Eleven patients with advanced ovarian carcinoma who had large quantities of ascites during the course of previous chemotherapy were tested with intraperitoneal injections of tranexamic acid, followed by combination chemotherapy. A 4-g dose of tranexamic acid was administered intraperitoneally every day for at least 2 weeks. Seven out of 11 patients (63.6%) showed changes from positive to negative in Papanicolaou smears of the ascitic fluid after treatment with tranexamic acid. A marked reduction of ascitic fluids was observed in 4 of 11 patients (36.4%). If 2 cases with partial reduction of ascites are included, the response rate improved to 54.5%. Median survival time after initiation of treatment with tranexamic acid was significantly longer in patients with good response to tranexamic acid than in patients with poor response. Proliferation of cells in cultures established from ovarian cancer tissue of a patient with good response to tranexamic acid was inhibited at all concentrations of tranexamic acid used in this study, in contrast to non-inhibition of similar cells cultured from a patient with poor response, at any concentration of tranexamic acid. These results suggest that treatment with tranexamic acid suppresses malignant cells in the ascites, followed by reduction of ascites themselves, and an improvement in the response rate to subsequent chemotherapy.

The present study was designed to elucidate the mechanism of resistance to cisplatin. A cisplatin‐resistant cell line (KFr) was established from KF cells derived from human serous cystadenocarcinoma of the ovary. The DNA histogram revealed an increase of S‐phase cells and a decrease of G1‐phase cells in cultured KFr cells, compared to that in cultured KF cells. Although the cisplatin content in the KF cells incubated with cisplatin at 10 μg/ml increased in a time‐dependent manner, that in the KFr cells remained unchanged during the experimental period. When 0.5 mg of cisplatin was administered ip to nude mice with KF or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF tumor. The KFr cells showed a cross‐resistance to L‐phenylalanine mustard, while no cross‐resistance to vincristine or 5‐fluorouracil was observed. These findings suggest that the mechanism of cisplatin resistance in the KFr cells involves a decrease of cisplatin accumulation in the tumor cells.

No abstract

The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin‐2 (IL‐2) production and expression of IL‐2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL‐2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL‐2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL‐2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL‐2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL‐2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL‐2 production was restored to benign control levels. On the other hand, the expression of IL‐2 receptor remained unchanged even if PSK was given after completion of chemotherapy.