picibanil and Uterine-Neoplasms

Recently, successful treatment of peritonitis carcinomatosa by intraperitoneal administration of lymphokine-activated killer (LAK) cells followed by intraperitoneal recombinant interleukin 2 (rIL-2) has been reported by several authors, in spite of the well documented results of the immunosuppressive activity of malignant ascitic fluid. We investigated the effect of malignant ascitic fluid on in vitro induction of LAK cells obtained from patients' peripheral blood mononuclear cells. We also examined whether Streptococcal preparation OK-432, which has been instilled into the peritoneal cavity to treat malignant ascites, is able to synergize with rIL-2 to induce LAK activity, and the following results were obtained; 1. A little augmentation of LAK activity was observed at a lower concentration of malignant ascitic fluid, while the results were diversified at a concentration higher than 10%. In two cases out of six, a severe suppressive effect was observed at a concentration higher than 40%. At the higher concentration, fewer cells were recovered after a 5 day culture in all cases. 2. No augmentation of LAK activity following the combination of OK-432 with rIL-2 was observed. At a lower concentration of OK-432 (ranging from 0.01-0.04KE/ml), the number of cells increased in comparison with rIL-2 alone. These results suggest that the potential of adoptively transferred LAK cells followed by rIL-2 was not effectively suppressed by malignant ascitic fluid in vivo and that the administration of OK-432 followed by rIL-2 could induce a larger number of various killer cells than rIL-2 alone.

Topics: Ascites; Cytotoxicity, Immunologic; Female; Humans; Interleukin-2; Killer Cells, Lymphokine-Activated; Neutrophils; Ovarian Neoplasms; Picibanil; Tumor Cells, Cultured; Uterine Neoplasms

The natural killer (NK) and antibody-dependent cellular cytotoxic (ADCC) activities were determined in peripheral blood lymphocytes of patients with gynecologic malignancy. The effects of a preparation of Streptococcus pyogenes (OK-432) and of interferon were determined. Patients with advanced cancer exhibited lower natural cytotoxicity than normal women. NK and ADCC activities were decreased following surgery and NK activity was decreased following chemotherapy. Radiation reduced the percentage of Leu-7-positive cells in the circulation of the patients. OK-432 augmented the NK activity of both healthy women and patients with early malignancy. Interferon was less effective than OK-432 in augmenting NK activity.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Cytotoxicity, Immunologic; Female; Flow Cytometry; Genital Neoplasms, Female; Humans; Interferon Type I; Killer Cells, Natural; Middle Aged; Ovarian Neoplasms; Picibanil; T-Lymphocytes; Uterine Cervical Neoplasms; Uterine Neoplasms; Vulvar Neoplasms

Topics: alpha-Fetoproteins; Antibodies; Antineoplastic Agents; Cisplatin; Female; Humans; Ovarian Neoplasms; Picibanil; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

A combination immunochemotherapy regimen containing cisplatin (20 mg, days 1-5), peplomycin (20 mg, days 2, 9, 16), +/- vinblastine (5 mg, days 1, 2), and picibanil (3-5 KE/week) was performed in twelve patients with advanced or recurrent uterine and ovarian cancers under intravenous hyperalimentation (IVH), except one patient receiving peplomycin by a continuous infusion method using IVH bag (10 mg/day for 5 days). This regimen was repeated every three weeks. Five (71.4%) of seven evaluable patients showed partial response. No patients yielded the complete disappearance of disease. No severe and lethal pulmonary or renal dysfunction occurred and all was well tolerated. In a regimen without vinblastine, myelosuppression, especially thrombocytopenia, occurred later compared to the regimen including vinblastine.

Topics: Adenocarcinoma; Aged; Biological Products; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Drug Therapy, Combination; Female; Humans; Immunotherapy; Middle Aged; Ovarian Neoplasms; Peplomycin; Picibanil; Uterine Cervical Neoplasms; Uterine Neoplasms; Vinblastine

We investigated alteration in nonspecific cell-mediated immunity with the progress in the stages of gynecologic cancer, effects of carcinostatics on this alteration, and the significance of immunotherapy given for recovery of the affected cell-mediated immunities for cancers of the uterine neck, uterine body, and ovaries using the count of leukocytes, lymphocytes, T-cells, B-cells, IgGFcR+ T-cells, SI, and ADCC as indicators. The number of T-cells and SI began to decrease from stage I, showing their importance as parameters most accurately reflecting progress of the stage of the cancers. The number of IgGFcR+ T-cells showed no increasing tendency until stage III. ADCC decreased in stage IV, reflecting the pathosis of cancer in the end stage. Alteration in the number of T-cells and SI with time due to administration of carcinostatics has clearly showed that degree of impairment of nonspecific cell-mediated immunity is more dependent upon the kind of carcinostatics that the performance status of subject patients, and administration of ADR, MMC or CQ resulted in decreases not only in the number of T-cells and SI but also in ADCC and number of IgGFcR+ T-cells. Decreases in nonspecific cell-mediated immunity during treatment with such potent carcinostatics could not be prevented with OK-432 and PSK--even an improving tendency was not obtained. These immunotherapeutic agents exerted their effects to activate nonspecific cell-mediated immunity when they were given during the time when carcinostatics were stopped. But it cannot be readily judged whether these activating effects produce improvements in convalescence from gynecologic cancers as a nonspecific active immunotherapy. Follow-up study on effects of the multiple combination therapy should be carefully performed.

Topics: Female; Fluorouracil; Humans; Immunity, Cellular; Leukocyte Count; Mitomycin; Mitomycins; Ovarian Neoplasms; Picibanil; Rosette Formation; T-Lymphocytes; Uterine Neoplasms

The cancer chemotherapy combined with immuno-potentiators, OK-432 and/or PSK, had yielded an improvement in survival rate of choriocarcinoma patients in our clinic as previously reported elsewhere. In the present study, for the purpose of evaluation of direct antitumor activity of OK-432 and PSK, inhibitory effects of the drugs on cell growth of GCH-1 and GCH-2 (in vitro cell lines of human choriocarcinoma) were analyzed referring to those of MTX (methotrexate) and Act-D (actinomycin D). 1) IC 50 (50% inhibitory concentration) of OK-432 and of PSK were 0.56 KE/ml on GCH-1 and 0.48 KE/ml on GCH-2, and 310 micrograms/ml on GCH-1 and 460 micrograms/ml on GCH-2, respectively. 2) The morphological changes of the target cells, observed by light and electron microscope, induced by OK-432 and PSK seemed to be not different from those by MTX and Act-D. 3) Serial changes of hCG levels in the culture media in which OK-432 or PSK was added were roughly comparable with those in MTX or Act-D. Thus, the direct antitumor activity of OK-432 and PSK on GCH-1 and GCH-2 was exquisitely weak judging from their IC50 and it was suggested that their direct antitumor effects in vivo might be clinically negligible in choriocarcinoma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Cell Line; Cell Survival; Choriocarcinoma; Cricetinae; Dactinomycin; Female; Humans; Methotrexate; Mice; Mice, Nude; Picibanil; Pregnancy; Proteoglycans; Uterine Neoplasms

Topics: Adult; Biological Products; Choriocarcinoma; Female; Humans; Middle Aged; Picibanil; Pregnancy; Pregnancy Complications, Neoplastic; Uterine Neoplasms