multivariate Cox proportional hazards analysis was used to predict cause-specific survival in PCa patients with bone metastasis.. Serum total alkaline phosphatase, bone-specific alkaline phosphatase, 1CTP, tartrate-resistant acid phosphatase type 5 b, and PSA levels were significantly elevated in patients with bone metastasis, and correlated significantly with the extent of disease on bone scintigraphy. Multivariate stepwise logistic regression analysis demonstrated that serum PSA and 1CTP were significant predictors of bone metastasis. Receiver operating characteristics analyses showed that serum 1CTP level was the most reliable predictor of bone metastasis (area under the curve = 0.85). Multivariate Cox proportional hazards analysis revealed that only serum 1CTP was an independent prognostic factor for PCa-related death.. Serum 1CTP level was a more reliable marker than the others to detect bone metastatic spread and to predict survival probability in PCa patients with bone metastasis.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Analysis of Variance; Biomarkers, Tumor; Bone Neoplasms; Cohort Studies; Collagen Type I; Humans; Immunohistochemistry; Isoenzymes; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Probability; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Tartrate-Resistant Acid Phosphatase

Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real-time PCR to evaluate the mRNA levels of the tartrate-resistant acid phosphatase (ACP5), colony stimulating factor-1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p = 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process.

Topics: Acid Phosphatase; Adolescent; Biopsy; Bone Morphogenetic Protein 7; Bone Neoplasms; Bone Resorption; Calcification, Physiologic; Child; Collagen Type XI; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Male; Osteosarcoma; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Receptor, Macrophage Colony-Stimulating Factor; RNA, Messenger; Survival Analysis; Tartrate-Resistant Acid Phosphatase; Young Adult

Serum tartrate-resistant acid phosphatase 5b (TRACP 5b) activity is a marker of osteoclast number and is elevated in breast cancer (BC) patients with extensive bone metastasis, which might in turn reflect the tumour burden. We tested the hypothesis that baseline serum TRACP 5b activity and its interval change are potential prognostic markers of survival in BC patients with bone metastasis.. We analyzed the data from previous prospective studies. A total of 100 patients with newly diagnosed bone metastasis were included. Cox proportional regression model was used to evaluate the correlation between the overall survival time (OS) and baseline serum TRACP 5b activity and its interval changes. The least significant change (LSC) of TRACP 5b was calculated from data obtained from 15 patients with early BC.. Estrogen receptor status (Hazard Ratio (HR) = 0.397; p = 0.003) and visceral metastasis (HR = 0.492; p = 0.0045) were significantly correlated with OS. The OS was significantly shorter in those patients with higher baseline TRACP 5b activity based on a cut-off value to delineate the highest tertile (HR = 3.524; p < 0.0001). Further analysis demonstrated that among patients in the highest tertile, OS was significantly longer in those patients who had achieved a decrease of serum TRACP 5b activity greater than the LSC (38.59%) (p = 0.0015).. We found that TRACP 5b activity and its interval change after treatment bore a prognostic role in BC patients with bone metastasis and a high baseline serum TRACP 5b activity. Further prospective phase II study is necessary to confirm these results.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Chi-Square Distribution; Female; Humans; Isoenzymes; Middle Aged; Proportional Hazards Models; Retrospective Studies; Survival Analysis; Tartrate-Resistant Acid Phosphatase; Time Factors; Treatment Outcome; Up-Regulation

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Neoplasms; Dogs; Estrogens; History, 20th Century; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone; United States

Bone metastases contribute to morbidity in patients with common cancers, and conventional therapy provides only palliation and can induce systemic side effects. The development of nanostructured delivery systems that combine carriers with bone-targeting molecules can potentially overcome the drawbacks presented by conventional approaches. We have recently developed biodegradable, biocompatible nanoparticles (NP) made of a conjugate between poly (D,L-lactide-co-glycolic) acid and alendronate, suitable for systemic administration, and directly targeting the site of tumor-induced osteolysis. Here, we loaded NP with doxorubicin (DXR), and analyzed the in vitro and in vivo activity of the drug encapsulated in the carrier system. After confirming the intracellular uptake of DXR-loaded NP, we evaluated the anti-tumor effects in a panel of human cell lines, representative for primary or metastatic bone tumors, and in an orthotopic mouse model of breast cancer bone metastases. In vitro, both free DXR and DXR-loaded NP, (58-580 ng/mL) determined a significant dose-dependent growth inhibition of all cell lines. Similarly, both DXR-loaded NP and free DXR reduced the incidence of metastases in mice. Unloaded NP were ineffective, although both DXR-loaded and unloaded NP significantly reduced the osteoclast number at the tumor site (P = 0.014, P = 0.040, respectively), possibly as a consequence of alendronate activity. In summary, NP may act effectively as a delivery system of anticancer drugs to the bone, and deserve further evaluation for the treatment of bone tumors.

Topics: Acid Phosphatase; Alendronate; Animals; Antineoplastic Agents; Biological Transport; Bone Density Conservation Agents; Bone Neoplasms; Carcinoma; Cell Count; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Female; Humans; Isoenzymes; Mice; Mice, Nude; Nanocapsules; Osteoclasts; Osteolysis; Radiography; Tartrate-Resistant Acid Phosphatase; Xenograft Model Antitumor Assays

NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma. This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined. Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of hormone naïve metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. NKX3.1 seems

Topics: Acid Phosphatase; Adenocarcinoma; Antibody Specificity; Biomarkers, Tumor; Bone Neoplasms; Cell Differentiation; Homeodomain Proteins; Humans; Immunohistochemistry; Lymph Nodes; Male; Neoplasms, Unknown Primary; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Sensitivity and Specificity; Soft Tissue Neoplasms; Tissue Array Analysis; Transcription Factors

Osteosarcoma (OS) is the most common primary malignant bone tumour, and mainly affects adolescents and young adults. Although there has been substantial improvement in management of OS with surgery and chemotherapy, further survival increase has not been achieved over the past two decades.. We focused on the receptor activator of nuclear factor kappaB ligand (RANKL)-osteoclast (OCL) system as a biological target for OS. RANKL is a critical factor for OCL formation and bone resorption activity. The primary lesion in bone and ensuing metastasis in OS both require the induction of OCLs. RANK-Fc is a potent RANKL antagonist and inhibitor of OCL formation and activity.. In an orthotopic model in Balb/c nu/nu mice, a twice weekly dosing regimen of 350 microg of RANK-Fc per mouse subcutaneously (n= 5) reduced lung metastasis (P > 0.05), preserved bone structure and reduced tartrate-resistant acid phosphatase (TRAP)(+) OCLs (P < 0.005) in OS-bearing bone. In vitro, RANK-Fc suppressed OCL formation (P < 0.005), bone resorption activity (P < 0.005) and RANKL-induced anti-apoptosis (P < 0.5) of OCLs.

Topics: Acid Phosphatase; Animals; Apoptosis; Bone and Bones; Bone Neoplasms; Bone Resorption; Disease Models, Animal; Humans; Isoenzymes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Osteoclasts; Osteosarcoma; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Recombinant Fusion Proteins; Tartrate-Resistant Acid Phosphatase

Breast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.. The effects of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.. In vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)(2)D(3) inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49±0.08 mm(2) versus 1.68±0.15 mm(2), P<0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81±0.13 mm(2) versus 0.52±0.11 mm(2) in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.. Vitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.

Topics: Acid Phosphatase; Adipose Tissue; Animals; Apoptosis; Bone and Bones; Bone Neoplasms; Bone Remodeling; Breast Neoplasms; Calcitriol; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Mice; Osteolysis; Osteosclerosis; Radiography; Tartrate-Resistant Acid Phosphatase; Tumor Burden; Vitamin D Deficiency; Xenograft Model Antitumor Assays

We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without metastases. In addition, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. Therefore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5(+) osteoclasts and contribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts with zoledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Animals; Biopsy; Bone Neoplasms; Child; Female; Humans; Isoenzymes; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Middle Aged; Osteoclasts; Osteosarcoma; Tartrate-Resistant Acid Phosphatase; Young Adult

The purpose of this study was to elucidate the clinical significance of acid phosphatase in giant cell tumour of bone.. Serum acid phosphatase levels were measured in 32 patients with this tumour both preoperatively and postoperatively.. Serum acid phosphatase value before surgery was high in 15 patients, whereas it was within normal limits in 17 patients. The serum acid phosphatase values of all the 15 patients with high preoperative serum level fell within normal limits postoperatively. In the remaining 17 patients in whom preoperative serum acid phosphatase values were within normal limits, postoperative serum acid phosphatase levels were lower than that of preoperative ones in all the patients. In addition, there was a statistically significant positive correlation between the tumour volume and the preoperative serum acid phosphatase level.. It is concluded that serum acid phosphatase is a useful tumour marker for giant cell tumour of bone.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged; Young Adult

The skeleton is the most common site of breast cancer metastasis, which can occur in up to 85% of patients during their lifetime. The morbidity associated with bone metastases in patients with breast cancer includes pathological fractures, bone pain, hypercalcaemia, and spinal cord compression. When breast cancer metastasizes to bone, the balance of bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts) favors bone resorption, which leads to net bone destruction (i.e., osteolysis). Anti-resorptive agents such as bisphosphonates are commonly used to treat bone resorption in osteoporosis or osteolytic cancer patients. However, bisphosphonates by themselves are unable to rebuild lost bone tissue, and can cause severe side effects. In this study, we developed a bovine bone explant culture system and have observed that murine osteoblasts can modulate the activity of osteotropic human breast cancer cells on this substrate. Using markers of bone metabolism, we observe diminished bone turnover in organ culture following the addition of exogenous osteoblasts. The data presented in this study supports further investigation into the use of cytotherapies to limit breast cancer mediated osteolysis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Neoplasms; Breast Neoplasms; Cattle; Cell Line, Tumor; Coculture Techniques; Humans; Mice; Organ Culture Techniques; Osteoblasts; Osteolysis

Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activity, have been found to alleviate bone cancer symptoms. In this study, the bisphosphonate risedronate and its phosphonocarboxylate derivative NE-10790 was tested in a murine bone cancer pain model. Risedronate decreased bone cancer-related bone destruction and pain-related behavior and decreased the spinal expression of glial fibrillary acidic protein, whereas NE-10790 had no effect on these parameters. Furthermore, risedronate but not NE-10790 induced dose-dependent toxicity in NCTC-2472 cells in vitro. Furthermore, the direct toxic effect of risedronate on tumor cells observed in vitro opens the possibility that a direct toxic effect on tumor cells may also be present in vivo and be related to the efficacy of bisphosphonate compounds. In conclusion, these results suggest that risedronate treatment may lead to an increased life quality, in patient suffering from bone cancer, in terms of decreased osteolysis and pain, and merits further study.

Topics: Acid Phosphatase; Animals; Behavior, Animal; Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Cell Proliferation; Cells, Cultured; Diphosphonates; Etidronic Acid; Fibroblasts; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Isoenzymes; Male; Mice; Mice, Nude; Pain; Pyridines; Risedronic Acid; Tartrate-Resistant Acid Phosphatase; Xenograft Model Antitumor Assays

Bone metastases have a considerable impact on quality of life in patients with breast and other cancers. Tumors produce osteoclast-activating factors, whereas bone resorption promotes the growth of tumor cells, thus leading to a "vicious cycle" of bone metastasis. Sagopilone, a novel, fully synthetic epothilone, inhibits the growth of breast cancer cells in vitro and in vivo, and here we report its activity in the MDA-MB-231(SA) breast cancer bone metastasis mouse model.. The potency of sagopilone was determined in treatment models simulating the adjuvant (preventive) and metastatic (therapeutic) settings in the clinic.. We showed that sagopilone inhibited tumor burden and bone destruction, in addition to reducing tumor-induced cachexia and paraplegia. The reduction in osteolytic lesions, tumor growth in bone, and weight loss was statistically significant in the preventive model compared with the vehicle group. In the therapeutic model, sagopilone treatment significantly lowered the number of activated osteoclasts and significantly reduced the osteolytic lesion area, bone volume loss, and bone resorption compared with vehicle treatment while simultaneously inhibiting tumor burden. An in vitro assay confirmed that sagopilone inhibited osteoclast activation without cytotoxic effects, whereas paclitaxel resulted in lower inhibition and high levels of cytotoxicity.. Sagopilone seems to inhibit the vicious cycle at both the tumor growth and bone resorption stages, suggesting the possibility for substantial benefit in the treatment of patients with breast cancer at risk from bone metastases or with bone lesions already present. Phase II clinical trials with sagopilone in patients with breast cancer are ongoing.

Topics: Acid Phosphatase; Animals; Antineoplastic Agents, Phytogenic; Benzothiazoles; Bone and Bones; Bone Neoplasms; Bone Resorption; Cachexia; Cell Line, Tumor; Dose-Response Relationship, Drug; Epothilones; Female; Humans; Isoenzymes; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Osteoclasts; Osteolysis; Paclitaxel; Tartrate-Resistant Acid Phosphatase; Tumor Burden; Xenograft Model Antitumor Assays

Bone metastasis is a frequent and catastrophic consequence of prostate cancer for which only palliative treatment is available. Animal models of bone metastatic prostate cancer are necessary for understanding disease mechanisms but few models exist.. We have used the murine prostate carcinoma cell line RM1 to generate a bone metastatic model of prostate cancer. Repeated intracardiac injection of RM1 cells followed by isolation of cells from bone tumors has yielded a cell line with strong bone-metastatic potential, RM1 bone metastatic (BM).. This cell line metastasizes to multiple bony sites in over 95% of injected C57BL/6 mice and is far less tropic to soft tissues. Bone tumors produced by the RM1(BM) cell line show no preference for particular skeletal sites as most bones are affected. Histology, and micro-computed tomography show that RM1(BM) cells form osteolytic tumors, but with evidence of osteoblastic changes. In vitro the RM1 cells express E-cadherin but not vimentin, do not form colonies in soft agar, are non-invasive but are more motile than the parent cell line.. This model provides a novel means for identifying cellular and molecular mechanisms that contribute to bone metastasis and allow for preclinical testing of therapies to prevent and treat tumor metastasis to bone. Finally as the syngeneic tumor cells are injected into immunocompetent mice, this model will provide a means to study interactions between the immune system, tumors and bone, and therapies that target such interactions.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Adhesion; Cell Line, Tumor; Cell Movement; Disease Models, Animal; Histocytochemistry; Immunocompetence; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Osteocalcin; Prostatic Neoplasms; Tomography, X-Ray Computed

A novel immunoassay specific for the osteoclast-produced tartrate-resistant acid phosphatase TRAP isoform 5b was developed some years ago. By means of this assay, the usefulness of serum TRAP in monitoring the response to palliative treatment with clodronate in breast cancer patients with bone metastases was studied. Serum TRAP was examined for correlation with the activity of bone osteoclasts in these patients.. Seventeen patients took part in this study taking 1600 mg clodronate daily as a tablet for five months. Eleven of these patients were evaluated.. TRAP activity correlated well with the grade of bone metastases and with the number of locations in the body. During the therapy with clodronate, TRAP activity in serum decreased.. We conclude that the measurement of TRAP is useful in monitoring treatment with bisphosphonate clodronate in patients with bone metastatic breast cancer.

Topics: Acid Phosphatase; Biomarkers; Bone Density Conservation Agents; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Clodronic Acid; Female; Humans; Isoenzymes; Palliative Care; Tartrate-Resistant Acid Phosphatase

Osteosarcoma (OS) is a highly malignant primary skeletal tumor with a striking tendency to rapidly destroy the surrounding bone and metastasize, since metastases are frequently present at clinical onset. The basis for the aggressiveness of this tumor is largely unknown. However, recent studies in in vivo models indicate that the anti-osteolytic drugs, bisphosphonates, can inhibit the tumor local expansion and the formation of metastases. We further investigated the association between the presence of active osteoclasts and the aggressiveness of OS. We evaluated the presence of osteoclasts and the mRNA of different osteoclast-related genes in tumor biopsies from 16 OS patients and in three OS cell lines and the serum levels of bone resorption markers in the same series and in 28 other patients. Tumor-associated osteoclasts were found in 63 and 75% of cases by histological and mRNA analysis. Among different serum markers, only MMP-9 was significantly higher in OS cases (p=0.0001), whereas TRACP 5b was significantly higher in metastatic patients compared to nonmetastatic patients (p=0.0509). Serum TRACP 5b was significantly correlated to serum NTX (p<0.0001) and cathepsin K mRNA in tumor tissues (p=0.0153). In 8 patients we also analyzed TRACP 5b serum level at follow-up and we verified a significant decrease of TRACP 5b after primary tumor removal (p=0.0117). In conclusion, tumor-infiltrating osteoclasts are frequently found in OS and increased serum TRACP 5b levels and the presence of active osteoclast at primary sites were positively associated with tumor aggressiveness.

Topics: Acid Phosphatase; Adolescent; Adult; Biomarkers; Bone Neoplasms; Bone Resorption; Case-Control Studies; Cathepsin K; Cathepsins; Cell Differentiation; Cell Line, Tumor; Child; Child, Preschool; Collagen Type I; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Isoenzymes; Macrophage Colony-Stimulating Factor; Male; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Osteoclasts; Osteosarcoma; Parathyroid Hormone-Related Protein; Peptides; RANK Ligand; Receptor, Parathyroid Hormone, Type 1; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Time Factors; Young Adult

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cathepsin K; Cathepsins; Cell Line, Tumor; Disease Models, Animal; Female; Gene Expression Profiling; Immunoenzyme Techniques; Interleukin-6; Isoenzymes; Macrophage Colony-Stimulating Factor; Mammary Neoplasms, Experimental; Osteoblasts; Osteoclasts; RANK Ligand; Rats; Rats, Inbred F344; Stromal Cells; Tartrate-Resistant Acid Phosphatase

The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.. TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.. Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without (P < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.. Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers; Bone Neoplasms; Humans; Isoenzymes; Male; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Tartrate-Resistant Acid Phosphatase

To determine if a correlation exists between the semiquantitative bone scintigraphy index (SQBSI) and serum tartrateresistant acid phosphatase 5b (TRACP5b) activity, a novel osteoclast marker that has been shown to be useful for monitoring bone metastasis in breast cancer (BC) patients.. Among patients enrolled in 2 prospective studies conducted at Tri-Service General Hospital, Taipei, Taiwan, between December 2000 and July 2002, we identified post hoc 52 patients with both BC and bone metastasis who had detailed records of clinical condition, bone scintigraphy, and concordant serum TRACP5b levels. Between January 1, 2003, and December 31, 2005, we performed bone scintigraphy and serum TRACP5b activity assays to monitor these patients, while they were treated according to clinical need. To assess clinical condition, we obtained information from patient records, such as performance status and visual analogue pain score, as well as from selected laboratory tests for tumor markers and serum TRACP5b activity. Those patients with BC and bone metastasis who had undergone whole-body bone scintigraphy and serum TRACP5b activity determination before any therapeutic intervention were designated the pretreated group (n=30). We developed our own formula for calculating SQBSI on the basis of bone scintigraphy findings.. A significant correlation was observed between SQBSI and serum TRACP5b activity in pretreated BC patients with bone metastasis, but the strength of the correlation lessened after treatment. No significant correlation was noted between the change in serum TRACP5b activity and the change in SQBSI in treated patients. Compared with the change in SQBSI, the change in TRACP5b activity had higher sensitivity, specificity, and positive predictive value as well as a greater likelihood ratio for reflecting the clinical scenarios of bone morbidity over time.. As monitors of the response of bone metastasis in BC to treatment, serial determinations of serum TRACP5b activity and SQBSI were both shown to be useful by our preliminary findings. However, serum TRACP5b activity proved the better monitoring tool. If follow-up studies were conducted within 6 months, the combined use of SQBSI and TRACP5b would allow distinction of genuine disease progression from the "flare" phenomenon, in which bone metastasis can appear to progress in bone scintigraphic images although clinical symptoms improve. Larger prospective studies are needed to confirm these findings.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Disease Progression; Female; Follow-Up Studies; Humans; Isoenzymes; Middle Aged; Osteoclasts; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Remission Induction; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase; Technetium Tc 99m Medronate; Whole Body Imaging

Novel prognostic indexes clinically applicable for patients with Stage IV prostate cancer are needed because prostate-specific antigen (PSA) tests occasionally fail to reflect the prognostic outcome. We investigated various clinicopathologic parameters in men with Stage IV prostate cancer and evaluated the utility of the PSA/prostatic acid phosphatase (PAP) ratio as a prognostic index.. We reviewed 241 patients with Stage IV prostate cancer, who were treated in Niigata Cancer Center Hospital from 1992 to 2004. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate analyses of survival associations, including age, performance status, clinical presentation, disease localization, pathologic findings, and serologic markers, were conducted using the log-rank test and Cox proportional hazard models.. The 5-year overall survival rate using the Kaplan-Meier method for all 241 patients was 43.0%. No significant difference was found in the survival rates according to PSA level. However, the 5-year survival rate was significantly lower in patients with a PSA/PAP ratio of less than 3.0 (P = 0.0022): 24.2% and 48.0% in those with a PSA/PAP ratio of less than 3.0 and 3.0 or greater, respectively. On multivariate analysis using the proportional hazards model, the statistically significant prognostic factors of overall survival were alkaline phosphatase (P = 0.0413), lactate dehydrogenase (P = 0.0409), and the PSA/PAP ratio (P = 0.0113).. The PSA/PAP ratio is a valuable prognostic indicator in men with Stage IV prostate cancer. Although our study found that other laboratory tests also had a prognostic influence, the PSA/PAP ratio was an essential index implicated in the physiopathology of prostate cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Hemoglobins; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Survival Rate

The aim of this study was to assess the dynamics of osteoclast migration and the degradation of unmineralized extracellular matrix in an osteolytic metastasis by examining a well-standardized lung cancer metastasis model of nude mice. SBC-5 human lung small carcinoma cells were injected into the left cardiac ventricle of 6-week-old BALB/c nu/nu mice under anesthesia. At 25-30 days after injection, the animals were sacrificed and their femora and/or tibiae were removed for histochemical analyses. Metastatic lesions were shown to occupy a considerable area extending from the metaphyses to the bone marrow region. Tartrate resistant acid phosphatase (TRAPase)-positive osteoclasts were found in association with an alkaline phosphatase (ALPase)-positive osteoblastic layer lining the bone surface, but could also be localized in the ALPase-negative stromal tissues that border the tumor nodules. These stromal tissues were markedly positive for osteopontin, and contained a significant number of TRAPase-positive osteoclasts expressing immunoreactivity for CD44. We thus speculated that, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration after their formation associated with ALPase-positive osteoblasts. We next examined the localization of cathepsin K and matrix metallo-proteinase-9 (MMP-9) in osteoclasts. Osteoclasts adjacent to the bone surfaces were positive for both proteins, whereas those in the stromal tissues in the tumor nests showed only MMP-9 immunoreactivity. Immunoelectron microscopy disclosed the presence of MMP-9 in the Golgi apparatus and in vesicular structures at the baso-lateral cytoplasmic region of the osteoclasts found in the stromal tissue. MMP-9-positive vesicular structures also contained fragmented extracellular materials. Thus, osteoclasts appear to either select an optimized function, namely secreting proteolytic enzymes from ruffled borders during bone resorption, or recognize the surrounding extracellular matrix by mediating osteopontin/CD44 interaction, and internalize the extracellular matrices. Microsc.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Carcinoma, Small Cell; Cathepsin K; Cathepsins; Cytoplasmic Vesicles; Disease Models, Animal; Extracellular Matrix; Femur; Golgi Apparatus; Humans; Hyaluronan Receptors; Immunohistochemistry; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Immunoelectron; Osteoclasts; Osteolysis; Osteopontin; Sialoglycoproteins; Tibia

Cherubism (CBM) and central giant cell granuloma (CGCG) of the jaw and giant cell tumor (GCT) of the long bone are clinically different diseases. Histologically, they are all multinucleated giant cell (MGC)-containing lesions. This study aims to evaluate the expression of c-Src and cytologic features in CBM, CGCG and GCT and to clarify whether there is a common mechanism underlying the formation of multi-nucleated giant cells (MGCs) in these lesions. Specimens and paraffin blocks were collected from patients with CBM (12 cases), CGCG (24 cases) and GCT (37 cases). Histomorpho-metric differences in MGCs were compared among the three types of lesions. The expression of c-Src by immunohistochemistry and in situ hybridization and the expression of TRAP by enzyme histochemical staining were examined. Expression of c-Src mRNA and protein, as well as TRAP staining, was detected in both MGCs and a fraction of mononuclear cells in all investigated lesions. There are no quantitative differences for cytologic features and c-Src expression among the lesions. The results suggested that CBM, CGCG and GCT have overlapping cytological features at the histological level, and c-Src may be involved in the formation of MGCs in the three different diseases.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Cherubism; Child; Gene Expression; Giant Cell Tumor of Bone; Giant Cells; Granuloma, Giant Cell; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Middle Aged; Proto-Oncogene Proteins pp60(c-src); Tartrate-Resistant Acid Phosphatase

Metabolic markers of bone metabolism may be useful for the diagnosis and monitoring of bone metastasis in breast cancer patients. Serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity is a novel bone resorption marker. The treatment response of serum TRACP5b activity, bone alkaline phosphatase (BAP) activity, and concentrations of NH(2)-terminal telopeptide of type 1 collagen (NTX) in 68 breast cancer patients with bone metastasis were determined. These patients were treated and followed up as clinically indicated. Fifty-four healthy women were recruited as control. Serum TRACP5b activity, BAP activity, and NTX level of breast cancer patients with bone metastasis were significantly higher than those of normal controls. In normal subjects, serum TRACP5b activity and NTX level are significantly correlated (P < 0.0001). Neither was correlated with BAP activity. In breast cancer patients with bone metastasis, all marker pairs correlated to each other significantly (P < 0.0001). Biomarkers were examined repeatedly in 38 patients who were evaluable for treatment response. Based on clinical criteria, 20 patients were responders and 18 were nonresponders. In the 20 responders, serum TRACP5b activity and NTX level decreased significantly (P < 0.0001 and 0.0107, respectively) after treatment. In the 18 nonresponders, only NTX level showed significant increase (P = 0.0342) after treatment; TRACP5b and BAP were unchanged. By means of multiple logistic regression with stepwise selection, we determined that TRACP5b activity has a higher probability than NTX level to indicate treatment response as a function of percent change after treatment (18 times versus 12 times). Our data support the use of either TRACP5b activity or NTX level to follow up breast cancer patients with bone metastasis after treatment instead of the prevailing BAP activity.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Case-Control Studies; Combined Modality Therapy; Female; Humans; Isoenzymes; Middle Aged; Monitoring, Physiologic; Neoplasm Staging; Odds Ratio; Probability; Prognosis; Reference Values; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

We assessed the diagnostic accuracy of bone markers in the serum of patients with renal cell carcinoma to detect bone metastases and evaluate the prognostic potential concerning renal cell carcinoma caused mortality.. The bone formation markers total and bone specific alkaline phosphatase, the bone resorption markers cross-linked N-terminal and tartrate-resistant acid phosphatase isoenzyme 5b, and the osteoclastogenesis markers osteoprotegerin and ligand of the receptor activator of nuclear factor-kappaB, were measured in the serum of 72 patients with renal cell carcinoma, including 28 with pN0M0, 8 with pN1M0 and 36 with M1, and in 32 female and 36 male controls by enzyme-linked immunosorbent assay techniques. Data were evaluated by receiver operating characteristics and survival analysis.. Bone specific alkaline phosphatase, tartrate-resistant acid phosphatase isoenzyme 5b and ligand of the receptor activator of nuclear factor-kappaB did not significantly differ between patients with renal cell carcinoma and controls. Compared with controls tartrate-resistant acid phosphatase isoenzyme 5b, cross-linked N-terminal and osteoprotegerin showed increased concentrations in patients with nonbone metastases but not in those with bone metastases. No bone turnover marker led to differentiation between patients with nonbone and bone metastases. Increased osteoprotegerin above the upper 95% cutoff limit, tumor stage and distant metastatic spread were associated with renal cell carcinoma related survival on Kaplan-Meier analyses. A multivariate Cox proportional hazards regression model revealed that these 3 variables were independent prognostic factors for cancer related death.. Bone turnover markers are hardly useful to diagnose bone metastases in patients with renal cell carcinoma. However, osteoprotegerin together with clinicopathological characteristics may be helpful as prognosticator of cancer specific death.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Biomarkers; Bone Neoplasms; Bone Remodeling; Carcinoma, Renal Cell; Carrier Proteins; Female; Glycoproteins; Humans; Isoenzymes; Kidney Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reproducibility of Results; Retrospective Studies; Tartrate-Resistant Acid Phosphatase

Primary and metastatic bone cancers are difficult to eradicate and novel approaches are needed to improve treatment and extend life. As bone cancer grows, osteoclasts, the principal bone-resorbing cells of the body, are recruited to and activated at sites of cancer. In this investigation, we determined if osteoclast lineage cells could function as a cell-based gene delivery system to bone cancers. We used the cytosine deaminase (CD) 5-fluorocytosine (5-FC) enzyme/prodrug system and studied bone marrow and bones from transgenic mice expressing a novel CD gene regulated by the osteoclast tartrate-resistant acid phosphatase (TRAP) gene promoter (Tg/NCD). DsRed2-labeled 2472 sarcoma cells were placed in Tg/NCD osteoclastogenic cultures and treated with 5-FC. 5-FC treatment resulted in profound bystander killing (90%; P < 0.05). The effect of 5-FC treatment on osteoclast lineage cells was most dramatic when administered at the beginning of the 7-day cultures, suggesting that mature osteoclasts are less sensitive to 5-FC. Evaluation of osteoclast-directed bystander killing in vivo revealed dramatic killing of bone cancer with only a modest effect on osteoclast number. Specifically, 5-FC treatment of tumor-bearing Tg/NCD mice or Tg/NCD bone marrow transplanted C3H mice (Tg/NCD-C3H) resulted in 92% and 44% reductions in tumor area, respectively (P < 0.05). Eight of ten 5-FC-treated Tg/NCD mice had complete bone tumor killing and five of six 5-FC-treated Tg/NCD-C3H mice had reduced tumor compared with controls. In addition, Tg/NCD osteoclasts were resistant to 5-FC treatment in vivo, a very important feature, as it identifies osteoclasts as an ideal CD gene delivery system.

Topics: Acid Phosphatase; Animals; Antimetabolites, Antineoplastic; Bone Neoplasms; Cell Line, Tumor; Coculture Techniques; Cytosine Deaminase; Flucytosine; Genetic Therapy; Isoenzymes; Mice; Mice, Inbred C3H; Mice, Transgenic; Osteoclasts; Promoter Regions, Genetic; Sarcoma; Tartrate-Resistant Acid Phosphatase

In bone metastatic lesions, osteoclasts play a key role in the development of osteolysis. Previous studies have shown that macrophage colony-stimulating factor (M-CSF) is important for the differentiation of osteoclasts. In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions. We developed small molecule inhibitors against ligand-dependent phosphorylation of c-Fms and examined the effects of these compounds on osteolytic bone destruction in a bone metastasis model. We discovered a novel quinoline-urea derivative, Ki20227 (N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]-2-methoxyphenyl}-N'-[1-(1,3-thiazole-2-yl)ethyl]urea), which is a c-Fms tyrosine kinase inhibitor. The IC(50)s of Ki20227 to inhibit c-Fms, vascular endothelial growth factor receptor-2 (KDR), stem cell factor receptor (c-Kit), and platelet-derived growth factor receptor beta were found to be 2, 12, 451, and 217 nmol/L, respectively. Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro. Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibited the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner. In in vivo studies, oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. Moreover, Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo. Therefore, Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Cell Differentiation; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Isoenzymes; Mice; Mice, Transgenic; Osteoclasts; Osteolysis; Phenylurea Compounds; Protein Kinase Inhibitors; Proto-Oncogene Mas; Rats; Rats, Inbred F344; Rats, Nude; Receptor, Macrophage Colony-Stimulating Factor; Tartrate-Resistant Acid Phosphatase; Thiazoles

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2'-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Bone Neoplasms; Bone Remodeling; Bone Resorption; Cell Line, Tumor; Humans; Male; Mice; Osteocalcin; Osteogenesis; Parathyroid Hormone; Prostatic Neoplasms

Previous studies showed that serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity was increased in 70% to 94% of breast cancer (BC) patients with bone metastasis (BM). This study aims to determine whether serum TRACP5b is useful for identifying limited or extensive BM in BC patients.. Serum TRACP5b activity was measured in 168 BC patients, including 81 who were newly diagnosed with early BC, 20 with extraosseous metastasis, 24 with limited BM, and 43 with extensive BM. Serum TRACP5b activity was also measured monthly in 151 patients with early BC until they developed BM. Four hundred and twenty-seven (427) healthy women ages 18 to 90 served as control. One-way ANOVA was used to compare serum TRACP5b among groups. The sensitivity and specificity of serum TRACP5b as a marker for BM were estimated by receiver operator characteristic (ROC) curves.. Serum TRACP5b increased with age in healthy women ( P < 0.0001). It was significantly elevated in patients with extensive BM compared with all other groups ( P < 0.0001). ROC analysis established a cutoff value of 4.026 units/L to identify patients with extensive BM with a specificity of 98% and a sensitivity of 93% (area under the curve = 0.9807; 95% CI = 0.9698-0.9915). Among the 151 patients with early BC, 6 developed limited BM and 2 developed extensive BM during the follow-up period. Serum TRACP5b remained below the cutoff value in patients with limited BM, but became significantly increased in those whose BM became extensive.. Serum TRACP5b activity is a useful diagnostic marker for extensive BM in patients with BC.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Case-Control Studies; Female; Humans; Isoenzymes; Middle Aged; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Osteoclast-like giant cells (GCs) in giant cell tumors (GCTs) are thought to derive from a monocyte-macrophage lineage. Microphthalmia transcription factor (MITF) is necessary for osteoclast gene expression and tartrate-resistant acid phosphatase (TRAP) activation; c-Kit plays a role in regulation of MITF.. To gain insight into the differentiation of GCTs of bone (GCTBs) and GCTs tendon sheath (GCTTSs) by investigating immunohistochemical staining for c-Kit, MITF, TRAP, and HAM-56 in the GCs and stroma.. Immunoreactivity for CD117 (c-Kit), MITF, TRAP, and HAM-56 was studied in 35 GCTBs, 15 GCTTSs, and 5 foreign-body GC controls.. Across tumors, MITF and TRAP but not c-Kit were generally expressed in GCs; TRAP was variably expressed in stromal cells. The MITF was expressed more consistently in stromal cells of GCTTSs than GCTBs (P < .001). The GCTBs showed more intense MITF stromal (P < .001) and TRAP GC staining (P = .04) than GCTTSs. HAM-56 staining by stromal cells was associated with MITF stromal staining (r2 = 0.6, P < .001).. Results suggest that MITF and TRAP are expressed during osteoclast differentiation and that a proportion of mononuclear cells in GCTs express the macrophage marker HAM-56. Both GCTBs and GCTTSs show similar patterns of immunohistochemical expression.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Antibodies, Monoclonal; Bone Neoplasms; Connective Tissue; DNA-Binding Proteins; Female; Giant Cell Tumors; Humans; Isoenzymes; Male; Microphthalmia-Associated Transcription Factor; Middle Aged; Neoplasm Recurrence, Local; Osteoclasts; Proto-Oncogene Proteins c-kit; Soft Tissue Neoplasms; Tartrate-Resistant Acid Phosphatase; Tendons; Transcription Factors

Transitional cell carcinoma (TCC) of the urinary tract is a chemosensitive tumor. Most deaths from TCC of the urinary tract are caused by metastasis, which is resistant to conventional chemotherapy. Frequent sites of metastases from TCC of the urinary tract are regional lymph nodes, liver, lung, and bone. Of these distant metastases, bone metastasis is consistently resistant to cisplatin-based conventional chemotherapy. Therefore, in this study, we investigated whether or not a newly developed minodronate, YM529, could prevent osteolytic bone metastasis of human TCC and also enhance the effect of docetaxel in a bone tumor model of athymic nude mice.. In the present study, we evaluated the effect of in vitro treatment with minodronate and/or docetaxel on the proliferation by cell count, the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and the biological activity of osteoclast by pit formation assay in human bladder cancer cell line, UMUC-14, and mouse osteoclast cells. In vivo, we examined the effect of minodronate in a bone tumor model of athymic nude mice, in which the percutaneous intraosseal injection in the tibia of UMUC-14, leads to osteolytic bone tumor, as a bone metastasis model. To examine whether or not minodronate could inhibit tumorigenicity and enhance the effect of the chemotherapeutic agent, docetaxel, we gave minodronate i.p. and/or docetaxel i.p. to nude mice 3 days after an intraosseal tumor implantation. Moreover, proliferation and the induction of apoptosis of cancer cells and osteoclasts in bone tumors were determined by immunohistochemistry and the TUNEL assay.. In vitro: In vitro treatment with docetaxel inhibited proliferation and resorption pit-forming activity and induced apoptosis of mouse osteoclast cells and UMUC-14 cells. In vitro treatment with minodronate inhibited proliferation and activity and induced apoptosis of mouse osteoclast cells but not UMUC-14 cells. The treatment with minodronate enhanced the inhibition of proliferation and activity by docetaxel in osteoclasts. In vivo: In vivo combination therapy with docetaxel and minodronate significantly reduced the tumor incidence compared with the control (P < 0.05) and also growth of intraossal TCC in athymic nude mice compared with the control (P < 0.001), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). Drug-induced body weight loss was not significantly different in any treatment group. Therapy with minodronate significantly enhanced inhibition of proliferation by docetaxel in osteoclasts of bone tumors compared with the control (P < 0.01), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05).. These studies indicate that combination therapy with minodronate and docetaxel may be beneficial in patients with bone metastasis of human TCC in the urinary tract.

Topics: Acid Phosphatase; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Bone Resorption; Carcinoma, Transitional Cell; Cell Line; Cell Line, Tumor; Cell Proliferation; Diphosphonates; Docetaxel; Dose-Response Relationship, Drug; Humans; Imidazoles; Immunohistochemistry; In Situ Nick-End Labeling; Isoenzymes; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoblasts; Proliferating Cell Nuclear Antigen; Tartrate-Resistant Acid Phosphatase; Taxoids; Tibia; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays

Skeletal metastases are a significant problem in prostate cancer (PC). The patients are also exposed to treatment-related skeletal changes. This cross-sectional study evaluated a marker of bone resorption, TRACP 5b in relation to the standard analyte total alkaline phosphatase (tALP) as a marker of skeletal changes. Serum levels of TRACP 5b, tALP and PSA were measured in 130 prostate cancer patients. Comparison was made between patients with (BM+, n = 25) and without (BM-, n = 105) skeletal metastases, and between those treated with (n = 64) or without (n = 66) androgen deprivation (AD). Sensitivities and specificities were calculated for each marker and diagnostic accuracy was evaluated by ROC curve analysis. ROC curves indicated the superior accuracy of tALP, whereas TRACP 5b and PSA were comparable. With tALP the best combination of sensitivity (96%) and specificity of (91%) was reached at a cut-off point 224 U/L, the corresponding values were for TRACP 5b sensitivity (76%), specificity (89%) with a cut-off point 4.89 U/L, and for PSA sensitivity (65%), specificity (81%) at 23 ng/L for skeletal metastases. Patients treated with AD showed with increasing duration an increase in TRACP 5b values. TRACP 5b was less specific than tALP as a marker of skeletal metastases. TRACP 5b may have a role in the diagnostics of skeletal changes in PC with a focus on treatment-related skeletal changes.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Cross-Sectional Studies; Humans; Isoenzymes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Giant cell tumor of bone (GCT) is a bone-destroying tumor that sometimes recurs locally after treatment. A recent study showed increased levels of serum total acid phosphatase (TACP).. We assessed TACP in the serum of 26 patients with primary GCT, and in 5 of them who developed a local recurrence.. We found a correlation between TACP level in serum and tumor size. TACP levels that were elevated preoperatively in patients with GCT became normalized after surgery, but increased in 3 of the 5 patients with local recurrence.. TACP could be used as a tumor marker for monitoring response to treatment of GCT.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged; Neoplasm Recurrence, Local

The authors treated a 6-month-old boy with malignant infantile osteopetrosis using bone marrow transplantation. The patient's clinical response was compared with his biochemical response for bone metabolic markers such as tartrate-resistant acid phosphatase 5b (TRAcP 5b) and bone-specific alkaline phosphatase (BAP). Treatment was successful, resulting in a decrease in the serum TRAcP 5b level. These bone-specific markers may be useful for the early assessment of malignant infantile osteopetrosis patients with stem cell transplantation.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone Marrow Transplantation; Bone Neoplasms; Graft Survival; Humans; Infant; Isoenzymes; Male; Osteoblasts; Osteoclasts; Osteopetrosis; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

Tumor metastasis and invasion to bone is one of major medical issues in our modern societies. Osteopontin deficiency decreased tumor invasion in bone based on knockout mouse study. In bone, osteopontin is a positive factor to increase tumor invasion.. Osteopontin is an arginine-glycine-aspartate (RGD)-containing protein and is recognized by integrin family members. Osteopontin promotes cell attachment to bone, where it is abundantly present. Because osteopontin levels were reported to be elevated in patients bearing highly metastatic tumors, this molecule has been implicated in the metastasis of tumors. However, the effect of osteopontin on the invasion of tumor cells in bone microenvironment has not been clear. The purpose of this paper is to elucidate the effect of host osteopontin on the behavior of tumor cells in bone.. Bone marrow ablation was conducted in the femora of mice, and B16 melanoma cells were injected directly into the ablated bone marrow space of the osteopontin-deficient and wildtype mice.. Invasion foci of B16 melanoma cells in the cortical bone was observed 7 weeks after tumor cell implantation. The number of the foci was 5-fold less in osteopontin-deficient mice compared with that in wildtype mice. In wildtype mice, trabecular bone formation was not observed in the ablated marrow space where tumor cells were injected. In contrast, significant levels of trabecular bone were observed in the marrow space of osteopontin-deficient mice even after tumor cells were injected. To examine cellular mechanisms underlying these observations, co-cultures of bone marrow cells and B16 cells were conducted. While the presence of B16 cells promoted TRACP+ cell development in wildtype bone marrow cells, such enhancement in TRACP+ cell formation by the co-cultures with B16 cells was reduced in the case of bone marrow cells from osteopontin-deficient mice.. Osteopontin deficiency reduced the bone loss caused by tumor cell implantation into the bone marrow space.

Topics: Acid Phosphatase; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Bone Regeneration; Cell Division; Coculture Techniques; Female; Femur; Isoenzymes; Male; Melanoma, Experimental; Mice; Mice, Knockout; Neoplasm Metastasis; Osteoclasts; Osteopontin; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.

Topics: Acid Phosphatase; Adult; Aged; Antineoplastic Agents; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Case-Control Studies; Diphosphonates; Female; Humans; Isoenzymes; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aminoglutethimide; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Fatal Outcome; Humans; Ketoconazole; Lymphatic Metastasis; Male; Neck; Neoplasm Proteins; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms

Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N-terminal cross-linking telopeptide of type-I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2-microglobulin, paraprotein, interleukin-6 (IL-6), were also performed. Levels of TRACP-5b were increased (p <.0001), while OPG was decreased in MM patients compared to controls (p <.01). TRACP-5b levels were associated with the radiographically assessed severity of bone disease (p <.0001) as well as with levels of NTX, IL-6 and beta2-microglobulin (p <.001, for each biochemical parameter, respectively). The combination of pamidronate with VAD-chemotherapy produced a reduction in TRACP-5b, NTX, IL-6, paraprotein and beta2-microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP-5b and changes in NTX, IL-6 and beta2-microglobulin, while TRACP-5b predicted the disease progression in 5 patients. These findings suggest that TRACP-5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; C-Reactive Protein; Cytarabine; Dexamethasone; Diphosphonates; Female; Glycoproteins; Humans; Interleukin-6; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteocalcin; Osteoclasts; Osteogenesis; Osteoprotegerin; Pamidronate; Paraproteins; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reference Values; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase; Vincristine

Bone destruction is primarily mediated by osteoclastic bone resorption, and cancer cells stimulate the formation and activation of osteoclasts next to metastatic foci. Accumulating evidences indicate that receptor activator of NF-kB ligand (RANKL) is the ultimate extracellular mediator that stimulates osteoclast differentiation into mature osteoclasts. In contrast, osteoprotegerin (OPG) inhibits osteoclast development. In order to elucidate a mechanism for cancer-induced osteoclastogenesis, cells from a human breast cancer line, MDA-MB-231, were directly co-cultured with ST2, MC3T3-E1, or with primary mouse calvarial cells. Osteoclast-like cells and tartarate resistant acid phosphatase (TRAP) activities were then quantitated. We examined these cell lines and samples from breast cancer by RT-PCR for the expressions of OPG and RANKL mRNA. Compared to controls, co-culture of MDA-MB-231 cells with stromal or osteoblastic cells induced an increase in number of osteoclasts and TRAP activities. MDA-MB-231 cells alone or breast cancer samples did not express RANKL mRNA. However, co-culture of these cancer cells with stromal or osteoblastic cells induced RANKL mRNA expression and decreased OPG mRNA expression. These experiments demonstrate that direct interactions between breast cancer and stromal or osteoblastic cells induce osteoclastogenesis in vitro through modulating RANKL expression.

Topics: 3T3 Cells; Acid Phosphatase; Animals; Bone Neoplasms; Breast Neoplasms; Carrier Proteins; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Glycoproteins; Humans; Isoenzymes; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Osteoblasts; Osteoclasts; Osteoprotegerin; Protein Binding; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Time Factors

To detect the expression of multidrug resistance-associated protein 1 (MRP1) in human ostesarcoma and to explore its relationship with clinicopathologic characteristics.. Six normal bone specimens and 45 osteosarcomas from patients were analysed for MRP1 expression by immunohistochemistry. The expression levels of MRP1 with the clinicopathologic parameters of the patients were examined using Chisquare test.. The expression of MRP1 was observed in 32 (71.11%) osteosarcoma specimens. More(P < 0.05) specimens expressed MRP1 in high-grade osteosarcomas(30/38, 78.95%) than in low-grade osteosarcomas (2/7, 28.57%). The correlation coefficient between expression of MRP1 and grade of pathology was 0.844. In a limited number of patients, the expression of MRP1 was not related to the the age and sex of the patients, Enneking surgical stage, osteosarcoma size, serum concentration of ALP and duration before diagnosis. No expression of MRP1 in 6 normal bone specimens was observed.. MRP1 is expressed in osteosarcoma and its expression is positively correlated with the malignancy of osteosarcoma.

Topics: Acid Phosphatase; Adolescent; Adult; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bone Neoplasms; Child; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Humans; Immunohistochemistry; Male; Middle Aged; Osteosarcoma

When monocytes were cocultured with human osteosarcoma-derived cells (HOS cells), multinucleated giant cell formation of monocytes was induced. Intriguingly, even when a filter was interposed between monocytes and HOS cells, polykaryocytes also appeared. The multinucleated giant cells have characters similar to osteoclast-like cells. These findings indicate that soluble factor(s) secreted from HOS cells play an important role in polykaryocyte formation from monocytes. Twelve cloned cells were established from HSOS-1 cells and their capacities of inducing osteoclasts were investigated. Three cloned cells inducing nos. 4 and 9 had an ability of inducing osteoclasts (multinucleated giant cells, TRAP, calcitonin receptor and c-src mRNAs, osteoresorbing activity), and three cells, including nos. 1 and 5, did not show the ability. HOS cells and the cloned cells expressed several cytokine mRNAs. M-CSF was detected in the culture fluids of HOS cells, which also expressed RANK and RANK/ODF/OPGL mRNAs. Intriguingly, HOS cells secreting a soluble osteoclast inducing factors(s) expressed TNF-alpha converting enzyme mRNA. Furthermore, OCIF/OPG inhibited HOS cell-induced osteoclastogenesis and soluble RANKL could be detected in the culture fluids of HOS cells expressing TACE, suggesting that one of soluble osteoclast-inducing factor(s) is soluble RANKL. When blood monocytes were indirectly cocultured with HSOS-1 cells or cloned no. 9 cells in the presence of OCIF for 14 days, HOS cell-mediated osteoclastogenesis was suppressed, indicating that RANK-RANKL system is involved in the HOS cell-mediated osteoclastogenesis.

Topics: Acid Phosphatase; Adolescent; Animals; Biological Factors; Bone Neoplasms; Bone Resorption; Cell Differentiation; Cell Fusion; Cell Line; Child; Clone Cells; Coculture Techniques; Coloring Agents; DNA, Complementary; Electrophoresis, Polyacrylamide Gel; Female; HeLa Cells; Humans; Isoenzymes; Mice; Monocytes; Osteoclasts; Osteosarcoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Topics: Acid Phosphatase; Animals; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Dogs; Estradiol; Estradiol Congeners; Follow-Up Studies; History, 20th Century; Humans; Male; Orchiectomy; Prognosis; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Reference Values; Testosterone

Neuroblastoma originates from neural crest cells and is the most common extracranial solid tumor in childhood. Bone metastasis in neuroblastoma is an unfavorable prognostic factor even with intensive therapy. In the present study, we screened four cell lines of human neuroblastoma (NB-1, NB-16, NB-19, and NH-6) for tumorigenicity and metastatic capacity in nude mice and found that NB-19 cells caused osteolytic lesions after s.c. injection into mice. To detect micrometastases in the host tissue, we performed two kinds of PCR-based metastasis assays: (a) genomic PCR assay using the primers for human genome-specific Alu sequence; and (b) reverse transcription-nested PCR assay that detects the expression of tyrosine hydroxylase, a marker specific for neuroblastoma. The results of these PCR assays revealed the colonization of human neuroblastoma cells in the bone marrow of the mice that had received the s.c. injection of NB-19 cells. Because osteoclastic bone resorption has been reported to play important roles in osteolysis in some cancers such as breast cancer, we next examined the osteoclast (OC)-inducing activity of NB-19 cells using a coculture system in which NB-19 cells were cultured with murine bone marrow cells containing OC precursors and stromal cells. NB-19 cells induced tartrate-resistant acid phosphatase-positive multinucleated OC-like cells without requirement of 1,25-dihydroxyvitamin D3 or other osteoclastogenic stimulators. To investigate the factors involved in the osteoclastogenesis in the coculture of mouse marrow cells and NB-19 cells, we performed reverse transcription-PCR analysis and revealed the increased expression of receptor activator of nuclear factor kappaB ligand (RANKL) in the coculture compared with the culture of bone marrow cells alone. Interleukin-1alpha and cyclooxygenase-2 expression in the murine marrow cells was also increased in the presence of NB-19 cells. To further study the role of RANKL in the OC-like cell formation in the coculture of NB-19 cells and murine marrow cells, an expression vector encoding the active portion of the murine osteoprotegerin, which is the native inhibitor of RANKL action, was constructed and introduced into COS-7 cells. The conditioned media of the COS-7 cells transfected with the osteoprotegerin expression vector effectively blocked OC-like cell formation in the coculture of the bone marrow cells and NB-19 cells. These results suggested that in the bone microenvironment of NB-19-bearing mi

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Bone Neoplasms; Carrier Proteins; Cell Communication; Coculture Techniques; COS Cells; Cyclooxygenase 2; Female; Glycoproteins; Humans; Interleukin-1; Isoenzymes; Membrane Glycoproteins; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neuroblastoma; Osteoclasts; Osteoprotegerin; Prostaglandin-Endoperoxide Synthases; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Transplantation, Heterologous; Tumor Cells, Cultured

In the present study, four bone metabolic markers were examined to clarify them meaning and clinical value in the detection of bone metastasis (BM) from breast cancer.. we examined serum carboxyterminal telopeptide of type I collagen (ICTP), tartrate resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP) and urinary type I collagen cross-linked N-telopeptides (NTx) as potential markers. These bone markers were evaluated simultaneously in 156 breast cancer patients; 114 patients without metastasis (group A), 23 patients with BM (group B) and 19 patients with metastasis at sites other than bone (group C).. The mean values of ICTP and TRACP in group B were significantly greater than those in group A. Group B consisted of the patients with varying degrees of BM and variation in their treatments. The patients in group B were divided into BM (+) and BM (++) according to hot spots in bone scan. ICTP and TRACP were elevated in BM (++) patients compared to BM (+) patients (p<0.05). The values of ICTP and TRACP of the twelve patients without treatment in group B were significantly higher than those in group A. In the treated patients of group B, the mean values of ICTP and TRACP were lower in responders and cases of stable disease than those with progression. NTx and ALP were inferior to ICTP and TRACP for clinical evaluation of BM.. We confirmed that ICTP and TRACP might be useful markers for screening and monitoring BM in breast cancer.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Collagen; Collagen Type I; Female; Humans; Isoenzymes; Middle Aged; Peptides; Tartrate-Resistant Acid Phosphatase

We investigated the clinical usefulness of measuring the serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen (PICP) as markers for monitoring metastatic bone activity in patients with prostate cancer.. Serum levels of ICTP, PICP, alkaline phosphatase, prostatic acid phosphatase and prostate specific antigen (PSA) were analyzed in 104 untreated patients with prostate cancer, including 62 with and 42 without bone metastasis. Serial measurements of ICTP, PICP and PSA were performed during hormonal therapy in 35 of 62 prostate cancer patients with bone metastasis.. Serum levels of all markers except prostatic acid phosphatase were significantly higher with than without bone metastasis. The median values of each marker increased according to the extent of bone metastasis. Serial ICTP, PICP and PSA in 19 patients with a partial response or no change in bone scans demonstrated a downward trend after treatment, while in 16 with progression they showed an upward trend after treatment. The rate of detecting bone metastasis and progression using ICTP were highest compared with other markers based on the percent clinical effectiveness and receiver operating characteristic curves.. Measuring serum ICTP may be useful for detecting bone metastasis and prostate cancer progression, and may augment PSA and bone scan monitoring of metastatic bone activity.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Collagen; Collagen Type I; Humans; Male; Middle Aged; Peptide Fragments; Peptides; Procollagen; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases

The serum acid phosphatase value was examined in nine patients with giant cell tumour of bone. Five showed a high level of acid phosphatase, which fell to within normal limits after surgery. Although the remaining four patients showed a normal acid phosphatase level before surgery, the postoperative acid phosphatase level was lower than the preoperative level in each case. Therefore, it is strongly suggested that serum acid phosphatase is a useful tumour marker in diagnosing giant cell tumour of bone as well as in evaluating the efficacy of treatment.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Female; Giant Cell Tumor of Bone; Humans; Male; Middle Aged

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

We cloned the human tartrate-resistant acid phosphatase (TRAP) gene from human osteosarcoma cells (Saos-2), and produced recombinant human TRAP (rhTRAP) using a baculovirus vector expression system. RhTRAP from Sf9 culture medium was purified by cation exchange chromatography, gel filtration and affinity chromatography. The molecular mass and amino acid composition of the rhTRAP were consistent with the deduced amino acid composition from the TRAP gene. The N-terminal amino acid sequence of rhTRAP was identical to that of TRAP purified from osteoclastoma and hairy cell leukemia spleen. The monoclonal antibodies generated against rhTRAP also reacted to human placental TRAP (pTRAP). The optimum pH of rhTRAP and pTRAP were pH 5.0-5.5 and pH 6.0-6.5, respectively. The enzymatic activities of rhTRAP and pTRAP were activated by reducing agents such as 2-mercaptoethanol, dithiothreitol and ascorbic acid. The activities of rhTRAP and pTRAP were enhanced by Fe2+ ions, but were inhibited by Fe3+ ions. The present results indicate that rhTRAP has similar properties to the native human TRAP, and suggest that the enhancement of TRAP activity by reducing agents might be expressed via the reduction of Fe ions at the metal center.

Topics: Acid Phosphatase; Adult; Amino Acids; Animals; Antibodies, Monoclonal; Base Sequence; Bone Neoplasms; Cell Line; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydrogen-Ion Concentration; Insecta; Isoenzymes; Mice; Mice, Inbred BALB C; Osteosarcoma; Placenta; Pregnancy; Recombinant Proteins; Reducing Agents; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption, but the mechanism responsible for tumor-mediated osteoclast activation has not yet been clarified. In the present study we utilized a well-known human breast cancer cell line (MDA-231) in order to assess its capability to influence osteoclastogenesis in human bone marrow cultures and bone resorption in fully differentiated osteoclasts. We demonstrated that conditioned medium (CM) harvested from MDA-231 increased the formation of multinucleated TRAP-positive cells in bone marrow cultures. Bone resorption activity of fully differentiated human osteoclasts and of osteoclast-like cell lines, from giant cell tumors of bone (GCT), was highly increased by the presence of MDA-231 CM. Moreover, while MDA-231 by themselves did not produce IL-6 tumor cell, CM increased the secretion of IL-6 by primary human osteoclasts and GCT cell lines compared to untreated controls. These data suggest that MDA-231 produce osteoclastic activating factor(s) that increase both osteoclast formation in bone marrow culture and bone resorption activity by mature cells. Moreover, breast cancer cells stimulate IL-6 secretion by osteoclasts that is one of the factors known to supports osteoclastogenesis.

Topics: Acid Phosphatase; Biomarkers; Bone Marrow Cells; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Differentiation; Cells, Cultured; Culture Media, Conditioned; Female; Giant Cell Tumors; Humans; Isoenzymes; Liver Neoplasms; Osteoclasts; Osteogenesis; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

The report discusses a study of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) as biochemical markers of bone resorption as well as total bone alkaline phosphatase level (APh) and that of its bone fraction as criteria of osteogenesis in skeletal lesions in breast, prostate and lung cancer and multiple myeloma. The investigation established a significantly enhanced Pyd and Dpyd excretion with urine and increased blood-serum APh levels in skeletal cancers (n = 271) as compared with healthy subjects (n = 173) and patients without bone metastases (n = 94). A case has been made for determination of total excretion of Pyd crosslinks of collagen to diagnose bone metastases. Most pronounced hyperenzymemia was found in prostate cancer which points to the leading role of APh as a bone metastasis marker. Pyd and Dpyd excretion and APh levels were significantly higher among patients multiple metastases with than in those with single bone metastases. The universality of pyridinoline crosslinks as skeletal damage markers has been confirmed by establishing a significant correlation between drug and therapeutic effect for Pyd and Dpyd only, in patients receiving ibandronate.

Topics: Acid Phosphatase; Amino Acids; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Bone Remodeling; Clinical Enzyme Tests; Female; Humans; Male; Neoplasms; Osteoporosis; Reference Values

Spectrometry has been employed to assess the levels of collagenase, catepsin D, trypsin-like proteinases and their inhibitors as well as bone acid and alkaline phosphatase both in the center and along the periphery of giant cell tumor of bone (GCTB) and chondrosarcoma. The levels of collagenase, trypsin-like proteinases and their inhibitors in the center of chondrosarcoma were much higher while those of alkaline phosphatase--lower than along tumor periphery. The catepsin D and acid phosphatase concentrations of the center and periphery of chondrosarcoma were similar. It was suggested that an extremely low concentration of trypsin-like inhibitors may contribute to degradation of the matrix in tissues adjacent to chondrosarcoma and, consequently, to tumor invasion development.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Cathepsin D; Chondrosarcoma; Collagenases; Femoral Neoplasms; Femur; Giant Cell Tumor of Bone; Humans; Ilium; Statistics, Nonparametric; Tibia; Trypsin; Trypsin Inhibitors

The osteolytic activity of metastases of prostate cancer was evaluated in relation to total body bone mineral content (TBBMC) and regional bone mineral content (RBMC).. Bone mass was determined by dual-energy X-ray absorptiometry (DXA). Tartrate-resistant acid phosphatase (TRAP) was measured as a biochemical marker of bone resorption.. In 32 patients (mean age 72+/-4 years) compared with 32 controls (mean age 73+/-5 years), there were significant differences in TRAP (P < 0.0001), TBBMC (P < 0.0001), and RBMC in the pelvis (P < 0.0001), legs (P=0.0001), and trunk (P<0.05), but not in the arms and head (P=ns). In the overall group of subjects, the correlation between TBBMC and TRAP was r=-0.68, P < 0.0001. The correlations remained significant in the patient and control groups separately.. The loss of bone mass observed in patients with metastatic prostate cancer was caused mainly by the predominance of bone resorption in the osteoblastic metastases.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Alkaline Phosphatase; Analysis of Variance; Biomarkers; Bone Density; Bone Neoplasms; Bone Remodeling; Bone Resorption; Calcium; Humans; Isoenzymes; Male; Neoplasm Metastasis; Prostatic Neoplasms; Reference Values; Regression Analysis; Tartrate-Resistant Acid Phosphatase

A 63-year-old man, who had undergone prostatectomy for prostate cancer that was positive for prostate-specific antigen (PSA) was examined and found to have metastatic disease, proven radiologically and pathologically, but with an undetectable PSA and highly elevated prostatic acid phosphatase (PAP). Prostatic acid phosphatase levels fell in response to chemotherapy but his clinical status continued to deteriorate. A review of the literature is presented and several possible explanations for PSA remaining undetectable in these situations are discussed. The authors conclude that although PSA can be used to monitor the majority of patients postprostatectomy, physicians may still need to rely on clinical suspicion, serum PAP, and bone scan for the detection of recurrent disease.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Humans; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

It is reported that Chinese hamster ovary cells transfected with human alpha4 cDNA (alpha4CHOs) and expressing functional alpha4beta1 integrin developed bone metasasis in nude mice. To clarify the role of alpha4beta1 integrin in bone metastasis, in terms of tumor-mediated bone destruction, we examined whether alpha4CHOs stimulate osteoclast formation in cocultures with mouse bone marrow cells. The number of osteoclast-like cells identified as tartrate-resistant acid phosphatase positive multinucleated cells (TRAP(+) MNCs) formed from bone marrow cells increased with the increasing number of alpha4CHOs cocultured. The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and prostaglandin E2 (PGE2) on TRAP(+) MNC formation were enhanced in cocultures with alpha4CHOs. TRAP(+) MNCs induced by alpha4CHOs possessed calcitonin receptors and resorbed calcified tissues. In cocultures, alpha4CHOs and bone marrow stromal cells were in contact with each other and bone marrow stromal cells expressed vascular cell adhesion molecule-1 (VCAM-1), which is one of the ligands for alpha4beta1 integrin. TRAP(+) MNC formation was not stimulated in cocultures where direct contact between alpha4CHOs and bone marrow cells was inhibited by membrane filters. Alpha4CHOs do not support TRAP(+) MNC formation in cocultures with spleen cells but do support TRAP(+) mononuclear cell and MNC formation from spleen cells in the presence of osteoblastic cells. Cultured media from alpha4CHOs, bone marrow cells, and cocultures of alpha4CHOs and bone marrow cells did not stimulate TRAP(+) MNC formation or enhance the effects of 1,25(OH)2D3 and PGE2 in bone marrow cultures. The concentrations of PGE2 and interleukin-6 (IL-6) in cultured media were not different between the cultures of bone marrow cells and the cocultures of bone marrow cells and alpha4CHOs. Anti-human alpha4 and anti-mouse VCAM-1 antibodies inhibited TRAP(+) MNC formation induced by alpha4CHOs. These results indicate that alpha4CHOs stimulated TRAP(+) MNC formation through direct cell-to-cell interaction between alpha4beta1 and VCAM-1. It is suggested that in addition to various soluble factors regulating osteoclast formation, cell-to-cell interaction between tumor cells and bone marrow cells is important for inducing osteoclasts at the site of bone metastasis and leading to bone destruction.

Topics: Acid Phosphatase; Animals; Bone Development; Bone Marrow Cells; Bone Neoplasms; Calcitriol; Cell Communication; Cell Line, Transformed; CHO Cells; Coculture Techniques; Cricetinae; Dinoprostone; Immunohistochemistry; Integrin alpha4beta1; Integrins; Interleukin-6; Isoenzymes; Male; Mice; Osteoclasts; Receptors, Lymphocyte Homing; Spleen; Tartrate-Resistant Acid Phosphatase; Vascular Cell Adhesion Molecule-1

Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16 patients with advanced prostatic cancer before and after treatment with luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum LH and testosterone levels was observed on day 2 of the treatment. Subsequently, serum concentrations of PAP and PSA showed a transient increase on day 5 of the treatment. This indicates that LHRH analogues had better be given in combination with antiandrogens in patients with metastatic carcinoma of the prostate.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Follow-Up Studies; Humans; Immunoenzyme Techniques; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Treatment Outcome

Eleven hundred and seven patients referred for urological evaluation including measurement of serumprostate specific antigen (PSA) measurement are reviewed. Prostate cancer was diagnosed in 105 patients. PSA was found to be superior to prostatic acid phosphatase in the discrimination between prostate cancer and benign prostatic conditions. In 105 patients with newly diagnosed prostate cancer, scintigraphic evidence of osseous metastases was found in thirty-seven. No patients with a serum PSA value less than three times the upper normal limit of the assay had a positive bone scan. Isotope bone scan can be omitted in these patients, if they are not considered candidates for curative treatment.

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Rectum; Retrospective Studies

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result o

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Androstenediol; Antineoplastic Agents, Hormonal; Bone Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Testosterone

The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients.. Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test.. The levels of PSA showed significant differences among 8 pairs of clinical stages. In contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis.. PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Reproducibility of Results; Retrospective Studies; ROC Curve

The effects of a third-generation bisphosphonate, YM175 (disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate), on bone resorption induced by a metastatic human melanoma cell line (A375) were investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 in the left cardiac ventricle produced multiple osteolytic lesions. Then, 4 weeks after the cell injection, we administrated YM175 (1 mg/kg) intravenously once and sacrificed the animals 3 days later. On histochemical observation, there was a layer of stromal cells with numerous mononuclear and multinucleated tartrate-resistant acid phosphatase (TRAPase)-positive cells in the untreated control group. In contrast, this layer was extensively reduced in most areas, and only a few TRAPase-positive cells were seen around tumor nests and on the bone surface in the experimental group. Most of the TRAPase-positive cells were stained only weakly and/or homogeneously, and there was little evidence of cell polarity. Some of them were vacuolated. Ultrastructurally, they were round and devoid of ruffled borders and clear zones. The findings suggest that YM175 decreases the number and activity of osteoclasts. In addition, a few showed the morphology of cell death, which seemed to be one of the reasons leading to the decrease of osteoclasts. There was no substantial change in the morphological relationships or ultrastructure of osteoclast precursor cells, stromal cells, extracellular matrices, and tumor cells between the experimental and the control groups. In the experimental group, the distribution of extracellular matrices (heparan sulfate proteoglycan and fibronectin) was less conspicuous, but the localization of osteotropic cytokines (interleukin-6 and prostaglandin E2) was essentially similar to that of the control group. The cause leading to the decrease of osteoclast precursor cells remains to be clarified. In conclusion, YM175 inhibits bone resorption induced by tumor, by decreasing the activity of mature osteoclasts and possibly affecting the production of osteoclast precursor cells.

Topics: Acid Phosphatase; Animals; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Diphosphonates; Humans; Immunohistochemistry; Isoenzymes; Male; Melanoma; Mice; Mice, Nude; Neoplasm Transplantation; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Osteoclasts (OCs), which form by fusion of hematopoietic precursor cells, are typically present in large numbers in giant cell tumors of bone (GCTBs). These tumors may, therefore, contain cells which secrete factors that stimulate recruitment and differentiation of OC precursors. Multinucleated cells resembling OCs also form in cultures of human cord blood monocytes (CBMs) stimulated by 1.25 dihydroxyvitamin D3, but these cells lack the ability to form bone resorption pits, the defining functional characteristic of mature OCs. CBMs may thus require additional stimulation to form OCs; we therefore investigated whether GCTBs are a source of such a stimulus. CBMs were stimulated in long term (21 day) culture by medium conditioned by explants of GCTBs; media collected within 15 days of explant (early-CM) and after 15 days (late-CM) were employed. We also cocultured CBMs with primary GCTB-derived stromal cells as well as immortalized bone marrow stroma-derived cells. CBMs stimulated by early-CM formed resorption pits on cortical bone slices; however, stimulation by late-CM resulted in virtually no resorption. Both early-CM and late-CM increased CBM proliferation, but not the proportion of vitronectin receptor positive or multinucleated cells. Coculture of CBMs with stromal cells of GCTBs or bone marrow did not result in bone resorption, although these stromal cells (most expressing alkaline phosphatase but progressively losing parathyroid hormone receptor expression) expressed mRNA for cytokines involved in OC differentiation, including macrophage-CSF, granulocyte-macrophage-CSF, IL-11, IL-6, and stem cell factor. Our results indicate that CBMs are capable of terminal OC differentiation in vitro, a process requiring 1,25 dihydroxyvitamin D3 as well as diffusible factor(s) which can be derived from GCTB. Stromal cells of GCTB may produce such factors in vivo, but do not support OC differentiation in vitro, possibly through phenotypic instability in culture.

Topics: Acid Phosphatase; Alkaline Phosphatase; Base Sequence; Bone Neoplasms; Bone Resorption; Cell Differentiation; Cytokines; DNA Primers; Fetal Blood; Giant Cell Tumors; Humans; Molecular Sequence Data; Monocytes; Osteocalcin; Osteoclasts; Osteolysis; Receptors, Parathyroid Hormone; Tumor Cells, Cultured

The evaluation of "new" and "traditional" markers of osteoblastic and osteoclastic activity, in patients with bone metastases.. Our series consist of 40 patients with clinical, radiological, and scintigraphic evidence of bone metastases, and 40 age-matched healthy subjects. In all samples, traditional markers were evaluated by measuring total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TrACP) activity, and osteocalcin (BGP) concentration. To assess new biochemical bone markers, bone isoenzyme of alkaline phosphatase (ALP-B) activity, carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal telopeptide of type I collagen (ICTP) concentrations were measured.. Our findings showed that the best diagnostic efficiency is provided by ICTP (0.94) followed by total ALP (0.90), ALP-B (0.80), and TrACP (0.76). The efficiency of BGP and PICP was, instead, very low (0.64 and 0.60, respectively).. Our results confirm the utility of the new serum markers such as ALP-B and ICTP assays in detecting bone metastases.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Neoplasms; Collagen; Collagen Type I; Humans; Isoenzymes; Middle Aged; Osteoblasts; Osteocalcin; Osteoclasts; Peptide Fragments; Peptides; Procollagen; ROC Curve; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

This study evaluated the ability of bisphosphonate to prevent bone resorption induced by metastatic tumor cells.. Autopsy specimens of a bone metastasis from a woman with a primary squamous cell carcinoma of the tongue who developed multiple osteolytic lesions and hypercalcemia and was treated with pamidronate were studied histologically, histochemically, and ultrastructurally. In an animal experiment, cultured tumor cells (1 x 10(5)) obtained from a metastatic submandibular lymph node in the same patient were injected in the left ventricle of nude mice, and a resulting metastatic bone lesion was studied histologically and histochemically.. In the autopsy specimens, despite the presence of many resorption lacunae on bone surface, only a few small tartrate-resistant acid phosphatase (TRAPase)-positive cells were observed, and most of them were stained weakly and detached from the bone surface. In the animal experiment, 1 of 10 animals (10%) formed osteolytic bone metastasis, and many TRAPase-positive cells were observed histochemically.. Biphosphonate inhibits bone resorption induced by tumor, possibly by decreasing the number of osteoclasts and inhibiting their function.

Topics: Acid Phosphatase; Aged; Animals; Bone Neoplasms; Bone Resorption; Carcinoma, Squamous Cell; Diphosphonates; Female; Humans; Hypercalcemia; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoclasts; Pamidronate; Spinal Neoplasms; Tartrate-Resistant Acid Phosphatase; Thoracic Vertebrae; Tongue Neoplasms; Tumor Cells, Cultured

The possible application of proteinase inhibitors in the support of anti-tumor chemotherapy requires profound knowledge of the proteinases involved in malignant processes. Therefore, the occurrence of cathepsins B, D, H, L and S and of gelatinases, urokinase plasminogen activator and stromelysins was studied in biopsies of aggressive human bone metastases, of low invading basal cell carcinomas, and in normal placenta as control, by activity measurements and zymographic techniques. Cathepsin B and L, as well as gelatinase B, were shown to be overexpressed in bone metastases, suggesting a function during the metastatic process. Subcellular fractionation allowed detection of differential sorting of cathepsin B and gelatinases in metastatic tissue and also in normal human placenta. Plasma membrane binding could be demonstrated for both cathepsin B and gelatinase B. Whereas cathepsin B is at least partially bound to plasma membranes via alpha 2-macroglobulin and its LRP/alpha 2-macroglobulin receptor, gelatinase B binds to plasma membranes by an unknown mechanism.

Topics: 1-Phosphatidylinositol 4-Kinase; 5'-Nucleotidase; Acid Phosphatase; beta-N-Acetylhexosaminidases; Bone Neoplasms; Cathepsin B; Cathepsin L; Cathepsins; Cell Membrane; Collagenases; Cysteine Endopeptidases; Endopeptidases; Gelatinases; Humans; L-Lactate Dehydrogenase; Matrix Metalloproteinase 9; Neoplasm Metastasis; Phosphotransferases (Alcohol Group Acceptor); Subcellular Fractions; Urokinase-Type Plasminogen Activator

To compare the relative sensitivity and specificity of prostate-specific antigen (PSA) as a test for prostate cancer over a range of PSA values in a variety of patient groups, and to compare the sensitivity and specificity of PSA and prostatic acid phosphatase (PAP).. Receiver operating characteristic (ROC) curves (sensitivity plotted against 1-specificity) were constructed to compare the ability of PSA to discriminate men with prostate cancer (n = 257) from those with benign prostatic hyperplasia (BPH) (n = 220) or control patients (n = 164). Receiver operating characteristic curves were also constructed to compare PSA and PAP in 173 men with either BPH or prostate cancer.. When patients with symptomatic BPH and those with advanced prostate cancer are excluded, a PSA of 8 ng/mL has a sensitivity of 94% and a specificity of 98% for prostate cancer. In patients presenting with symptoms suggestive of bladder outflow obstruction, PSA remains a sensitive marker for prostate cancer (93% sensitivity at 10 ng/mL) but its specificity (65%) is poor. PSA is a sensitive test for skeletal metastases but levels of 60-80 ng/mL are required to achieve a specificity of 70% or more. The sensitivity of PSA is far superior to that of PAP.. Serum PSA provides good discrimination between patients with and without prostate cancer. The sensitivity and specificity of PSA can be improved by excluding men with symptomatic BPH. The specificity of PSA as a diagnostic test for prostate cancer is reduced in men with symptoms of bladder outflow obstruction. For reasonable sensitivity and specificity, a PSA of 60-80 ng/mL is required for differentiating non-metastatic from metastatic prostate cancer. The ROC curve comparing PSA and PAP provides a graphical demonstration of the superiority of PSA as a tumour marker. The ability of PSA to identify prostate cancer can be improved by selecting out groups of patients and by adjusting the cut-off level of PSA to the population under study.

Topics: Acid Phosphatase; Biomarkers; Bone Neoplasms; Humans; Male; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Sensitivity and Specificity; Urinary Bladder Diseases; Urinary Retention

Recent reports suggest that radionuclide bone scan (BS) may not be necessary in the standard staging evaluation of patients with prostate cancer when serum prostate-specific antigen (PSA) levels are normal. To evaluate the ability of PSA to predict BS findings, we retrospectively reviewed the case records of 118 consecutive patients (median age 73 years, range 50-90 years) with newly diagnosed, untreated, pathologically proven prostate cancer who underwent BS and serum PSA sampling within a period of no more than 3 months. Fifty-four out of 118 BSs demonstrated metastatic bone disease. A PSA value of less than 10 ng/ml excluded bone metastasis; of 35 patients with a serum PSA level of 20 ng/ml or less, seven had a positive BS (negative predictive value of 80%). These findings provide additional confirmation of the value of low serum PSA concentrations in excluding the need for a staging BS, although the threshold for a high value of negative predictive accuracy is lower than previously reported.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biopsy; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; ROC Curve

The aim of the present investigation was the evaluation of cost-effectiveness of variables used in monitoring patients with inoperable prostate cancer. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and radionuclide bone scan were considered. The tumor marker positivity was assessed according to dynamic criteria (> 50% increase between consecutive samples). 108 patients entered the study; 72 patients treated with a luteinizing hormone-releasing hormone analogue were followed up for periods ranging from 12 to 64 months. PSA and PAP levels were measured using immunometric assays. Both cutoff-based and dynamic, serial sample-based decision criteria were employed. With respect to a positive bone scan, PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points. Progression of the disease to the bone occurred in 20 patients: in 17 PSA was the first indicator of progression, in the other 3 PAP anticipated PSA for a very short time (3-4 months), which was not of relevance to clinical decisions. PAP is less specific and sensitive than PSA; PAP may eventually provide information on disease status in a limited percentage of patients with advanced prostate cancer treated with androgen ablation, being differently regulated with respect to PSA. No increasing PSA profile was detected in patients who responded to the therapy. From the results of the present investigation, we draw the following conclusions: (1) PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease, and (2) dynamic criteria of evaluation of serial PSA determinations probably provide more effective and earlier clinical information.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Cost-Benefit Analysis; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Immunoradiometric Assay; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Tomography, X-Ray Computed

Bone metastases frequently occur in prostate carcinoma. Total body radionuclide scan with diphosphonate methylene labelled with 99Tc is commonly used to diagnose such metastases. However this technique is aspecific and frequently unreliable. In recent years several biological markers dealing with bone metabolism were studied. Serum determination of skeletal alkaline phosphatase (ALP) and moreover of its bone isoenzyme (BAP) could be considered a reliable index of osteoblastic activity. In this preliminary report we analyzed a group of 43 patients affected by prostate carcinoma with or without bone metastases. The American Urological Association (AUA) staging system was adopted. Sixteen patients were D2, bone metastases had been suspected by means of radionuclide bone scan and confirmed by Computerized Tomography and/or aimed X-rays. Tandem R-Ostase by Hybritech was used to measure BAP, normal value is set to 20 micrograms/L. All D2 tumours had pathological BAP values (mean value 87.50 micrograms/l); 1/3 stage A, 5/13 stage B, 5/9 stage C and 0/2 stage D1 patients had pathological findings. One of this patients, stage C, revealed a bone metastase at a later bone scan.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Humans; Isoenzymes; Male; Neoplasm Proteins; Neoplasm Staging; Osteoblasts; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

Osteoclasts are terminally differentiated cells that express tartrate-resistant acid phosphatase (TRAP) at a higher level than other normal cells. Therefore, in an attempt to develop immortalized osteoclasts, we produced two lines of transgenic mice in which expression of the simian virus 40 T antigen oncogene was targeted to osteoclasts using the TRAP gene promoter. Osteoclasts were increased in number in bones from both lines. More than 50% of them appeared morphologically transformed, 2-5% were mitotic, but, unexpectedly, 5% were apoptotic. Osteoclast tumors were observed occasionally in one line of mice (line 4), and sheets of TRAP-positive cells (tumorlets) developed in most mice in both lines. Although cells isolated from these tumorlets formed multinucleated TRAP-positive cells that resorbed bone in vitro, to date we have been unable to develop an immortalized osteoclast cell line from them. Osteoclasts from one line (line 5) had reduced ruffled border formation and a higher level of T-antigen expression than osteoclasts in the other line (line 4), and these features were associated with the presence of osteopetrosis. However, osteoclasts from these osteopetrotic mice and from line 4 mice resorbed bone normally when the mice were treated with interleukin-1. These findings indicate that T antigen can be targeted to osteoclasts in transgenic mice and causes osteoclast transformation, tumors, mitosis, and apoptosis. When T antigen is expressed at high levels, functional impairment of osteoclasts can be detected. Furthermore, these results suggest that T antigen is insufficient on its own to immortalize cells in the osteoclast lineage.

Topics: Acid Phosphatase; Animals; Antigens, Polyomavirus Transforming; Apoptosis; Bone Neoplasms; Cell Transformation, Neoplastic; Female; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Osteoclasts; Osteopetrosis; Simian virus 40

We report a total of 169 serial bone scan studies conducted in 21 patients with histologically proven metastatic cancer of the prostate. Aim of the study was to investigate the concordance of findings on bone scans with serum acid phosphate (AP) levels and the clinical performance status (CPS) of the patients, and to see how important bone scan is by itself in determining the metastatic progression in the follow-up. Eighty-seven and 86% of scans demonstrated changes concordant with AP and CPS levels subsequently. It was also found that 100% of the progressions on bone scans along with elevated levels of AP had been confirmed as metastatic progression, whereas only 41% of progressions on bone scans solely had been shown to be metastases in the follow-up investigations. Findings on bone scans not in correlation with clinical findings and serum AP levels are mostly misleading. Use of bone scans in conjunction with serum AP levels and most probably with prostate-specific antigen and CPS is the most reliable and therefore treatment modality changes should not be based on bone scans only.

Topics: Acid Phosphatase; Adenocarcinoma; Bone and Bones; Bone Neoplasms; Clinical Enzyme Tests; Follow-Up Studies; Humans; Karnofsky Performance Status; Male; Middle Aged; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Medronate; Time Factors

Bone resorption resulting from the metastatic human melanoma cell line (A375) was investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 (1 x 10(5)) in the left ventricle produced multiple osteolytic lesions. Many TRAPase-positive multinucleated cells, identified by EM as osteoclasts, were observed on the bone surface at the site of metastases. The findings suggest that bone resorption was caused by osteoclasts developed in the presence of tumor cells. Even where tumor cells were juxtaposed to bone surface, small and flat TRAPase-positive cells were shown to exist on the bone surface. Thus, bone resorption was mainly associated with the occurrence of osteoclasts. A large number of osteoclast progenitor cells were also observed adjacent to tumor cells and/or stromal cells located apart from bone, indicating possible participation of tumor cells and/or stromal cells in the differentiation of osteoclasts. Ultrastructurally, stromal cells and/or extracellular matrices were present between tumor cells and osteoclast progenitor cells. Immunohistochemical observation clarified the localization of heparan sulfate proteoglycan (HSPG) and fibronectin (FN) around osteoclast progenitor cells. These findings suggest that they play an important role in providing a microenvironment favorable for osteoclast differentiation and activation. The immunohistochemical localization of IL-6, PGE2, and TGF-alpha also indicates that they are involved in osteoclast differentiation and activation. In conclusion, bone resorption at the metastatic sites of A375 is mediated via osteoclasts and A375 cells may be involved in the differentiation and activation of osteoclasts in association with stromal cells, extracellular matrices (HSPG, FN) and osteotropic cytokines (IL-6, PGE2, TGF-alpha).

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Bone Resorption; Cell Differentiation; Dinoprostone; Disease Models, Animal; Fibronectins; Giant Cells; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Immunohistochemistry; Interleukin-6; Male; Melanoma, Amelanotic; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Osteoclasts; Proteoglycans; Stem Cells; Stromal Cells; Transforming Growth Factor alpha; Tumor Cells, Cultured

The pretreatment bone scintigrams of 58 patients with prostate cancer with bone metastasis were reviewed and the prognostic value of the initial extent of bone involvement was compared with that of other pretreatment characteristics. The extent of bone metastasis revealed by the scan was related to survival. The serum level of alkaline phosphatase at pretreatment and pathological grade also had some predictive value. Although the pathological grade of primary tumours was related to prognosis, the survival of patients with the same histological grade differed according to the initial extent of disease; patients with extensive disease along with raised serum alkaline phosphatase (twice or more as high as the cut-off value) had poorer prognosis than did those with lower alkaline phosphatase or smaller extent of disease. The extent of bone involvement in combination with serum alkaline phosphatase level therefore apparently has higher prognostic value than does disease extent alone.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Neoplasms; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Survival Rate

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Whole-Body Counting

The ALVA-41 cell line was derived from a bony metastasis from a human prostatic carcinoma. The line has a number of distinct, advantageous properties that should make it useful as a tool for the study of prostate cancer. It grows rapidly and is easy to work with. It has receptors for androgens and glucocorticoids but not for estrogens. Its growth is enhanced by physiological concentrations of dihydrotestosterone. It does not secrete prostate specific antigen, but does secrete prostatic acid phosphatase. Further, the secretion of prostatic acid phosphatase is enhanced by dihydrotestosterone.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Cell Adhesion; Cell Division; Cholestenone 5 alpha-Reductase; Humans; Male; Oxidoreductases; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Glucocorticoid; Tumor Cells, Cultured

In a retrospective analytical study the authors evaluated in 86 patients, mean age 69 years (range 55-85 years), with a newly diagnosed untreated prostate carcinoma the sensitivity, specificity, positive and negative predictive value of specific prostatic antigen (PSA), acid phosphatase (AP), alkaline phosphatase (AP') and pain in relation to possible affection of bones by secondaries. The authors found a highly negative predictive value for assessment of bone metastases when PSA values were lower than 10 ng/ml (96%), at levels under 20 ng/ml (94%) and a highly positive predictive value at levels higher than 50 ng/ml (97%). When AP and AP' are negative and there is no pain the occurrence of secondaries is of low probability. These results make it possible to differentiate some patients where scintigraphy of the skeleton is not inevitable. This procedure can be applied above all in patients where radical prostatectomy is not indicated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity

We report a case of advanced prostate cancer in which an initial response to hormonal therapy with surgical castration and estramustine phosphate (EMP) was followed by disease progression, as shown by sequential elevations in serum prostate specific antigen (PSA) and prostate acid phosphatase (PAP) and the development of new symptoms, during maintenance endocrine and anti-cancer chemotherapy. Discontinuation of EMP resulted in sustained reductions in serum PSA and PAP levels and a sustained improvement in symptoms.

Topics: Acid Phosphatase; Adenocarcinoma; Biomarkers, Tumor; Bone Neoplasms; Castration; Estramustine; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Current clinical trials in disseminated prostatic cancer mostly use M0 or M1 to identify two prognostically different groups of patients. Soloway et al. [Cancer 1988;61:195-202] have shown a significant difference in survival depending on the extent of disease (EOD) on bone scan in M1 disease. Seventy-three prostatic cancer patients with bone-scan-proven metastases (T0-4 Nx M1 G1-3) from the Aust-Agder County in Norway with observation time 2-9 years were followed. The impact of T stage, grade, serum acid phosphatase status and EOD on survival was analyzed. EOD was assessed according to Soloway et al. No statistically significant difference could be demonstrated according to T stage or histological grade. A statistically significant difference in survival could be demonstrated both for normal versus elevated serum acid phosphatase and for EOD. EOD I/II had a better prognosis than EOD III/IV. Stratification of patients in EOD categories seems relevant, but the relative importance of the different EOD categories is not yet established.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Humans; Male; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Risk Factors; Survival Analysis; Survival Rate

Cells harvested from 12 human giant cell tumors of bone and kept in culture for several passages were characterized for bone-resorbing capability, total and tartrate-resistant acid phosphatase activity, response to the calciotropic hormone calcitonin, cell proliferation, multinucleation after passages, and presence of calcium sensing. Cells obtained from three tumors presented a complete panel of osteoclast characteristics and maintained their multinuclearity after several passages. Cells from four other tumors increased their cAMP levels after treatment with calcitonin, and the other five apparently consisted of cells of stromal origin. These human cell populations with osteoclast characteristics may provide valid in vitro models for the investigation of osteoclastic differentiation and activity.

Topics: Acid Phosphatase; Adult; Bone Neoplasms; Bone Resorption; Calcitonin; Calcium; Cell Differentiation; Cell Division; Cell Nucleus; Cyclic AMP; Female; Giant Cell Tumors; Humans; Male; Microscopy, Phase-Contrast; Middle Aged; Osteoclasts; Tumor Cells, Cultured

The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta-E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts.

Topics: Acid Phosphatase; Adult; Base Sequence; Bone Neoplasms; Bone Resorption; Cathepsin B; Cathepsin D; DNA Primers; Estradiol; Female; Gene Expression; Giant Cell Tumor of Bone; Humans; Isoenzymes; Male; Molecular Sequence Data; Osteoclasts; Receptors, Estrogen; RNA, Messenger; RNA, Neoplasm

25 patients with measurable or evaluable metastatic prostate cancer, progressive after hormonal treatment, were treated weekly with carboplatin 150 mg/m2 intravenously. The weekly schedule allowed higher dose intensity carboplatin administration with respect to the common monthly cycles. Toxicity was manageable even in elderly patients with extensive bone metastases and consisted primarily of myelosuppression. 4 out of 24 evaluable patients (17%) had a partial response and 12 (50%) had disease stabilisation. The median response duration was 7 months. Prostate-specific antigen and prostatic acid phosphatase serial values showed a correlation with disease response in only 47 and 50% of patients, respectively. These results suggest that carboplatin possesses a moderate but definite activity in prostate cancer patients.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bone Neoplasms; Carboplatin; Drug Administration Schedule; Drug Resistance; Hormones; Humans; Infusions, Intravenous; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Carcinoma of the prostate is the commonest malignancy of the genitourinary tract in the male and is frequently associated with metastatic bone disease. Serial isotope bone scans for screening secondary deposits are not cost-effective. We have evaluated the serum prostate markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as an alternative to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those who presented with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study period. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 micrograms/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 micrograms/l was 90.6%. During the follow-up period the sensitivity was 94.4%, the positive predictive value 100% and the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. When compared with PAP, PSA was found to be a statistically superior marker of bone metastases both at presentation and follow-up (p < 0.05). We recommend that PAP measurements are no longer necessary and should be replaced by PSA, and that serial serum PSA estimations should determine the need for future isotope bone scans in the patient with established prostate cancer.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Follow-Up Studies; Humans; Male; Predictive Value of Tests; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sensitivity and Specificity; Technetium Tc 99m Medronate; Time Factors

We have studied the effect of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) on the morphology of rat bone and the metastatic behavior of Walker 256 (W256) cancer cells in the rat skeleton. Male Fischer rats (150-175 g) received s.c. injections for 7 days with APD (0.5 mg/kg body weight/day) (+ APD; n = 20) or with vehicle (-APD; n = 20). Subsequently, 10 + PD and 10 -APD rats received i.m. injections with W256 cells (+ W256), and the remaining rats received injections of vehicle (-W256). All rats were killed 14 days later. Trabecular bone volume was increased by 46 +/- 3% by APD treatment alone and was decreased by 56 +/- 7% (SEM) by W256 tumor burden alone. After 14 days of tumor burden, + APD/+ W256 rats had 3-fold more trabecular bone than did -APD/+W256 rats. Despite this bone-sparing effect, APD treatment of +W256 rats was associated with a 2.6-fold increase in skeletal tumor burden, while metastatic tumor burden in the liver, lungs, and kidneys was unaffected. The increased skeletal tumor burden in + APD/+ W256 rats was accompanied by an increase in the growth rate of W256 cells located in bone. Independent of APD treatment, W256 cells located adjacent to trabecular bone surfaces had greater growth rates than did W256 cells in the marrow, located > 50 microns from trabecular bone. In summary, the APD-induced increase in trabecular bone volume in rats is associated with a selective increase in skeletal tumor burden and an increased growth rate of W256 cells in the skeleton.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Neoplasms; Carcinoma 256, Walker; Cell Division; Diphosphonates; Femoral Neoplasms; Male; Pamidronate; Pilot Projects; Rats; Rats, Inbred F344; Thymidine

Quantitative bone scintigraphy was performed in 24 patients with prostatic carcinoma before orchiectomy and up to one to four years after operation. The gamma camera count rate was recorded over the lower thoracic and all lumbar vertebrae 4 h after injection of 99mTc-MDP. Twelve patients had normal bone scintigrams throughout the study. They showed from two years after operation a slight increase in count rate values compared with the preoperative values, probably due to hormonal changes after orchiectomy and to age-related alterations in skeletal metabolism. Twelve patients had abnormal bone scintigrams. They showed as a response to treatment the flare phenomenon with an increase in count rate over the abnormal vertebrae when measured two weeks after operation followed by a decrease after two months. The lowest count rate values were obtained between six months and one year after operation. Thereafter the count rate seemed to remain on the same level. An increase in count rate was connected to progression of disease and the patients died of prostatic carcinoma within one year thereafter.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate; Treatment Outcome

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Humans; Male; Orchiectomy; Prognosis; Prospective Studies; Prostatic Neoplasms; Treatment Outcome

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Follow-Up Studies; Goserelin; Humans; Life Tables; Male; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Testosterone; Time Factors; Treatment Outcome

To study the effects of osteoblast products on osteoclast formation, we added the conditioned medium (CM) of rat osteoblastic cell line ROS17/2.8 to rat bone marrow cultures, in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleate cells (MNCs) formed in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The formation of 1,25(OH)2D3-dependent TRAP-positive MNC at day 7 of culture was strongly inhibited by the > 10 kDa fraction of ROS17/2.8 cell-CM (ROSCM), but heat treated ROSCM (htROSCM) expressed marked stimulation in the formation of the MNCs. The expression of several osteoclastic phenotypes of the MNCs induced by htROSCM and 1,25(OH)2D3 was more enhanced compared with that of the MNCs induced by 1,25(OH)2D3 alone. The MNCs induced by htROSCM and 1,25(OH)2D3 were highly motile, were sensitive to calcitonin (CT), and had high bone resorbing activity. These data suggest that htROSCM promotes the osteoclast differentiation in the presence of 1,25(OH)2D3 in a rat bone marrow culture system. The stimulatory activity of TRAP-positive MNC formation in htROSCM is derived from heat-stable protein(s) that is (are) thought to be different from colony-stimulating factors (CSFs) such as macrophage-CSF (M-CSF) or granulocyte-macrophage-CSF (GM-CSF).

Topics: Acid Phosphatase; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Bone Resorption; Calcitonin; Calcitriol; Cell Differentiation; Cell Movement; Cells, Cultured; Culture Media, Conditioned; Dentin; Hot Temperature; Male; Osteoblasts; Osteoclasts; Osteosarcoma; Phenotype; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Time Factors; Tumor Cells, Cultured

The objective of this study was to determine whether demineralized rat incisor matrices were a more potent inducer of ectopic endochondral bone formation than demineralized diaphyseal bone matrices derived from the same donors. Twenty-five-milligram disks of demineralized bone or tooth matrix obtained from adolescent Long-Evans rats were implanted in a standardized ectopic site. Biochemical and histometric measurements of bone formation revealed that the two matrices were functionally equivalent inducers of endochondral bone formation. The induced pellicle of bone reached a maturation point 18 days after implantation. Dentin matrix implants generated a significantly greater amount of mineralized tissue than did bone matrix implants. This difference could be explained on the basis of remineralization of the dentin particles to a greater degree than the bone matrix particles. Initial observations suggesting a more robust osteoinductive activity in demineralized incisor matrix can be attributed to the decreasing activity of bone matrix from older donors when compared to younger donors. The extent of osteoinduction by the two substrata was equivalent when the matrices were matched for age.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone and Bones; Bone Development; Bone Neoplasms; Calcium; Choristoma; Dental Pellicle; Histocytochemistry; Male; Rats; Tissue Fixation; Tooth; Transplantation, Homologous

Enzymatic activity and cell membrane proteins were characterized in cells from five giant cell tumors of bone (GCTs). Naphthyl alpha esterase (NAE) and acid phosphatase (AP) activity was noted within both the mononuclear and multinucleated cells of each tumor. In each tumor, all mononucleated cell populations displayed tartrate-sensitive AP activity, whereas the multinucleated cell populations demonstrated variable expression of tartrate-sensitive and tartrate-resistant AP activity. Analysis of cell membrane proteins included attempts at immunodetection of mannose receptor, OKM-1 antigen (OKM-1a), colony-stimulating factor-1 receptor (CSF-1r), and platelet-derived growth factor receptor (PDGFr). None of these membrane antigens were elicited on multinucleated cells. In contrast, the mannose receptor, OKM-1a, and PDGFr all were detected on the mononucleated cells within each tumor. These data demonstrate that a population of mononucleated, not multinucleated cells, expresses features unique to mature mononuclear phagocytes and establishes the presence of a membrane receptor, PDGFr, associated with mitogenesis of mesenchymal cells.

Topics: Acid Phosphatase; Bone Neoplasms; Cell Membrane; Giant Cell Tumors; Histocytochemistry; Humans; Immunohistochemistry; Mitosis; Naphthol AS D Esterase; Neoplasm Proteins; Phagocytes; Receptor, IGF Type 2; Receptors, Platelet-Derived Growth Factor; Tumor Cells, Cultured

Between 1981 to 1991, 126 patients were diagnosed with prostatic cancer from histological reports. Stage D2 prostatic cancer was confirmed in 38 of these cases at the time of the initial diagnosis (group alpha). Of 38 patients in group alpha, 13 had recurrence of disease after a good response to the initial treatment, 19 had no recurrence after the treatment and the other 6 patients showed no response to the initial treatment for prostatic cancer. Seven patients showed progression of the disease to stage D2 during the observation period (group beta). These forty-five patients with stage D2 prostatic cancer were analyzed. Poorly differentiated adenocarcinoma was the most frequently observed histological grade, followed by moderately differentiated. The grade of the extent of the disease (EOD) on bone scan was classified as EOD I in 26, EOD II in 13 and EOD III in 4, with no significant differences in the survival rate found among these groups. The sensitivity rate of prostate specific antigen was higher than that of other serum tumor markers. Twenty-three patients died during the observation period. 18 of the 23 died of prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

The ability of serum prostate specific antigen (PSA) and serum acid phosphatase (SAP) to identify skeletal spread was evaluated in untreated patients with prostatic cancer. Twenty patients with scintigraphic evidence of metastatic disease in bone (M1) at diagnosis were compared with 50 untreated patients in whom scans were repeatedly negative during long-term surveillance. Using the present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise discriminant analysis demonstrated that SAP was able to stage patients correctly (bone scan positive or negative) with 81% predictive accuracy at an optimum cut-off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are highly indicative of spread to the skeleton, even in the absence of radiological or scintigraphic evidence of metastases.

Topics: Acid Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

Osteocalcin, a K-dependent vitamin protein, was studied in a group of advanced prostatic carcinoma patients to test the usefulness of this marker for diagnosing bone metastases. Osteocalcin levels were above the norm in 22 out of 27 patients with bone metastases, although high levels were not observed in patients without bone metastases. High sensitivity and specificity levels of serum osteocalcin appear to be strongly correlated to metastatic bone involvement and disease relapse after hormone treatment. Although these results must be confirmed on a larger series of patients, this protein appears to be a useful biological marker in prostatic cancer.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Osteocalcin; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity

Prostate carcinoma is usually highly responsive to initial endocrine therapy. However, when relapse occurs, the subsequent clinical course is very poor. In this study, we tried to reveal the clinical aspects of bone-related relapse in 392 patients who received endocrine therapy for prostate carcinoma. In 17 stage B patients who had relapsed, 76% experienced relapse within 4 years following the start of treatment, 76% within 3 years in 27 stage C patients, and 71% within 2.5 years found in 45 stage D patients. Pre-treatment levels of serum enzymes and initial response of the primary lesion and of serum enzymes failed to predict relapse. The Gleason sum tended to be correlated with relapse. In particular, patients with a Gleason sum of 9-10 had a lower non-relapse rate during the follow-up period than patients with lower sums. With the recent use of more sophisticated measurements of PSA and/or PAP, the reduction rate or interval to normalization of the markers must be more relevant to predicting relapse.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Combined Modality Therapy; Estrogens; Humans; L-Lactate Dehydrogenase; Male; Neoplasm Proteins; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Treatment Outcome

Topics: Acid Phosphatase; Bone Neoplasms; Carbonic Anhydrases; Giant Cells; Humans; Isoenzymes; Tartrates

Increased bone resorption in the vicinity of myeloma cells is mediated by local stimulating factors. Other malignancies of the B cell lineage are also able to produce resorbing factors responsible for increased bone resorption. We have studied three groups of subjects: 10 patients with overt multiple myeloma, 10 patients with a B cell malignancy, and 10 healthy human subjects as controls. Patients were studied at the time of diagnosis and had a transiliac bone biopsy. Osteoclasts were evident on histological sections by their acid phosphatase activity. A software was developed on an automatic image analyzer (Leitz TAS+) for measuring the maximal Feret's diameter (Oc.Le) of each osteoclast (corresponding to the osteoclast length). The histogram of Oc.Le frequency distribution was supplied in each group. In myeloma patients, the Oc.Le frequency distribution was similar to that in normal subjects and showed the histogram to be asymetric with a positive skew (maximum peak at 20-25 microns). With a graphical analysis, this distribution was shown to follow a lognormal distribution corresponding to a homogeneous osteoclast population. In other B cell malignancies, Oc.Le displayed a bimodal distribution with a peak at 20-25 microns and a lower peak at 10-15 microns. The graphical analysis showed that small (mononucleated?) osteoclasts are present in B cell malignancies with normal osteoclasts. This might reflect the secretion of different soluble factors by malignant cells of the B lymphocyte lineage.

Topics: Acid Phosphatase; B-Lymphocytes; Biopsy; Bone and Bones; Bone Neoplasms; Humans; Multiple Myeloma; Osteoclasts; Software; Staining and Labeling

The aim of this study was to assess the diagnostic value of five biological markers--prostate acid phosphatase (PAP), prostate specific antigen (PSA), tartrate resistant (Tr-ACP), and tartrate labile (TI-ACP) acid phosphatases, and alkaline phosphatase bone isoenzyme (B-ALP)--for the detection of bone metastases in patients with prostate carcinoma. Using the Tc-99m HMDP bone scans of 80 patients scored from 0 (normal) to 2 (diffuse bone involvement) as the "gold standard," a receiver operating characteristic (ROC) analysis was performed. This method allows the determination of different threshold values (corresponding to different couples of sensitivity and specificity) for the assays. An ROC curve comparison was also performed. Results show that B-ALP is the best test for such detection (area under the ROC curve = 0.93; Spearman Rank correlation with bone scan r' = 0.81). Among the other markers, PSA was found to be the best (area under the ROC curve = 0.81; Spearman Rank correlation with bone scan r' = 0.58). In addition to the prostatic tumor markers (PSA and PAP), we suggest the use of the low-cost B-ALP assay in the follow-up of prostate carcinoma patients to determine the optimum moment to perform a bone scan. A normal result of this assay indicates a very low probability of bone metastasis; conversely, raising of B-ALP concentration must lead to a bone scan.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Evaluation Studies as Topic; Humans; Isoenzymes; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Medronate

Bone alkaline phosphatase (b-ALP) and tartrate resistant acid phosphatase (tr-ACP) are markers of the activity of osteoblasts and osteoclasts, respectively. We have already shown that the serum activity of these isoenzymes was elevated in breast cancer patients with bone metastasis (BM); we show here that the serum activity of b-ALP and tr-ACP were also elevated in prostate cancer patients with BM. Specificity and sensitivity of b-ALP for BM were 0.90 and 0.75, respectively; and for tr-ACP, 0.60 and 0.60, respectively. The accuracy of b-ALP as a BM marker was higher than the accuracy of usual markers of prostatic carcinoma (tartrate labile ACP [tl-ACP], prostatic acid phosphatase [PAP] and prostate specific antigen [PSA]). The highest value predictive of a positive bone scan was obtained with b-ALP (0.88); this increased to 0.97 when b-ALP was coupled with PAP.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Isoenzymes; Male; Prostatic Neoplasms

Using routinely processed, paraffin-embedded tissue specimens, osteoclast-like giant cells in giant cell tumour of bone (GCT), chondroblastoma, osteoblastoma and osteoblastic osteosarcoma were examined histochemically for osteoclast-specific enzymes tartrate-resistant acid phosphatase (TRAP) and carbonic anhydrase isoenzyme II (CA-II). Osteoclast-like giant cells and some mononuclear cells possessed TRAP activity. These were further classified with respect to CA-II immunoreactivity, i.e. cells with CA-II were seen in GCT and chondroblastoma, while those in osteoblastoma and osteoblastic osteosarcoma were negative for CA-II. All the cellular components in malignant fibrous histiocytoma and various extraosseous inflammatory lesions including malignant giant cells and macrophage polykaryons were negative for both TRAP and CA-II. These results indicate that osteoclast-like giant cells in GCT, chondroblastoma, osteoblastoma and osteoblastic osteosarcoma are all osteoclasts and generated by fusion of mononuclear cells with the same histochemical characteristics as osteoclast-like giant cells. The difference in CA-II immunoreactivity suggests the functional or maturational difference between osteoclast-like giant cells in GCT and chondroblastoma and those in osteoblastoma and osteosarcoma.

Topics: Acid Phosphatase; Bone Neoplasms; Carbonic Anhydrases; Drug Resistance; Giant Cells; Histocytochemistry; Humans; Osteoclasts; Tartrates

The value of routine bone scans as a staging procedure was assessed in patients with newly diagnosed prostate cancer. Records from 277 patients were reviewed retrospectively to determine the serum acid and alkaline phosphatases, the presence or absence of bone pain, and the results of bone scans and other radiographic studies at the time of initial diagnosis. We determined the sensitivity and specificity of an abnormal acid phosphatase, an abnormal alkaline phosphatase, and the presence of bone pain used in combination for assessing bone metastases. If at least one of these three parameters was present, the sensitivity was 97 percent, whereas if all three tests were normal, the specificity was 78 percent. The negative predictive value for all three tests combined is 99 percent. These results suggest that a routine bone scan to stage patients with newly diagnosed prostate cancer who have no bone pain and normal acid and alkaline phosphatases may not be warranted in all cases.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

Of 438 consecutive cases of newly diagnosed prostate cancer, 178 (41%) had skeletal metastases (T0-4 M1) at the time of diagnosis according to skeletal scintigraphy; 139 men had serum prostatic acid phosphatase (PAP) greater than twice the upper limit of normal on 2 separate occasions at the time of diagnosis and 65% of them had metastases on bone scan. However, 49 men with normal bone scans were found to have similarly raised serum PAP. (Such patients are defined as having skeletal metastases in the current Medical Research Council immediate versus deferred orchiectomy study and stratified accordingly). The actuarial survival of this group was calculated by life table methods and was compared with that of 2 other subgroups: those patients having metastases demonstrated on bone scan, and those patients having both normal bone scans and normal serum PAP. The survival of the "metastatic by acid phosphatase" group was significantly better than that of the "metastatic by bone scan" group but did not differ from that of patients having both normal scans and PAP. For patients with no scintigraphic evidence of skeletal metastases at diagnosis, those with a raised PAP were at a significantly greater risk of scan conversion, although this was more powerfully predicted by high histological grade.

Topics: Acid Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

The introduction of new tumours markers poses the problem of assessing their real predictive power and of considering all their possible uses. The following questions have been examined: 1) is PSA able to offer early diagnosis of prostate Ca 2) is there a relationship between cancer grading and PSA levels? 3) is it possible to use PSA to monitor patients under treatment? 4) can PSA predict the existence of bone metastasis?

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Monitoring, Physiologic; Neoplasm Staging; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay

The correlation of technetium-99m-HMDP bone scintigraphic findings, serum osteocalcin as a measure of bone turnover and prostate-specific antigen (PSA) and/or prostate acid phosphatase (PAP) was determined in 19 men with bone metastasis due to prostatic carcinoma. Six of the 19 patients with metastases on bone scan showed elevation of osteocalcin. These patients had extensive metastatic disease. All 19 men with positive bone scans had high serum PSA and/or PAP levels. Serum osteocalcin measurement is less sensitive to detection of bone deposits than PSA/PAP measurements (p less than 0.0008).

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Osteocalcin; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate

Serum acid phosphatase activity, prostate specific phosphatase and prostate specific antigen were measured in 100 patients with prostatic cancer. The patients were divided according to the differentiation grade into 3 groups: G1 (well), G2 (moderately) and G3 (poorly differentiated) carcinoma. Bone metastases were identified by scintigraphy. Among the 76 M0 patients the mean levels of all 3 markers were slightly higher in patients with moderately differentiated prostatic carcinoma. Among the 24 M1 patients the primary tumour was either G2 (18 patients) or G3 (6 patients); none had G1 lesions. Significantly higher serum ACP and PAP levels were found in patients with G2 tumours than in those with G3 lesions. It was concluded that the histological differentiation grade of prostatic carcinoma did affect serum levels of prostatic tumour markers; the tendency towards higher levels in the G2 group was noticeable in both non-metastatic and metastatic cases despite the limited number of patients in the latter category. In clinical practice this information may be an important additional tool in staging prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

We report two cases of osteoclast-like giant cell tumour of urinary bladder associated with papillary transitional cell tumours. Both cases were morphologically identical to giant cell tumour of bone. The giant cells stained strongly for acid phosphatase which was resistant to tartrate digestion, a staining reaction typical of osteoclasts. In view of the ability of urinary bladder to induce metaplastic and neoplastic bone, we believe that these tumours may represent extraosseous giant cell tumours of bone.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Carcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; Muramidase; Osteoclasts; S100 Proteins; Urinary Bladder Neoplasms; Vimentin

Serum activities of bone alkaline phosphatase (b-ALP) and of tartrate resistant acid phosphatase (tr-ACP) were evaluated in 271 cancer patients; 120 of them had bone metastases (BM) and 151 had none. Correlation coefficients, specificities, sensitivities, negative and positive predicting values were computed. They showed the important contribution that these isoenzymes can bring to the diagnosis of BM in 80 patients with prostate cancer, and to the followup of 191 patients with breast cancer. The assay results were analysed in parallel with bone scan and radiography. They were also compared to those of serum antigens: PSA and PAP for prostate cancer, and CEA and CA15.3 for breast cancer. These results clearly indicate that both isoenzymes are better correlated with BM than antigens, these antigens being markers of the whole tumor burden--primary tumor, metastases, recurrence--whereas b-ALP and tr-ACP are specific markers of bone metabolism.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Female; Humans; Male; Prostate; Prostatic Neoplasms

The Gunma Urological Oncology Study Group has performed a multivariate statistical analysis of prognostic factors based on 353 patients with prostate cancer diagnosed between 1974 and 1984. This paper discusses the prognostic significance of erythrocyte sedimentation rate (ESR) in these patients with prostate cancer. Based on three ranges (less than 20, greater than 20- less than 50, greater than 50 mm/h) of ESR, a significant difference of survival rates among the patients was found by means of univariate analysis. ESR apparently includes components which represent anemia or infection. Hemoglobin, frequently used as a prognostic factor, was compared with ESR by means of multivariate analysis, and ESR was found to be a more useful prognostic factor than hemoglobin. Moreover ESR showed the highest partial coefficient value among the items studied (clinical stage, pathological differentiation, age, acid phosphatase, gait disturbance). It seems that ESR includes not only anemia and infection components but also provides a clue to the degree of bone metastasis or the degree of prostate cancer progression.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Blood Sedimentation; Bone Neoplasms; Gait; Hemoglobins; Humans; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Prostatic Neoplasms

The predictive value of serum alkaline phosphatase (SAP) and of prostatic acid phosphatase (PAP) for response to treatment (NPCP criteria) was retrospectively assessed in patients with bone metastases from prostate cancer. Fifty-one patients had SAP measured at the start of treatment and at 1 and 2 months. In 31 of these, corresponding PAP levels were also available at each time point. SAP/PAP profiles at 2 months were classified as "increased" (increment 15% or greater), "decreased" (reduction greater than 15%) or "stable", compared with baseline levels. An additional category, SAP "flare", was also identified (SAP increment greater than 15% at 1 month, with subsequent fall at 2 months). There was a strong association between the SAP profile at 2 months and the response category, whereas the PAP profile at 2 months was more weakly associated. Using results from the 31 patients with both SAP and PAP profiles, the level of SAP was significantly better in predicting the category of response (SAP: sensitivity 94%, specificity 79%; PAP: sensitivity 53%, specificity 57%). An SAP "flare" was associated with response in 8 of 12 patients. An increase in SAP at 1 month is therefore a poor guide to progressive disease and should not be used in isolation to discontinue treatment early. The SAP profile is of value as an earlier predictor of response than X-rays or bone scans and is more reliable than the PAP profile in monitoring patients with prostate cancer and bone metastases.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antineoplastic Agents; Bone Neoplasms; Clinical Enzyme Tests; Humans; Male; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Retrospective Studies; Sensitivity and Specificity; Time Factors

Acid phosphatase (E.C.3.1.3.2) in a giant cell bone tumor and a spleen infiltrated with hairy cells was extracted by citrate buffer and then by 0.3 mol/L NaCl. The cationic acid phosphatase in the crude extract was isolated by CM-cellulose chromatography, and further separated by high pressure liquid chromatography. The majority of the tartrate resistant acid phosphatase in the hairy cell spleen was unabsorbed on CM-cellulose and was insensitive to iron. A much larger portion of the acid phosphatase in the bone tumor, than in the spleen, was cationic and was eluted from the column by 0.8 mol/L NaCl. The cationic acid phosphatase was further separated into consecutive peaks of acid phosphatases with different sensitivity to iron. A major portion of acid phosphatase in the giant cell bone tumor was enhanced by iron, while the amounts of iron-enhanced and iron-insensitive acid phosphatase were about the same in the spleen. The differences of the phosphatases in these two types of pathologic specimens indicate the occurrence of two types of enzymes with different biological significance.

Topics: Acid Phosphatase; Bone Neoplasms; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Colorimetry; Giant Cell Tumors; Humans; Iron; Leukemia, Hairy Cell; Neoplasm Invasiveness; Spleen; Tartrates

A tartrate-resistant acid phosphatase (TrACP), which has been suggested to be very similar to the osteoclastic TrACP, was partially purified from the spleen of a patient with hairy cell leukemia. The purification procedure consisted of carboxymethyl-Sepharose, phosphocellulose, Sephacryl S-200, and phenyl-Sepharose chromatographies. Polyclonal antibodies were generated in guinea pigs with a titer of at least 1:6000. Immunohistochemical staining of fetal rat tibia with the antisera revealed that only the lysosomes of osteoclasts, but not osteoblasts, were stained. An enzyme-linked immunosorbent assay (ELISA) was developed with the antisera. There was no cross-reactivity with 1) partially purified acid phosphatases (ACPs) from normal human and beef spleens, 2) ACPs in extracts of human osteoblastic cells, 3) purified bovine bone matrix TrACP, or 4) commercial prostatic ACP. However, extracts of giant cell bone tumors, containing large amounts of bona fide osteoclasts, showed large amounts of cross-reactive material, which diluted in parallel with the partially purified hairy cell leukemic TrACP in the ELISA. Commercial serum band 5b TrACP also displaced in parallel with the partially purified hairy cell leukemic TrACP. Immunoblotting studies revealed that the antiserum, but not nonimmune guinea pig serum, reacted with the homogeneous hairy cell leukemia splenic band 5 TrACPs, which were recently purified by our laboratory. Preliminary application of the ELISA to sera of patients with metabolic bone diseases revealed that normal healthy individuals had measurable amounts of the immunoreactive material, and patients with Paget's disease or hyperparathyroidism, who should have high bone turnover, had elevated levels of this immunoreactive material in their sera. In contrast, the level of serum osteoclastic TrACP in a patient with an acute lymphatic leukemia was normal. In summary, 1) we have shown that hairy cell leukemia splenic TrACP shares significant immunological similarity with the osteoclastic TrACP and with the serum band 5b TrACP, and 2) the ELISA holds promise for a sensitive and specific assay for bone resorption.

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Chromatography, Affinity; Chromatography, Ion Exchange; Cross Reactions; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Histocytochemistry; Humans; Isoenzymes; Leukemia, Hairy Cell; Osteoblasts; Osteoclasts; Osteosarcoma; Rats; Spleen; Tartrates; Tumor Cells, Cultured

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Diseases; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Response of prostatic cancer bone metastases to therapy (androgen withdrawal and Estracyt) was studied in 43 patients by applying scintiscanning and radioimmunodetective measurement of serum osteocalcin (OC) values. The prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) concentrations, as sensitive probes for the overall tumor spread, were used in parallel in a monitoring procedure. A significant rise in OC levels to values elevated from a pretreatment normal level has been found in patients with a partial osseous tumor remission, and this may be easily distinguished from normal and/or subnormal OC level in bony tumor progression (P less than 0.01) and during stabilization in metastatic spread (P less than 0.01). On these bases, differences between disease progression and the "no change" response category could not be statistically recognized (P greater than 0.05). A sharp increase in circulating OC level has been recorded 1 months after the beginning of the treatment leading to bone remodeling processes and precedes improvements in scintiscan appearance. Blood OC concentration seems also to be of utility 1) in distinguishing scintigraphic flare phenomenon from a slight bone scan progression and 2) when related to scans with regions of both disease improvement and worsening. Furthermore, serum OC concentration can frequently be measured through a noninvasive procedure, thus serving as a significant addition to bone scintigraphy.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Bone Neoplasms; Carcinoma; Humans; Male; Middle Aged; Osteocalcin; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

The pretreatment bone scans on 40 patients with prostate cancer with bone involvement were reviewed and the prognostic impact of the initial extent of bone metastasis was evaluated. On the bases of the number or extent of bone metastasis, the patients were divided into 2 groups and survival for each group was compared. We also assessed the correlations between the extent on bone metastasis and other pretreatment characteristics: age, symptoms, serum acid phosphatase, serum alkaline phosphatase, and the histological differentiation of primary tumor. At the same time, the prognostic impacts of these pretreatment characteristics were evaluated. The extent of bone metastasis on the scan correlated with survival, but other characteristics did not have a predictive value except for histological grade. Though the histological differentiation of primary tumor was related to survival, the survival rates differed by the initial extent of disease among the same histological grade patients. Thus the extent of bone metastasis was shown to predict survival in metastatic prostate cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Radionuclide Imaging

We analyzed 110 patients with metastatic prostate cancer (stage D2) to determine the associations between interval until progression and the pretreatment testosterone level, extent of bone metastases, performance status, race, age and pretreatment level of prostatic acid phosphatase. The median followup was 21 months (4 to 89 months). All patients received androgen deprivation therapy when metastases were identified. This multivariate analysis demonstrated that the pretreatment serum testosterone was the most significant variable (p less than 0.01) associated with interval until progression and the extent of bone metastases observed on the bone scan was the second most important variable (p less than 0.05). Age, race and prostatic acid phosphatase were not significantly correlated with the interval free of progression. Performance status was significantly correlated but it was nonsignificant in the multivariate analysis if the model already included testosterone level and extent of metastasis. Patients with a pretreatment testosterone level of less than 300 ng. per 100 ml. and more than 6 areas of increased uptake on the bone scan had the most rapid progression. We conclude that serum testosterone and extent of bone metastases are the most important of the analyzed factors in terms of interval to progression in patients with prostate cancer following androgen deprivation.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Diethylstilbestrol; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Statistics as Topic; Testosterone; Time Factors

Thirty three cases of prostatic adenocarcinoma treated by total perineal prostatectomy were studied clinicopathologically and immunohistochemically. There were 17 patients with clinical stage B, 12 with stage C and 8 with stage D. Interrelationship of tumor grade, surgical local tumor extent, vessel invasion, perineural invasion and bone metastasis was examined. For the identification of the vessel invasion, Ulex europaeus agglutinin 1 was adopted immunohistochemically. Tumor grade and local tumor extent were respectively correlated with bone metastasis. Vessel invasion was correlated with local tumor extent. Eight of 18 cases (44%) with vessel invasion and none of 15 cases without vessel invasion had bone metastasis. Although correlated with grade, perineural invasion had no significant effect on bone metastasis. The investigation of tumor staining used by monoclonal antibody for prostatic acid phosphatase (PSAP) disclosed that negative stained cases were associated with lower grade tumors and that one of 14 positive stained cases (7%) and 7 of 19 negative stained cases (36%) had bone metastasis. We concluded that vessel invasion may be a new prognostic pathological parameter and that monoclonal PSAP staining is also a useful method to predict malignant potential of prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Blood Vessels; Bone Neoplasms; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Prostatectomy; Prostatic Neoplasms

The therapeutic indications in prostatic cancer depend on the regional and distant extension of the cancer and are difficult to assess before lymphadenectomy. Radioimmunodetection of lymph node involvement with monoclonal anti-prostatic acid phosphatase (PAP) antibodies can be proposed as a noninvasive alternative to lymphadenectomy. Fifteen patients with various stages of histologically proven prostatic cancer were examined by immunolymphoscintigraphy (ILS) before treatment to detect lymph node metastases. These patients had Stage A (n = 7), Stage B (n = 3), Stage C (n = 2), and Stage D (n = 3) tumors. They received between 100 and 400 micrograms of monoclonal antibody 227 A in the form of F(ab')2 fragments labeled with iodine 123 (123I). The antibody was injected directly into the periprostatic area. ILS images were obtained after 1, 3, 6, and 24 hours. Three days later, each patient underwent a lymphadenectomy for histologic examination. The results of the histologic examination and ILS were compared. In ten patients, the examination did not show any images capable of being interpreted as lymphadenopathy and histologic examination confirmed the integrity of the nodes examined. In five cases, scintigraphy suggested the presence of lymph node invasion by prostatic cancer and this was confirmed by histologic examination in three of the five cases. Overall, in terms of lymphadenopathy, this examination had a sensitivity of 100% and a specificity of 83%. Therefore, ILS appears to be capable of detecting lymph node metastases in prostatic cancer.

Topics: Acid Phosphatase; Aged; Antibodies, Monoclonal; Bone Neoplasms; Humans; Immunoglobulin Fab Fragments; Iodine Radioisotopes; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Radionuclide Imaging

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers, Tumor; Bone Neoplasms; Evaluation Studies as Topic; Humans; Hydroxyproline; Magnetic Resonance Imaging; Pain Measurement; Peptide Fragments; Procollagen; Tomography, X-Ray Computed

Tartrate-resistant acid phosphatase is one of the major enzymes produced and secreted by osteoclasts. To obtain sufficient enzyme for biochemical characterization, we have purified this enzyme from human osteoclastomas by sequential chromatography on SP-Sephadex, CM-Sephadex, hydroxylapatite, Sephadex G-150 and concanavalin A-Sepharose. The purification over the original tumour extract was about 2000-fold, with a yield of 10%. The enzyme appeared to be homogeneous when assessed by SDS/polyacrylamide-gel electrophoresis. Both gel filtration and SDS/polyacrylamide-gel electrophoresis indicated an Mr of about 30,000. The reduced and alkylated enzyme consists of two subunits with Mrs of 15,000 and 17,500. The N-terminal amino acid sequence of both subunits indicates that there is a high degree of identity between the osteoclastoma enzyme and similar enzymes purified from spleen and uterus. Using 4-methylumbelliferyl phosphate as substrate, the specific activity of the purified enzyme was 387 units.mg-1, and the Km was 284 microns. The pH optimum was 5.7. Unlike similar enzymes purified from human and bovine bone, osteoclastoma acid phosphatase is not activated by reducing agents (2-mercaptoethanol or ascorbic acid). The enzyme contains 4.8 mol of Fe2+/3+, 0.3 mol of Mn2+ and 1.7 mol of Mg2+ per mol of enzyme. Although the enzyme loses 50% of its activity in the presence of EDTA, it is not inhibited by the iron chelator 1,10-phenanthroline. However, the enzyme is activated to a small extent by Mn2+ and Mg2+. Using a variety of substrates and inhibitors, we demonstrate that there are differences between the osteoclastoma acid phosphatase and the enzyme purified from other sources.

Topics: Acid Phosphatase; Amino Acid Sequence; Bone Neoplasms; Giant Cell Tumors; Humans; Molecular Sequence Data; Substrate Specificity; Tartrates

One hundred ten patients with metastatic prostate cancer (Stage D2) were analyzed to determine the associations among time until progression and the pretreatment testosterone level, extent of bone metastases as indicated by a semiquantitative grading scale for extent of disease, performance status, race, age, and the pretreatment level of prostatic acid phosphatase (PAP). The median follow-up period was twenty-one months, with a range of four to eighty-nine months. All patients received androgen deprivation at the time metastases were identified. A multivariate analysis demonstrated that pretreatment serum testosterone was the most significant variable associated with time until progression (P less than 0.01) and that the extent of bone metastases observed on the bone scan was the second most important variable (P less than 0.05). The following factors did not significantly correlate with progression-free intervals: age, race, and PAP. The performance status was significantly correlated, but was nonsignificant in the multivariate analysis when the model already included the testosterone level and the extent of bone metastases. Patients with a pretreatment testosterone level of less than 300 ng/dL and with more than six areas of increased uptake on the bone scan progressed more rapidly.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Bone Neoplasms; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Statistics as Topic; Testosterone; Time Factors

Osteosarcoma in the metaphysis to epiphysis of the left femur of a 17-year-old male is reported. The lesion appeared osteolytic with sclerotic foci on roentgenographs, accompanied by an extensive tumor shadow in the surrounding soft tissue. While 60% of the tumor was necrotic, histological examination of the remaining viable tissue revealed that it consisted almost entirely of a sheet of epithelioid cells, separated by thin, fibrovascular septa with an alveolar-like pattern, suggestive of metastatic carcinoma. Only a few areas were characterized by malignant osteoid tissue intermingled with the above cells, showing significant positivity for bone-specific alkaline phosphatase and 5'-nucleotidase, thus permitting a diagnosis of osteosarcoma. Autopsy findings revealed that the metastatic foci were histologically similar to those of the primary tumor. Electron microscopy revealed poor development of cytoplasmic organelles, supporting possible derivation from an osteoblastic cell lineage at an early stage.

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Epithelium; Humans; Male; Osteosarcoma; Prognosis

The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.

Topics: Acid Phosphatase; Bone Neoplasms; Giant Cell Tumors; Humans; Osteoclasts; Tumor Cells, Cultured

Sixty seven cases of stage D prostatic carcinoma were analyzed according to age, chief complaints, histopathological types, metastatic sites, and serum acid and alkaline phosphatase levels. In spite of metastasis, which were in 62 cases (92.5%) to bone, in 17 cases (25.4%) to lymph nodes, and in 3 cases (4.5%) to the lung, the most common chief complaints were symptoms related to the primary lesion, such as dysuria and urinary frequency. There was no significant correlation between the incidence of bone metastasis and histopathological type. However, higher incidence of lymph node metastasis was observed in the histological types of moderate and poorly differentiated adenocarcinoma than well differentiated type. When cases were divided into two groups by age, significant differences were observed between younger (64 less than or equal to years old) and older (greater than or equal to 65 years old) groups in the following points: 1) Histopathologically, well differentiated type was not recognized in the younger group, while three histological types of well, moderate and poorly differentiated adenocarcinoma, were equally distributed among the older one. 2) Although there was no significant difference in the incidence or the numbers of metastatic sites to bone between the two groups, the younger patients had less symptoms related to bone metastasis. The prominent symptoms in the younger group were complaints about voiding.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Aging; Alkaline Phosphatase; Bone Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms

An immunohistochemical study of six giant cell tumors of bone and eight related lesions (aneurysmal bone cyst, fibrous histiocytoma, and giant cell tumor of tendon sheath) was performed using a panel of monoclonal antibodies directed to the Ia and monocyte-macrophage lineage antigens. In all types of lesion, osteoclastlike multinucleate giant cells were negative for both types of antigen, but a proportion of mononuclear cells gave positive reactions. While the possibility that these cells are reactive cannot be excluded, in giant cell tumor and malignant fibrous histiocytoma, their frequency and their morphologic similarity to the rest of the tissue suggest that they may be an intrinsic part of the neoplasm. This finding is consistent with the presumed fibrohistiocytic nature of these tumors.

Topics: Acid Phosphatase; Antigens, Differentiation; Bone Cysts; Bone Neoplasms; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Staining and Labeling; Tendons

Expression of the p21 protein of the ras oncogene family was studied in a case of human prostatic adenocarcinoma tissue and the cell line was derived from the primary tumor. Flow cytometry analysis of the tumor cells obtained from the primary tumor indicated that approximately 25 per cent of the cells were positive for this oncogene product. However, by the immunoperoxidase method almost all of the tumor cells at the vertebral metastatic sites in the same patient were positive for the p21 protein. The cell line established from the primary tumor displayed 2 distinct subpopulation growth patterns in vitro: a monolayer, density-inhibited growth and a multicellular aggregate type growth morphology. These 2 subpopulations could be separated by density elutriation centrifugation. The isolated subpopulation cells were noted to express prostatic acid phosphatase and prostate specific antigen at high frequency. High levels of expression of these 2 prostatic markers also were found in the tumor cells at the vertebral metastatic sites. However, when the isolated subpopulations were analyzed for the expression of p21 protein, the multicellular grown cells were almost 90 per cent positive for the p21 antigen, whereas only approximately 5 per cent of the monolayer grown cells were positive for the same protein. Our findings suggest that primary prostatic carcinomas are composed of heterogeneous subpopulations of neoplastic cells while only specific subpopulations have metastatic potential. Quantification of prostatic acid phosphatase and prostate specific antigen in the primary tumor cells probably will not offer a predictive value for the eventual behavior of the tumors. However, evaluation of oncogene products, such as the p21 protein, may be useful as a clinical predictor for metastatic potential.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Cell Line; Flow Cytometry; Fluorescent Antibody Technique; Humans; Male; Oncogene Protein p21(ras); Oncogene Proteins, Viral; Prostate-Specific Antigen; Prostatic Neoplasms

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

We reviewed 721 consecutive samples submitted for measurement of prostate-specific antigen (PSA) over five months. We identified three patients with extremely high PSA concentrations: 650, 1840, and 3280 micrograms/L (their acid phosphatase activities were 3.2, 1337, and 2.8 U/L, respectively), and present case reports for the latter two. Serial dilutions of samples obtained from the patient with the highest PSA concentration indicated that the one-step Tandem-PSA assay gave falsely low values for high concentrations of PSA, an observation consistent with the phenomenon of the "hook effect." This effect was not observed when the sample was reanalyzed for PSA by a two-step procedure.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Bone Neoplasms; False Negative Reactions; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate-specific antigen (PSA) was compared to prostatic acid phosphatase (PAP) in patients with prostatic cancer suspected to have bone metastases. Bone scans were classified according to metastatic skeletal involvement. The sensitivity of PSA in predicting the presence of metastatic disease (68%) was better than that of PAP (53%). Specificity was 79% for PSA and 90% for PAP. Thirty-five patients had a positive PSA level and a normal scintigraphy (false-positive); 14 of them had only endoscopic prostate resection. Thirty-eight patients underwent a further exploration 3-18 months later. PSA level during disease was correlated to scintigraphy in 32 of 38 patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sensitivity and Specificity

In this study we provide evidence that MB1, a newly developed monoclonal antibody which reacts with B lymphocytes and a proportion of T cells and monocytes, can be successfully used for the direct immunohistochemical identification of osteoclasts on paraffin-embedded surgical specimens. The antigen(s) recognized by MB1 is present at high density in the cytoplasm of osteoclasts of fetal bone and in the multinucleated cells of human giant cell tumour of bone (osteoclastoma), but is weakly expressed or absent in the giant cells of granulomas. MB1 is thus proposed as a new immunohistochemical marker for osteoclasts on paraffin-embedded material.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Bone and Bones; Bone Neoplasms; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Giant Cell Tumors; Humans; Immunoenzyme Techniques; Osteoclasts

Topics: Acid Phosphatase; Androgen Antagonists; Bone Neoplasms; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

This study investigated the effect of metastatic prostatic carcinoma on bone density. Thirty patients underwent a lumbar spine scan with a dual photon absorptiometer. Of these patients, 9 had proven skeletal metastatic deposits in the area being investigated. Comparison of results with a non-matched control population with proven benign prostatic histology showed a significantly elevated linear bone mineral content (BMC) in the disease group. Patients scanned after a 3- or 6-month period of hormonal therapy demonstrated a rise in BMC values, although the trend was not statistically significant. Indices of calcium metabolism have also been investigated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Calcium; Cyproterone; Diethylstilbestrol; Humans; Male; Middle Aged; Minerals; Prostatic Neoplasms

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.

Topics: 1-Carboxyglutamic Acid; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Calcium-Binding Proteins; Humans; Hydroxyproline; Male; Middle Aged; Neoplasms, Hormone-Dependent; Osteocalcin; Prostatic Neoplasms; Radionuclide Imaging; Vitamin K

In 62 patients with histologically confirmed carcinoma of the prostate bone scintigraphy, radiographic survey and serum prostatic acid phosphatase determinations were carried out to evaluate the progression of the disease and to compare the relative sensitivity of the diagnostic tools. Thirty-five patients had scintigraphic evidence of skeletal metastases, whereas abnormal X-ray survey and elevated prostatic acid phosphatase levels were found in only 4 and 19 patients, respectively, all of whom had positive scintigraphic findings. Radiographic evidence of metastases was not found in any of the patients with normal scintigraphy, while elevated prostatic acid phosphatase was found in two patients. It is concluded that bone scintigraphy is far more sensitive than either radiographic survey or determination of prostatic acid phosphatases in the diagnosis of skeletal involvement in prostatic carcinoma, and should be the method of choice for this purpose.

Topics: Acid Phosphatase; Bone Neoplasms; Carcinoma; Clinical Enzyme Tests; Humans; Male; Prostate; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Sensitivity and Specificity

The daily variation of serum levels of prostatic acid phosphatase (PAP) determined by the Roy enzymatic method was investigated in 10 patients with metastatic prostatic cancer and in 10 patients without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis of the mean PAP levels at the four sampling times in both groups of patients demonstrated no evidence of circadian or diurnal rhythmic variation. Prostate cancer patients did show significantly greater variability in daily PAP than patients without prostatic disease, although a distinct pattern of secretion was not observed in either group. These results underscore the potential inaccuracy of the use of single determination of serum PAP as a parameter of response in patients with metastatic prostatic cancer and in the staging of patients with clinically localized prostatic malignancy. Evaluation of trends of PAP levels over time, however, continues to play a major role in the assessment and management of patients with prostatic carcinoma.

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Carcinoma; Circadian Rhythm; Humans; Male; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Clinical Enzyme Tests; Humans; Male; Middle Aged; Predictive Value of Tests; Prostate; Prostatic Neoplasms; Radionuclide Imaging

The etiology of aneurysmal bone cyst is still unknown. Most theories of the histogenesis of this lesion assume a vascular origin and speculation has focused on the characteristic pseudoendothelial lining of the cyst walls. In the present study, this structure has been subjected to enzyme histochemical, electron microscopical, and immunohistochemical investigation. Of the enzymes tested only alkaline phosphatase was present in the cyst lining. Electron microscopy revealed fibroblast-like cells covering the walls of cystic cavities, but no genuine endothelium, basement membranes or pericytes were identified. For the immunohistochemical studies a panel of poly- and monoclonal antibodies against HLA-DR antigens, mature and immature macrophages/histiocytes, smooth muscle fibers and endothelial cells, as well as the lectin Ulex europaeus I agglutinin were used. None of these markers demonstrated the presupposed vascular characteristics in the cells constituting the pseudoendothelial lining of the cyst walls. Despite current theories to the contrary, it was concluded that aneurysmal bone cyst is unlikely to originate from the vascular system, and that a new concept of its pathogenesis must be sought.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Bone Neoplasms; Cysts; Endothelium; Factor VIII; HLA-DR Antigens; Humans; Immunologic Techniques; Microscopy, Electron; von Willebrand Factor

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Random Allocation; Testosterone

In osteoclastic giant cells of six different tumors of bones and joints (fibrous dysplasia, proliferating giant cell tumor, malignant giant cell tumor, osteosarcoma after chemotherapy, malignant synovioma and Ewing's sarcoma) activities of tartrate-resistant acid phosphatase, NADH-tetrazolium-oxidoreductase and, in three of them, of non-specific esterase are determined by enzyme histochemical methods. Quantitative microphotometry makes it possible to determine relative enzyme activities in the cut sections of giant cells of different sizes. Giant cells of the various tumors reveal similar trends: With an increase in cell size, mean extinctions of NADH-tetrazolium-oxidoreductase and non-specific esterase decrease. Mean extinctions of tartrate-resistant acid phosphatase increase in cells of medium size, whereas the large cells reveal in part low activities. An additional ultrastructural examination of the giant cells in the proliferating giant cell tumor as well as in the osteosarcoma shows morphological signs of degeneration in the large cells. Electron probe microanalysis of the proliferating giant cell tumor exhibits evidence of phagocytosis of Ca and/or Fe containing particles. The similar size dependent reaction pattern of enzymes in osteoclastic giant cells of different tumors favors the concept of a common histogenesis, i.e. a host reaction.

Topics: Acid Phosphatase; Bone Neoplasms; Carboxylesterase; Carboxylic Ester Hydrolases; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; NADH Tetrazolium Reductase; Osteoclasts; Osteosarcoma; Sarcoma, Ewing; Sarcoma, Synovial

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate; Time Factors; Whole-Body Counting

The authors' 5-year experience in the management and care of prostatic carcinoma are summarized. Their method differs essentially from earlier practice. They have found a new diagnostic and therapeutic method by introducing the TECO irradiation therapy, extensively using bone scintigraphy, by introducing cytostatics, extensively applying the prostate-specific acid phosphatase and by performing rectal biopsy of the prostate. They describe their own observations on the diagnostics and therapy of prostatic carcinoma. They stress that none of the therapies is the method of choice, the use of the various kinds of treatment are defined by strict indications. They state that care of prostatic cancer patients is highly important because only observation of the course of the disease may ensure the evaluation of treatment results and the indication of the adequate therapeutic method.

Topics: Acid Phosphatase; Adenocarcinoma; Biopsy; Bone Neoplasms; Carcinoma; Hormones; Humans; Male; Prostate; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Radiotherapy, High-Energy

Effect of chemotherapy for relapse of prostatic cancer was evaluated with new response criteria, in which four objective parameters including the prostate, bone metastasis, soft tissue metastasis and the serum acid phosphatase level estimated by radioimmunoassay or enzyme immunoassay were judged separately and then summarized to evaluate the response as complete response (CR), partial response (PR), stable and progressive disease (PD). Eighty-two patients were included in the study. Rate of PR and stable were 19% and 27%, respectively, and these two groups showed longer survival than those with PD. Evaluation of prostate and bone showed tendency to be discrepant with total judgement. Evaluation of soft tissues and prostatic acid phosphatase reflected the effect of chemotherapy. Chemotherapy often improved subjective symptoms but the effect did not parallel the total judgement in many cases. Factors influencing response of chemotherapy were mode of pretreatment, performance status, age, number of affected areas and clinical stage, but the grade at initial treatment was not correlated to response. The new criteria used in this study was valid for evaluation of response in prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Drug Evaluation; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prostatic Neoplasms; Soft Tissue Neoplasms

Bone marrow macrophages were found to express tartrate-resistant acid phosphatase (TRAP) under pathological conditions. In chronic granulocytic leukemia and metastatic carcinoma in the bone marrow this phenomenon was striking, all or almost all of the marrow macrophages being reactive. In other conditions, such as hypertransfusion or chemotherapy-induced marrow aplasia, the phenomenon did occur but was clearly a minor one. These observations indicate that tissue macrophages may become TRAP positive under the effect of unknown stimuli operating in certain pathological conditions. The results further suggest that the synthesis of the isoenzyme of acid phosphatase resistant to tartrate inhibition is a marker of macrophage activation rather than of differentiation towards particular subsets of the mononuclear phagocyte system.

Topics: Acid Phosphatase; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Bone Neoplasms; Carcinoma; Histocytochemistry; Humans; Leukemia, Myeloid; Macrophages; Tartrates

A total of 25 patients with histologically proved adenocarcinoma of the prostate, whose disease was staged clinically as D2 by appropriate radiographic and nuclear medicine studies, received increasing doses of PAY 276, an antiprostatic acid phosphatase monoclonal antibody for radioimmunological imaging. The patients were divided into 5 groups of 5. Groups 1 through 5 received an infusion of 5, 10, 20, 40 or 80 mg. monoclonal antibody, respectively, 1 mg. of which was labeled to 5 mCi. of 111indium, while stable monoclonal antibody was added to achieve the desired antibody concentration. No patient had an allergic reaction, and no significant change in serial hemoglobin levels, platelet count, chemistry profile or results of urinalyses was noted. The monoclonal antibody scan visualized at least 1 lesion in 19 of 25 patients (76 per cent): 4 in groups 1 and 2, and all 15 in groups 3 to 5. With results of conventional radiography and bone scintigraphy considered definitive for metastases, monoclonal antibody scans detected 7 of 32 metastases (21.8 per cent) in group 3 (20 mg.), 31 of 58 (53.4 per cent) in group 4 (40 mg.) and 101 of 134 (75.4 per cent) in group 5 (80 mg). In group 5 the incidence of false positive and false negative scans was 2.3 per cent (3 of 132) and 24.6 per cent (33 of 134), respectively. The detection of metastatic lesions increased as the concentration of unlabeled monoclonal antibody increased. Radioimmunological imaging of prostatic cancer with antiprostatic acid phosphatase monoclonal antibody seems to be feasible.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antibodies, Monoclonal; Bone Neoplasms; Humans; Indium; Male; Prostatic Neoplasms; Radioisotopes; Radionuclide Imaging

The origin and characteristics of so-called stromal cells (stromal cell) and the osteoclast-like giant cell series of 19 cases of giant cell tumor (G.C.T.) of bone were studied. Immunohistochemically, two interesting cases were found. The stromal cells of one case were alpha-1-antitrypsin positive and those of the other case were alpha-1-antichymotrypsin positive. The histiocytic stromal cells of the latter case seemed to be surely neoplastic since they showed mild to moderate cell atypism. There were foci consisting of fibroblastic cells or osteoid and osteoblasts within the tumor. Those cells in the foci were apparently continuous with the surrounding stromal cells, and they were, therefore, also considered to be neoplastic. These findings strongly indicate that the stromal cells originate from the undifferentiated mesenchymal cells in the bone marrow and may differentiate to osteoblastic, fibroblastic, and histiocytic cells. All cells of these three series were not stained for a high stable form of acid phosphatase (SAPhase). SAPhase activity was demonstrated only in osteoclast-like giant cells and some mononuclear cells, which are recently believed to be non-neoplastic. Therefore, the cell atypia of SAPhase negative stromal cells is considered to have a prognostic value.

Topics: Acid Phosphatase; Adult; Bone Neoplasms; Carcinoma; Giant Cell Tumors; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Staining and Labeling

D-Trp-6-LH-RH, a long acting LH-RH agonist was given in a phase II trial to 85 patients aged 52 to 88 (mean 69) with advanced prostatic carcinoma, stage B (8 pts), C (9 pts) and D (68 pts). Twenty-five patients were previously untreated, 40 had received previous hormonal therapy but none was considered has having hormone resistant tumor; 20 patients had received surgery or radiotherapy or both. D-Trp-6-LH-RH was given s.c. at a daily dose of 500 micrograms during the first seven days, followed by 100 micrograms daily. Antitumor activity was assessed after 90 days and treatment was continued in responders. The results were the following: plasmatic levels of LH were sharply decreased and those of testosterone were in all cases under 1 ng/ml by the 90th day of treatment; urinary symptoms and bone pain disappeared or were greatly improved in almost all patients; the volume of the prostate measured by ultrasonography and/or computerized tomography regressed by more than 50% of initial volume in 44% of the 34 patients for which this parameter was evaluable; bone scintiscans were improved in 18% of evaluable patients; plasmatic levels of prostatic acid phosphatases determined by radio immuno-assay were elevated in 28 patients, 61% of which presented a decrease superior to 50% or normalisation of this parameter. No disease flare up was observed on initiation of therapy. Impotence was constant but reversible on discontinuation of therapy. No other side effect could be attributed to therapy.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Neoplasms; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Hyperplasia; Prostatic Neoplasms; Triptorelin Pamoate; Urination Disorders

We have compared the concentrations in serum of gamma-seminoprotein (gamma-SM) and prostate specific antigen (PSA), two antigens of prostatic origin that are synthesized independently of prostatic acid phosphatase (PAP, EC 3.1.3.2), to assess their potential in monitoring prostatic cancer. At presentation, 27/30 (90%) patients with metastases had a PSA concentration greater than 10 ng/mL, and 29/30 (97%) a gamma-SM concentration greater than 10 ng/mL; 21/61 (34%) with disease but without metastases had an abnormal content of PSA, and 23/61 (38%) an abnormal gamma-SM. Concentrations of PSA and gamma-SM were significantly correlated (r = 0.68, p less than 0.001). In 20 patients without metastases followed longitudinally, the median concentrations of gamma-SM, PSA, and PAP in the 13 patients who developed bony metastases or showed signs of local spreading of the tumor were 58 ng/mL, 34 ng/mL, and 2.1 U/L, respectively. The corresponding median values in the seven patients who remained clinically stable were 2.5 and 3.9 ng/mL, and 2.3 U/L. We conclude that either PSA or gamma-SM can warn of disease progression when PAP activities are still within normal limits.

Topics: Acid Phosphatase; Adult; Antibodies, Monoclonal; Antigens; Bone Neoplasms; Humans; Immunoenzyme Techniques; Longitudinal Studies; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatic Secretory Proteins; Proteins; Seminal Plasma Proteins

Topics: Acid Phosphatase; Adolescent; Antineoplastic Agents; Bone Neoplasms; Child; Combined Modality Therapy; Humans; Hyperthermia, Induced; Osteosarcoma

Topics: Acid Phosphatase; Adenocarcinoma; Black People; Bone Neoplasms; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Middle Aged; Prostatic Neoplasms; Testicular Neoplasms

Prostatic cancer is commonly manifested by obstructive uropathy, regional lymphatic metastases, and hematogenous metastases to the axial skeleton. It is relatively rare that initial signs begin with the involvement of other sites. Intracranial metastases especially are seldom found and may be unfamiliar to not only pathologists but also to physicians. In this article, we present a case where the metastasis was first manifest as a sphenoid sinus tumor prior to the demonstration of the primary site and the prostate was confirmed to be primary by biopsy specimen with immunoperoxidase method. In addition to discussing the route of the tumor spread, we deal with a prostatic specific antigen efficient for identifying the primary site.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Male; Paranasal Sinus Neoplasms; Prostatic Neoplasms; Sphenoid Sinus; Tomography, X-Ray Computed

Radioimmunoassay (RIA) of prostatic acid phosphatases (PAP) using the Gammadab (R) PAP pack supplied by Clinical Assays in an effective method for determining extension of prostatic cancer. In patients with lymph node or metastatic invasion serum assay values are almost always elevated (sensitivity = 94%), especially with well differentiated cancer. Elevated levels of this variable are practically pathognomonic of external extension (specificity = 94%). This is of importance in therapy since the degree of invasion determines the choice between palliative and curative treatment. Strategy leading to this therapeutic choice can be greatly simplified and thus modified by RIA of PAP.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Clinical Enzyme Tests; Hormones; Humans; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Decalcified bone marrow biopsies containing metastatic tumor from 36 patients were stained for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) using the avidin biotin complex (ABC) immunoperoxidase technique. Of these patients, 22 had known prostate primaries, ten had known nonprostatic, and four female patients had unknown primaries. Prostate-specific antigen was identified in 86% (19/22) of the metastatic prostatic carcinomas. Prostatic acid phosphatase was present in only 36% (8/22). None of the patients with nonprostatic primaries or unknown primaries showed positive staining for either antigen (0/14). This study indicates that immunoperoxidase staining for PSA is very sensitive and specific in the diagnosis of metastatic prostate carcinoma, while PAP was less sensitive using decalcified bone marrow specimens. We believe that immunostaining with PSA should be of great value in diagnosis of prostatic carcinoma metastatic to the bone.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Bone Marrow; Bone Neoplasms; Decalcification Technique; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms

By studying histochemically and ultrastructurally a case of malignant fibrous histiocytoma (MFH) of bone with neoplastic osteoid elements, the distinction of the tumor from osteosarcoma was discussed. MFH was likely to originate from undifferentiated mesenchymal cells that induced a histiocytic line of differentiation, and some histiocytes seemed to be transformed into well differentiated fibroblastic cells which accordingly differentiated into fibroblasts and osteoblasts. This may explain the existence of the osseous elements in MFH. Sarcoma showing the bimodal--histiocytic and fibroblastic--differentiation should be diagnosed as malignant fibrous histiocytoma, even if it contains tumorous osteoid; it must be clearly distinguished from osteosarcoma, in which the various cells only on a fibroblastic line of differentiation can be identified and the osteoblasts are the predominant cells.

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Female; Histiocytoma, Benign Fibrous; Histocytochemistry; Humans; Microscopy, Electron; Tibia

A new technique was applied to the study of human osteosarcoma. Ten slices of 10 micron were cut serially from 2 X 2 X 6 mm shock frozen blocks of human osteosarcoma for chemical analysis. Before and after each series of 10 slices, one slice of 10 micron was separated for morphological analysis. Four different types of osteosarcoma were investigated: Case 1 was an atypical osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma, case 3 a well-differentiated parosteal osteosarcoma grade I, and case 4 a highly malignant anaplastic osteosarcoma. Alkaline phosphatase, acid phosphatase, beta-glucuronidase and proteolytic activities were analysed as well as matrix collagen and hexosamine, phosphorus (Pi and Po), protein, DNA, and water content. In accordance with the morphology, the obtained data illustrate the great heterogeneity of osteosarcomas. Although case 1, 2 and 3 all represent calcifying types of the tumor, characteristic differences exist with regard to the matrix and the degree of calcification. In contrast to these three, case 4 presents a noncalcified type of osteosarcoma whose matrix contains relatively high amounts of hexosamine and low amounts of collagen, whereas DNA and water contents are high. The data from the analysis of osteosarcoma were compared with previous results from the calf epiphyseal growth plate in order to define differences and similarities between the formation of tumor bone and the physiological formation of hard tissue.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Glucuronidase; Humans; Osteosarcoma; Registries

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Female; Humans; Isoenzymes; Liver; Tomography, Emission-Computed

Human osteosarcoma specimens were sliced in a cryomicrotome under strict morphological guidance. Serial sections of ten 10 micron slices each were collected in two groups according to morphologic criteria, one containing mostly undifferentiated tumor tissue, the other predominantly well-differentiated tumor tissue. The two series were analysed chemically for alkaline phosphatase (APase) acid phosphatase (acPase), beta-glucuronidase and proteolytic activities; protein, phosphorus, hydroxyproline, hexosamine, water and collagen contents were also determined. Four different types of osteosarcoma were studied: case 1 was a highly malignant osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma case 3 a well-differentiated osteosarcoma, and case 4 a highly malignant anaplastic osteosarcoma. The types of cases 1, 2 and 3 are known as osteoid-forming tumors. In their less well differentiated areas APase activity was about twice as high as in better differentiated osteosarcoma. In contrast, no APase was found in the wholly undifferentiated areas of case 4, while the enzyme showed a marked increase in the areas of incipient differentiation of this tumor. The matrix of tumors differs with regard to collagen and hexosamine contents, in accordance with the general state of differentiation. In general, increasing hexosamine contents together with decreasing hydroxyproline contents will reflect the anaplastic, dedifferentiated osteosarcoma. Calcification evident in the better differentiated areas of osteosarcoma is indicated by the phosphorus content, highest in case 2, with cases 3, 1, and 4 following in sequential order.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Collagen; Glucuronidase; Hexosamines; Humans; Hydroxyproline; Neoplasm Proteins; Osteosarcoma; Peptide Hydrolases

In a proliferating giant cell tumor of bone the activities of tartrate-resistant acid phosphatase (acPase) and of NADH-tetrazolium reductase were demonstrated by enzyme histochemical methods. Quantitative microphotometry made it possible to determine the relative enzyme activities per given volume unit in the cytoplasm of giant cells of several sizes. The activity of tartrate-resistant acid phosphatase increases with increasing cell size, whereas the activity of tetrazolium reductase will decrease in proportion. This coincidence of high acPase activity and low tetrazolium reductase activity in larger giant cells is interpreted as an expression of degenerative change.

Topics: Acid Phosphatase; Adult; Bone Neoplasms; Cytoplasm; Female; Femoral Neoplasms; Giant Cell Tumors; Humans; NADH Tetrazolium Reductase; NADH, NADPH Oxidoreductases; Photometry

Histochemical staining for three hydrolytic enzymes were performed in 35 bone tumours and 43 soft tissue tumours, malignant as well as benign. Osteosarcoma, intra-osseous as well as extra-osseous, revealed characteristic rich staining for alkaline phosphatase, no matter how dedifferentiated the tumour was. Haemangioendothelioma (and normal endothelium), too, showed strong reaction for alkaline phosphatase whereas haemangiopericytoma did not. Alkaline phosphatase furthermore was found in slight to moderate amounts in fibrous proliferations. All other tumours examined were negative. Acid phosphatase was found in almost every tumour investigated except Ewing sarcoma and chondromyxoid fibroma. However, high activity was characteristic of giant cell tumours and malignant fibrous histiocytoma. The inhibition of acid phosphatase by tartrate was complete except in osteosarcoma and giant cell tumours, where only a partial inhibition was seen. There were non-specific esterase reactions in a variety of tumours, but very strong reactions were characteristic of malignant fibrous histiocytoma and giant cell tumours. The reaction could be completely inhibited by the addition of fluoride. In an era of increasing application of immunohistologic techniques in surgical pathology it might be of value to remember that simple enzyme histochemical stainings may provide helpful diagnostic features in the classification of bone and soft tissue tumours.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Carboxylesterase; Carboxylic Ester Hydrolases; Histocytochemistry; Humans; Soft Tissue Neoplasms

One hundred and twenty-seven patients with locally advanced prostatic cancer were evaluated for the presence and progress of bone metastases before and during hormonal therapy, by serial radionuclide imaging and frequent measurement of plasma acid (tartrate-labile) and alkaline phosphatase. For comparison, serial changes in imaging and phosphatases were classified in each patient into one of six groups. Of 71 patients with negative imaging before treatment, 82% had normal alkaline phosphatase levels and 83% had normal acid phosphatase levels. Of 56 patients with bone metastases at presentation, false negative alkaline and acid phosphatase levels were noted in 18% and 36% respectively, though a few patients eventually developed abnormal levels. Serial plasma biochemistry and particularly alkaline phosphatase showed a response to treatment which was not always obvious on imaging. An assessment of the hepatic component of alkaline phosphatase by reference to plasma gamma glutamyl transpeptidase and isoenzyme electrophoresis was helpful in the evaluation of a false positive result but unnecessary where imaging was positive and phosphatase elevated. It is concluded that serial alkaline phosphatase estimation is essential in the follow-up of patients with prostatic cancer and bone metastases, and probably renders serial imaging studies superfluous once the presence of skeletal metastases has been proven. By comparison, acid phosphatase is a much less effective marker.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Diethylstilbestrol; Estramustine; Follow-Up Studies; Humans; Male; Middle Aged; Prostatic Neoplasms; Radionuclide Imaging

Twenty-five patients with metastatic prostate cancer resistant to primary hormone therapy, received high-dose intravenous diethylstilbestrol diphosphate (Stilphostrol [Miles Pharm], DES-P) in a Phase II study using established response criteria. Objective response rate was 17%, while 22% of the patients were subjectively improved. Moderate gastrointestinal toxicity was reported in 10 patients (40%). Thromboembolic complications were seen in 2 (8%). The role of high-dose Stilphostrol in the treatment of hormone-resistant prostate cancer is limited.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Bone Neoplasms; Castration; Combined Modality Therapy; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms

The prognostic significance of skeletal scintigraphy has been reassessed in relation to other tests by extended follow-up of 220 patients. Skeletal metastases increased in prevalence with T stage and were associated with shorter survival irrespective of age. Early disease, a normal acid or alkaline phosphatase at presentation and well differentiated tumours were associated with longer survival. Alkaline phosphatase alone accounted for all of the differences in survival. Scintigraphic change preceded elevation of the prostatic acid phosphatase in 81% of the patients whose initial scintigraphy and prostatic acid phosphatase were normal but who developed evidence of distant metastases on follow-up. The mean interval between scintigraphic conversion and the development of overt symptoms was 5.8 months. Our findings discount the value of skeletal scintigraphy for determining prognosis but do indicate that it is more sensitive than the acid phosphatase in identifying patients before they become symptomatic. Scintigraphy is indicated as a routine staging procedure in all new patients with carcinoma of prostate. In patients with a normal alkaline phosphatase, a baseline and regular follow-up are needed to identify patients likely soon to develop symptoms. If the alkaline phosphatase is elevated at presentation, scintigraphy is necessary to distinguish benign from malignant causes and to determine the extent of skeletal involvement.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Prognosis; Prostatic Neoplasms; Radionuclide Imaging

Topics: Acid Phosphatase; Adenocarcinoma; Androgen Antagonists; Bone Neoplasms; Combined Modality Therapy; Humans; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Four hundred and four prostatic cancer patients diagnosed in the years 1979-1982 in nine Finnish hospitals have been followed up for a mean period of three years. The aim of this study is to evaluate the situation of this malignancy in the Finnish male population and to discuss the diagnostic procedures and treatment modalities. In one fifth of the patients the carcinoma was as incidental finding on microscopical examination of tissue removed by transurethral resection or enucleation for presumed benign prostatic hyperplasia. At the diagnostic moment 69% of the tumours were locally advanced beyond the prostatic capsule and one third of all cases had metastasized. 134 out of 404 (33%) have died and 45% of these of prostatic cancer. Survival was adversely affected by the tumour differentiation grade. In non-metastasized cases the local extent of the tumour had no notable effect on prognosis. Some early comparisons are made between orchidectomy and oestrogen therapy.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Estradiol; Estradiol Congeners; Ethinyl Estradiol; Follow-Up Studies; Humans; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Random Allocation

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Diagnosis, Differential; Female; Fibrosarcoma; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Lymphoma; Male; Middle Aged; Osteosarcoma

Computerized bone scanning (CBS), a technique used to measure quantitative changes in bone scans, is described. Ten patients with histologically proven metastatic carcinoma of the prostate had sequential CBS performed. Good correlation was found between marked improvement in CBS (more than 50% average decrease in counts) and objective responses. Two patients had partial remission with more than 50% average decrease in uptake by prostatic cancer project criteria; both of them had good pain control. Three patients had worsening of their disease by CBS, which correlated with other parameters of disease progression (new lesions in bone survey, loss of weight and poor survival). In those patients with less than 50% average change the correlation is not so clear cut. An increase in percentage of uptake occurs in the first month after beginning of therapy, and no significant change is observed until 3 months. CBS is a technique that allows for objective measurement of quantitative changes in bone uptake, which is potentially useful for the evaluation of response to treatment in patients with metastatic bone disease from carcinoma of the prostate.

Topics: Acid Phosphatase; Aged; Body Weight; Bone and Bones; Bone Neoplasms; Diphosphonates; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.

Topics: Acid Phosphatase; Alkaline Phosphatase; Analgesia; Bone Neoplasms; Buserelin; Goserelin; Hormones; Humans; Male; Prostatic Neoplasms

Conventional antibodies against prostatic acid phosphatase, labeled with iodine-131, have been administered to patients with prostatic carcinoma for the external scintigraphic imaging of tumors containing prostatic acid phosphatase (radioimmunodetection). The method has been found to be safe and reliable for imaging of primary tumors and non-bone metastases, even differentiating between lung tumors of prostatic and pulmonary origin.

Topics: Acid Phosphatase; Animals; Antibodies; Bone Neoplasms; Carcinoma; Goats; Humans; Iodine Radioisotopes; Isotope Labeling; Lung Neoplasms; Male; Prostate; Prostatic Neoplasms; Rabbits; Radionuclide Imaging; Serum Albumin; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Aggregated Albumin

The clinical application of an immunohistochemical technique for prostatic acid phosphatase allowed the accurate diagnosis of metastatic prostatic carcinoma in 17 patients whose condition was not recognized by either clinical or histologic observations. The cardinal manifestations in these 17 patients included supraclavicular lymphadenopathy in 7, hilar lymphadenopathy in 1, pulmonary infiltration in 2, simulating carcinoma of the rectum in 4, fracture of femur in 1, orbital tumor in 1, and brain tumor in 1. A retrospective analysis of the radiologic features of these patients showed that the unusual manifestations were due to the route of metastasis, that is, direct invasion, lymphatic, and hematogenous. Radiologic studies, even in these unusual cases, are both useful in establishing the diagnosis and helpful in delineating the mode of metastasis of prostatic carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Brain Neoplasms; Histocytochemistry; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; Male; Middle Aged; Paranasal Sinus Neoplasms; Prostatic Neoplasms; Rectal Neoplasms; Retroperitoneal Neoplasms; Tomography, X-Ray Computed

Tartrate-resistant acid phosphatase activity determined by enzyme immunoassay was higher in the serum of cancer patients than that in normal blood donors. The highest activity was found among patients having malignancy metastatic to bone. The classic colorimetric method showed a broad range of values among normal blood donors, and the contrast between normal and cancer patients was less obvious. Most of the cancer patients had normal to low alkaline phosphatase activities.

Topics: Acid Phosphatase; Adult; Bone Neoplasms; Breast Neoplasms; Colorimetry; Female; Humans; Immunoenzyme Techniques; Isoenzymes; Male; Prostatic Neoplasms

The cytogenesis of giant cell tumors of bone was studied in 6 cases by combined electron microscopical, histochemical and autoradiographical investigations. Electron microscopy identified two different types of mononuclear stromal cells: fibroblast-like cells with spindly shape and numerous membranes of the granular ER occur together with macrophages bearing many large lysosomes and a prominent Golgi apparatus. Enzyme histochemical results reflect the same diversity: One portion of mononuclear cells exhibits strong alpha-naphthyl acetate esterase (ANAE) activity, known as a marker for cells of the mononuclear phagocyte system, while the other, fibroblast-like cell type is ANAE negative. Tumor giant cells contain numerous membranes of granular ER, mitochondria, and a few isolated lysosomes. They lack the typical brush border of osteoclasts. Moderate to strong ANAE activity of these giant cells reflects their belonging to the mononuclear phagocyte system. Consequently, the giant cell tumor of bone consists of two different cell types, i.e. fibroblast-like cells and cells of the mononuclear phagocyte system, and so is appraised as a fibrohistiocytic tumor. A new inference from our autoradiographic findings is that tritiated thymidine is incorporated only by mononuclear cells, but not by giant cells. Electron microscopical autoradiography demonstrated that among the mononuclear cells, only fibroblasts are found to proliferate, but not macrophages. Thus, the giant cell tumor of bone is seen as a neoplasm of fibroblastic cells with a strong reactive infiltration of cells from the mononuclear phagocyte system.

Topics: Acid Phosphatase; Alkaline Phosphatase; Autoradiography; Bone Neoplasms; Giant Cell Tumors; Histocytochemistry; Humans; Microscopy, Electron; Naphthol AS D Esterase; Organoids

Bone scintigraphy, serum acid phosphatase activity (ACP), prostatic acid phosphatase by radioimmunoassay (PAP) and alkaline phosphatase activity (ALP) were studied in 117 consecutive patients with prostatic cancer. Serum PAP was more sensitive than ACP in indicating prostatic cancer in the 63 patients with normal bone scans: 28% had positive PAP tests and 15% positive ACP tests. In the 54 patients with bone metastases no difference in the frequency of positive PAP (84%) and ACP (85%) test was observed. Serum PAP and ACP, but not ALP, were useful for the assessment of the response to therapy particularly in patients without bone metastases. In the follow-up of patients with bone metastases the scan was more informative than any of the phosphatase assays studied.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging

A radioimmunodetection technique using 99mTc-labelled polyclonal antibodies raised in rabbits against human prostate-specific acid phosphatase was used to detect metastases of prostatic carcinoma. All the metastases observed by X-rays or bone scintigraphy in the four patients with M1-disease were revealed by the novel technique employed. In addition, in one of the patients studied, a distinct incorporation of radioactivity was also observed in the left inferior scapular region, which was not seen by conventional bone scanning, but was later confirmed by X-ray studies to be a metastatic process.

Topics: Acid Phosphatase; Bone Neoplasms; Humans; Immunoglobulin Fab Fragments; Immunoglobulins; Male; Prostate; Prostatic Neoplasms; Radionuclide Imaging; Technetium

9 of 12 patients with advanced metastatic carcinoma of the prostate treated with luteinising-hormone-releasing-hormone (LHRH) analogue ICI 118630 for a mean period of 6 months showed objective evidence of response to treatment. Of 8 patients with bone pain, 7 obtained relief. After 6 weeks of treatment testosterone concentrations were reduced to castrate levels (range less than 2 to 5.5 nmol/l) from a pretreatment mean value of 15.7 nmol/l (range 10.3-24 nmol/l). Basal gonadotropin levels and gonadotropin responses to acute LHRH stimulation were suppressed within 2 weeks of treatment. However, the testosterone response to stimulation with human chorionic gonadotropin was unimpaired 4 weeks after the start of treatment. Therefore suppression of the basal testosterone concentration by ICI 118630 was due to inhibition of pituitary luteinising-hormone secretion rather than direct inhibition of testicular Leydig-cell function. ICI 118630 offers an alternative treatment to orchidectomy and oestrogen therapy.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Chorionic Gonadotropin; Depression, Chemical; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Pain; Pelvis; Prostatic Neoplasms; Radiography; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Female; gamma-Glutamyltransferase; Humans; Hydroxyproline; Liver Neoplasms

The authors discuss the pathological value of acid phosphatase measurement. One of its main applications is the diagnosis of prostatic cancer. The emergence of immunological methods of measuring the enzyme, which are more sensitive and more specific, has led to renewed interest as acid phosphatase measurement can now be used in the early diagnosis of prostatic cancer, or at least in the early diagnosis of its extraprostatic extensions.

Topics: Acid Phosphatase; Bone Neoplasms; Counterimmunoelectrophoresis; Humans; Immunoenzyme Techniques; Isoenzymes; Male; Prostatic Neoplasms; Radioimmunoassay; Substrate Specificity

In a retrospective correlative analysis of postmortem findings and antemortem transurethral resection specimens from 81 patients with prostatic carcinoma a simple and reliable prediction index was found. This index was derived from the transurethral resection specimen in regard to the probability of ultimate bone metastasis by tumor and was obtained by dividing the number of prostatic tissue chips involved with tumor by the total number of prostatic tissue chips examined microscopically. We found that when 75 per cent or more of the transurethral resection chips were involved with tumor, regardless of the degree of tumor differentiation, the probability of bone metastasis was more than 9.0 (greater than 90 per cent), whereas the probability was 0.58 for 50 to 75 per cent involvement, 0.38 for 30 to 50 per cent involvement, 0.27 for 20 to 30 per cent involvement, 0.10 for 10 to 20 per cent involvement and 0.06 for less than 10 per cent involvement. Other tumor grading systems, such as the Gleason system, also were compared. A good correlation was obtained by the Gleason grading system in the prediction of bone metastasis but the system is not as simple or as reproducible as the tumor involvement index described herein. Other parameters, such as prostatic acid phosphatase and prostatic specific antigen as determined by the immunoperoxidase method, had no specific or significant value in the prediction of bone metastasis. Our findings reaffirm the relatively old concept that the extensiveness of tumor involvement in the transurethral resection specimen is the single most important factor in the prediction of the clinical behavior of the prostatic carcinoma.

Topics: Acid Phosphatase; Antigens, Neoplasm; Bone Neoplasms; Humans; Immunoenzyme Techniques; Male; Probability; Prostatic Neoplasms; Retrospective Studies

Giant cell tumors of bone dissociated by collagenase digestion were found to be composed of four different cell types defined by morphology, growth in culture, and pattern of staining with monoclonal antibodies. Giant cells comprised an average of 0.8% of the cells recovered, with the remainder consisting of small stromal cells. Of the giant cells, 20-57% expressed Ia antigens, while all lacked IgG Fc receptors and five differentiation antigens associated with mature members of the monocyte-macrophage lineage (M phi S-1, M phi P-9, M phi P-15, M phi S-39, and 63d3). One antigen, M phi U-50, found on early monocytoid forms was expressed on Ia+ giant cells. 6-36% of the remaining stromal tumor cells formed a second subpopulation that assumed either a rounded or elongated shape in culture. These cells bore Ia antigens, IgG Fc receptors, and five antigens of the monocyte-macrophage lineage usually found on blood monocytes. However, these cells differed from monocytes or macrophages in that the antigen M phi R-17 generally found on tissue macrophages was absent, and the M phi U-50 antigen present on more primitive cells was well expressed. A very limited endocytic capacity was demonstrable. A third population of up to 24% of the tumor cells was defined by the presence of intense staining for Ia antigens but the absence of antigens of mature monocytes. A proportion of these cells expressed M phi U-50 and a minority had IgG Fc receptors. The two Ia(+) populations of stromal cells were not identifiable after 2 wk of culture, nor did tumor cells selected for the presence of Ia antigens proliferate in culture. A fourth population of cells lacked Ia and monocyte lineage antigens, but showed pronounced intracellular staining for acid phosphatase. These cells had a distinctive plump epitheloid to fibroblastoid morphology and were readily established in long-term culture where they gave rise to large multinuclear Ia(-) cells containing acid phosphatase. The possibility is discussed that the cell types of these tumors relate to various stages in the development of osteoclasts from precursors in the mononuclear phagocyte lineage.

Topics: Acid Phosphatase; Antigens, Neoplasm; Bone Neoplasms; Cell Differentiation; Cells, Cultured; Giant Cell Tumors; Histocompatibility Antigens Class II; Histocytochemistry; Humans; Immunoglobulin G; Macrophages; Monocytes; Receptors, Fc

Twelve osteosarcomas treated according to the COSS 80 protocol (preoperative chemotherapy, resection) were studied by light and electron microscopic, histochemical, and autoradiographic methods. Evidence of regressive and necrotic changes was found in many tumor cells, but the alterations were unspecific. Viable tumor cells of high malignancy were also observed regularly, often at the S phase. As the tumor regression continued, a strong reaction of the mononuclear phagocyte system was manifested by the presence of macrophages and giant cells.

Topics: Acid Phosphatase; Adolescent; Adult; Autoradiography; Bone Neoplasms; Carboxylic Ester Hydrolases; Child; Female; Histocytochemistry; Humans; Macrophages; Male; Microscopy, Electron; Naphthol AS D Esterase; Osteosarcoma

In a patient with an unclassifiable primary or metastatic neoplasm, with or without a history of prostatic cancer, immunostaining for PA or PSAP may prove invaluable. The procedure is simple, rapid, inexpensive, and extremely accurate in demonstrating the prostatic origin of tumors. It should be noted however, that the specificity of results is entirely dependent upon the specificity of the primary antibody, which should be meticulously defined before the procedure is used for diagnostic purposes.

Topics: Acid Phosphatase; Antigens, Neoplasm; Bone Neoplasms; Breast Neoplasms; Carcinoma; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

The acid phosphatase in the cells of bone and soft parts tumors, and of other tumorous conditions in our Department of Orthopedic Surgery in Kumamoto University Medical School from mid-1979 through mid-1983 were analysed by light microscopic and electron microscopic histochemical studies and their inhibition studies. The histochemical and their inhibiting studies of acid phosphatase by azo dye method in the cells of bone and soft parts tumors and of other tumorous conditions were undertaken in order to characterize them with a view to providing helpful diagnostic features. The acid phosphatase in some giant cells and tumor cells of several kinds of tumors, whose reaction against inhibitors was different from that of lysosomal acid phosphatase, was observed. In the giant cells of giant cell tumor of bone, acid-para-nitrophenyl phosphatase was demonstrated by the method of Miyayama , et al. using sodium-para-nitrophenyl phosphate as a substrate. In addition, the fine structural localization of acid phosphatase in giant cell tumor of bone was studied by Gomori's method and by the method of Miyayama , et al. By Gomori's method, acid phosphatase activity was demonstrated in lysosome, secondary lysosome-like organelles and the digestive vacuoles in the giant cells. In the stromal cells, that activity was demonstrated in lysosomes. By the method of Miyayama , et al., acid para-nitrophenyl phosphatase was demonstrated in the Golgi complex and the cisternae of the rough endoplasmic reticulum in the giant cell. Therefore, in the giant cells and the tumor cells of some kinds of tumors, non-lysosomal acid phosphatase besides lysosomal acid phosphatase was recognized. The demonstration of non-lysosomal acid phosphatase was a useful tool for the differential diagnosis of tumors and tumorous conditions in bone and soft parts.

Topics: Acid Phosphatase; Bone Neoplasms; Giant Cell Tumors; Histocytochemistry; Humans; Osteosarcoma; Soft Tissue Neoplasms

The whole body bone scintigraphy of 13 patients whose prostatic cancer were histologically confirmed, was processed in four colors, and the bone metastases were quantitatively estimated. On the basis of this estimation, the extent of bone metastases was classified into 4 divisions (grades 0, 1, 2 and 3). And then, the correlation between the extent of bone metastases and prostatic acid phosphatase, acid phosphatase, and alkali phosphatase levels in serum were investigated.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay; Radionuclide Imaging

Random bone marrow aspiration biopsies of iliac crests and bone scans/skeletal X-rays were evaluated in 163 new cases of carcinoma of the prostate in order to assess the incidence of bone metastases and to compare the sensitivity of these two methods. Bone marrow biopsy revealed cancer cells in 18.4% of all cases. The detection rate of skeletal metastases of bone scan/skeletal X-ray was 32.5%. In this series all patients with positive biopsies had also positive scans. The superior sensitivity of bone scans compared with bone marrow biopsies in detecting metastatic spread of prostatic cancer is shown.

Topics: Acid Phosphatase; Aged; Biopsy, Needle; Bone and Bones; Bone Marrow; Bone Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatic Neoplasms; Radionuclide Imaging

The results of clinical examination, skeletal X-ray, bone scan and phosphatase determinations in serum were analyzed in 30 patients with metastatic prostatic cancer prior to and during anti-androgenic treatment. Bone scan revealed skeletal metastases in all 30 patients, whereas X-ray showed bone metastases in only 22 patients. Radiological pseudoprogression and scintigraphic flair reaction were relatively frequent findings during the first 3-8 months of effective hormone therapy. Later on progressive changes on X-ray and bone scan were well related to clinical progression of the disease and indicated a poor prognosis in the individual patient. Soft tissue metastases most often responded well to the initial hormone treatment, but regrew only rarely during later disease progression. Changes of the radioimmunologically determined prostatic acid phosphatase seemed most often to indicate the presence of advanced disease and subsequent disease progression. Second line treatment of hormone-unresponsive prostatic cancer is at best palliative and has not been proved to prolong the survival in most of the patients. In routine clinical practice, the need for such second line therapy is dependent on the patient's symptoms and not on the early detection of progressive changes on X-ray, bone scan or blood tests. Therefore it seems unnecessary to perform these examinations regularly in hormone-treated asymptomatic patients with advanced prostatic cancer unless the patient is entered into a clinical research program.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Castration; Diethylstilbestrol; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Soft Tissue Neoplasms

Topics: Acid Phosphatase; Bone Neoplasms; Carcinoma; Female; Humans; Male; Prostatic Neoplasms; Radionuclide Imaging

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Bone Neoplasms; Creatinine; Humans; Hydroxyproline; Male; Prostatic Neoplasms

Sixty-two per cent of 61 patients with prostatic carcinoma showed elevated levels of serum acid phosphatase, analysed by radioimmunoassay (RIA). Enzymatically determined serum acid phosphatase was raised in only 38% of the same patients. Bone marrow acid phosphatase determined by RIA was raised in 41%. In untreated metastatic patients with prostatic carcinoma, radioimmunologically determined serum acid phosphatase was elevated in 12 of 13 patients, whereas bone marrow acid phosphatase (RIA) and enzymatically determined serum prostatic acid phosphatase were increased only in about half of the patients. In a control group the upper reference limit of bone marrow acid phosphatase determined by RIA was significantly raised above that obtained by serum analyses. This indicates that nonprostatic acid phosphatases (possibly from bone marrow cells) cross-react with prostatic acid phosphatase in an unpredictable way, even when using a specific radioimmunoassay. In patients with metastatic carcinoma of the prostate, the results of bone marrow acid phosphatase determinations, analysed by RIA, seem to lack diagnostic and/or prognostic information additional to that obtainable by serum acid phosphatase (RIA) analysis.

Topics: Acid Phosphatase; Aged; Bone Marrow; Bone Neoplasms; Humans; Male; Middle Aged; Prostate; Prostatic Neoplasms; Radioimmunoassay

Clinical and pathological staging furnishes valuable information upon which the clinician can base his treatment and compare results. Staging refinements occur as we learn more about the natural history of the disease and the efficacy of our treatment. We observed that clinical stage B patients with minimal (less than twice normal) elevation of the serum acid phosphatase have similar pathologic stage B (75%) and disease-free survival rates following total prostatectomy as stage B patients with normal acid phosphatases. Intraglandular crystalloids were found in 26% of clinical stage B patients treated by total prostatectomy, and none of this subgroup of patients has had a recurrence of disease. Pathologic staging frequently confirms the presence of a greater extent of tumor than was clinically anticipated. In general, prognosis for patients with a small tumor mass will be more favorable than that for patients with a large tumor mass. Staging permits the estimation of prognosis of groups of patients with similar tumor burdens; however, the survival of an individual within any such group is unpredictable.

Topics: Acid Phosphatase; Bone Neoplasms; Crystallization; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Prognosis; Prostatectomy; Prostatic Neoplasms

Measurements of human prostate-specific acid phosphatase by radioimmunoassay in peripheral and bone marrow sera were compared. We studied 20 patients with benign prostatic hyperplasia, 27 with untreated prostatic cancer without bone metastases and 11 with metastases, in addition to 7 with cancer treated by hormonal therapy. The prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum samples were equal and did not exceed the upper limit of our health-associated reference interval, 2.8 microgram. per 1. (mean plus 2 standard deviations) in patients with prostatic hyperplasia. Of 27 prostatic cancer patients without bone metastases the concentration of prostate-specific acid phosphatase was elevated in the peripheral sera of 20 and in the bone marrow sera of 21, and 21 had an extracapsular tumor (stage T3 to T4). Prostate-specific acid phosphatase concentrations were elevated in peripheral and bone marrow serum specimens of all 11 patients with metastases and bone marrow cytology studies were positive in 2. There was no difference in prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum specimens from prostatic cancer patients undergoing hormonal treatment. We conclude that the use of bone marrow serum for the measurement of radioimmunoassayable prostate-specific acid phosphatase in prostatic cancer patients does not provide any further information in regard to the detection of prostatic cancer compared to the use of peripheral serum specimens. Falsely positive findings in bone marrow specimens were not observed with the method used.

Topics: Acid Phosphatase; Aged; Bone Marrow; Bone Neoplasms; Clinical Enzyme Tests; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

Three giant cell tumors of bone (2 benign and 1 malignant) were examined enzyme-histochemically, and a tissue culture study of the malignant case was performed. Multinucleated giant cells and mononuclear round cells had similar activities of ACPase and non-specific esterase with a diffuse strong reaction. ATPase and 5'-nucleotidase reactions were strongly positive in the cytoplasm of multinucleated giant cells, and were seen not only in the cytoplasm but also on the cell membrane of round cells. The proliferating spindle cells in the malignant case were faintly positive for ACPase and non-specific esterase and were less positive for ATPase and 5'-nucleotidase on the cell membrane. The multinucleated giant cells and mononuclear round cells resembled histiocytes in the activities of 4 hydrolytic enzymes, and the multinucleated giant cells had enzyme activities similar to those of osteoclasts from new-born rat skull. The malignant giant cell tumor and cells in its tissue culture showed ALPase activity preferentially on the cell membrane of the spindle cells, and rarely on round cells or multinucleated giant cells. ALPase was resistant to heat treatment and was found to be the type IV isoenzyme by diffusion electrophoresis. The origin of the giant cell tumor of bone and the significance of the ALPase activity are discussed.

Topics: 5'-Nucleotidase; Acid Phosphatase; Adenosine Triphosphatases; Adult; Aged; Alkaline Phosphatase; Animals; Bone Neoplasms; Culture Techniques; Esterases; Female; Giant Cell Tumors; Histocytochemistry; Humans; Isoenzymes; Male; Microscopy, Electron; Nucleotidases; Rats

A total of 19 cases with bone tumors, including six osteosarcomas. three giant cell tumors of bone, one malignant fibrous histiocytoma, four nonossifying fibromas, four chondromas and one chondrosarcoma, were examined as to enzyme histochemistry; the enzymes consisted of alkaline phosphatase (ALPase), acid phosphatase (ACPase), nonspecific esterase (NSE), adenosine triphosphatase (ATPase), 5'-nucleotidase (5'-Nucl) and beta-glucuronidase (beta-Gl). Osteosarcoma was strongly positive for ALPase followed by 5'-Nucl. Giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma showed enzyme histochemistry similar to each other: multinucleated giant cells and round cells in these tumors were strongly positive for ACPase, NSE, ATPase and 5'-Nucl simulating osteoclasts and histiocytes, whereas spindle cells were positive for ATPase and 5'-Nucl in their cytoplasm and weakly positive for ACPase. Chondroma and chondrosarcoma were focally positive for ACPase and NSE; the ACPase was sensitive to tartaric acid treatment. These observations showed that ALPase activity is very characteristic to osteosarcoma, and is useful for its diagnosis. From enzyme histochemistry, giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma can be regarded as a histiocyte-derived tumor of bone in contrast to osteosarcoma and cartilaginous tumors.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Adult; Aged; Alkaline Phosphatase; Animals; Bone Neoplasms; Child; Child, Preschool; Chondroma; Chondrosarcoma; Female; Fractures, Bone; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Male; Metatarsus; Middle Aged; Osteosarcoma; Rabbits; Wound Healing

Electrophoresis and ion-exchange column chromatography were used to separate the wide varieties of acid phosphatases with different biological and clinical significance. Band 0 was very strong in ascitic cells with many autophagic vacuoles, indicating a role in autophagic function. Band 1 was a membrane-bound acid phosphatase, seen mainly in the microsomal fraction. Band 3 was the major lysosomal acid phosphatase of all nonprostatic tissues. Bands 2 and 4 were antigenically identical to each other, and were observed in unusually high amounts in the prostate. The different electrophoretic mobility between bands 2 and 4 was due to their carbohydrate content. Band 5 was a characteristic enzyme of the osteoclast. The tartrate-sensitive enzymes included bands 0 through 4. Only band 5 was tartrate resistant. The tartrate-resistant acid phosphatase of erythrocytes was not detected by the electrophoresis method. Clinical applications were seen for both bands 2 and 5. Band 2 was a secretory enzyme, normally secreted into the seminal plasma. Band 2 was absorbed into the blood circulation in some prostatic cancer patients. A small amount of bands 2 and 4 was observed in nonprostatic tissues. The diagnostic value of band 2 resulted from its extremely high concentration in the prostate. Band 5 was not observed in the normal prostate. A high concentration of band 5 was observed in hairy cells, Gaucher cells, and osteoclasts. The serum level of band 5b was an indicator of osteoclastic activity in the bone. Elevation of band 5b in serum was observed in normal children during physiological bone growth, in Gaucher's disease, and in malignancies metastasized to bone.

Topics: Acid Phosphatase; Animals; Ascites; Bone Neoplasms; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Gaucher Disease; Humans; Leukemia L1210; Male; Mice; Osteoclasts; Phagocytes; Prostate; Prostatic Neoplasms; Tartrates

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Clinical Enzyme Tests; Evaluation Studies as Topic; Female; Humans; Hyperplasia; Male; Mass Screening; Middle Aged; Neoplasm Staging; Prostate; Prostatic Neoplasms; Radioimmunoassay; Time Factors

The morphology of 26 cases of osteogenic sarcoma was studied using electron microscopic techniques, and the localization of acid and alkaline phosphatase activity at the ultrastructural level elucidated. Four different cells were present in the tumours: osteoblast-like, fibroblast-like, chondroblast-like, and multinucleated giant cells. The osteoblast-like cell was present in most of the tumours studied. Acid phosphatase activity was present in lysosome-like structures of almost all the cell-types studied. Alkaline phosphatase activity was noted in or on the plasma membranes and associated vesicles of osteoblast-like, fibroblast-like, and multinucleated giant cells. The abundant reaction product deposition of alkaline phosphatase as compared with the lower acid phosphatase activity is in agreement with the nature of this bone-forming tumour. The results of the histochemical studies have added to the understanding of the pathobiology of the different cells composing osteogenic sarcomas.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Histocytochemistry; Humans; Osteosarcoma

Topics: Acid Phosphatase; Age Factors; Bone Neoplasms; Castration; Hormones; Humans; Lymphatic Metastasis; Male; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Female; Humans; Male; Tartrates

Twenty-five patients with metastatic prostate cancer were treated with a combination of Adriamycin 50 mg/m2 and cis-platinum (CDDP) 50 mg/m2 every three weeks. Response was evaluated using radioisotope bone scan, serum acid phosphatase levels, and clinical status. Response rates of 6% bone, 21% acid phosphatase, and 24% clinical status were noted. Major toxicity was gastrointestinal (due to CDDP). Treatment was well tolerated even in patients with extensive bone metastases and prior irradiation. Using the response criteria described here, patients with metastatic prostate cancer without measurable soft tissue disease are eligible for Phase II and III study.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Cisplatin; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Radionuclide Imaging

The results of a study of the ultrastructural and enzymatic features of extracellular matrix vesicles in human osteogenic neoplasms are reported. Specimens from three osteosarcomas, a chondrosarcoma, and an osteoblastoma were processed for electron microscopic study and for preparation of vesicular, membrane, and cellular fractions. Electron micrographs of each lesion showed primary mineralization comprised of matrix vesicles and calcifying nodules. There was a distinct pattern of distribution of enzymatic activity among fractions from the osteosarcomas; namely that the highest values for specific activity of alkaline and pyrosphosphatases and adenosine triphosphases (ATPases) in the vesicle fractions and lowest in the cell fractions. This pattern was not consistent in fractions from the other neoplasms. The aforementioned enzymes are considered essential for the onset of mineralization. The data presented establish the role of matrix vesicles in neoplastic calcification and suggest the need for further studies into the diagnostic value of the vesicles.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Chondrosarcoma; Extracellular Space; Humans; Middle Aged; Neoplasms, Connective Tissue; Osteoma, Osteoid; Osteosarcoma; Pyrophosphatases

Our radioimmunoassay for prostatic acid phosphatase was compared to commercial radioimmunoassay kits. A close correlation among all 3 assays was found in control groups, and in patients with benign prostatic hyperplasia and adenocarcinoma of the prostate. These results also were compared to recent reports from other centers using similar methodologies. In 7 to 15 per cent of the patients with bone metastasis normal levels of serum prostatic acid phosphatase were found. Variability in prostatic acid phosphatase production by the tumor may account for this finding. Elevated levels of prostatic acid phosphatase were associated more commonly with less differentiated primary tumors. A low percentage of prostatic acid phosphatase elevations in patients with early localized and incidental adenocarcinoma was found for the 3 assays evaluated. These factors, along with the falsely positive rates in patients with benign disease, limit severely the application of these assays to the screening of male patients at risk for adenocarcinoma of the prostate.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Bone Neoplasms; Female; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay

The low incidence of measurable or evaluable metastases in patients with prostatic cancer makes evaluation of response difficult. This is particularly true in patients with bone metastases only. With a digital model it is possible to measure quantitatively from the radioisotope bone scan the total area of skeletal involvement by metastatic tumor. Definitions of response in bone have been derived from this model. These response criteria have been compared to response in acid phosphatase determinations and clinical status in a study of 44 patients with advanced prostatic cancer treated with estramustine phosphate. Based on serial quantitative bone scans, serial measurements of acid phosphatase levels and repeat clinical evaluations a system is proposed for defining response to systemic therapy that is applicable to the majority of patients with metastatic prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Aged; Bone Neoplasms; Diphosphates; Diphosphonates; Estramustine; Humans; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Radionuclide Imaging; Technetium

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Diphosphates; Diphosphonates; Humans; Male; Middle Aged; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

In six patients with known prostatic adenocarcinoma, extraprostatic (metastatic) tumor was suspected on radiographic or radionucleotide studies. When cytological examination of tissue obtained by needle aspiration or biopsy was nondiagnostic, radial gel immunodiffusion was used to identify the presence of prostatic acid phosphatase in the tissue. Four specimens demonstrated prostate-specific acid phosphatase activity, permitting the diagnosis of metastatic prostatic adenocarcinoma. The technique is simple and highly specific.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Immunodiffusion; Lung Neoplasms; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Adolescent; Adult; Arm; Bone Neoplasms; Child; Female; Humans; Hyperbaric Oxygenation; Hypoxia; Leg; Lymphocyte Activation; Male; Osteosarcoma; T-Lymphocytes; Tourniquets

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Humans; Male; Prostatic Neoplasms

Of 31 patients with prostatic cancer, 21 have skeletal metastases proven by bone scintigraphy and/or radiology. The sensitivity and specificity of the following measurements are compared: total urinary hydroxyproline, urinary hydroxyproline/creatinine ratio, free serum hydroxyproline, alkaline and prostatic phosphatases and serum calcium. The hydroxyproline/creatinine ratio is the most sensitive measurement for the diagnosis of bone metastasis, while total urinary hydroxyproline excretion per 24 hours is the most specific. Free serum hydroxyproline has no particular significance for this diagnosis. The alkaline and acid phosphatases are elevated but are not specific. Serum calcium decreases when skeletal metastases are present.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Calcium; Creatinine; Humans; Hydroxyproline; Male; Middle Aged; Prostatic Neoplasms; Radiography

Clinical followup of 112 patients staged by the immunochemical determination of prostatic acid phosphatase from bone marrow aspirates is presented. This represents a 94 per cent (112 of 118) retrieval rate of a group studied more than 2 years previously. Of the 11 patients judged to be at high risk 4 (36 per cent) have suffered bony metastases, whereas only 3 of 86 patients (3 per cent) with normal bone marrow acid phosphatase by radioimmunoassay have done so. An additional 184 patients with carcinoma and 77 controls have been studied. Although radioimmunoassay greatly improves specificity in bone marrow aspirates a few falsely positive results can occur. This finding may be secondary to cross reaction from leukocyte acid phosphatase and/or interference from lipid.

Topics: Acid Phosphatase; Adult; Aged; Bone Marrow; Bone Neoplasms; Cross Reactions; Evaluation Studies as Topic; False Positive Reactions; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Radioimmunoassay; Reference Values

In a retrospective review the response of 67 patient with metastatic adenocarcinoma of the prostate to the administration of exogenous testosterone was analyzed. Among 52 patients in whom objective and/or subjective responses were evaluable 45 experienced unfavorable responses. There was prompt regression of most unfavorable responses with testosterone withdrawal. The duration of treatment required to evoke an unfavorable response was related to the clinical status of the patient. Twenty-five per cent of patients with symptomatic metastases who had received no prior treatment, 36 per cent in symptomatic remission after endocrine therapy and 94 per cent with symptomatic relapse after endocrine therapy experienced unfavorable responses within 30 days of treatment. No patient had objective evidence of tumor regression during testosterone therapy but 7 patients, 6 with remission and 1 untreated, experienced symptomatic benefit. We conclude that the response of patients with metastatic prostate cancer to exogenous testosterone is related to the mass and endocrine treatment status, and that exogenous testosterone can stimulate prostatic neoplasms that proliferate in the absence of normal endogenous testosterone levels.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Injections, Intramuscular; Male; Methyltestosterone; Middle Aged; Prostatic Neoplasms; Testosterone

The efficacy of specific immunotherapy was examined in patients suffering from metastatic prostatic cancer. For this purpose determination of prostatic acid phosphatase and carcino-embryonic antigen in serum was performed using conventional enzymatic and radioimmunological techniques before and after therapy. The results were as following: 1. A significant decrease of the above mentioned parameters was demonstrable after therapy. 2. The determination of prostatic acid phosphatase was helpful for immediate control of therapy, the determination of carcino-embryonic antigen was more helpful in follow-up studies. 3. Contrary to disappointing relevance of radioimmunological determined prostatic phosphatase in early prostatic cancer this parameter seemed to be more suitable in follow-up studies than conventional determined phosphatase.

Topics: Acid Phosphatase; Bone Neoplasms; Carcinoembryonic Antigen; Humans; Immunotherapy; Male; Prostatic Neoplasms; Radionuclide Imaging

The tumor burden of 98 patients with metastatic prostatic cancer was compared longitudinally with the activities of bone (BAP) and liver isoenzymes (LAP) of alkaline phosphatase, total acid phosphatase (AcP), and prostate-specific acid phosphatase (PAP). A quantitative association between these enzyme markers and the tumor mass was suggested by comparing the enzymes with 1) both the treatment response and the estimation of metastasis by radionuclide bone scanning; 2) metastasis based upon radiographic evidence. In addition, an apparent extensive pretreatment bone tumor load was predictive for an elevated BAP activity, which was also a suggestive poor prognosis as previously reported. An elevation of PAP, in contrast to AcP, may precede the clinical disease progression in some patients. Data presented in this report have indicated that the levels of these enzymes compared well with the extent of tumor involvement and therefore may be considered suitable as adjuvant and even quantitative biochemical markers of bone and liver metastasis.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Humans; Isoenzymes; Liver; Liver Neoplasms; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Radiography; Radionuclide Imaging

Topics: Acid Phosphatase; Age Factors; Bone Neoplasms; Cyclophosphamide; Estrogens; Humans; Hydroxyproline; Lymph Node Excision; Male; Neoplasm Staging; Palpation; Prostatectomy; Prostatic Neoplasms; Radioimmunoassay; Radionuclide Imaging

Topics: Acid Phosphatase; Aged; Bone and Bones; Bone Neoplasms; Humans; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay; Radionuclide Imaging; Reagent Kits, Diagnostic

Ninety patients with poorly differentiated prostatic carcinoma have been treated with Estramustine phosphate (Estracyt). Seventeen of them had clinically metastases and had had no previous therapy. Seventy-three were initially given oestrogens and/or irradiation. Objective response was observed in 59%. The best effect was seen in patients primarily untreated.

Topics: Acid Phosphatase; Bone Neoplasms; Estramustine; Humans; Lymphatic Metastasis; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Pain; Prostatic Neoplasms

Topics: Acid Phosphatase; Biochemistry; Bone Neoplasms; History, 20th Century; Humans; Male; Prostatic Neoplasms; United States

Tissues from sixty-nine cartilage tumors in sixty-six individuals were obtained at the time of operation and each lesion was graded as benign (seventeen) or as a low-grade (thirty-three) or high-grade (nineteen) chondrosarcoma according to histological and roentgenographic criteria. The material obtained was analyzed by biochemical techniques for its content of water, ash, DNA, total protein (composed of collagen and so-called excess protein), and carbohydrate. In addition, proteoglycan subunit was isolated and the chain lengths of chrondroitin sulphate and keratan sulphate were determined. Analysis of the data showed that for the most part the tumors differed only quantitatively from articular cartilage controls, with the principal variations noted in water, ash, protein, and collagen content. Sugar concentrations were highly variable, but analysis of the proteoglycan subunit showed a distribution of glycosaminoglycans characteristic of immature articular cartilage. Marked shortening of the keratan sulphate chains was noted without significant alteration in the chain lengths of chondroitin sulphate, The wide variations in pattern suggest that the cartilage tumors are not biochemically homogeneous and therefore probably do not represent a single group of genetic errors.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Body Water; Bone Neoplasms; Carbohydrate Metabolism; Cartilage, Articular; Child; Chondrosarcoma; Collagen; Female; Glycosaminoglycans; Humans; Male; Middle Aged; Proteins; RNA

Comparisons of the bone marrow and serum acid phosphatase values obtained by counter-immunelectrophoresis and the Roy biochemical test were made in 72 patients with and in 13 patients without prostatic cancer. The counter-immunoelectophoresis test, when positive at more than 1 international unit per liter, showed only 4.4 per cent falsely positive results. The Roy biochemical test, which used sodium thymolphthalein monophosphate as the substrate, had 65 per cent falsely positive bone marrow acid phosphatase levels. Conflicting reports regarding the value of bone marrow acid phosphatase determinations in patients with prostatic cancer result from the use of non-specific substrates in biochemical methods for measurement and from the trauma incidental to bone marrow aspiration, which releases many non-prostatic acid phosphatase enzymes. The use of immunoassay such as counter-immunoelectrophoresis minimizes this source of error.

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Clinical Enzyme Tests; Counterimmunoelectrophoresis; False Positive Reactions; Humans; Immunoelectrophoresis; Male; Prostatic Neoplasms

In patients with nonprostatic cancer serum acid phosphatase activity is usually elevated when bone metastasis is present but not when bone metastasis is absent. The fraction responsible for serum enzyme elevation is a normal component of serum; it appears in gel electrophoresis as band 5; and is tartrate-resistant. It is suggested that the origin of acid phosphatase elevation is bone osteoclasts rather than cancer tissue, as is the case with prostatic carcinoma. Determination of serum acid phosphatase activity may be useful in the detection of bone metastasis.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Breast Neoplasms; Electrophoresis, Polyacrylamide Gel; Female; Humans

Topics: Acid Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms

An atypical variant of Ewing's sarcoma, located in the left hip of a nine-year-old girl, is discussed at optical, histochemical and electron microscopical level. The endothelial appearing cells seem to play a main role in its histogenesis. Tumoral cells of an undifferentiated blastemic nature show round nuclei and bright lucent cytoplasm, being organized in solid sheets or vascular-like profiles. Alkaline and acid phosphatases are very prominent in all tumoral cells, and some of them also show PAS positive material. Its ultrastructure demonstrates an active pinocytic capacity, cytoplasmic filaments and Weibel-Palade bodies. Simultaneously a review is performed on 27 cases of typical Ewing's sarcoma of bone in order to compare its vessels of a reactive nature with this tumor. A differential diagnosis with hemangioendothelioma primary to bone is established.

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Vessels; Bone Neoplasms; Child; Endothelium; Female; Hip; Humans; Microscopy, Electron; Pinocytosis; Sarcoma, Ewing

Topics: Acid Phosphatase; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Humans; Male; Prostatic Neoplasms; Radiography; Radionuclide Imaging

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; gamma-Glutamyltransferase; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms

Eleven benign giant cell tumors of bone were studied in the electron microscope, and the fine structural localization of acid phosphatase was elucidated. Three distinct cell types are always present in these tumors: stromal cells type 1; stromal cells type 2; and multinucleated giant cells. Small mononuclear cells may also occur, but are not likely to be actively participating in the neoplastic process. The range of variability in the fine structure of the different cell types constituting this tumor has been established. Variations in appearances include: a) presence of nuclear pseudoinclusions in stromal cells type 1 and multinucleated giant cells; b) aberrations in the structure of the rough surfaced endoplasmic reticulum in the same cell types; c) occurrence of ruffled borders, ectoplasmic layers and cytoplasmic labyrinths containing acid phosphatase in the giant cells. Some giant cells show evidence of marked phagocytic activity and contain large and numerous residual bodies carrying acid phosphatase. The significance of the interrelations between the different cell types are discussed and the possible role of stromal cells type 2 in immunological mechanisms directed against the tumor cells are mentioned.

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Endoplasmic Reticulum; Female; Giant Cell Tumors; Humans; Inclusion Bodies; Lysosomes; Male; Microscopy, Electron; Middle Aged; Phagocytosis

Topics: Acid Phosphatase; Adenocarcinoma; Adult; Bone Neoplasms; Diagnosis, Differential; Femoral Neoplasms; Gaucher Disease; Humans; Kidney Neoplasms; Male; Neoplasm Metastasis; Ribs

Three cases of giant cell tumor of bone were studied with the light and electron microscopes to determine the histochemical and cytochemical distribution of acid phosphatase isoenzymes. Using beta-glycerophosphate as a nonspecific substrate, acid phosphatase was found in the giant cells as well as the stromal cells. Ultrastructurally, using this substrate, the enzyme was found to be associated with lysosomes in the stromal cells and giant cells and also with the profuse system of tubules and vesicles in the cytoplasm of the giant cells. Using phosphorylcholine and D-ephedrinephosphate, which are substrates for a specific secretory isoenzyme of acid phosphatase, activity was found only in the vesicles of the giant cell cytoplasm. Lysosomes did not show activity with these substrates. Multinucleated cells of giant cell tumor contain a specific secretory type of acid phosphatase which is not present in the stromal cells. This suggests that the giant cells are attempting to form a secretory system similar to osteoclasts and that the vesicles in the cytoplasm which contain this acid phosphates are the morphologic expression of an abortive secretory system.

Topics: Acid Phosphatase; Adolescent; Aged; Bone Neoplasms; Cytoplasm; Dysgerminoma; Female; Femoral Neoplasms; Histocytochemistry; Humans; Humerus; Lysosomes; Metacarpus; Middle Aged; Osteoclasts

The diagnostic value of bone pain in 227 consecutive patients with known primary tumor was investigated and bone scans were obtained. Eighty-two of 130 patients with bone pain had metastases with positive scans. In contrast, 80 of 97 patients without pain did not have metastases and the scans were negative; 13, however, did have metastases and positive scans, and in 10 of these the lesions were osteoblastic. Osteoblastic metastases may not produce pain. In a group of 70 patients with bone pain of unknown origin or elevated phosphatase levels, bone scans were also obtained and evaluated. Only one had metastatic disease, 40 were negative, and 29 had positive scans due to benign disease. It is concluded that in the assessment of malignancies, bone pain is a good indication for bone scintigraphy, except in those patients with osteoblastic lesions. However, when malignant disease has not yet been established, bone pain is not a reliable indication for scanning and radiographic examination is the initial examination of choice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Diagnostic Errors; Female; Humans; Pain; Radionuclide Imaging

This is a case of carcinoma of the gallbladder, which clinically, chemically, and radiographically simulated metastatic prostate cancer. Other causes of elevated serum and bone marrow acid phosphatase and axial skeletal osteoblastic metastases are reviewed.

Topics: Acid Phosphatase; Adult; Bone Marrow; Bone Neoplasms; Diagnosis, Differential; Gallbladder Neoplasms; Humans; Male; Prostatic Neoplasms

Carcinoma of the prostate can be easily detected by rectal examination which is a part of the routine check-up for the early recognition of cancer in males after 45 years. Approximately 14,000 to 16,000 new cases with prostatic carcinoma are found in West-Germany annually. In former times patients with advanced carcinoma were treated with little success. Today the aim is the early detection of the disease in a curable stage. Exact clinical staging and morphological grading is fundamental for optimal therapy.

Topics: Acid Phosphatase; Biopsy, Needle; Bone and Bones; Bone Marrow Examination; Bone Neoplasms; Germany, West; Humans; Lymph Nodes; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Urography

Adenocarcinoma of the prostate is responsible for one of every nine deaths from cancer in Canada. In this review epidemiologic factors are considered and current staging systems are outlined. The American Urological System is recommended for staging because of its ability to reflect changes in the understanding of the biologic behaviour of this neoplasm. The adoption of a quantitative grading scheme is suggested to complement the information obtained from the staging assessment. The routes of spread of this disease, along with the procedures used to assess metastatic involvement, are described. Immunologic methods for the analysis of prostatic acid phosphatase have been shown to be superior to the enzymatic methods previously used, and the role of the new techniques is discussed. Emphasis is placed on radiotherapy and endocrine therapy for the treatment of this neoplasm, and the concept of withholding endocrine therapy until symptoms appear is discussed. Potential future developments in this field are considered.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Clinical Enzyme Tests; Ethinyl Estradiol; Evaluation Studies as Topic; Humans; Immunologic Techniques; Lymph Nodes; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Ontario; Prostate; Prostatic Neoplasms; Radiotherapy, High-Energy; Seminal Vesicles

The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.

Topics: Acid Phosphatase; Adult; Bone Neoplasms; Female; Fibroblasts; Giant Cell Tumors; Humans; Inclusion Bodies; Lipids; Lysosomes; Mitochondria

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Cell Membrane; Cell Nucleus; Cytoplasm; Endoplasmic Reticulum; Female; Giant Cell Tumors; Histocytochemistry; Humans; Lipid Metabolism; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria; Osteolysis; Phagocytosis; Vacuoles

Bone marrow acid phosphatase has been reported to be a sensitive indicator of early bony metastasis from adenocarcinoma of the prostate. In order to evaluate this hypothesis, we measured bone marrow acid and alkaline phosphatase, lactic dehydrogenase, and calcium levels in a group of 84 patients with a variety of problems, including 18 with cancer of the prostate. We found that the bone marrow acid and alkaline phosphatase and lactic dehydrogenase were elevated and calcium was depressed in most patients. Among patients with prostate cancer, bone marrow acid phosphatase was not significantly different between those with or without bone metastases. In addition, the patients with prostatic cancer did not have higher levels of bone marrow acid phosphatase than subjects with other malignant and nonmalignant conditions. The level of acid and alkaline phosphatase, lactic dehydrogenase and calcium varied predictably with the aspiration technique used and was independent of sex, disease state or method of chemical determination. Due to this variation, we believe that bone marrow enzyme and calcium levels are of no value in the detection of metastases in patients with prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Bone Marrow; Bone Neoplasms; Calcium; Female; Humans; L-Lactate Dehydrogenase; Male; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms

Electron microscopy of two osteoblastomas revealed the existence of three distinct types of cells in this tumor: osteoblast like, macrophage like, and multinucleated giant cells. In addition to the lysosomes, most Golgi cisternae and vesicles in the osteoblast like cells showed evidence of acid phosphatase activity. Deposits of lead phosphate indicating the site of this enzyme in the macrophage like cells were confined to the large and abundant lysosomes. Wide spread deposition of final product was noted in the cytoplasm of the multinucleated giant cells, both in conventional lysosomes, Golgi regions and special organelles probably corresponding to GERL. With regard to nonspecific alkaline phosphatase, final product indicating the location of enzyme activity was confined to the plasma membranes and associated vesicular and vacuolar structures in the osteoblast like cells. The findings suggest that the giant cells in osteoblastomas participate in lytic bone destructive and resorptive processes while osteoblast like cells appear to be osteoid and bone forming carriers of the neoplastic properties of the tumor.

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Golgi Apparatus; Humans; Lysosomes; Male; Organoids; Osteoma, Osteoid

To evaluate the reliability of bone marrow acid phosphatase in the staging of prostatic carcinoma we analyzed 50 bone marrow samples collected at random from the hematology service at this hospital. The samples were assayed for acid phosphatase content by a colorimetric method using sodium thymolphthalein monophosphate as a substrate and by 2 immunochemical assays developed at our laboratory (counter immunoelectrophoresis and radioimmunoassay). We found a high percentage (61 per cent) of falsely positive results in patients with various hematological diseases without evidence of prostatic carcinoma by the colorimetric evaluation. All of these patients except 1 had negative immunochemical assay. Until a specific assay for prostatic acid phosphatase is developed for clinical use we caution the use of a single elevation of bone marrow acid phosphatase as a parameter of metastatic disease.

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Counterimmunoelectrophoresis; Evaluation Studies as Topic; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms

Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was administered. Increasing skeletal metastases were observed in 6 patients, whereas significant reduction of metastases took place in 2 patients. Objective relief of stranguria was observed only in 3 patients. The amount of residual urine increased in 3 patients and was reduced in 5. In about one third of the patients, the prostate gland became smaller and softer. The acidic phosphatases decreased from pathological to normal values in 7 patients. There were no observed hepatic, renal or haemotological side-effects. However, serious cardio-vascular complications occurred in 6 patients, while arterial hypertension developed in 4. It is suggested that Cyproterone acetate cannot be recommended as the only kind of hormonal treatment of prostatic cancer.

Topics: Acid Phosphatase; Administration, Oral; Aged; Blood Pressure; Bone Neoplasms; Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Urination

Bone scanning with 99mTc-Sn-HEDP, radiographic skeletal survey and determination of plasma acid and alkaline phosphatase values were carried out in a consecutive series of 90 untreated patients with carcinoma of the prostate. 99mTc-Sn-HEDP provided satisfactory bone imaging and was convenient in use. The addition of bone scanning to radiographic survey increases the detection rate of skeletal metatases by 16%. Radiography increases the accuracy of bone scanning by identifying false positive scans due to benign disease and false negative scans when there are diffuse symmetrical bony metastases. The plasma phosphatases alone are less accurate staging tests. The acid phosphatase data support the validity of scan positive--X-ray negative findings. Bone scan abnormalities due to secondary deposits usually precede elevation of plasma alkaline phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Diagnostic Errors; Evaluation Studies as Topic; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging

Fifty new cases of carcinoma of the prostate were assessed prior to treatment to determine the incidence of bony metastases. The radioisotope bone scan was the most sensitive method of detecting metastases and of localising them. It was twice as accurate as the serum acid phosphatase estimation. Skeletal X-rays were the least accurate method. Forty-six per cent of patients had abnormal bone scans at presentation. The histological grade of the tumour correlated well with the bone scan. The higher the grade, the more likely was the bone scan to be abnormal. There is need for greater accuracy in detecting metastases, and the bone marrow acid phosphatase estimation, either alone or in conjunction with the bone scan, may provide this accuracy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Sedimentation; Bone Neoplasms; Evaluation Studies as Topic; Hemoglobins; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Technetium

The levels of total and l-tartrate labile acid phosphatase were studied in 49 patients with prostatic carcinoma. The results were compared with the results from a control group. The acid phosphatase levels from the bone marrow were above the upper normal limit of serum acid phosphatase both in the control group and in patients with prostatic carcinoma. This may be due to acid phosphatase released from blood cells during haemolysis. There was a positive correlation between serum and bone marrow acid phosphatase levels in patients with prostatic carcinoma. Significantly raised levels of bone marrow acid phosphatase (above the upper limit of the normal range from the control group) were observed only in advanced stage IV patients with significantly increased serum levels. The levels of bone marrow acid phosphatase gave no supplementary diagnostic information in any of the patients with prostatic carcinoma. Doubt is expressed concerning the hypothesis that raised levels of bone marrow acid phosphatase are diagnostic of early metastases from prostatic carcinoma.

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Hemolysis; Humans; Male; Prostatic Neoplasms

Serial bone scans and radiographic surveys were performed in 167 patients with histologically proven carcinoma of the prostate: 435 scans and surveys were performed. Nineteen of 99 patients with negative findings on diagnosis have become positive on follow-up. Forty-nine patients had positive findings on presentation; 8 have regressed on follow-up and 26 have progressed; 15 have remained unchanged. This is a sensitive method of follow-up in patients with carcinoma of prostate. Changes occurred in bone scans and skeletal surveys before any alteration in serum acid or alkaline phosphatases, symptoms of metastases or change in prostatic size in the majority of cases. The documentation of progression from MO to M1 disease presents no problems. However, problems in quantitation may arise in patients presenting with M1 disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Remission, Spontaneous

Enzyme activity of lactate dehydrogenase, glutamate-oxalacetate and glutamate-pyruvate transaminase, creatine phosphokinase, cholinesterase, alkaline, acid and prostatic phosphatase and aldolase has been studied in a total of 213 subjects, of whom 97 were of good health, 63 had bone tumors and 53 suffered from osteomyelitis. The activities of the majority of the enzymes were found to become significantly changed in comparison with the norm. In both patient groups, the more striking differences being noted in that of osteomyelitis. However, enzymatic activity alone does not allow to differentiate the group of bone tumors from that of osteomyelitis, the differences between these two groups not being of significance in any one of the enzymes followed.

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bone Neoplasms; Cholinesterases; Creatine Kinase; Fructose-Bisphosphate Aldolase; Humans; L-Lactate Dehydrogenase; Osteomyelitis; Phosphoric Monoester Hydrolases

24-hour urinary hydroxyproline excretion (THP), a marker of bone collagen metabolism, has been measured in 35 patients with carcinoma of the prostate. 21 patients had bone metastases diagnosed by bone scanning (99mTc MDP). All 9 patients with metastases studied before hormonal treatment and the majority of those on treatment had elevated levels. Patients with negative bone scans invariably had normal THP levels. Furthermore, THP reflected the presence of bone metastases more accurately than plasma alkaline or acid phosphatase. Serial THP levels altered predictably with symptomatic response to treatment. These results suggest that THP is more reliable than other markers of the presence and activity of bone metastases in response to treatment and may have been neglected in favour of more elaborate and costly X-ray and isotope investigations.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Calcium; Creatinine; Humans; Hydroxyproline; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

Recent reports have indicated that bone marrow acid phosphatase is the most sensitive test in detecting bony metastases. The experience reported herein suggests that falsely positive results may be common, especially in patients with primary hematologic disorders. A plea is made that caution be given to the interpretation of this test so that some patients will not be denied appropriate therapy and the role of bone marrow acid phosphatase can be better defined by long-term followup in such patients.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Marrow Examination; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

To stage accurately the extent of the disease comprehensive investigations were done on 75 patients with histologically documented carcinoma of the prostate. Estimation of bone marrow acid phosphatase appears to be the most sensitive test to detect blood-borne metastases. Serum acid phosphatase appears to be of little value in the detection of early blood spread and may have a role only in monitoring the effect of treatment on advanced disease. Bone scanning with technetium compounds has the disadvantage of non-specificity but has far greater sensitivity than a skeletal survey. Bone marrow cytology was not rewarding in the detection of early metastatic disease. Pedal lymphangiography is a highly inaccurate method to detect lymphatic spread of carcinoma of the prostate and pelvic lymphadenectomy, when indicated, remains the only truly adequate method to assess lymph node involvement. There was a 37 per cent incidence of metastatic lymph node pathology in 30 patients undergoing this procedure before either radical prostatectomy or deep x-ray therapy. A close correlation was found between stage and grade of disease and incidence of nodal pathology. There was some correlation between degree of nodal involvement and evidence of blood spread as detected by elevated bone marrow acid phosphatase levels. The significance of this finding remains unclear.

Topics: Acid Phosphatase; Aged; Bone and Bones; Bone Marrow; Bone Neoplasms; Humans; Lymph Node Excision; Lymphatic Metastasis; Lymphography; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Seminal Vesicles; Technetium

785 combined diagnostic procedures are reported which were carried out on 353 patients with microscopically proven carcinoma of the prostate in order to detect metastases. X-ray films of the thorax, spine and pelvis were taken. Also bone-scintigraphy was done with 87MSr or 99MTc-polyphosphate. Additionally the alcaline, acid and prostate phosphatases were determined. A diagnostic coincidence between radiological results and bone-scan was found in 95.1% of cases. The bone-scan was false negative in 3.7%. Only in 1.2% metastases were detected earlier by the bone-scan than by x-ray examinations. Referring to the number of studies identical results were found. In roentgenologically detected metastases an increased serum level of the alcaline phosphatase was found in 61%, of the acid phosphatase in 31% and of the prostate-phosphatase in 25%.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging

Acid phosphatase was determined in bone marrow aspirates in a consecutive series of 28 patients, 19 of whom had a proven carcinoma of the prostate. The value of this procedure is pointed out in respect to the diagnosis and staging of a prostatic carcinoma and the literature is reviewed.

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms

In addition to a light-microscopical and histochemical investigation of primary and metastic lesions in 27 cases of Ewing's sarcoma, biopsy materials from the primary bone lesions of 7 patients with this neoplasm were examined histochemically, enzyme-cytochemically and electron microscopically to elucidate the histogenesis and nature of the neoplasm. Ultrastructural observation has revealed that besides intracytoplasmic and extracellular deposition of glycogen the tumor cells possess several cytological features characterized by intracytoplasmic microfilaments of varying thickness up to 80 A, occasional appearance of dense patches, fat droplets, desmosomal connections and reminiscent attachment bodies. The tumor cells are mostly round, oval or polygonal in shape, but spindle or elongated cells are intermingled and occasionally contain well-developed rough endoplasmic reticulum, resembling pericytes or fibroblasts. In the intercellular spaces amongst the tumor cells, varying amounts of variable-shaped amorphous materials are found, which are compatible with acid mucopolysaccharides and glycoproteins histochemically verified. These findings may suggest that Ewing's sarcoma is a highly malignant neoplasm originating from a transitional cell developed from pericytes to vascular smooth muscle cells in the bone marrow.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Bone Neoplasms; Glycogen; Humans; Sarcoma, Ewing

Prostatic acid phosphatase and alkaline phosphatase values in bone marrow were correlated with skeletal surveys and diagnoses during a six-month study. In cases of biopsy-proven adenocarcinoma of the prostate, bone marrow prostatic acid phosphatase was the most consistently abnormal value. Diagnoses other than prostatic cancer involving the bone marrow, e.g., myeloma and leukemias, were associated with elevated prostatic acid phosphatase and alkaline phosphatase values. In cases in which the bone marrow was not involved by metastasis, these values were normal. Bone marrow prostatic acid phosphatase assay was found to be a very good tool for detecting early osseous metastases from any site, including prostatic adenocarcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Bone Marrow; Bone Neoplasms; Humans; Leukemia; Male; Multiple Myeloma; Neoplasm Metastasis; Prostatic Neoplasms

Patients (219) with prostatic adenocarcinoma were classified on the basis of whether or not their bone scans were positive for metastasis. Acid and alkaline phosphatase determinations and clinical evaluations for bone metastases were reviewed. Of those with proved metastases, 43% had no bone pain, 39% had normal acid phosphatase levels, 23% normal alkaline phosphatase levels, 19% normal levels of both enzymes, and 15% normal enzyme levels without bone pain. Twenty-four per cent of the patients with normal enzyme levels and clinically unsuspected bone metastases had bone scans which proved positive for metastasis; 62% of these had normal radiographs.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Pain; Prostatic Neoplasms; Radiography; Radionuclide Imaging

The symptoms and physical findings in patients with transitional cell carcinoma of the prostate were similar to those in patients with prostatic adenocarcinoma. Usually the neoplasm was poorly differentiated and advanced when the diagnosis was first established. Osseous metastases were commonly osteolytic. Frequently, elevations of serum alkaline or acid phosphatase levels were associated with metastasis. Tartrate-inhibited fractions of the serum acid phosphatase were not elevated. The best form of treatment is radical ablation of the prostate and radiation therapy is next best. Because these neoplasms are not hormonally dependent, hormonal manipulation is not indicated. Prognosis for patients with this malignancy is guarded.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Carcinoma, Transitional Cell; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostatectomy; Prostatic Neoplasms

Topics: Acid Phosphatase; Antineoplastic Agents; Bone Neoplasms; Estrogens; Humans; Isoenzymes; L-Lactate Dehydrogenase; Luteinizing Hormone; Lymphocyte Activation; Male; Neoplasm Metastasis; Prognosis; Prostatectomy; Prostatic Neoplasms; Testosterone

In recent years, histochemistry and electron microscopy have been applied more and more to the investigation of bone tumors. The contributions and limitations of these methods in differential diagnosis are discussed. The levels of glycosaminoglycans in cartilaginous tumors display distinct differences between slow- and fast-growing types. All cartilaginous tumors are poor in phosphatase activity. Demonstration of these enzymes at acid and alkaline pH in bone-forming conditions reveals differences between benign and malignant tumors. Osteosarcomas display a rich activity of both phosphatases in bone-forming and in bone-free regions. Acid phosphatase may play a rôle in the breakdown of the host tissue infiltrated by the tumor. Electron microscopy of bone tumors has brought out some interesting findings. In fibrous dysplasia a particular kind of very fine fibrillar structures was observed besides the regular collagen fibrils. This may indicate retardation of collagen maturation. Cell organelles in benign and malignant bone tumors usually differ quantitatively. They resemble active fibroblasts. In bone- and in cartilage-forming tumors we observed large quantities of microfilaments in the cytoplasm. Nuclear indentations and invaginations probably indicate increased nuclear activity. The intense acid phosphatase activity demonstrated histochemically seems inconsistent with the low number of lysosomes in the cytoplasm of osteosarcoma cells, but other organelles (Golgi apparatus and vesicles) may also contain the enzyme. Virus-like particles have not been observed in human osteosarcomas up to now. Other authors have observed a correlation between the number of cell organelles and the grade of differentiation, but this was not detected in our sample of benign and malignant cartilaginous tumors. Histochemistry and electron microscopy of bone tumors are still in the early stage of material gathering. Some histochemical findings, however, can already be used as diagnostic tools.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Cartilage Diseases; Cell Nucleus; Chondrosarcoma; Collagen; Cytoplasm; Cytoskeleton; Fibrous Dysplasia of Bone; Humans; Osteosarcoma

The diagnosis and detection of genitourinary cancer covers a broad range of physical signs and instrumental observations which are not necessarily diagnostic. The primary diagnosis in most entities remains dependent upon histologic confirmation. Adenocarcinoma of the prostate is the most common, and at times, most difficult urogenital cancer to diagnose and detect. Many newer techniques today are designed to evaluate the stage of disease, and to detect heretofore occult metastatic foci. Immunologic assays may be of future prognostic value.

Topics: Acid Phosphatase; Adenocarcinoma; Biopsy; Bone Marrow Examination; Bone Neoplasms; Carcinoembryonic Antigen; Humans; Isoenzymes; L-Lactate Dehydrogenase; Lymphatic Metastasis; Lymphography; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Seminal Vesicles; Ultrasonics

Topics: Acid Phosphatase; Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Female; Fibrosarcoma; Fibrous Dysplasia of Bone; Giant Cell Tumors; Humans; Infant; Isoenzymes; Male; Middle Aged; Osteosarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms

A case of hypophosphataemic osteomalacia occurring in association with a carcinoma of prostate is described. Although only palliative treatment to the primary tumour was possible, worthwhile remission of bone symptoms, due to osteomalacia, was achieved with pharmacological doses of vitamin D. The presence of extensive skeletal metastases modified the radiological features of osteomalacia. Major alterations in the distribution of calcium within the skeleton were observed during a period when total body calcium remained unaltered. This observation may be of relevance to other cases in which osteosclerotic metastases develop.

Topics: Acid Phosphatase; Aged; Body Weight; Bone and Bones; Bone Neoplasms; Calcium; Carcinoma; Ergocalciferols; Humans; Male; Neoplasm Metastasis; Osteomalacia; Prostatic Neoplasms; Radiography; Vitamin D

The results of bilateral pedal lymphography in 83 patients with adenocarcinoma of the prostate gland are presented. The patients were divided into two groups: 45 new cases and 38 late or old cases presenting several years after the onset of the disease. Altogether 25 of the new patients and 29 of the late patients had lymphographic evidence of lymph node metastases. The lymphogram results in relation to local tumour size, histological grade, the presence of skeletal metastases, and acid phosphatase levels are discussed. Of the new patients with T1 and T2 tumors--that is, those still localized within the prostatic capsule--41% had positive lymphograms. The inaccuracy of acid phosphatase estimations in detecting early extraprostatic spread is shown and compared with the greater accuracy of lymphography. Lymphography should be used as an initial investigation in all cases where aggressive therapy is being considered, and the importance of regular follow-up radiographs is emphasized.

Topics: Acid Phosphatase; Adenocarcinoma; Bone Neoplasms; Follow-Up Studies; Humans; Lymphatic Metastasis; Lymphography; Male; Neoplasm Metastasis; Prostatic Neoplasms

We evaluated bone marrow acid phosphatase in 30 patients as another parameter in staging prostatic carcinoma. This method is reliable and useful as part of the staging precedures. No falsely positive results were found and the procedure provided the only indication of metastatic diseases in 4 cases.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Biopsy, Needle; Bone Marrow; Bone Neoplasms; Humans; Ilium; Male; Methods; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

A radiologic method of measuring metastases was developed and statistically analyzed with respect to survival based on 103 patients with known metastases at diagnosis. The analysis revealed a significant correlation between shortened patient survival and the combination of number of sites involved and the extent of involvement within each site. These quantitative analysis are useful in predicting patient survival and in studying response to treatment.

Topics: Acid Phosphatase; Bone Neoplasms; Humans; Lumbar Vertebrae; Lung Neoplasms; Male; Models, Biological; Neoplasm Metastasis; Pelvis; Prognosis; Prostatic Neoplasms; Radiography, Thoracic; Risk; Thoracic Vertebrae

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Calcium; Drug Therapy, Combination; Humans; Male; Middle Aged; Neoplasm Metastasis; Palliative Care; Parathyroid Hormone; Phosphorus; Phosphorus Radioisotopes; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Esterases; Glucuronidase; Histocytochemistry; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Monoamine Oxidase; Multiple Myeloma; Neoplasm Metastasis; Neuroblastoma; Plasmacytoma; Sarcoma, Ewing

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Calcitonin; Calcium; Hexestrol; Humans; Hydroxyproline; Male; Middle Aged; Neoplasm Metastasis; Phosphorus; Prostatic Neoplasms

Topics: Acid Phosphatase; Administration, Oral; Adrenal Glands; Aged; Alkaline Phosphatase; Aminoglutethimide; Biopsy; Bone and Bones; Bone Neoplasms; Cortisone; Diethylstilbestrol; Drug Therapy, Combination; Estrogens; Fludrocortisone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Urography

Topics: Acid Phosphatase; Aged; Biopsy, Needle; Bone and Bones; Bone Marrow; Bone Neoplasms; Castration; Humans; Ilium; Male; Middle Aged; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Strontium Radioisotopes

Topics: 17-Ketosteroids; Acid Phosphatase; Adrenalectomy; Aged; Alkaline Phosphatase; Bone Neoplasms; Castration; Estrogens; Evaluation Studies as Topic; Humans; Hypophysectomy; Male; Middle Aged; Neoplasm Metastasis; Pennsylvania; Prognosis; Prostatic Neoplasms; Radiography; Recurrence; Remission, Spontaneous; Testosterone

Topics: Acid Phosphatase; Adenocarcinoma; Age Factors; Aged; Alkaline Phosphatase; Bone Marrow Examination; Bone Neoplasms; Hematocrit; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging

Skeletal scintigraphy using Technetium-99m ((99m)Tc) complexes was carried out in a series of 332 cancer patients. The results of scintigraphy were compared with the results of roentgenography and with the diagnostic usefulness of serum alkaline and acid phosphatase levels and the presence or absence of bone pain. In 25 percent of cases, lesions were first identified with scintigraphs. When metastastic lesions were present on both scintigraphs and roentgenograms, the number was greater on scintigraphs in 72 percent of cases. Six false negative studies were recorded (1 percent). Sixty percent of patients with early metastasis-that is, those with abnormal scintigraphs and negative roentgenograms-were asymptomatic. Serum alkaline and acid phosphatase levels were normal in 40 percent and 42 percent respectively of those with early skeletal involvement. Skeletal scintigraphy with (99m)Tc complexes is superior to other commonly employed techniques used to assess bone metastasis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Humans; Neoplasm Metastasis; Radiography; Radionuclide Imaging; Technetium

Topics: Acid Phosphatase; Adrenalectomy; Alkaline Phosphatase; Bone Neoplasms; Castration; Diethylstilbestrol; Humans; Hypophysectomy; Lung Neoplasms; Male; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms; Radiography; Retrospective Studies

Topics: Acid Phosphatase; Bone Neoplasms; Electrophoresis, Polyacrylamide Gel; Humans; Isoenzymes; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Metastasis; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Aged; Bone Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Estrogens; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Palliative Care; Prognosis; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Calcium; Humans; Male; Neoplasm Metastasis; Prostatic Hyperplasia; Prostatic Neoplasms; Urinary Bladder Neoplasms

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Blood Urea Nitrogen; Bone Neoplasms; Cryosurgery; Follow-Up Studies; Humans; Hydronephrosis; Immunoglobulins; Male; Middle Aged; Neoplasm Metastasis; Pain Management; Palliative Care; Postoperative Complications; Prostate; Prostatic Neoplasms; Time Factors; Urinary Tract Infections; Urination Disorders

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Bone Neoplasms; Humans; Male; Middle Aged; Pain; Parathyroid Hormone; Phosphorus Isotopes; Prostatic Neoplasms; Radiography

Topics: Acid Phosphatase; Bone Marrow Examination; Bone Neoplasms; Carcinoma; Clinical Enzyme Tests; Evaluation Studies as Topic; Humans; Male; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Estrogens; Humans; Male; Methods; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Strontium Isotopes

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Neoplasms; Carcinoma; Cyproterone; Estrogens; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pregnadienes; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Marrow; Bone Neoplasms; Fluorine; Humans; Ilium; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radioisotopes; Radionuclide Imaging

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Female; Hematologic Diseases; Humans; Injections, Intravenous; Male; Middle Aged; Movement; Multiple Myeloma; Neoplasm Metastasis; Pain, Intractable; Radionuclide Imaging; Remission, Spontaneous; Strontium Radioisotopes; Urinary Bladder Neoplasms; Uterine Neoplasms

Topics: Acid Phosphatase; Biopsy; Bone Marrow; Bone Neoplasms; Clinical Enzyme Tests; Humans; Ilium; Male; Neoplasm Metastasis; Prostatic Neoplasms; Retrospective Studies

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; Esterases; Female; Histocytochemistry; Humans; Leukemia; Lipids; Lymphatic Metastasis; Male; Methods; Neoplasms; Peroxidases; Polysaccharides; Salivary Gland Neoplasms; Sex Chromatin; Skin Neoplasms; Staining and Labeling; Uterine Neoplasms

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Neoplasms; Breast Neoplasms; False Positive Reactions; Female; Humans; Iron Isotopes; Lung Neoplasms; Male; Mandibular Neoplasms; Mouth Neoplasms; Neoplasm Metastasis; Osteosarcoma; Pelvic Neoplasms; Pharyngeal Neoplasms; Prostatic Neoplasms; Radionuclide Imaging; Spinal Neoplasms; Strontium Isotopes

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Bone Neoplasms; Child; Child, Preschool; Esterases; Female; Femoral Neoplasms; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Glucuronidase; Humans; Humerus; Hydrolases; Infant, Newborn; Leucyl Aminopeptidase; Male; Mandibular Neoplasms; Middle Aged; Osteosarcoma; Tibia

Topics: Acid Phosphatase; Bone Marrow; Bone Neoplasms; Humans; Immune Sera; Immunodiffusion; Male; Neoplasm Metastasis; Prostatic Neoplasms

Radiostrontium ((85)Sr) skeletal scintiscanning was done on 640 cases and 520 were included in a review. Forty-eight percent of 359 patients with biopsy-proved malignant disease had secondary skeletal involvement; in 17 percent the involvement was identified by scintiscanning alone. False-negative scintiscans were recorded in 0.9 percent. Unusual (85)Sr localization was found in a bone infarct, in proteus bursitis and in a pulmonary aspergillosis infiltrate. Serum alkaline phosphatase levels were found to be of little value in the evaluation for osseous metastasis, and normal acid phosphatase values in patients with prostatic carcinoma did not exclude the possibility of spread to the skeleton. Both the scintiscan and roentgenograms are essential in the evaluation of patients for metastatic bone disease.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Aspergillosis; Bone Neoplasms; Bursitis; False Negative Reactions; Female; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radionuclide Imaging; Strontium Isotopes

Topics: Acid Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Strontium Isotopes; Time Factors

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Neoplasms; Carcinoma, Ehrlich Tumor; Esterases; Female; Glucuronidase; Histocytochemistry; Male; Mice; Neoplasm Transplantation; Oxidoreductases

Topics: Acid Phosphatase; Adenocarcinoma; Age Factors; Aged; Biopsy; Bone Neoplasms; Bone Resorption; Calcium; Humans; Male; Middle Aged; Neoplasm Metastasis; Pain; Paraplegia; Phosphorus; Prostatic Neoplasms; Urography

Topics: Acid Phosphatase; Age Factors; Aged; Biopsy; Bone Neoplasms; Humans; Male; Methods; Middle Aged; Neoplasm Metastasis; Palpation; Pelvis; Prostatic Neoplasms; Time Factors; Urography

Topics: 17-Ketosteroids; Acid Phosphatase; Adrenalectomy; Alkaline Phosphatase; Androgens; Bone Neoplasms; Cryosurgery; Follicle Stimulating Hormone; Follow-Up Studies; Growth Hormone; Humans; Hypophysectomy; Luteinizing Hormone; Male; Neoplasm Metastasis; Palliative Care; Pelvic Neoplasms; Prostatic Neoplasms; Remission, Spontaneous

Topics: Acid Phosphatase; Animals; Bone Neoplasms; Ear, Inner; Fluorides; Guinea Pigs; Histocytochemistry; Injections; Organ of Corti; Otosclerosis; Sodium; Staining and Labeling

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Bronchial Neoplasms; Carcinoma; Esterases; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; Kidney Neoplasms; L-Lactate Dehydrogenase; Leukocytes; Lymphoma, Non-Hodgkin; Male; Melanoma; Neoplasms; Peroxidases; Pharyngeal Neoplasms; Rectal Neoplasms; Sarcoma; Staining and Labeling; Succinate Dehydrogenase; Testicular Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Blood Cell Count; Blood Platelets; Bone Neoplasms; Humans; Radiography

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Cell Membrane; Cell Nucleus; Cell Transformation, Neoplastic; Child; Clone Cells; Cytoplasm; Diagnosis, Differential; Humans

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Neoplasms; Histocytochemistry; Humans; Middle Aged; Radiation Injuries; Radiodermatitis; Radiotherapy; Skin; Stomach Neoplasms

Topics: Acid Phosphatase; Biopsy; Bone and Bones; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Pelvis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Strontium Isotopes

Topics: Acid Phosphatase; Aged; Biopsy; Bone Marrow; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Histocytochemistry; Humans; Lymphoma, Large B-Cell, Diffuse; Osteosarcoma; Sarcoma, Ewing

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Carcinoma; Female; Gaucher Disease; Humans; Hyperparathyroidism; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Estrogens; Humans; Male; Middle Aged; Neoplasm Metastasis; Pain Management; Phosphorus Isotopes; Prostatic Neoplasms; Testis; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Bile Acids and Salts; Bone Neoplasms; Electrophoresis; Histidine; Humans; Hydrogen-Ion Concentration; Kidney; Liver; Male; Neoplasms; Nucleotidases; Organ Specificity; Phenylalanine; Phosphoric Monoester Hydrolases; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; Aged; Blood Platelet Disorders; Bone Diseases; Bone Neoplasms; Female; Gaucher Disease; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Pulmonary Embolism

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Giant Cell Tumors; Glucuronidase; Humans; Lysosomes; Male; Microscopy, Electron; Middle Aged; Osteoclasts; Succinate Dehydrogenase; Tibia

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Chondroma; Chondrosarcoma; Diagnosis, Differential; Giant Cell Tumors; Hemangiosarcoma; Histocytochemistry; Humans; Lymphoma, Large B-Cell, Diffuse; Methods; Osteoma, Osteoid; Osteosarcoma; Sarcoma, Ewing; Sarcoma, Synovial

Topics: Acid Phosphatase; Adult; Animals; Bone Neoplasms; Cats; Child; Clinical Enzyme Tests; Dogs; Guinea Pigs; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Rabbits; Rats

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Child; Female; Humans; Infant, Newborn; Lactation; Male; Methods; Pregnancy; Prostatic Neoplasms

Topics: Acid Phosphatase; Age Factors; Bone Neoplasms; Brain Neoplasms; Humans; Male; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Blood Sedimentation; Bone Neoplasms; Diagnosis, Differential; Estrogens; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostatectomy; Prostatic Neoplasms; Radiography

Topics: Acid Phosphatase; Adolescent; Aged; Alkaline Phosphatase; Biopsy; Blood Sedimentation; Bone Marrow; Bone Marrow Examination; Bone Neoplasms; Carcinoma; Female; Humans; Ilium; Leukocytes; Male; Middle Aged

Topics: Acid Phosphatase; Acute Disease; Age Factors; Alkaline Phosphatase; Animals; Avitaminosis; Bone Neoplasms; Carcinoma; Chronic Disease; Diabetes Mellitus; Esophageal Neoplasms; Estrus; Female; Hematologic Diseases; Hemoglobinuria, Paroxysmal; Histocytochemistry; Hodgkin Disease; Humans; Infections; Leukemia; Leukocytes; Liver Diseases; Lung Neoplasms; Male; Myocardial Infarction; Neutrophils; Pregnancy; Prostatic Neoplasms; Radiation Injuries; Stress, Physiological

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Humans; Male; Pelvic Bones; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Strontium Isotopes

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; L-Lactate Dehydrogenase; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Ovarian Neoplasms; Transaminases

Topics: Acid Phosphatase; Bone Neoplasms; Humans; Male; Neoplasm Metastasis; Prostatic Hyperplasia; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Proteins; Bone Neoplasms; Calcium; Child, Preschool; Female; Humans; Phosphates

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Neoplasms; Carcinoma; Glycosaminoglycans; Humans; Neoplasm Metastasis; Sarcoma, Ewing; Staining and Labeling

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Bone Neoplasms; Child; Cytoplasm; Cytoplasmic Granules; Erythrocytes; Female; Hematologic Diseases; Humans; Iron; Male; Middle Aged; Reticulocytes; Splenectomy

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Bone Neoplasms; Carboxylesterase; Child; Chondroblastoma; Chondroma; Chondrosarcoma; Coloring Agents; Esterases; Fibroma; Fibrosarcoma; Fibrous Dysplasia of Bone; Geriatrics; Giant Cell Tumors; Glucuronidase; Histocytochemistry; Histological Techniques; Humans; Osteosarcoma; Pathology; Phosphoric Monoester Hydrolases; Sarcoma, Synovial; Staining and Labeling

Topics: Acid Phosphatase; Adenocarcinoma; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bone Neoplasms; Clinical Enzyme Tests; Dysgerminoma; Female; Fructose-Bisphosphate Aldolase; Glutathione; Hexoses; Humans; Isocitrate Dehydrogenase; Isomerases; Kidney Neoplasms; L-Lactate Dehydrogenase; Liver Function Tests; Liver Neoplasms; Malate Dehydrogenase; Male; Neoplasm Metastasis; Ovarian Neoplasms; Oxidoreductases; Prostatic Neoplasms; Transaminases; Ureteral Neoplasms; Urinary Bladder Neoplasms

Topics: Acid Phosphatase; Biomedical Research; Bone Neoplasms; Breast Neoplasms; Collagen; Humans; Hydroxyproline; Male; Neoplasm Metastasis; Neoplasms; Prostatic Neoplasms; Urine

Topics: Acid Phosphatase; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Diethylstilbestrol; Drug Therapy; Enzyme Inhibitors; Geriatrics; Humans; Male; Neoplasm Metastasis; Neoplasms; Osteosclerosis; Pathology; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Radiography; Tartrates

Topics: Acid Phosphatase; Alkaline Phosphatase; Blood Chemical Analysis; Bone Neoplasms; Castration; Drug Therapy; Estrogens; Geriatrics; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Neoplasms; Orchiectomy; Phosphorus; Prognosis; Prostatic Neoplasms; Radiography; Testis

Topics: Acid Phosphatase; Blood Chemical Analysis; Bone Neoplasms; Diethylstilbestrol; Humans; Japan; Male; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Statistics as Topic

Topics: Acid Phosphatase; Bone Neoplasms; Estradiol Congeners; Estrogens; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenoma; Alkaline Phosphatase; Ameloblastoma; Arthritis; Bone Cysts; Bone Neoplasms; Chondrosarcoma; Fibroma; Fibrous Dysplasia of Bone; Geriatrics; Giant Cell Tumors; Humans; Neoplasm Metastasis; Osteitis Fibrosa Cystica; Osteoma; Osteosarcoma; Prognosis; Radiography; Sarcoma, Ewing; Tuberculosis; Tuberculosis, Osteoarticular

Topics: Acid Phosphatase; Bone Diseases; Bone Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Gaucher Disease; Humans; Hyperparathyroidism; Male; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteogenesis Imperfecta; Osteopetrosis; Osteosclerosis; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenocarcinoma; Blood Chemical Analysis; Blood Protein Disorders; Blood Protein Electrophoresis; Bone Neoplasms; C-Reactive Protein; Carcinoma; Estrogens; Geriatrics; Glycoproteins; Hexosamines; Hexoses; Humans; Male; Neoplasm Metastasis; Neuraminic Acids; Prostatic Neoplasms