phosphorus-radioisotopes and Adenocarcinoma

Metabolic radiotherapy is a new therapy for management of bone pain in patients with bone metastatic prostate carcinoma. Strontium-89 and Samarium-153 concentrate in bone metastases and radiate them. A pain decrease is obtained in 60-70% of cases. Side effects are a significant hematological depression without great clinical consequences if good therapeutic indications are respected. Our multidisciplinary experience of these radionuclides in 54 performed treatments shows a rate of good responders of 66% with a rate of excellent results (total decrease of pain) in 47%. The therapeutic effectiveness is correlated with pain intensity measured by Visual Analogic Scale (VAS) and equivalent dose of morphine. Radionuclide therapy should be applied to patients as early as possible after establishment of bone metastases.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Analgesics, Opioid; Bone Neoplasms; Clinical Trials as Topic; Double-Blind Method; Forecasting; France; Hematologic Diseases; Humans; Male; Middle Aged; Organometallic Compounds; Organophosphorus Compounds; Pain; Palliative Care; Phosphorus Radioisotopes; Prospective Studies; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Rhenium; Samarium; Strontium; Strontium Radioisotopes; Treatment Outcome

This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (. Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and. 12 patients with LAPC (median age 69 years [interquartile range 61.5-73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm. EUS-guided

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Male; Pancreatic Neoplasms; Phosphorus Radioisotopes; Pilot Projects; Ultrasonography, Interventional

This prospective randomized trial was undertaken to determine the added efficacy of (32)P in treating locally advanced unresectable pancreatic cancer. Thirty patients with biopsy proven locally advanced unresectable adenocarcinoma of the pancreas were assessable after receiving 5-fluorouracil and radiation therapy with or without (32)P, followed by gemcitabine. Intratumoral (32)P dose was determined by tumor size and volume and was administered at months 0, 1, 2, 6, 7, and 8. Tumor cross-sectional area and liquefaction were determined at intervals by computed tomography scan. Tumor liquefaction occurred in 78% of patients receiving (32)P and in 8% of patients not receiving (32)P, although tumor cross-sectional area did not decrease. Serious adverse events occurred more often per patient for patients receiving (32)P (4.2 +/- 3.1 vs. 1.8 +/- 1.9; p = 0.03) leading to more hospitalizations. Death was because of disease progression (23 patients), gastrointenstinal hemorrhage (4 patients), and stroke (1 patient). One patient not receiving (32)P and one receiving (32)P are alive at 28 and 13 months, respectively. (32)P did not prolong survival (7.4 +/- 5.5 months with (32)P vs. 11.5 +/- 8.0 months without (32)P, p = 0.16). (32)P promoted tumor liquefaction, but did not decrease tumor size. Intratumoral (32)P was associated with more serious adverse events and did not improve survival for locally advanced unresectable pancreatic cancer.

Topics: Adenocarcinoma; Aged; Female; Fluorouracil; Humans; Male; Middle Aged; Pancreatic Neoplasms; Phosphorus Radioisotopes; Prospective Studies; Treatment Outcome

In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival.. Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies.. Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found.. Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Chromium Compounds; Digestive System Neoplasms; Drug Resistance, Neoplasm; Female; Head and Neck Neoplasms; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phosphates; Phosphorus Radioisotopes; Survival Rate

Lung cancer is the leading cause of cancer-related death. Among the new modalities to treat cancer, internal radiotherapy seems to be very promising. However, the achievable dose-rate is two orders of magnitude lower than the one used in conventional external radiotherapy, and data has to be collected to evaluate the cell response to highlight the potential effectiveness of low-dose-rate beta particles irradiation. This work investigates the phosphorus beta irradiation ((32)P) dose response on the clonogenicity of human A549 non-small cell lung adenocarcinoma cells and compares it to high-dose-rate X-irradiations results.. Cell survival was evaluated by a colony forming assay eight days after low-dose-rate (32)P beta irradiations (0.8 Gy/h) and high-dose-rate X-ray irradiations (0.855 Gy/min).. Survival curves were obtained for both types of irradiations, and showed hyper-radiosensitivity at very low doses. Radiosensitivity parameters were obtained by using the linear-quadratic and induced-repair models.. Comparison with high-dose-rate X-rays shows a similar surviving fraction, confirming the effectiveness of beta particles for tumor sterilization.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Beta Particles; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Radiation; Humans; Lung Neoplasms; Phosphorus Radioisotopes; X-Rays

Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope (32)P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the (32)P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different (32)P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of (32)P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients.

Topics: Adenocarcinoma; Autoradiography; Cell Line, Tumor; Colorectal Neoplasms; Electrophoresis, Polyacrylamide Gel; Humans; Peptides; Phosphorus Radioisotopes; Phosphorylation

The rapidly growing field of targeted tumor therapy often utilizes an antibody, sometimes tagged with a tumor-ablating material such as radioisotope, directed against a specific molecule.. This report describes the discovery of nine novel decapeptides which can be radioactively labeled, bind to, and deliver (32)P to colon cancer cells. The decapeptides vary from one another by one to three amino acids and demonstrate vastly different binding abilities. The most avidly binding decapeptide can permanently deliver very high levels of radioisotope to the adenocarcinoma cancer cell lines at an efficiency 35 to 150 times greater than to a variety of other cell types, including cell lines derived from other types of cancer or from normal tissue.. This experimental approach represents a new example of a strategy, termed peptide binding therapy, for the potential treatment of colorectal and other adenocarcinomas.

Topics: Adenocarcinoma; Caco-2 Cells; Cell Line, Tumor; Chemistry, Pharmaceutical; Colonic Neoplasms; Drug Delivery Systems; Drug Design; Humans; Immunotherapy; Medical Oncology; Peptides; Pharmaceutical Preparations; Phosphorus Radioisotopes; Protein Binding; Technology, Pharmaceutical

Lung cancer is the most common cause of cancer death among women in Taiwan. Epidemiological studies of lung cancer in Chinese women indicate that factors other than cigarette smoking are related to lung cancer risk. One such factor may be exposure to carcinogens formed during the cooking of food. The carcinogenic compounds in oil smoke particulates from Chinese cooking practice have not yet been characterized. To reveal the relationship between the high mortality rate of lung cancer in Chinese women and exposure to cooking oil fumes (COF), DNA adduct formation, induced by COF collected from frying fish under domestic conditions, was assessed in human lung adenocarcinoma CL-3 cell lines using the (32)P-postlabeling assay. DNA adduct levels were induced by COF in CL-3 cells in a dose-dependent manner. DNA adducts with a diagonal radioactive zone (DRZ) were observed when CL-3 cells were treated with COF. Surprisingly, only one spot of the DNA adduct profile was in the DRZ. The DNA adduct was analyzed by HPLC coupled with an on-line radioactive detector. The retention time of the major DNA adduct corresponded to that of authentic benzo[a]pyrene 7,8-diol 9, 10-epoxide N2-deoxyguanonsine (BPDE-N2-dG). Moreover, the mass spectrum of the major DNA adduct in CL-3 cells was confirmed to be BPDE-N2-dG by liquid chromatography/mass spectrometry. In conclusion, BPDE-N2-dG adduct formation in human lung cells supports epidemiological findings of an association between cooking fume exposure and lung cancer in Chinese women.

Topics: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; Adenocarcinoma; Air; Carcinogens; Chromatography, High Pressure Liquid; Cooking; Deoxyguanosine; DNA Adducts; Humans; Isotope Labeling; Lung Neoplasms; Mass Spectrometry; Oils; Phosphorus Radioisotopes; Polycyclic Aromatic Hydrocarbons; Tumor Cells, Cultured

To find the mechanisms of the ongoing clinical trials in intralesional colloidal chromic 32P (32P-CP) brachytherapy, the cellular uptake of 32P-CP, changes in tumor interstitial fluid pressure (TIFP), and tumor blood flow (TBF) using two (AsPC-1, Ls174T) human tumors were measured.. After exposure to 32p-CP using exponential and plateau-phase cells, cells were trypsinized at various time intervals, then measured for the levels of radioactivity using a y-counter. Also measured were TIFP using the WIN technique and TBF with laser Doppler flowmetry.. The plateau growth-phase of both tumors showed the maximal uptake of 32P-CP at approximately 100 min. TBF decreased within 10 min after an intratumoral (i.t.) injection of 32P-CP, and reached 75% of control value by 1 h.. If 32P-CP was introduced i.t., it maintained highly efficient tumor targeting, mainly due to two physiological mechanisms: the high adherence of 32P-CP to the infused regions and the reduction in TBF by this therapeutic colloid.

Topics: Adenocarcinoma; Animals; Brachytherapy; Colloids; Colonic Neoplasms; Female; Humans; Injections, Intralesional; Laser-Doppler Flowmetry; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Phosphorus Radioisotopes; Radiotherapy

Gastric cancer is the most common cancer in Korea. The causes are still unknown but it has been speculated that gastric cancer is associated with consumption of foods rich in nitrates/nitrites or a high dietary intake of salt or pickled food. In the present study, we studied the level of alkylated DNA adducts formed in gastric cancer tissues in comparison with that in normal gastric mucosa. DNA was extracted from surgically removed gastric cancer tissues and patient-matched normal gastric mucosa. The level of N7-methyldeoxyguanosine was measured by 32P-postlabelling assay after high performance liquid chromatography (HPLC) enrichment. We found that the level of N7-methyldeoxyguanosine of gastric cancerous tissues was significantly higher than that of normal gastric mucosa (P=0.01685).

Topics: Adenocarcinoma; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Adducts; DNA Damage; DNA Methylation; DNA, Neoplasm; Humans; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Stomach Neoplasms

The purpose of this work is to study the physicochemical properties of Pirocarbotrat to explain its radiopharmacological behavior. We also studied a mixture of charcoal plus chromic [32P]phosphate and charcoal plus sodium [32P]orthophosphate only for comparative purposes. The results show that the mean diameter of the Pirocarbotrat particles was 2.5 microm with an homogeneous distribution, while the other products show an heterogeneous distribution of the particle sizes, with a mean size diameter between 0.5 and 0.9 microm. Hydrolysis studies with a solution of 0.1 N HCl and with sulfochromic mixture revealed that in Pirocarbotrat the 32P is strongly bound to the charcoal particles. Bioelimination studies of Pirocarbotrat show that the total eliminated activity was 12.70 +/- 3.90%, with a higher amount in urine (8.30 +/- 1.80%) than in feces (4.40 +/- 3.50%). When biodistribution studies of Pirocarbotrat were carried out, we found that the 84.50 +/- 2.60% of the activity remained in the tumor with almost null irradiation of the other organs under study. When therapeutic action was evaluated, we observed that the percentage of tumor regression was 78.3% for the tumors injected with Pirocarbotrat. The other dispersions under study showed different behaviors with high activity percentages distributed throughout the organism. These studies demonstrate that Pirocarbotrat has the best radiopharmacological properties to ensure irradiation of the tumor with the least concomitant irradiation of surroundings or other organs or tissues.

Topics: Adenocarcinoma; Animals; Charcoal; Female; Mammary Neoplasms, Experimental; Metabolic Clearance Rate; Methylnitrosourea; Phosphates; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Tissue Distribution

6-aminonicotinamide (6AN) has been shown to enhance radiosensitivity in vitro, although previous in vivo studies failed to show an effect. 31P NMR spectra were obtained by using a one-dimensional chemical shift imaging technique on a first generation transplant of the CD8FI spontaneous mammary carcinoma tumor model. Spectra were obtained both before and 10 h after treatment with 6AN (20 mg/kg). Changes in pH, nucleoside triphosphate/inorganic phosphate, and phosphocreatine/ inorganic phosphate measured at 10 h post-6AN were not significant. A new peak was detected 10 h post-6AN, which was assigned to 6-phosphogluconate (6PG), indicating inhibition of the pentose phosphate pathway (PPP). Based on the spectral data demonstrating inhibition of the PPP at 10 h post-6AN, tumor-bearing mice were irradiated (15 Gy x 3 fractions) on Days 1, 10 or 11, and 21 10 h after administration of 6-aminonicotinamide (20 mg/kg). Tumor-bearing mice receiving 6AN alone (20 mg/kg x 3), radiation alone (15 Gy x 3), or saline were also studied. Tumor growth delay studies indicated that 6AN alone induced a small but significant tumor growth delay (4.3 +/- 0.8 days). Radiation alone induced a tumor growth delay of 34.5 +/- 2.7 days. Treatment with 6AN followed by radiation induced a tumor growth delay of 57.0 +/- 3.8 days. This was significantly greater than the TGD values for treatment with 6AN alone or radiation (P < 0.01). No complete regressions were noted after treatment with 6AN or radiation alone. Concomitant therapy with 6AN plus radiation yielded 6/28 complete regressions (21%), which was significantly greater than radiation (P < 0.05) or 6AN alone (P < 0.01) on this mammary carcinoma.

Topics: 6-Aminonicotinamide; Adenocarcinoma; Animals; Combined Modality Therapy; Female; Gluconates; Magnetic Resonance Spectroscopy; Mammary Neoplasms, Experimental; Mice; Neoplasm Transplantation; Pentose Phosphate Pathway; Phosphorus Radioisotopes; Teratogens

In order to evaluate the effectiveness of an intratumorally single dose of chromic [32P] phosphate for the treatment of solid tumors, studies of bioelimination, biodistribution, and therapeutic action were carried out. Only for comparative purposes were similar studies undertaken using a solution of sodium [32P] orthophosphate-gelatin. Results show that when sodium [32P] orthophosphate-gelatin was intratumorally injected, the percentage of total elimination, after 32 days of treatment, was equal to 85.90 +/- 8.70%, with a higher percentage in urine (64.50 +/- 13.70%) than in feces (21.40 +/- 4.50%). In biodistribution studies, the greater percentage was found in bone (15.54 +/- 2.21%), whereas only 2.51 +/- 0.39% remained in the tumor. When chromic [32P] phosphate was intratumorally injected, we found that the total elimination was equal to 51.70 +/- 6.90%, with a higher amount in feces (32.70 +/- 4.80%) than in urine (19.00 +/- 3.60%). Biodistribution studies demonstrated that 28.93 +/- 1.30% was still in the tumor and 19.01 +/- 1.30% of the injected activity was found in the liver. On the other hand, when therapeutic action was evaluated, no tumoral regression was observed. These results demonstrate that the colloid of chromic [32P] phosphate cannot be used in the treatment of solid tumors as it mobilizes from the injection point, delivering a high dose to the entire organism.

Topics: Adenocarcinoma; Animals; Chromium Compounds; Colloids; Female; Mammary Neoplasms, Experimental; Metabolic Clearance Rate; Phosphates; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Tissue Distribution

Treatment with estradiol-17 beta and testosterone induces epithelial dysplasia and, subsequently, adenocarcinoma in the dorsolateral prostate of NBL rats. The purpose of this study was to determine whether this carcinogenic effect is mediated by genotoxicity. Analogous to adducts produced by estrogens in the male hamster kidney, a target of estrogen carcinogenicity, induction of DNA adducts detectable by 32P-postlabeling was investigated in the prostate target tissue. NBL rats were treated with separate Silastic tubing implants containing testosterone and estradiol-17 beta. Control animals received empty implants. Animals were killed at 8, 16 and 24 weeks after initiation of treatment, and accessory sex glands were sampled for adduct analysis. DNA of the dorsolateral and ventral prostate and the coagulating gland (= anterior prostate) was isolated and analyzed by nuclease P1-enhancement of the 32P-post-labeling assay. DNA adducts were quantitated by Cerenkov counting. An adduct occurred selectively in DNA of the dorsolateral prostate of rats treated with estradiol plus testosterone for 16 or 24 weeks with relative adduct level values of approximately 10 x 10(9), but not in DNA of the ventral or anterior prostate. The adduct was not present in DNA of prostate tissue of rats treated for 8 weeks or in DNA of control tissues. This adduct was unique with respect to chromatographic location and has not been observed before in any tissue of control or hormone-treated animals. Neither the structure of the treatment-induced adduct nor the mechanism of its formation is known. However, the selective occurrence of this adduct in the tissue of origin of the carcinomas and its appearance coinciding with putative preneoplastic lesions and preceding carcinoma development suggests a causal relation between adduct formation and prostate cancer development in testosterone plus estradiol-17 beta-treated rats.

Topics: Adenocarcinoma; Animals; Autoradiography; Cricetinae; DNA; DNA Adducts; Estradiol; Male; Phosphorus Radioisotopes; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

For many years, 32P-chromic phosphate (32P-CP) intraperitoneal instillations and platinum analogue chemotherapy have been used to treat disseminated ovarian cancer. To investigate possible enhancement of 32P-CP irradiation due to the concomitant administration of chemotherapy, in vitro studies were undertaken. Based on those laboratory investigations, a clinical regimen of combined 32P-CP and platinum analogue chemotherapy was developed.. In vitro enhancement of 32P-CP cytotoxicity by cisplatin was studied in cultured human ovarian adenocarcinoma (CHOA) cell lines and in a fibroblast cell strain. In addition, ovarian cancer cells obtained from the malignant abdominal ascites and pleural effusions of 10 individual patients were also studied ex vivo. As part of routine clinical care, 30 patients with disseminated ovarian adenocarcinoma underwent up to eight monthly cycles of platinum analogue chemotherapy with concomitant intraperitoneal instillation of 5 mCi of 32P-CP at each monthly chemotherapy cycle.. There was an enhanced and possibly supra-additive effect of cisplatin on the cytotoxicity from 32P-CP irradiation. For the 30 patients, the survival rate at 3 yr was 63%.. Phosphorus-32 CP low-dose intraperitoneal treatments in conjunction with platinum analogue chemotherapy is a promising approach for the treatment of disseminated intraperitoneal ovarian cancer.

Topics: Adenocarcinoma; Cell Survival; Chromium Compounds; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Radiotherapy Dosage; Survival Rate; Tumor Cells, Cultured

We report a patient with well-differentiated adenocarcinoma of the endometrium who developed a recurrence in the anterior abdominal wall probably secondary to wound seeding at the time of her original surgery. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy. She then received 15 mCi of 32P for positive peritoneal washings. She was free of disease until 2 years later when a large lower incision mass developed. She had no evidence for intra-abdominal disease and a radical resection with a myocutaneous flap was undertaken. Radical resection for isolated metastases may be of benefit for patients with endometrial cancer. Patients with positive cytology should be observed closely for incisional recurrence.

Topics: Adenocarcinoma; Adult; Endometrial Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Seeding; Phosphorus Radioisotopes

DNA of normal mucosa and the adjacent muscular layer from 18 adults suffering from colorectal neoplasms was examined by 32P-post-labeling analysis in order to estimate the exposure of the human colon and rectum to environmental carcinogens. Colorectal DNA samples obtained from six newborns were also examined as a normal control because they were presumed to have been minimally exposed to environmental carcinogens. One common mucosa-specific DNA adduct was found in the normal colorectal wall in all adults at the level of 0.10-34.13 adducts/10(8) nucleotides (mean +/- SD: 3.64 +/- 7.92 adducts/10(8) nucleotides), however, these were absent from the newborns' colons. Although several common spots were present in the mucosa, muscular layer and newborn tissues, there was no muscular layer-specific DNA adduct. The relationship between the levels of the mucosa-specific DNA adduct in the non-cancerous part and the histological degree of malignancy was not significant. The presence of this mucosa-specific DNA adduct in adult colon suggests that the human colon is commonly exposed mainly to one environmental carcinogen. This carcinogen is supposed to originate from foods, because the incidence of colorectal carcinoma is closely linked to dietary habits and the mucosa-specific DNA adduct was not present in newborns who had never ingested food. The incidence of adult colonic cancer originating from its mucosa is high, while cases of muscular origin or in newborn colon are rare. Therefore, the mucosa-specific DNA adduct is presumably responsible for the development of colonic cancer of epithelial origin.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinogens; Colon; Colorectal Neoplasms; DNA; Female; Humans; Infant, Newborn; Intestinal Mucosa; Isotope Labeling; Male; Middle Aged; Phosphorus Radioisotopes; Rectum; Sensitivity and Specificity

The cycle of phospholipid turnover has been found to be under the negative control of hormonal cytostatics (progesterone) and under the positive control of proliferation stimulants (17 beta-estradiol, epidermal growth factor). Specific changes in the synthesis of phospholipids are shown when tamoxiphen, an antiestrogen and an inhibitor of protein kinase C, was used. The findings suggest that changes in the turnover rate of phospholipids are one of the key stages of steroid action on target cells and may be regarded as an additional criterion of tumor genetic sensibility.

Topics: Adenocarcinoma; Breast Neoplasms; Drug Screening Assays, Antitumor; Epidermal Growth Factor; Estradiol; Female; Humans; Phospholipids; Phosphorus Radioisotopes; Progesterone; Protein Kinase C; Tamoxifen; Tumor Cells, Cultured; Uterine Neoplasms

The in vitro effects of the epidermal growth factor (EGF) and progesterone on phospholipid turnover in cells of 19 human adenocarcinomas (postsurgical material) have been studied. In 58% of tumours EGF increased the 32P incorporation into two basic cell phospholipids--phosphatidylcholine and phosphoinositides. In EGF-insensitive cells progesterone induced no noticeable changes in the basal level of phospholipid metabolism. However, in 10 out of 11 positively responding to EGF adenocarcinomas progesterone inhibited the EGF-dependent activation of 32P incorporation into the phospholipids already on the 15th min after its addition to the cells. Analysis of effects of EGF and the anti-estrogen drug tamoxifen on phospholipid turnover in 22 human mammary tumours did not reveal any significant differences in tamoxifen effect on tumour cells differing in their sensitivity to EGF. Independently of cell sensitivity to EGF, tamoxifen caused some decrease in the 32P incorporation into phosphatidylcholine but increased the label incorporation into phosphoinositides. Tamoxifen added to tumour cells prestimulated with EGF or 17 beta-estradiol failed to abrogate the effect of these compounds on phospholipid turnover. At the same time, treatment of cells with the protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate fully inhibited the effect of tamoxifen on phospholipid metabolism. The results obtained suggest that the EGF-dependent activation of intracellular phospholipid turnover is under the negative control of progesterone. As for tamoxifen, its effect on cells is independent of EGF and consists, apparently, in the inhibition of protein kinase C activity.

Topics: Adenocarcinoma; Breast Neoplasms; Chromatography, Thin Layer; Epidermal Growth Factor; Estradiol; Female; Humans; Phospholipids; Phosphorus Radioisotopes; Progesterone; Tamoxifen; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Uterine Neoplasms

From 1975 to 1982, 25 evaluable patients with FIGO Stage I ovarian cancer were treated with intraperitoneal chromic phosphate (32P). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy with (28%) or without (72%) omentectomy, with no other surgical staging procedures prior to referral. Patients were restaged by laparoscopy (inspection of diaphragms, abdomen, and pelvis), biopsy of suspicious lesions, and peritoneal cytologic washings prior to intraperitoneal chromic phosphate therapy. For the 25 patients, the estimated 5- and 10-year recurrence-free rates and the 5- and 10-year survival rates are 84% and 75%, respectively. Excellent 10-year recurrence-free rates were achieved for Stages IA and IC, nonruptured cysts, and Grade I and II tumors. In contrast, very low 10-year survival rates were achieved for patients with Stage IB, ruptured cysts, or Grade III tumors.

Topics: Adenocarcinoma; Adult; Aged; Chromium; Chromium Compounds; Female; Humans; Injections, Intraperitoneal; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prospective Studies; Time Factors

The use of intraperitoneal radioisotopes in the management of women with ovarian cancer is controversial. We analyzed the experience with intraperitoneal chromic phosphate P 32 at our institution, from October 1979 to February 1983, in 22 patients with various stages and grades of ovarian malignancy. Survival in stage I is 87.5% and in stage II, 50%. Survival is 88.9% among patients with grade 1 tumors and 33.3% for those with grade 3 lesions. Morbidity related to chromic phosphate P 32 was minimal; small bowel obstruction occurred in only one patient who had also received external pelvic irradiation. Our results suggest that chromic phosphate P 32 is a safe, well tolerated, inexpensive, and effective adjuvant to surgery in the management of selected patients with ovarian malignancy.

Topics: Adenocarcinoma; Brachytherapy; Chromium; Chromium Compounds; Cystadenocarcinoma; Endometriosis; Female; Humans; Middle Aged; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes

Thirty-four patients with fallopian tube cancer were evaluated at the Mayo Clinic between 1964 and 1985 and received radiation therapy postoperatively. Employing a system analogous to FIGO ovarian cancer staging, there were 9 patients with stage I disease, 13 with stage II, and 12 with stage III/IV. Residual disease was present in 15 patients and absent in 19. Nodal metastases were documented in 12 patients or 35% (10 at presentation, two at relapse), with para-aortic nodes most commonly involved (67%) and 7 of the 12 having disease otherwise limited to the pelvis at presentation. Fifteen of 34 (44%) patients survived disease-free until intercurrent death or to a median follow-up of 70 months. Seven patients were treated with palliative intent for massive disease, and 27 patients were treated with curative intent (21 radiation alone, six radiation plus chemotherapy). Of those treated with curative intent, 15 patients received pelvic irradiation (with or without para-aortic nodal irradiation), 10 received whole abdominal irradiation, and 2 received intraperitoneal radiophosphorus. In the potentially curative group, seven of nine (78%) patients with stage I disease, five of 12 (42%) with stage II, and 2 of 6 (33%) with stage III have remained disease-free. Among the 21 patients with stage I or II disease, only four of the 11 (36%) patients who received pelvic irradiation alone were disease-free, but four patients had an isolated upper abdominal failure. In contrast, eight of 10 (80%) patients receiving treatment to the entire abdomen (including two patients who received 32P) were disease-free.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Evaluation Studies as Topic; Fallopian Tube Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Phosphorus Radioisotopes

Malignant peritoneal cytology in patients with endometrial carcinoma is a poor prognostic feature, identifying patients at high risk for early intra-abdominal recurrence. Between 1977 and January, 1983, 65 women with endometrial carcinoma who had malignant peritoneal cytology were treated with adjuvant intraperitoneal radioactive chromic phosphate P 32 suspension. Fifty-three patients (80%) were clinical Stage I, nine (14%) were Stage II, and three (7%) were clinical Stage III. Life-table estimates of disease-free survival were 89% for clinical Stage I patients and 94% for surgical Stage I patients beyond 24 months. One patient developed an intraperitoneal recurrence, four had simultaneous intraperitoneal and extraperitoneal recurrences, and six developed recurrences outside of the peritoneal cavity. Few significant acute complications occurred after therapy with radioactive chromic phosphate P 32 suspension. Chronic intestinal morbidity that required surgical correction was encountered in five of 17 patients (29%) who received adjuvant pelvic radiation, compared to none of the 48 patients (0%) who received only radioactive chromic phosphate P 32 suspension (p less than 0.001). Intraperitoneal instillation of radioactive chromic phosphate P 32 suspension is effective therapy for patients with malignant peritoneal cytology from endometrial carcinoma. Caution should be exercised when radioactive chromic phosphate P 32 suspension and external radiation therapy are combined.

Topics: Adenocarcinoma; Brachytherapy; Catheters, Indwelling; Chromium; Chromium Compounds; Female; Follow-Up Studies; Humans; Hysterectomy; Injections, Intraperitoneal; Neoplasm Recurrence, Local; Neoplasm Staging; Peritoneal Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Uterine Neoplasms

Radionuclide peritoneoscintigraphy has been used prior to chromic phosphate P-32 (P-32CP) intraperitoneal therapy to assure proper placement of the catheter in the peritoneal cavity, to exclude loculation, and to predict inadequate distribution of P-32CP. This is a case report of the detection of a peritoneal catheter improperly placed into the bowel lumen by pretherapy radionuclide peritoneoscintigraphy, and this case demonstrates the distinguishing characteristics of the radiocolloid distribution secondary to an intraluminal injection relative to an intraperitoneal injection.

Topics: Adenocarcinoma; Brachytherapy; Catheterization; Chromium; Chromium Compounds; Colonic Neoplasms; Female; Humans; Middle Aged; Peritoneal Cavity; Peritoneal Neoplasms; Phosphates; Phosphorus Radioisotopes; Radionuclide Imaging; Technetium Tc 99m Sulfur Colloid

In the urological department of the Wilhelminenspital altogether 22 patients with incurable bone pains in metastasizing carcinoma were treated with radioisotopes between 1976 and 1980. 32P and 89Sr were used in a dosage of 3 times 3 mCi and once 1 mCi. A reaction to the therapy could be proved in 46%, in 23% the success could be estimated as very good. Clinic and therapy were discussed with the help of own cases and literature.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Carcinoma; Female; Humans; Kidney Neoplasms; Male; Neoplasm Staging; Palliative Care; Phosphorus Radioisotopes; Prostatic Neoplasms; Strontium Radioisotopes

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.

Topics: Adenocarcinoma; Ascitic Fluid; Chromium; Chromium Compounds; Female; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Uterine Cervical Neoplasms; Uterine Neoplasms

In an initial safety study, phosphorus-32 (as diphosphonate) was administered intravenously to five patients with painful bone metastases from prostatic carcinoma; two patients received 9 mCi and three were given 3 mCi. Hematological, biochemical, ECG, x-ray, bone-scan data, and clinical observation, were followed for 2 mo. At both dose levels, bone-marrow depression was noted. One of the patients, who received 9 mCi, had only a slight dip in the levels of circulating white blood cells and platelets. The other 9-mCi patient was the only one with discrete metastases by bone scan; he had bone-marrow depression, from which he recovered, and was the only one of the five who had relief of bone pain.

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Etidronic Acid; Humans; Male; Middle Aged; Neoplasm Metastasis; Phosphorus Radioisotopes; Prostatic Neoplasms; Radiotherapy Dosage

Forty-one cases of primary fallopian tube carcinoma treated at our institution over the years 1946 to 1976 are described. The overall 5-year survival rate was 34.4%, although patients with early tumors had a 72.7% survival rate. The single most important factor affecting survival appeared to be the extent of disease at the time of diagnosis. Past and present treatment modalities are discussed, and proposals for management of this disease are outlined.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; British Columbia; Dilatation and Curettage; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Staging; Phosphorus Radioisotopes; Radiotherapy, High-Energy

Six carcinomas of the canine thyroid were studied. Five of the six tumors were functional on 131I scan and caused hyperthyroidism in two cases. The tumors were all of predominantly compact cellular histology with rare to moderate numbers of microfollicles. After surgical removal tumor slices were incubated with 32P in Krebs-Ringer-tris buffer with or without 0.1 U/ml of bovine TSH, and the specific activity of the extracted phospholipids was measured. TSH stimulated phosphatide turnover clearly in 5 cases and probably also in the 6th. Analysis of fractionated phospholipids in 2 cases showed that the response to TSH was mainly in the phosphatidic acid and phosphatidylinositol. These studies show that a malignant tumor may still retain at least one complete control system extending from TSH receptors to the final metabolic response.

Topics: Adenocarcinoma; Animals; Dogs; Histocytochemistry; Phosphates; Phospholipids; Phosphorus Radioisotopes; Thyroid Gland; Thyroid Neoplasms; Thyrotropin

Arterial vascular occlusion of hypernephromas may be performed by obstructiing the tumor vascular tree with the injection of ferromagnetic silicone microspheres. The powerful superconducting electromagnet confines the embolized iron-silicone compound to the neoplastic target organ. Radioactive material may or may not be added to the iron-silicone compound to give local direct radioactive radiation therapy to the tumor area. In experimental dogs up to 70,000 rad of beta radiation from the P32 source had been delivered homogeneously within the kidney when mixed with the ferrosilicone. This technique may well be used in cases in which a major operation is contraindicated or when preoperative necrosis of the tumor is advisable. Since the entire procedure can be done with the patient under local anesthesia in a radiology department it may be a valuable new technique in the future management of urological tumors, unilateral renal hypertension, solitary kidney pathology and so forth. Ferrosilicone material has not been found to be toxic. The application of a powerful superconducting electromagnet to the technique provides a means of confining the embolized iron-silicone compound to the target organ.

Topics: Adenocarcinoma; Animals; Catheterization; Dogs; Embolism; Evaluation Studies as Topic; Femoral Artery; Humans; Injections, Intra-Arterial; Iron; Kidney; Kidney Neoplasms; Magnetics; Microspheres; Necrosis; Phosphorus Radioisotopes; Renal Artery; Silicones

Topics: Adenocarcinoma; Bone Neoplasms; Hematocrit; Humans; Iodine Radioisotopes; Phosphorus Radioisotopes; Thyroid Neoplasms

Topics: Adenocarcinoma; Aged; Bone Neoplasms; Female; Humans; Iodine Radioisotopes; Neoplasm Metastasis; Palliative Care; Phosphates; Phosphorus Radioisotopes; Technetium; Thyroid Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Castration; Diethylstilbestrol; Estrogens; Humans; Infusions, Parenteral; Iowa; Laminectomy; Male; Middle Aged; Neoplasm Metastasis; Nephrectomy; Paralysis; Paraplegia; Phosphorus Radioisotopes; Prostatic Neoplasms

Topics: Adenocarcinoma; Animals; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Triethylenemelamine

Topics: Adenocarcinoma; Animals; Breast Neoplasms; Cortisone; Humans; Mice; Neoplasm Transplantation; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Adenocarcinoma; Animals; Gastric Balloon; Mice; Phosphorus; Phosphorus Radioisotopes; Stomach Neoplasms