Phosphorus-32-chromic phosphate for ovarian cancer: I. Fractionated low-dose intraperitoneal treatments in conjunction with platinum analog chemotherapy.

UNLABELLED: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Optimization of the production of hCG beta-like material by CaSki human cervical carcinoma cells in roller bottle culture.

This study was aimed at optimizing large-scale roller bottle culture conditions for CaSki human cervical carcinoma cells, to produce ectopic hCG beta-like material in quantities sufficient for subsequent characterization studies. Several cell culture techniques contributed to the achievement of this goal: (1) use of serum-free culture medium; (2) use of intermittent recovery periods in presence of serum; and (3) ultrafiltration of the serum-free medium pool for initial concentration of 100-fold.

Choriocarcinoma: blocking factor and monoclonal antibody iodine 131 imaging.

Postoperative iodine 131 monoclonal antibody localization in metastatic choriocarcinoma was accomplished in this study. The monoclonal antibody was prepared to male choriocarcinoma which cross reacted with gestational choriocarcinoma. The antibody was raised against whole choriocarcinoma cells and human chorionic gonadotropin (hCG) cross reactivity was excluded. The purified antibody was iodinated with 131I and successfully imaged BeWo choriocarcinoma transplanted in nude mice; however, imaging of choriocarcinoma in a patient was verified only after resection. It is our belief that failure to sufficiently concentrate the antibody in the tumor before operation was due to blocking factor in the serum of the patient. Blocking factor and hCG dropped postoperatively. Blocking factor activity in 15 patients with metastatic trophoblastic disease was monitored and, like hCG, was found to be a sensitive indicator of the presence of disease. Its efficacy may be in the small number of patients without hCG but with persistent disease.

A human parathyroid carcinoma that produces parathyroid hormone: long term maintenance in tissue culture.

Parathyroid carcinoma cells from a pulmonary metastasis of a patient with a serum Ca of 17 mg/dl and an immunoreactive parathyroid hormone (PTH) of 6.4 ng eq bovine (b) PTH/ml (normal 40--400 pg/ml) have been maintained in tissue culture for more than 2 1/2 years. The cells secrete PTH into the culture media that 1) during immunoassay dilutes in parallel to human hyperparathyroid serum, 2) has a molecular weight similar to intact highly purified bPTH, and 3) stimulates bone resorption in a manner that is equivalent and additive to synthetic bPTH-(1--34).

Human chorionic gonadotropin in BeWo trophoblastic cells after 12 years in continuous culture: retention of intact human chorionic gonadotropin secretion in mechanically versus enzyme-dispersed cells.

Gel filtration and radioimmunological studies were used to demonstrate that BeWo malignant trophoblastic cells, subcultured for more than 12 yr as roller tube colonies using dissection by scalpel, retained the ability to secrete large quantities of intact hCG. By contrast, BeWo cells that had been subcultured weekly for 12 hr using proteolytic enzyme dispersion lost their ability to secrete intact hCG. Rather, a large form of hCG-alpha was the major secretory product, along with lesser amounts of heterogeneous low molecular weight forms of hCG-beta. The gradual loss of hormone secretory ability and fidelity of hormone product by cells in continuous culture is a well known phenomenon. Our results suggest that the habitual use of trypsin-EDTA to subculture cells may accelerate this process.

Immunodiagnosis in ovarian cancer: blocking factor activity.

Tumor immunology studies have been utilized for development of a blocking factor assay for therapy monitoring in ovarian cancer. The blocking factor index was defined as the arithmetic difference between assays conducted in the presence and absence of the patient's serum compared to incubations with normal control lymphocytes. Eighteen advanced ovarian epithelial malignancies have shown blocking factor activity during treatment. Blocking factor has abated in eight patients whose clinical disease completely regressed. Chemotherapy was discontinued after 18 to 24 months. In 10 patients, blocking factor persisted and chemotherapy has been continued. Some of these patients showed decreasing blocking factor; others have shown increases, which led to death due to disseminated disease in four cases. Blocking factor activity was found to correlate with tumor growth.

Expression of cell-mediated immunity and blocking factor using a new line of ovarian cancer cells in vitro.

A cell-mediated cytotoxicity test, quantitated by postlabeling with tritiated thymidine, was used to asses immune reactivity of cancer patients to the HeW cell line derived from serous cystadenocarcinoma of the ovary. Lymphocytes from 71.4% of serous and mucinous cystadenocarcinoma patients demonstrated a cytotoxic response towards the HeW cells, whereas no reactivity was observed towards target cells derived from nonovarian cancer. These observations indicated that the HeW cells express tumor-associated antigen. In some patients bearing similar tumors, cytotoxicity was blocked by ascitic fluid from other patients with cystadenocarcinoma. In addition, antigen obtained from the spent culture fluid of HeW cells exhibited blocking activity in a typical dose-response fashion, suggesting that blocking factor may be free tumor-associated antigen or an antigen-specific suppressor molecule. Thus, blocking of the lymphocytotoxic response of cystadenocarcinoma patients towards HeW cells may be utilized to monitor the isolation of ovarian carcinoma-associated antigen.

Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line.

Epidermoid cervical carcinoma cells (CaSki line) have been established in continuous culture. When leukocytes from cervical cancer patients were incubated with CaSki culture fluid concentrates, inhibition of leukocyte migration was observed in more than 70 percent of the patients tested. By contrast, significantly less inhibition was observed with normal donor leukocytes or leukocytes from patients with other types of cancer. These results were consistent with the expression of tumor-associated antigen by CaSki cells. Analysis of the serum from the donor of the cell line at the time of tumor biopsy, and of CaSki culture fluids, demonstrated the presence of the beta subunit of human chorionic gonadotropin.