acid-phosphatase and Breast-Neoplasms

This is the history of discoveries of several enzyme tumor markers in the awardees laboratory. The first, beta-glucuronidase, was originally related to the physiological actions of estrogens and androgens. Perfection of histochemical techniques based on new substrates demonstrated the dual localization of beta-glucuronidase in endoplasmic reticulum and lysosomes. Tumor tissues, in general, are enriched with beta-glucuronidase. Next, acid phosphatase of the prostate gland possesses the distinctive property of undergoing inhibition by L-tartrate. This organ-specific inhibitor was incorporated into the Fishman-Lerner method for measuring serum acid phosphatase of prostatic origin. This significantly increased the specificity of the measurement of serum acid phosphatase for prostatic cancer. Finally, the discovery of the Regan Isoenzyme, placental alkaline phosphatase (PLAP) in a patient with disseminated lung cancer provided a tumor marker useful in the management of gonadal tumors, in particular. Closely related to PLAP is germ cell alkaline phosphatase which is eutopically expressed in seminoma. Finally, radioimmunolocalization and radioimmunotherapy of PLAP in these tumors have been achieved by others.

Topics: Acid Phosphatase; Alkaline Phosphatase; Awards and Prizes; Biomarkers, Tumor; Breast Neoplasms; Female; Glucuronidase; Humans; Isoenzymes; Medical Oncology; Neoplasms; Societies, Medical; Societies, Scientific; Teratoma; United States

Bilateral breast mass was found in a 71-year-old male who had been placed on estrogen therapy for stage D2 prostatic adenocarcinoma. Microscopically the mass contained adenocarcinoma morphologically similar to that of the prostate, but the differential diagnosis was impossible between metastatic prostatic carcinoma and primary breast carcinoma. Formalin-paraffin sections of both tumors were stained positively by PSA (prostatic specific antigen) and PAP (prostatic acid phosphatase) using B-SA (biotin-streptavidin) system technique and prostatic origin of the breast mass was confirmed. Prostatic origin for metastatic carcinoma in the breast is are with only 30 reported cases in the literature including 5 Japanese cases. In most of them the diagnosis of the breast lesion as prostatic carcinoma has been made on morphologic and clinical grounds only. Accurate diagnosis is important for the prognosis of the patient, and immunohistochemical method is useful for he diagnosis of breast carcinoma metastasized from prostatic origin.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Breast Neoplasms; Diagnosis, Differential; Estrogens; Humans; Immunohistochemistry; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Sixteen tumor markers are reviewed, and measured to the ideal: produced by the tumor cell alone absent in health and in benign disease present in all patients with a given malignancy level in the blood representative of tumor mass detectable in occult disease. The only marker that approaches the ideal is human chorionic gonadotropin (HCG) in gestational trophoblastic tumors. In this malignancy, the HCG level suggests the diagnosis and stage, confirms response to therapy, and predicts relapse. The three most widely used and intensely studied tumor markers are carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and HCG. CEA cannot be used in screening for cancer, but in carcinoma of the colon its elevation preoperatively increases the likelihood of advanced disease and postoperative recurrence. Postoperatively, elevated titers are often but not invariably associated with recurrent disease. AFP and HCG are useful in the management of nonseminomatous germ cell testicular tumors. Like CEA, they cannot be used for screening. They are more likely to be increased with advancing stage, and after therapy rising levels almost always mean recurrent disease. Some markers are valuable in specific circumstances, such as calcitonin in screening for familial medullary carcinoma of the thyroid. In multiple myeloma, immunoglobulins are useful in determining the tumor mass and response to therapy. In neuroblastoma, catecholamine metabolites are useful primarily in making the diagnosis. In some malignancies, the absence of effective therapy lowers the value of the marker, as for AFP in hepatoma. The remaining markers are too unreliable or too little studied to be useful in the management of an individual patient with cancer. The purpose of this paper is to provide the clinician with an understanding of the limitations of the present tumor markers that will lead to wiser use of the tests, and to provide standards to which future tumor markers should be measured.

Topics: Acid Phosphatase; Adrenocorticotropic Hormone; Alkaline Phosphatase; alpha-Fetoproteins; Breast Neoplasms; Calcitonin; Carcinoembryonic Antigen; Catecholamines; Chorionic Gonadotropin; Colonic Neoplasms; Female; Ferritins; Humans; Hydroxyproline; Immunoglobulins; L-Lactate Dehydrogenase; Liver Neoplasms; Lung Neoplasms; Neoplasms; Neoplasms, Germ Cell and Embryonal; Parathyroid Hormone; Placental Lactogen; Polyamines; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Vasopressins

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

Topics: Acid Phosphatase; Animals; Antigens, Neoplasm; Aryl Hydrocarbon Hydroxylases; Blood Proteins; Breast Neoplasms; Calcitonin; Clinical Enzyme Tests; Clinical Laboratory Techniques; Female; Humans; Male; Neoplasms; Neoplasms, Experimental; Prostate; Prostatic Neoplasms; Rats; Receptors, Estrogen; Receptors, Progesterone; Thyroid Neoplasms

Topics: Acid Phosphatase; alpha-Fetoproteins; Antigens, Neoplasm; Blood Proteins; Breast Neoplasms; Calcitonin; Carcinoembryonic Antigen; Chorionic Gonadotropin; Clinical Enzyme Tests; Female; Humans; Isoenzymes; Male; Milk Proteins; Molecular Weight; Muramidase; Neoplasm Metastasis; Neoplasms; Nucleosides; Phosphoric Diester Hydrolases; Polyamines; Procollagen-Proline Dioxygenase; Sialyltransferases

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Catalase; DNA Nucleotidyltransferases; Fructose-Bisphosphate Aldolase; Glycine Hydroxymethyltransferase; Hexokinase; Hodgkin Disease; Intestinal Neoplasms; Isoenzymes; L-Lactate Dehydrogenase; Leukemia; Liver; Liver Neoplasms; Lung Neoplasms; Neoplasms; Pyruvate Kinase; Ribonucleotides; Sarcoma, Experimental; Stomach Neoplasms; Uridine Kinase

Topics: Acid Phosphatase; Blood Platelet Disorders; Bone and Bones; Bone Diseases; Breast Neoplasms; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Female; Hematologic Diseases; Humans; Isoenzymes; Leukemia; Leukocytes; Lipidoses; Male; Primary Myelofibrosis; Prostate; Prostatic Neoplasms; Spleen; Thromboembolism

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

To study the effect of Shugan Jiangu Recipe (SJR) on bone mineral density (BMD) and serum bone metabolic biochemical markers in postmenopausal breast cancer patients with osteopenia.. Totally 38 patients of postmenopausal women with breast cancer, who received aromatase inhibitors (AIs), were assigned to the treatment group (21 cases) and the control group (17 cases) by using random digit table. All patients took Caltrate D Tablet (containing Ca 600 mg and Vit D3 125 IU), one tablet daily. Patients in the treatment group took SJR, 6 g each time, twice daily for 6 successive months. The bone mineral density (BMD) level was detected before treatment and at months 6 after treatment. Levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type II collagen (CTX-II) were detected by enzyme linked immunosorbent assay (ELISA). The drug safety was also assessed.. Compared with before treatment, BMD of L2-4 and femur neck obviously increased in the treatment group at month 6 after treatment (P < 0.01), serum BALP and TRAP decreased (P < 0.05). Compared with before treatment, BMD of L2-4 and femur neck obviously decreased in the control group at month 6 after treatment (P < 0.05), serum BALP and TRAP increased (P < 0.01). Compared with the control group, lumbar and femur neck BMD obviously increased, serum levels of BGP and BALP obviously decreased, and serum levels of CTX-II and TRAP obviously increased in the treatment group at month 6 after treatment (P < 0.01). No serious adverse event occurred during the treatment period. Bone fracture occurred in one case of the control group (5.8%).. SJR could attenuate bone loss of postmenopausal women with breast cancer who received AIs, increase BMD and improve abnormal bone metabolism.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Aromatase Inhibitors; Bone and Bones; Bone Density; Breast Neoplasms; Collagen Type II; Drugs, Chinese Herbal; Female; Humans; Isoenzymes; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Peptide Fragments; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adult; Aged; Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Breast Neoplasms; Female; Humans; Immunoassay; Isoenzymes; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

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

Tartrate-resistant acid phosphatase (TRAP/ACP5/uteroferrin/purple acid phosphatase/PP5) has received considerable attention as a newly discovered proinvasion metastasis driver associated with different malignancies. This renders TRAP an interesting target for novel anti-cancer therapy approaches. TRAP exists as two isoforms, 5a and 5b, where the 5a isoform represents an enzymatically less active monomeric precursor to the more enzymatically active 5b isoform generated by proteolytic excision of a repressive loop domain. Recently, three novel lead compounds were identified by fragment-based screening and demonstrated to be efficient TRAP enzyme inhibitors in vitro. We conclude that one of the three compounds i.e. 5-phenylnicotinic acid (CD13) was efficient as a TRAP inhibitor with Kic values in the low micromolar range towards the TRAP 5b isoform, but was not able to inhibit the TRAP 5a isoform. Structure-based docking revealed similar interactions of CD13 with the active site in both TRAP isoforms. In stably TRAP-overexpressing MDA-MB-231 breast cancer cells, CD13 inhibited intracellular TRAP activity and showed no cytotoxicity at 200 µM. Furthermore, CD13 selectively blocked the TRAP 5b isoform compared to the TRAP 5a in cultured cells, indicating the usefulness of CD13 for assessing the different biological functions of the two TRAP isoforms 5a and 5b in cell systems. Moreover, inhibition of cell migration and invasion of stably TRAP-overexpressing MDA-MB-231 by CD13 was observed. These data establish a proof of principle that a small chemical inhibitor of the TRAP enzyme can block TRAP-dependent functions in cancer cells.

Topics: Acid Phosphatase; Blotting, Western; Breast Neoplasms; CD13 Antigens; Cell Movement; Cell Proliferation; Enzyme Inhibitors; Female; Humans; Hydroxybenzoates; Isoenzymes; Nicotinic Acids; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Infiltrating neutrophils, lymphocytes, macrophages, and cytokines constitute a state of chronic inflammation within the tumor microenvironment. Tartrate-resistant acid phosphatase 5a (TRACP5a) protein, a novel product of activated macrophage, is postulated to be a biomarker for systemic inflammatory burden in states of chronic inflammation. We aimed to investigate the clinical significance of TRACP5a expression in tumor-infiltrating macrophages and serum TRACP5a in patients with metastatic breast cancer (BC). We retrospectively analyzed the clinical data from 34 BC patients with confirmed skeletal/visceral metastasis upon or during first-line palliative treatment. Patients were stratified into 3 groups based on the therapeutic responses and follow-up disease course. The association of TRACP5a protein with other inflammatory and cancer biomarkers was assessed among the clinically distinct group of patients. Higher TRACP5a protein was significantly correlated with earlier disease progression and survival (P = 0.0045) in comparison to other inflammatory markers, CRP or IL-6. Patients with higher serum TRACP5a level and shorter survival and treatment refractoriness also had more TRACP+ tumor-infiltrating macrophages. Our data support a hypothesis that serum TRACP5a protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in BC patients with bone/visceral metastasis. The associations between overall survival and TRACP expression by macrophages require further prospective investigation.

Topics: Acid Phosphatase; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; C-Reactive Protein; Disease Progression; Female; Humans; Interleukin-6; Isoenzymes; Macrophages; Middle Aged; Neoplasm Metastasis; Prognosis; Retrospective Studies; Survival Analysis; Tartrate-Resistant Acid Phosphatase

Metastatic bone disease has a major impact on the morbidity and mortality of breast cancer patients, and studies on bone metastasis biology have led to the development of the most widely used drugs for bone metastases treatment: zoledronate (Zol) and denosumab (Den). The aim of the present study was to assess the effect of soluble mediators produced by breast cancer cells on human osteoclast maturation in a co-culture model. We also tested the ability of zoledronate, denosumab and 5H4, an antibody directed against CSF-1, to interfere with the osteoclastogenic potential of breast cancer. The study was performed on the triple negative cell line MDA-MB-231 and on human osteoclasts obtained from the differentiation of peripheral blood monocytes of a healthy volunteer. Osteoclastogenesis was evaluated by TRAP assay after 14days of differentiation with 10% MDA-MB-231-conditioned media or with CSF-1 and RANKL. Den, Zol and 5H4 were administered after 7days of differentiation. MDA-MB-231-conditioned media doubled the differentiation of monocytes into osteoclasts. MDA-MB-231 secreted CSF-1, especially when cells were cultured to confluence. Induced osteoclasts were sensitive to bone-targeted drugs: Den and 5H4 blocked osteoclast differentiation and survival, while Zol induced osteoclast apoptosis. Osteoclasts differentiated by breast cancer cells were less sensitive to Zol than those induced by differentiation factors, whereas sensitivity to Den was similar. Conversely, breast cancer-induced osteoclast activation resulted in a higher sensitivity to 5H4. A significant increase in CSF-1 secretion was observed in osteoclast precursors after treatment with the highest concentration of Den. Further research is ongoing to evaluate the efficacy of 5H4 combination with Den.

Topics: Acid Phosphatase; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Denosumab; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Isoenzymes; Macrophage Colony-Stimulating Factor; Monocytes; Osteoclasts; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Tartrate-Resistant Acid Phosphatase

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

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

Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine-induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen-receptor positive T47D and MCF-7 and the estrogen-negative SK-BR-3 and Hs-578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M-CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast-related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF-7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF-κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer-induced bone metastasis.

Topics: Acid Phosphatase; Actins; Bone Resorption; Breast Neoplasms; Cell Line, Tumor; Cells, Cultured; Female; Gene Expression; Humans; Isoenzymes; Osteoclasts; Paracrine Communication; Receptors, Calcitonin; Signal Transduction; Stem Cells; Tartrate-Resistant Acid Phosphatase; Vitronectin

Patients with locally advanced breast cancer treated with neoadjuvant chemotherapy are at risk of cancer treatment-induced bone loss and consequently of increased skeletal morbidity. In addition, this situation could be worsened by the fact that only a minority of patients with breast cancer have sufficient vitamin D. A comprehensive evaluation of bone homeostasis is critical in this context. We retrospectively evaluated the serum levels of calcium, vitamin D, TRAIL, RANK ligand (RANKL), Osteoprotegerin (OPG), Bone TRAP, CrossLaps and DKK1 in 77 patients (median age: 50 years; range 25-74), with locally advanced breast cancer treated in our institute with anthracyclines-taxane neoadjuvant chemotherapy (7 cycles of 21 days/each) between March 2007 and August 2008. Serum samples were collected before the first (baseline) and the last treatment cycle. Variations and correlations between biomarker levels were evaluated. At baseline, 79.5 % of patients had vitamin D insufficiency (<30 ng/ml), increasing to 97.4 % at the end of the neoadjuvant chemotherapy (p < 0.0001). Calcium and RANKL serum concentrations were also significantly decreased, while OPG was significantly increased, resulting in lower RANKL/OPG ratio. Calcium and vitamin D, RANKL and vitamin D and RANKL and OPG levels were significantly correlated (Spearman's coefficient r = 0.2721, p = 0.0006; r = 0.1916, p = 0.002; and r = -0.179, p = 0.03, respectively). Nearly all included patients suffered from vitamin D insufficiency by the end of the neoadjuvant chemotherapy with changes in the calcium/RANKL/OPG axis that are evocative of deregulation of a functional regulatory mechanism. Further studies are needed to determine how drugs modulate this regulatory mechanism to preserve bone homeostasis in patients with breast cancer.

Topics: Acid Phosphatase; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone and Bones; Breast Neoplasms; Calcium; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Collagen; Cyclophosphamide; Docetaxel; Epirubicin; Female; Fluorouracil; Humans; Intercellular Signaling Peptides and Proteins; Isoenzymes; Middle Aged; Neoadjuvant Therapy; Osteoprotegerin; Peptide Fragments; Prevalence; RANK Ligand; Retrospective Studies; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Taxoids; TNF-Related Apoptosis-Inducing Ligand; Vitamin D; Vitamin D Deficiency

The use of activable cell-penetrating peptides (ACPPs) as molecular imaging probes is a promising new approach for the visualization of enzymes. The cell-penetrating function of a polycationic cell-penetrating peptide (CPP) is efficiently blocked by intramolecular electrostatic interactions with a polyanionic peptide. Proteolysis of a proteinase-sensitive substrate present between the CPP and polyanionic peptide affords dissociation of both domains and enables the activated CPP to enter cells. This ACPP strategy could also be used to modify antitumor agents for tumor-targeting therapy. Here, we aimed to develop a conjugate of ACPP with antitumor drug doxorubicin (DOX) sensitive to matrix metalloproteinase-2 and -9 (MMP-2/9) for tumor-targeting therapy purposes. The ACPP-DOX conjugate was successfully synthesized. Enzymatic cleavage of ACPP-DOX conjugate by matrix metalloproteinase (MMP)-2/9 indicated that the activation of ACPP-DOX occurred in an enzyme concentration-dependent manner. Flow cytometry and laser confocal microscope studies revealed that the cellular uptake of ACPP-DOX was enhanced after enzymatic-triggered activation and was higher in HT-1080 cells (overexpressed MMPs) than in MCF-7 cells (under-expressed MMPs). The antiproliferative assay showed that ACPP had little toxicity and that ACPP-DOX effectively inhibited HT-1080 cell proliferation. These experiments revealed that the ACPP-DOX conjugate could be triggered by MMP-2/9, which enabled the activated CPP-DOX to enter cells. ACPP-DOX conjugate may be a potential prodrug delivery system used to carry antitumor drugs for MMP-related tumor therapy.

Topics: Acid Phosphatase; Antineoplastic Agents; Biological Transport, Active; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Female; Fibrosarcoma; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Nanomedicine; Protein Tyrosine Phosphatases

Puerarin, a daidzein-8-C glucoside, is the major isoflavonoid in Kudzu (Pueraria lobata), and is unique in that it contains C-C conjugated glucose at position 8 of the isoflavonoid structure. A puerarin diet at a dose of 5 mg/kg b.w./d to fed ovariectomized mice for 2 mo diminished the urinary deoxypyridinoline, a typical bone-degradation product. Since the bone absorption marker, serum tartarate-resistant acid phosphatase (TRAP) activity of puerarin-fed mice decreased but the bone formation marker, osteocalcin level, did not alter, the puerarin diet was proved to specifically depress the bone absorption, but not the overall bone metabolism. In accordance with that results, the femur structure of puerarin-fed mice was restored compared with that of puerarin-free diet mice. The atrophied uterine due to low estrogen (E2) level after ovariectomy was not restored by the puerarin diet, suggesting that puerarin exerted the anti-osteoporotic action through a non estrogen receptor (ER) mediated-pathway, in vivo. The growth of an ER-positive human breast cancer cell, MCF-70, was not enhanced by puerarin, suggesting that puerarin did not show estrogen-like action on MCF-7 cells, even at a ten thousand times higher concentration than that of E2. Furthermore, ICI182,780 (ICI), an estrogen antagonist, suppressed the enhanced growth of MCF-7 cells by E2, but not that by puerarin. In an ER-binding assay, puerarin was proved not to bind to ERα or β, or if all, extremely weakly, although daidzein, an aglycon of puerarin, showed a little stronger binding compared with puerarin. All these results strongly indicate that puerarin exerts its anti-osteoprotic action independently of the ER-mediated pathway.

Topics: Acid Phosphatase; Amino Acids; Animals; Breast Neoplasms; Cell Proliferation; Diet; Estradiol; Female; Fulvestrant; Humans; Isoflavones; MCF-7 Cells; Mice; Osteocalcin; Osteoporosis; Ovariectomy; Pueraria; Receptors, Estrogen

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

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

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

Tartrate-resistant acid phosphatase, although encoded by a single gene, exists as two isoforms in human serum, TRAP 5a and 5b, differing in post-translational modifications such as proteolytic processing and kinetic properties including pH optimum and specific activity. The biogenetic relationship between the TRAP isoforms was assessed in a stably transfected breast cancer epithelial MDA-MB-231 cell subline overexpressing 5a- and 5b-like TRAP isoforms intracellularly, with only the monomeric 5a-like isoform being secreted. As judged by immunolocalization and comparative N-glycan profiling by Con A lectin chromatography and glycanase analysis, the majority of the intracellular monomeric TRAP was destined for secretion, while a minor portion provided the putative precursor for the intracellular 5b-like isoform. Brefeldin A blocked secretion of 5a-like TRAP isoform as well as appearance of its putative intracellular precursor, and augmented the intracellular level of proteolytically processed 5b-like isoform, indicating a common early biosynthetic precursor for TRAP isoforms 5a and 5b. The cysteine proteinase inhibitor E64 partially blocked formation of the 5b-like isoform while augmenting the level of its putative monomeric precursor, but did not alter the levels of secreted TRAP or its intracellular precursor, suggesting that distinct precursors for secreted TRAP 5a and intracellular 5b-like isoform are segregated in the ER or Golgi prior to proteolytic processing. In conclusion, these data provide evidence that distinct monomeric TRAP populations are diverted early in the secretory pathway either giving rise to a secreted, monomeric 5a-like TRAP isoform or to an intracellular, proteolytically processed 5b-like TRAP isoform.

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; Blotting, Western; Breast Neoplasms; Brefeldin A; Chromatography, Affinity; Concanavalin A; Female; Fluorescent Antibody Technique; Humans; Isoenzymes; Lectins; Molecular Sequence Data; Protein Conformation; Protein Synthesis Inhibitors; Rats; Sequence Homology, Amino Acid; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

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

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

Breast cancer is the commonest malignancy of women in Nigeria. Change in serum levels of some biochemical parameters could assist diagnosis and follow-up of breast cancer.. To determine serum levels of calcium, inorganic phosphates, alkaline phosphatase (ALP) and acid phosphatase (ACP) activities in patients with breast cancer, and change in the serum levels over time.. Total serum calcium and inorganic phosphates, and serum ALP and ACP activities were determined in 25 women with breast cancer and 25 age-matched controls using colorimetric and enzymatic methods, over 6 months with bimonthly analysis.. The serum calcium level, ALP and ACP activities were significantly higher (p<0.05) in the study group than in the control group. No significant difference was seen in the inorganic phosphate levels of both groups. There were significant increases in serum calcium levels, ALP and ACP activities in the study group with time (p<0.05), whereas no significant increase was observed in the control group.. Breast cancer patients have higher calcium levels and higher ALP and ACP activities. The increase in the levels of these parameters with time shows that they could be of importance in monitoring treatment and disease progress in a resource-poor setting.

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Calcium; Case-Control Studies; Female; Follow-Up Studies; Hospitals, Teaching; Humans; Nigeria; Phosphates

Prostate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC), female breast carcinoma (FBC), and gynecomastia.. Immunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC.. PSA was positive in two of fifty-six FBC (3.7%), focally positive in one of thirty MBC (3.3%), and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82).. PSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

Topics: Acid Phosphatase; Aged; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma; Diagnosis, Differential; Female; Gynecomastia; Humans; Immunohistochemistry; Male; Middle Aged; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Receptors, Steroid; Tissue Array Analysis

Breast cancer frequently metastasizes to bone, where tumor cells induce osteoclasts to locally destroy bone. During bone resorption, growth factors are locally released that may support bone metastatic growth. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates and osteoprotegerin (OPG), are available for bone. We examined the hypothesis that inhibition of bone resorption by two different mechanisms may also affect the growth of cancer cells in bone. For this, we tested the effects of high doses of OPG and zoledronic acid (ZOL) on progression of MDA-231-B/Luc+ breast cancer cells in the bone microenvironment using whole body bioluminescent reporter imaging (BLI). Both treatments significantly inhibited the development of radiographically detectable osteolytic lesions. Histologic examination corroborated the radiographic findings, showing that both treatments preserved the integrity of bone trabeculae and prevented bone destruction (significantly higher trabecular bone volumes vs. vehicle). However, whereas practically no TRAcP-positive osteoclasts were observed in tibiae preparations of animals treated with Fc-OPG, TRAcP-positive osteoclasts were still present in the animals treated with ZOL. Intra-bone tumor burden was reduced with ZOL and Fc-OPG treatment. Although there appeared to be a trend for less overall total tumor burden upon treatment with both compounds, this was not significant as assessed by BLI and histomorphometric analysis due to the extramedullary growth of cancer cells which was not affected by these treatments. Collectively, anti-resorptive agents with different mechanisms of action - ZOL and OPG - significantly reduced cancer-induced osteolysis and intra-osseous tumor burden, but failed to restrain local tumor growth. However, interference with the bone micro-environmental growth support could still be of therapeutic relevance when given to patients early in the course of bone metastatic disease.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Resorption; Breast Neoplasms; Cell Count; Cell Line, Tumor; Cell Proliferation; Diphosphonates; Female; Humans; Imidazoles; Isoenzymes; Luminescent Measurements; Mice; Mice, Inbred BALB C; Mice, Nude; Osteoclasts; Osteolysis; Osteoprotegerin; Radiography; Tartrate-Resistant Acid Phosphatase; Whole Body Imaging; Zoledronic Acid

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

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

Tartrate-resistant acid phosphatase (TRAP) is expressed by osteoclasts, macrophages and dendritic cells. TRAP has been identified in a wide variety of tissues, however, its biological function is not fully understood. Serum TRAP is a marker of diseases involving excessive bone resorption including metastatic bone disease in breast cancer patients and can be used to monitor responses to treatment. Our aim in this study was to determine whether TRAP is expressed by human breast tumours. Four breast cancer cell lines were assayed for TRAP activity. MDA-MB-435, the most tumourigenic line, had an activity twofold higher than the other cell lines. Immunohistochemistry using a TRAP specific antibody confirmed that both cell lines and human breast tumours express TRAP. Expression was absent in benign tissues and abundant in more aggressive tumours. This work suggests that tumour derived TRAP contributes to the raised enzyme activity found in the serum of breast cancer patients.

Topics: Acid Phosphatase; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Immunohistochemistry; Isoenzymes; 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

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

Mammary carcinoma with multinucleated osteoclast-like giant cells (OGCs) is a rare, distinctive variant of breast carcinoma. To date, all of these instances have been described as part of an invasive carcinoma. Here, we report a case of ductal carcinoma in situ of the breast with numerous admixed OGCs present within gland lumens without an associated invasive component. Similar to invasive carcinomas with OGCs, both the in situ carcinoma and the OGCs exhibited overexpression for vascular endothelial growth factor. This case expands the spectrum of tumors associated with OGCs and provides further evidence for the possible role of vascular endothelial growth factor in the stromal-epithelial interactions of in situ mammary carcinoma.

Topics: Acid Phosphatase; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Giant Cells; Humans; Isoenzymes; Middle Aged; Osteoclasts; Tartrate-Resistant Acid Phosphatase; Vascular Endothelial Growth Factor A

Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies.. TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells.. A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines.. Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

Topics: Acid Phosphatase; Breast Neoplasms; Control Groups; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humans; Immunohistochemistry; Isoenzymes; Melanoma; Ovarian Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured; Up-Regulation

GM-CSF (granulocyte-macrophage colony stimulating fractor) is a hematopoietic growth factor. In vitro it stimulates the proliferation of myeloid progenitors and formation of granulocyte and macrophage colonies. It was found that GM-CSF in vitro also stimulates the phagocytic function of mature granulocytes. Indirect evidence of this might be the increase of the activity of granulocyte enzymes participating in phagocytosis. The aim of this study was to compare in vivo the level of GM-CSF in the plasma and activity of acid phosphatase (AcP), alkaline phosphatase (AP), peroxidase (MPO) and esterase in granulocytes of breast cancer patients. The activities of tested enzymes were measured by cytochemical methods in the blood of 14 patients before and 30 days after surgery (group A) and 15 patients before and in the course (12 week) of chemotherapy (groupB) and in 10 healthy subjects. GM-CSF concentration was measured in the plasma, using a sensitive sandwich ELISA. According to obtained results we can conclude that GM-CSF concentration in cancer patients before and after surgery compared to the control group was increased. GM-CSF concentration in patients before and in the course of chemotherapy was increased compared to the control group and patients before and after surgery. Enzyme activities participating in phagocytosis in cancer patients after surgery were increased compared to the enzyme activity in the control group. Enzyme activities in cancer patients in the course of chemotherapy were decreased when compared to the activities in the control group and when compared to the activities in cancer patients before and after surgery. The chemotherapy causes increase of GM-CSF concentration and enzyme activity.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Breast Neoplasms; Enzyme-Linked Immunosorbent Assay; Esterases; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Histocytochemistry; Humans; Middle Aged; Peroxidase; Phagocytosis; Poland; Reference Values

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

G-CSF is a stimulatory factor of granulocyte colony formation. In vitro and in vivo G-CSF stimulates the proliferation of granulocyte precursors and enhances phagocytic functions of mature cells. Indirect evidence of this might be the increase of the activity of granulocyte enzymes participating in phagocytosis.. The aim of this study was to compare in vivo the level of G-CSF in the plasma and the activity of: alkaline phosphatase (AP), acid phosphatase(AcP), peroxidase(MPO) and esterase in the granulocytes of breast cancer patients.. The activities of tested enzymes were measured by cytochemical methods in the blood of 10 patients with breast cancer before and 30 days after operation and in 10 healthy subject. GSF level was measured using a sensitive sandwich ELISA.. 1. On the basis of the obtained results we can conclude that G-CSF level was increased in cancer patients (18.30 pg/ml before operation and 20.70 pg/ml after operation) compared to the control group (15.73 pg/ml). This results suggest that G-CSF may be synthesized by phagocytic cells and/or cancer cells. 2. AP activity was decreased after surgery (135.00 score) in comparison to the activities before operation (182.3 score). 3. AcP (213.6 score), MPO (364.6 score) and esterase (184.2 score) activities were significantly increased after surgery in comparison to the activities before operation: AcP 188.6 score, MPO 316.3 score, esterase 154.8 score. 4. These results suggest that activities of tested enzymes might be dependent on G-CSF plasma level.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Breast Neoplasms; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Esterases; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Humans; Male; Middle Aged; Peroxidase; Poland; Time Factors

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

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

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

Little is known of the function and clinical significance of the androgen receptor (AR) in human breast cancer. Paradoxically, synthetic progestins, such as medroxyprogesterone acetate, are used for second line hormone therapy of breast cancer following tamoxifen failure. A sensitive and accurate assay for AR expression in breast tumors is thus required. Here we have developed and validated a real-time RT-PCR assay to quantify AR gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast tumors. AR expression varied widely in tumor tissues (by at least 3 orders of magnitude), being underexpressed in 24/131 (18.3%) and overexpressed in 45/131 (34.4%) relative to normal breast tissues. We observed links (or trends) between AR status and age, menopausal status, Scarff-Bloom-Richardson histopathological grade, lymph node status and estrogen receptor alpha and progesterone receptor status. High AR mRNA levels were negatively linked to MYC gene overexpression (P = 8 x 10(-6)), confirming previous in vitro studies. Our results also suggest a role of the ARA70 gene (which encodes a major AR co-activator) in the AR pathway dysregulation observed in breast cancer. This simple, rapid and semi-automated method will be useful for screening cancer patients for altered AR expression and for predicting the response to androgen therapy in AR-related cancer patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Cyclin D1; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Genes, myc; Genes, Retinoblastoma; Humans; Middle Aged; Nuclear Receptor Coactivators; Oncogene Proteins; Prostate-Specific Antigen; Protein Tyrosine Phosphatases; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Trans-Activators; Transcription Factors

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

Since the introduction of hormonal therapy for the treatment of metastatic prostatic adenocarcinoma, there have been 33 reports of metastases of prostate carcinoma to the breast. We report two cases of diethylstilbestrol (DES)-treated patients with metastatic prostate adenocarcinoma who developed breast masses. The lesions had infiltrative patterns simulating primary breast carcinoma. Immunoperoxidase stains, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) were positive, identifying these cases as metastatic prostatic carcinoma to the breast. Differentiating primary from secondary tumors in these patients is difficult since there have been 10 reports of primary breast carcinoma occurring in DES-treated patients with prostatic adenocarcinoma. Their differentiation is important to direct appropriate therapy, and PSA and PAP immunoperoxidase stains are important in their correct classification.

Topics: Acid Phosphatase; Adenocarcinoma; Antigens, Neoplasm; Breast Neoplasms; Diethylstilbestrol; Female; Humans; Immunohistochemistry; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane-associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of the tissue-unspecific alkaline phosphatase was time and dose dependent. The protein synthesis inhibitor cycloheximide blocks the enzyme synthesis and tunicamycin blocks the enzyme activity, showing that the induction was new synthesis of protein in its complete glycosylated form and not activation of a preexisting enzyme. To our knowledge this is the first report of progesterone-induced expression of a tissue-unspecific alkaline phosphatase gene of such magnitude (about 30- to 100-fold) in a progesterone-responsive tissue.

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Cell Line; Cycloheximide; Enzyme Induction; Female; Humans; Kinetics; Organ Specificity; Promegestone; Steroids; Tunicamycin

Tumour markers viz carcinoembryonic antigen (CEA), human chorionic gonadotrophin (HCG) in 30 cases of carcinoma breast and prostatic specific acid phosphatase (PSAP) in 30 cases of carcinoma prostate were studied by peroxidase antiperoxidase technique in paraffin blocks of tissue. Twenty three (76.7%) and 20 (66.7%) cases were positive for CEA and HCG respectively. No correlation was observed between CEA and HCG status, and histological differentiation of the tumours. All the 29 cases (100%) of adenocarcinoma prostate were PSAP positive while a single case, negative for PSAP, was of transitional cell carcinoma.

Topics: Acid Phosphatase; Adenocarcinoma; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Transitional Cell; Chorionic Gonadotropin; Female; Humans; Male; Prostatic Neoplasms

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

Prostatic carcinoma accounts for about 1% of all cancers that metastasize to the skin. The regions most frequently involved are the genital region, the head and the trunk. Clinically the lesions present as nodules; less often diffuse infiltrates, red macules and papules or tumors of an angiomatous appearance occur. Histopathological examination of skin biopsy specimens can reveal gland-like, epithelial or anaplastic differentiation of tumor cells. Prostatic origin can be proven by the immunohistological demonstration of acid prostatic phosphatase or prostatic specific antigen in paraffin-embedded specimens taken for routine histological examination.

Topics: Acid Phosphatase; Biomarkers, Tumor; Breast Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prostatic Neoplasms; Skin; Skin Neoplasms

The activity of the enzyme ornithine decarboxylase (ODC) is increased in confluent culture of two breast cancer cell lines (T47D and MCF-7) following a change of medium. The increase in activity is maximum at 12 hours and this level is reduced in cells treated with high concentrations of HuIFN-alpha. However, the increased level of ODC activity seen in the first few hours after medium change can be stimulated by low concentrations of interferon (10-100 units per ml). The activity of the acidic and alkaline phosphatase of the above cell lines are affected by HuIFN-alpha similar to ODC. In stimulating levels of ODC and phosphatases, interferon is acting similar to mitogens, and in T47D and MCF-7 cells this stimulatory effect precedes the inhibitory effect more commonly seen in interferon-treated cells.

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Cell Line; Female; Humans; Interferon Type I; Ornithine Decarboxylase; Tumor Cells, Cultured

A breast mass developed in a patient receiving estrogen therapy for prostatic cancer. The prostate tumor was adenocarcinoma of small acinar type, whereas that of the breast was infiltrating medullary adenocarcinoma. Histological features of the two tumors differed and double cancer was suspected by conventional pathological study. However, immunohistochemical staining with prostatic specific antigen and prostatic acid phosphatase was positive in each tumor. These results indicate the breast tumor to be a metastasis from the prostatic cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens, Neoplasm; Breast; Breast Neoplasms; Humans; Immunoenzyme Techniques; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Acid Phosphatase; Adult; alpha-Fetoproteins; Breast Neoplasms; Chorionic Gonadotropin; Clinical Enzyme Tests; Female; Humans; Male; Middle Aged; Prostate

A patient who was treated with estrogens for carcinoma of the prostate was later diagnosed with apparent primary cancer of the male breast. He received chest-wall radiation therapy with curative intent. Later, immunodiagnosis by immunoperoxidase staining for human prostate-specific acid phosphatase of the breast tissue revealed that the patient actually had metastatic prostate cancer to the breast rather than primary breast cancer secondary to estrogen therapy. Use of highly specific peroxidase-antiperoxidase tissue staining for human prostate-specific acid phosphatase is recommended to differentiate primary male breast cancer from metastatic prostate cancer.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Breast Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Male; Prostate; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenofibroma; Alkaline Phosphatase; Breast; Breast Neoplasms; Female; Glucosephosphate Dehydrogenase; Humans

Acid phosphatase (EC 3.1.3.2) isoenzyme 3 was purified from normal and malignant human mammary tissue and its properties in each were compared. The relative molecular mass of each was 53 000, as measured by sodium dodecyl sulfate gel electrophoresis. Several phosphomonoesters are good substrates for the isoenzymes, whereas organic and inorganic pyrophosphates and phosphoryl choline are hydrolyzed very slowly or not detectably. The optimum pH for interaction of these isoenzymes with p-nitrophenyl phosphate as substrate ranges from 3.5 to 4.5. L-(+)-Tartrate is a very strong inhibitor, Ki = 0.028 +/- 0.04 mmol/L (mean +/- SE), as are mercuric and fluoride ions in low concentrations. We conclude that type 3 isoenzymes obtained from normal and malignant tissue are very similar, though the malignant tissue appears to have a greater proportion of this type than does normal tissue.

Topics: Acid Phosphatase; Breast; Breast Neoplasms; Chromatography, DEAE-Cellulose; Chromatography, Gel; Electrophoresis, Polyacrylamide Gel; Female; Humans; Isoenzymes; Kinetics; Lysosomes; Mastectomy; Substrate Specificity

Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for lymphocyte subsets, monocytes, NK cells and major histocompatibility antigens (HLA-A, -B, -C; Ia-like). Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration, 77% of the patients without mononuclear cell infiltration had receptors for estrogens as compared to 51% of the patients with infiltration. The majority of the infiltrating mononuclear cells were T cells; generally the OKT8 cells were predominant. The Leu 3A/OKT8 cell ratio was not related to histological type, tumor size, age of the patient or presence of metastases. Some of the T cells had the Ia antigen and were thus probably activated. The B cells were either absent or less numerous than the T cells. There was no relation between their distribution and the various parameters studied. A few monocytes were heterogeneous according to their markers (OKM I and acid phosphatase). In 6 cases only there was a strong infiltration of mononuclear cells positive for acid phosphatase. The number of the natural killer cells was also low. Only a few mononuclear infiltrating cells had receptors for transferrin. There was a positive correlation between the inflammatory infiltration and the presence of HLA class-I antigens on tumor cells. Some of the antisera specific for lymphocyte subsets also stained the breast carcinoma cells. The great variations in the subsets of mononuclear cells in breast carcinomas may correspond to various systems of defense against neoplasm.

Topics: Acid Phosphatase; Adult; Aged; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Leukocytes; Lymphatic Metastasis; Middle Aged; Monocytes; Receptors, Estrogen

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

We have developed a simple in vitro method of evaluating the relative binding properties of anti-tumor antibodies to human tumor and normal tissues. Cryopreserved surgical explants of tissues as 1 mm cubes are incubated in microtiter plate wells containing media and radiolabeled antibody. We show that the accumulation of antibody in tumor tissue is a specific process which may be reduced by preincubation with saturating levels of unlabeled specific antibody. Evaluation of 7 anti-breast and 4 anti-colorectal tumor antibodies against their respective tumor tissues showed good reproducibility of repeat measurements and up to a 100-fold difference in accumulation among different antibodies to the same tissue. Equivalent results were obtained with the same tissues employed fresh and after cryopreservation. Because of the simplicity of the assay, panels of antibodies may be screened against the large numbers of tumor and normal tissues required to identify superior antibodies for human trials.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Breast Neoplasms; Carcinoembryonic Antigen; Colon; Colonic Neoplasms; Diffusion; Humans; Liver; Rectal Neoplasms

Topics: Acid Phosphatase; Breast; Breast Neoplasms; Female; Fibrocystic Breast Disease; Glucuronidase; Humans

In 132 patients suffering from various malignancies, including uterine carcinoma, breast cancer, gastric carcinoma, cancer of the colon, and additionally, patients with uterine myomas and endometriosis an increased activity of AP within the peripheral blood neutrophils could be stated by using a histochemical method. According to the author's opinion an increased activity of that enzyme reflects a response against local inflammatory processes frequently accompanying malignant tumours.

Topics: Acid Phosphatase; Breast Neoplasms; Colonic Neoplasms; Endometriosis; Female; Humans; Leiomyoma; Male; Neoplasms; Neutrophils; Stomach Neoplasms; Uterine Neoplasms

The presence of a high-molecular weight complex with acid phosphatase activity in the cytosol of human mammary tumors is reported. This complex appeared in the cytosol after tissue homogenization in the presence of dithiotreitol, with or without Triton X-100 and at acidic or neutral pH. Upon gel electrophoresis, this fraction showed only one band of enzyme activity which did not enter the fine pore gel. Lubrol or n-butanol had no apparent effect on this complex, and 8 M urea or 2% sodium dodecyl sulfate did not disaggregate this large molecule. After purification by gel filtration, ammonium sulfate precipitation and ion-exchange chromatography an apparent molecular weight or 10(6) was measured. It hydrolyzed typical acid phosphatase substrates such as p-NPP and alpha-NP, but also ATP and PPi. Only 44% inhibition was observed with L-(+)tartrate and it was still 40% active after 1 hr incubation at 60 degrees C. Reduction in the presence of SDS yielded several polypeptide bands. It was also detected in some samples of normal mammary tissues, but not in normal human placenta or liver.

Topics: Acid Phosphatase; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromatography, Gel; Cytosol; Detergents; Dithiothreitol; Female; Humans; Molecular Weight; Octoxynol; Polyethylene Glycols; Substrate Specificity

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

When the total acid phosphatase (AP) activity of mammary carcinoma was compared with those of benign pathology and normal mammary tissue the results showed statistically significant differences (P less than 0.05) when expressed per milligram of protein: 358 +/- 42 nmoles per hour (mean +/- standard error) in the malignant tumor, 216 +/- 30 in the benign pathology, and 96 +/- 45 in normal tissue and when expressed per milligram of DNA: 1858 +/- 234, 1227 +/- 140, 695 +/- 345 nmoles per hour, respectively. The polyacrylamide gel electrophoretic profiles showed different levels of isoenzymes 3 and 4 in the three tissue groups. The appearance of isoenzyme 1 is reported after treatment of the homogenates with 5% Triton X-100. It was also found by counterimmunoelectrophoresis that the 28,000 Xg mammary tumor supernatant cross reacts with an antiserum raised against AP isoenzyme 2 although the mammary tissue does not contain such an isoenzyme. To elucidate this point, isoenzymes 1, 3 and 4 were separated by columns of Sephadex G-200 and DEAE-Sephadex. By counterimmunoelectrophoresis, it was observed that only the fraction containing isoenzyme 4 cross-reacted with the antiserum anti-AP isoenzyme 2 maintaining the catalytic activity.

Topics: Acid Phosphatase; Breast Neoplasms; Counterimmunoelectrophoresis; Electrophoresis, Polyacrylamide Gel; Female; Humans; Isoenzymes

The advantage of using DNA content as a biochemical parameter because the results it gives are directly related to cellularity is discussed. As examples, comparisons of acid phosphatase and cathepsin D activities in rat liver and hepatoma and of acid phosphatase in human normal breast tissue and adenocarcinoma are considered. Contradictory results are obtained, depending whether they are related to DNA content, fresh tissue weight, or protein content.

Topics: Acid Phosphatase; Adenocarcinoma; Animals; Breast; Breast Neoplasms; Cathepsin D; Cathepsins; DNA; Female; Humans; Liver; Liver Neoplasms, Experimental; Male; Neoplasm Proteins; Proteins; Rats

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

We report 2 cases of primary prostatic carcinoma with subsequent carcinomatous lesions in the breast. Prostatic origin of these carcinomas was confirmed by immunocytochemical demonstration of prostatic acid phosphatase and prostate specific antigen within paraffin sections. Previously, only 20 cases of prostatic carcinoma metastatic to the breast have been reported in the literature. In most of these cases the designation of the breast lesion as prostatic carcinoma has been made on morphologic and clinical grounds only.

Topics: Acid Phosphatase; Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Humans; Immunoenzyme Techniques; Male; Prostate-Specific Antigen; Prostatic Neoplasms

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

Activity of acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase in peripheral blood neutrophils of 30 women with breast cancer has been studied by means of semiquantitative cytochemical methods. In comparison to 20 healthy women the patients showed an increased activity of acid phosphatase and beta-glucuronidase whereas that of N-acetyl-beta-D-glucosaminidase was significantly lowered. It has been suggested that observed intracellular enzymatic deficiency is of importance with regard to lowered antitumor activity of neutrophils. Analogous deficiency of N-acetyl-beta-D-glucosaminidase within the neutrophils has previously been observed by the authors in women with malignant tumors of reproductive organs.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adult; Breast Neoplasms; Female; Glucuronidase; Humans; Middle Aged; Neutrophils

Human mammary tumours were grown in diffusion chambers in the heterologous host--Charle's Foster rat. The effect of oophorectomy-induced alterations of the hormonal environment of the host in breast tumour cells grown in the diffusion chamber were studied with respect to their growth patterns and enzymatic characteristics. The tumour cells not only survived but actively proliferated as indicated by the increase in cell count and formation of cell sheets as well as by the presence of mitotic figures. Cytochemical studies of certain enzymatic activities, i.e. succinic dehydrogenase, alkaline phosphatase, acid phosphatase and beta-glucuronidase indicate--except for a slight depression of the overall activity--that the distribution patterns are more or less maintained following diffusion chamber culture. The alteration of the hormonal environment by oophorectomy influences the cell growth and the enzymatic activity of the human tumour cells inside the diffusion chambers. The results clearly indicate that D.C. culture technique provides a useful method for assessment of growth and hormonal responsiveness of human tumours.

Topics: Acid Phosphatase; Adenocarcinoma; Alkaline Phosphatase; Animals; Breast Neoplasms; Castration; Cell Division; Culture Techniques; Female; Glucuronidase; Histocytochemistry; Humans; Models, Biological; Neoplasm Transplantation; Rats; Succinate Dehydrogenase; Transplantation, Heterologous

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antigens; Breast Neoplasms; Carcinoma; Epitopes; Humans; Male; Neoplasms, Multiple Primary; Prostate; Prostatic Neoplasms

Acid phosphatase, leucine aminopeptidase, monoamine oxidase and non specific esterase activities were histochemically demonstrated in specimens derived from 15 infiltrating ductal carcinomas of female breast. The relative areas occupied by the enzyme-positive carcinoma cells were visually estimated and, in the cases of leucine aminopeptidase, assessed morphometrically. All enzyme activities were found to be subject to major variations within a single carcinoma and between individual carcinomas, and the activity of any single enzyme was independent of that of three others. None of the enzyme activities correlated with the estrogen and progesterone receptor values, nor the histological grade of malignancy of the tumour. Thus, histochemically demonstrable enzyme activities seem to be of no use in predicting the hormone receptor content in infiltrating ductal carcinomas of the female breast.

Topics: Acid Phosphatase; Adult; Aged; Breast Diseases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Esterases; Female; Fibrocystic Breast Disease; Humans; Leucyl Aminopeptidase; Middle Aged; Monoamine Oxidase; Phyllodes Tumor; Receptors, Cell Surface

Topics: Acid Phosphatase; Antibody Formation; Antigens, Neoplasm; B-Lymphocytes; Breast Neoplasms; Cytotoxicity, Immunologic; Female; Humans; Immunity, Cellular; Lymph Nodes; Lymphatic Metastasis; Lymphocytes; Plasma Cells; Prognosis; T-Lymphocytes

Forty-five human malignant tumours and three benign lesions were stained histochemically for non-specific esterase (NSE) and acid phosphatase (AP), and immunohistochemically for lysozyme. Most of the tumours contained small numbers of lysozyme positive macrophages (LPM), but colonic tumours showed moderate numbers of LPM around the edge of the lesions. Gastric and secondary duodenal tumours (n = 3) contained moderate numbers of intralesional LPM in addition. Most squamous and all mesenchymal tumours contained no lysozyme positive macrophages. The usefulness of the three staining methods was assessed and it was concluded that lysozyme was specific but detected only part of the macrophage population. Neutrophil polymorphs were also stained but could be recognised by nuclear morphology. AP and NSE detected more cells but stained tumour cells as well as macrophages, making these methods of limited use in tumours showing invasion of the stroma by single cells or small groups of cells.

Topics: Acid Phosphatase; Breast Neoplasms; Cell Count; Esterases; Female; Gastrointestinal Neoplasms; Humans; Immunoenzyme Techniques; Macrophages; Male; Muramidase; Neoplasms

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

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Dysgerminoma; Female; Humans; L-Lactate Dehydrogenase; Lymphoma; Male; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Succinate Dehydrogenase; Testicular Neoplasms

Acid phosphatase activity was studied in the cytosol fraction of breast cancer tissue. Serum, plasma, and extracts of leukocyte and platelet were used for reference. The breast cancer tissue fraction had an electrophoretic mobility intermediate to leukocyte-derived bands 2 and 4 and corresponding to the platelet-derived band 3. The enzymes derived from platelet and breast cancer tissue were both inhibited by L-tartrate and showed a similar pattern for preferred substrates. By contrast, the breast cancer tissue-derived enzyme was different from the enzyme fraction responsible for the elevated serum enzyme activity in some patients with disseminated breast cancer. The two fractions could be distinguished by electrophoretic mobility and tartrate sensitivity. These findings substantiate our previous report, which suggested that the fraction responsible for elevated serum enzyme activity in the course of breast cancer is not derived from cancer tissue. It is proposed that the osteolysis, resulting from bone metastases, may be responsible for elevated serum enzyme activity in this disease.

Topics: Acid Phosphatase; Breast Neoplasms; Cytosol; Electrophoresis, Polyacrylamide Gel; Humans; Tartrates

CEA as well as alkaline and acid phosphatase were measured in patients with fibrocystic breast disease. The values recorded from the punctured fluids were compared to those in peripheral blood. CEA concentrations in cyst fluid were elevated in patients with proliferative breast disease, whereas no correlations could be established between alkaline and acid phosphatase, on the one hand, and various histological forms of breast disease, on the other.

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Diseases; Breast Neoplasms; Carcinoembryonic Antigen; Female; Fibrocystic Breast Disease; Humans; Precancerous Conditions; Radioimmunoassay

Recently developed enzyme tests that are used in (a) identifying high risk populations, (b) diagnosing cancer, (c) following treatment response of cancer patients, and (d) the selection of cancer therapy are summarized. The diagnostic role of methionine adenosyltransferase and CSF monoamine oxidase activity measurements in the diagnosis of schizophrenia are discussed. The role of N-acetyltransferase in the conversion of serotonin to melatonin in the pineal gland and the importance of these changes for the synchronization of the functioning of cells throughout the organism are described. New developments in the determination of immunoreactive trypsin in the early diagnosis of pancreatic diseases are summarized.

Topics: Acid Phosphatase; Aryl Hydrocarbon Hydroxylases; Arylamine N-Acetyltransferase; Breast Neoplasms; Chemistry, Clinical; Clinical Enzyme Tests; Female; Galactosyltransferases; Humans; Male; Neoplasm Staging; Neoplasms; Pancreatitis; Pineal Gland; Prostatic Neoplasms; Schizophrenia; Sialyltransferases; Trypsin

A solid-phase immunoadsorbent assay for serum prostatic acid phosphatase (PAP) measurement has been developed as modified from our previously reported immunofluoroassay, utilizing the specific anti-PAP antibodies conjugated to CNBr-activated Sepharose 4B. The serum prostatic acid phosphatase was bound, and separated from other acid phosphatases and serum proteins, by the solid-phase anti-PAP IgG Sepharose 4B. The enzyme activity was quantitated by measuring the enzyme hydrolytic product, alpha-naphthol, from a primary standard solution. The entire procedure could be performed within four hours. The sensitivity of this method was 0.22 I.U./l of enzyme activity or 0.88 ng of prostatic acic phosphatase protein per ml of serum. Normal range of serum prostatic acid phosphatase as determined by this assay was found to be 0.4--2.4 I.U./l of enzyme activity (or 1.60--9.60 ng of enzyme protein per ml of serum). Initial clinical evaluation showed that 19 of 25 patients with early stages of prostatic cancer and 12 of 14 patients with metastatic prostatic cancer exhibited an elevated enzyme level (overall 79%), as compared with only six and eight patients, respectively (overall 36%), by a conventional chemical method.

Topics: Acid Phosphatase; Adult; Aged; Breast Neoplasms; Female; Humans; Immunoassay; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms; Prostate; Prostatic Neoplasms; Reference Values

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; Aged; Bone and Bones; Bone Neoplasms; Breast Neoplasms; Humans; Male; Prostatic Neoplasms; Radiography; Radionuclide Imaging

Topics: Acid Phosphatase; Adrenalectomy; Alkaline Phosphatase; Animals; Breast Neoplasms; Castration; Estrogens; Female; Fibrinolysin; Hormones; Humans; Hypophysectomy; Male; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Neoplasms; Phosphorus; Pregnancy; Progesterone; Prostatic Neoplasms; Semen

An ultramicrochemical technique has been adapted to the evolution of enzyme profiles within individual human mammary tumors. Tandem observation of adjacent stained and lyophilized sections permitted dissection of microgram quantities of freeze-dried material within confirmed regions of malignancy. Enzymes frequently monitored to examine glycolytic, respiratory, and metastatic capacity were microanalyzed successfully: lactic dehydrogenase (LDH), phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), acid phosphatase (AP), aldolase (ALD), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), alpha-glycerophosphate dehydrogenase (alpha-GOPDH), hexokinase (HK), and phosphofructokinase (PRK). All enzyme activities were higher in infiltrating ductal carcinomas than in fibroadenomas. Extracts of tumor cells mixed in varying proportions with brain or muscle extracts of rat evidenced no modification of expected activity. The technical adaptation described provided a sensitive methodology to resolve problems of relication, profile analysis, sample quantity, and selectivity within heterogeneous tissues.

Topics: Acid Phosphatase; Adenofibroma; Alcohol Oxidoreductases; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Fructose-Bisphosphate Aldolase; Glucose-6-Phosphate Isomerase; Humans; Microchemistry; Phosphotransferases

Topics: Acid Phosphatase; Breast Neoplasms; Clinical Enzyme Tests; Female; Glucose-6-Phosphate Isomerase; Glucuronidase; Humans; Isocitrate Dehydrogenase; Phosphoglucomutase

Twenty-six scirrhous carcinomas of the breast were divided into three histological grades of malignancy; low (Grade I), intermediate (Grade II), and high (Grade III), and the correlation of the grades with histochemical and electron microscopic findings in both tumor cells and host tissues was examined. The tumor cells contained increased amounts of lysosomal acid phosphatase and beta-glucuronidase. This increase was most marked in Grade I and II tumors and the increase was consistent with lysosome-like fine structures. Both intracytoplasmic lumina and microvilli against stroma were characteristic findings of carcinoma cells and they were mostly found in Grade I and II tumors. Segments of intact basal laminae and myoepithelial cells were also found in Grade I and II carcinomas. The stroma contained moderately increased amounts of intracellular acid phosphatase and beta-glucuronidase, independent of tumor grade. The stroma also contained a large amount of acid mucopolysaccharide ground substance, irrespective of the three grades. There was a striking difference in the ultrastructural organization of the stroma between normal and neoplastic tissues. Although fragmented elastic fibers and increased amount of acid mucopolysaccharide granules, and macrophages rich in phagolysosomes were prominent fine structures of the stroma of carcinomas, there was no apparent difference in them among the three grades of malignancy.

Topics: Acid Phosphatase; Adenocarcinoma, Scirrhous; Adult; Aged; Breast Neoplasms; Glucuronidase; Glycosaminoglycans; Histocytochemistry; Humans; Lysosomes; Middle Aged; Vacuoles

Topics: Acid Phosphatase; Adenofibroma; Alkaline Phosphatase; Breast Neoplasms; Histocytochemistry; Humans; Papilloma

Topics: Acid Phosphatase; Adolescent; Adult; Age Factors; Aged; Alkaline Phosphatase; Breast Neoplasms; Carcinoma; Female; Humans; India; Male; Middle Aged

Topics: Acid Phosphatase; Axilla; Breast Neoplasms; Female; Glucuronidase; Humans; Lymph Nodes; Lymphatic Metastasis; Lymphocytes; Lysosomes

The mechanism of stroma-formation and rearrangement of the stroma was studied on 221 cases of cancer of the lung, stomach and mammary gland using histological, histochemical and electron-microscopy methods of investigation. It was established that multiplying epithelial elements of teh tumour induced proliferation of histiogenic and vascular fibroblasts, activating them. Active fibroblasts play a double role: they either produce fibres and interstitial matter of the tumorous stroma, or participate in desintegration of preceding and newly formed collagenous structures. The processes of stroma-formation comply with the conventional schemes of normal fibrillogenesis and rearrangement of the interstitial tissue. It was shown that fibroblasts of the tumour stroma was capable of phagocytosis of a mature collagen. It is supposed that in the course of the tumorous growth correlation between the parenchyma and stroma is maintained, the leading role being played by the epithelium.

Topics: Acid Phosphatase; Breast Neoplasms; Collagen; Fibroblasts; Glycosaminoglycans; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Lung Neoplasms; Male; Microscopy, Electron; Stomach Neoplasms; Tropocollagen

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Aged; Alkaline Phosphatase; Breast; Breast Neoplasms; Cell Differentiation; Colon; Colonic Neoplasms; Epithelium; Esterases; Female; Histocytochemistry; Humans; Hydrolases; Leucyl Aminopeptidase; Male; Middle Aged; Naphthaleneacetic Acids; Nucleotidases; Rectal Neoplasms; Rectum

Histochemical studies of human breast tumors were performed with particular emphasis on the activity of alkaline phosphatase (AIP), acid phosphatase (AcP) and glucose-6-phosphate dehydrogenase (G6PDH). Enzyme activities in benign and malignant lesions were compared. AIP was prominent in normal mammary epithelium, limited to the myoepithelial layer in benign tumors and was absent in cords of malignant cells. AcP activity was faintly detected in normal mammary epithelium, increased in canalicular epithelium of fibroadenomas and was marked in malignant cells. G6PDH exhibited marked activity in neoplastic epithelium and the stroma of nearly all carcinomas studied, whereas in benign tumors, G6PDH activity was strictly limited to the connective tissue. The study suggests a strong correlation between G6PDH activity and malignancy. The different results obtained by various workers in this field are critically reviewed, and discussed in the light of the results of the present study.

Topics: Acid Phosphatase; Adenofibroma; Adolescent; Adult; Aged; Alkaline Phosphatase; Biopsy; Breast; Breast Neoplasms; Carcinoma; Epithelial Cells; Epithelium; Female; Glucosephosphate Dehydrogenase; Histocytochemistry; Humans; Lactation; Middle Aged; Pregnancy

Topics: Acid Phosphatase; Arylsulfatases; Breast Neoplasms; Carboxylic Ester Hydrolases; Colonic Neoplasms; Epithelial Cells; Epithelium; Galactosidases; Glucuronidase; Humans; Hydrolases; Lysosomes; Sulfatases

Elevated levels of glycoprotein:sialyltransferase activity (EC 2.4.99.1; CMP-N-acetylneuraminate: D-galactosyl-glycoprotein N-acetylneuraminyltransferase) were found in human malignant neoplastic tissues compared to normal, benign, and "preneoplastic" tissues. This increase was not due to the cell density of the tissue. Elevated levels of certain proteases and glycosidases were also found. The increase in transferase activity may be associated with altered membrane synthesis in the neoplastic state; changes in the activity of degradative enzymes may be associated with tumor invasiveness and maintenance of the neoplastic state. Measurements on human tumors are possibly more directly relevant to cancer than those described for transformed fibroblastic cells in vitro.

Topics: Acid Phosphatase; Adenocarcinoma; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Colonic Neoplasms; Female; Fucose; Galactosamine; Galactosidases; Glycoproteins; Glycoside Hydrolases; Hexosaminidases; Humans; Mannose; Neoplasm Metastasis; Neuraminic Acids; Neuraminidase; Peptide Hydrolases; Teratoma; Transferases

Topics: Acid Phosphatase; Adolescent; Adult; Age Factors; Animals; Animals, Newborn; Antibodies, Neoplasm; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Cell Line; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Hodgkin Disease; Humans; Infant; Leukemia; Lung Neoplasms; Lysosomes; Male; Melanoma; Microscopy, Electron; Middle Aged; Osteosarcoma; Rats; Sarcoma; Sex Factors; Statistics as Topic

Topics: Acid Phosphatase; Aged; Biopsy; Breast Neoplasms; Carcinoid Tumor; Castration; Diethylstilbestrol; Humans; Male; Mastectomy; Neoplasm Metastasis; Prostatic Neoplasms; Urination Disorders

Topics: Acid Phosphatase; Animals; Bone and Bones; Breast Neoplasms; Female; Histocytochemistry; Humans; Lactation; Mammary Glands, Animal; Organophosphonates; Pregnancy; Radionuclide Imaging; Rats; Technetium

Topics: Acid Phosphatase; Adenofibroma; Adult; Aged; Alkaline Phosphatase; Biopsy; Breast Diseases; Breast Neoplasms; Capillaries; Cell Division; Epithelial Cells; Epithelium; Female; Fibroblasts; Glucosephosphate Dehydrogenase; Glycerolphosphate Dehydrogenase; Gynecomastia; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; NADH, NADPH Oxidoreductases; Oxidoreductases; Staining and Labeling; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Clinical Enzyme Tests; Diagnosis, Differential; Esophageal Neoplasms; Hodgkin Disease; Humans; Leukocytes; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Rectal Neoplasms; Stomach Neoplasms

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; 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; Animals; Breast Neoplasms; Bromine; Carcinoma; Electrophoresis, Polyacrylamide Gel; Galactosidases; Glucuronidase; Histocytochemistry; Immunodiffusion; Immunoelectrophoresis; Lysosomes; Methods; Naphthols; Neoplasms, Experimental; Rabbits; Staining and Labeling

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; Adenocarcinoma; Aged; Biopsy; Breast; Breast Neoplasms; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Adenofibroma; Breast; Breast Diseases; Breast Neoplasms; Cysts; Epithelium; Esterases; Female; Histocytochemistry; Humans; Methods; Staining and Labeling; Ubiquinone

Topics: Acid Phosphatase; Adenocarcinoma, Scirrhous; Adenosine Triphosphatases; Age Factors; Alkaline Phosphatase; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Cell Nucleus; Cell Transformation, Neoplastic; Cytoplasm

Seven typical granular cell myoblastomas, 4 from the skin (2 multicentric) and 1 each from the tongue, vulva and breast, were studied with the electron microscope and with cytochemical procedures for the visualization of lysosomes, endoplasmic reticulum, mitochondria, Golgi apparatus and membranes. With these parameters, all of the lesions were found to be virtually identical. To the authors' knowledge, the apparent formation of the specific small granule from the Golgi apparatus and the large granule (cytolysome) by segregation of portions of cell cytoplasm as well as the apparent aging process in myoblastoma cells is described for the first time. The small granules resemble lysosomes, but do not stain with the lysosomal markers employed. The large granules (cytolysomes) contain acid phosphatase but only a few contain thiolacetic acid esterase activity, suggesting that there are at least two varieties of cytolysomes in myoblastoma. It is concluded that myoblastoma is a tumor-like lesion of Schwann cell origin, which is either a reactive cellular response or, more likely, a true neoplasm.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adult; Aging; Alcohol Oxidoreductases; Alkaline Phosphatase; Breast Neoplasms; Child; Endoplasmic Reticulum; Female; Golgi Apparatus; Histocytochemistry; Humans; Lysosomes; Male; Methods; Microscopy, Electron; Middle Aged; Mitochondria; Neoplasms, Muscle Tissue; Phosphoric Monoester Hydrolases; Schwann Cells; Skin Neoplasms; Tongue Neoplasms; Vulvar Neoplasms

Topics: Acid Phosphatase; Biliary Tract Diseases; Blood Platelets; Bone and Bones; Breast Neoplasms; Erythrocytes; False Positive Reactions; Female; Formaldehyde; Humans; Hydrogen-Ion Concentration; Kidney; Kidney Diseases; Liver; Liver Diseases; Male; Neoplasms; Phenolphthaleins; Phosphates; Prostate; Prostatic Diseases; Prostatic Neoplasms; Tartrates

Topics: Acid Phosphatase; Adenocarcinoma; Breast Neoplasms; Castration; Estrogens; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms; Staining and Labeling

Topics: Acid Phosphatase; Adenofibroma; Adult; Aged; Alkaline Phosphatase; Breast Neoplasms; Dihydrolipoamide Dehydrogenase; Female; Glucosephosphate Dehydrogenase; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Middle Aged; Succinate Dehydrogenase

Topics: ABO Blood-Group System; Acid Phosphatase; Adult; Alkaline Phosphatase; Blood Group Antigens; Brazil; Breast Neoplasms; Child; Diet; Electrophoresis; Female; Genetics, Medical; Hawaii; Humans; Intestines; Isoenzymes; Lewis Blood Group Antigens; Liver Cirrhosis; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Phosphoric Monoester Hydrolases; Placenta; Pregnancy; Saliva; Stomach Neoplasms; Sweden; Tartrates

Topics: Acid Phosphatase; Blood Platelets; Breast Neoplasms; Buffers; Citrates; Cystic Fibrosis; Female; Heart Failure; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Male; Phosphates; Prostate; Prostatic Diseases; Prostatic Neoplasms; Spectrophotometry; Stomach Neoplasms

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; Alkaline Phosphatase; Blood Sedimentation; Breast Neoplasms; Calcium; Female; Humans; Neoplasm Metastasis; Phosphorus; Radiography

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Humans; Hyperparathyroidism; Leucyl Aminopeptidase; Osteoblasts; Osteoclasts; Osteoporosis

Topics: Acid Phosphatase; Adenofibroma; Alkaline Phosphatase; Ameloblastoma; Aminopeptidases; Animals; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Glucosephosphate Dehydrogenase; Glucuronidase; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Malate Dehydrogenase; Male; Mice; Mouth Neoplasms; Sarcoma, Experimental; Skin Neoplasms; Succinate Dehydrogenase; Tumor Virus Infections

Topics: Acid Phosphatase; Animals; Brain Neoplasms; Breast Neoplasms; Esterases; Female; Granulation Tissue; Granuloma, Giant Cell; Histocytochemistry; Hodgkin Disease; Humans; Hydrolases; Leucyl Aminopeptidase; Neoplasms; Ovarian Neoplasms; Oxidoreductases; Rats

Topics: Acid Phosphatase; Breast Neoplasms; Humans; L-Lactate Dehydrogenase; Neoplasm Metastasis; Phosphorus Isotopes; Transaminases

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

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone and Bones; Bone Marrow; Breast Neoplasms; Calcinosis; Calcium; Cortisone; Dihydrotachysterol; Estrone; Femur; Humans; Hydrocortisone; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Neoplasm Transplantation; Pharmacology; Rats; Research

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Breast Neoplasms; Fibrosarcoma; Humans; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Ribonucleases

Topics: Acid Phosphatase; Adenocarcinoma; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Biochemical Phenomena; Biochemistry; Breast Neoplasms; Diethylstilbestrol; DNA; DNA, Neoplasm; Humans; Hydrocortisone; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Neoplasms; Nitrogen; Nucleotidases; Pharmacology; Progesterone; Rats; Research; RNA; RNA, Neoplasm; Testosterone

Topics: Acid Phosphatase; Alkaline Phosphatase; Aminopeptidases; Animals; Breast Neoplasms; Esterases; Glucuronidase; Histocytochemistry; Humans; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Research

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Amylases; Aspartate Aminotransferases; Breast Neoplasms; Clinical Enzyme Tests; Colonic Neoplasms; D-Alanine Transaminase; Humans; L-Lactate Dehydrogenase; Lipase; Lung Neoplasms; Male; Pancreatic Neoplasms; Stomach Neoplasms; Testicular Neoplasms

Topics: Acid Phosphatase; Breast; Breast Neoplasms; Glycoside Hydrolases; Humans; Intramolecular Transferases; Isomerases; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Breast; Breast Neoplasms; Glycoside Hydrolases; Humans; Intramolecular Transferases; Isomerases; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Breast; Breast Neoplasms; Carcinoma; Glycoside Hydrolases; Humans; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Body Fluids; Breast Neoplasms; Humans; Hypertrophy; Male; Phosphoric Monoester Hydrolases; Prostatic Hyperplasia; Prostatic Neoplasms; Urine