Prostaglandin D2 was found to have a potent cytotoxic effect on L1210 leukemia culture cells. When Prostaglandin D2 was added to the culture medium, at the concentration of over 5 micrograms/ml growth of L1210 cells was almost completely inhibited. IC50 of Prostaglandin D2 for L1210 cell was 2.4 micrograms/ml. Cells exposed this agent showed remarkable change in its cytoplasm with many vacuoles and lysis of cells were observed at the concentration over 5 micrograms/ml.

We have developed OMF treatment which is consisting of endoscopical injection of OK-432 into the perilesional area of cancer, intraarterial or intravenous injection of mitomycin C by one shot and oral administration of 5-FU, and applied it to the patients with preoperative gastric cancer to whom remarkable macroscopic effects were obtained. We determined its efficacy by establishing a response criteria. Although there were no excellent results, the clinical results were rated as good in 5 lesions (50%) and as fair in 5 lesions (50%) out of 10 lesions in 9 cases. In none of the cases, the treatment was ineffective.

For the purpose of examining the transfer of antitumor drug into the blood, pancreatic juice, bile and pancreatic tissue, Futraful suppository (FT-sup) 1500 mg were given to 10 patients with pancreatic or bile duct malignancies, measuring Futraful and 5-FU concentrations in the pancreatic juice, bile and pancreatic tissue with lapse of time. Futraful and 5-FU concentrations of the pancreatic juice and bile reached to the maximum 4 hours after administration. The peaks of Futraful and 5-FU concentrations in the pancreatic juice and bile about 2 hours after the maximum values in the blood. 5-FU concentration in the pancreatic tissue was higher than that in the blood in every case. Transfer rate of Futraful to the pancreatic tissue was higher especially in the cases with higher pancreatic parenchymal ratio.

UFT, antitumor agent containing uracil and futraful (FT-207), was given orally to 14 patients with recurrent or advanced carcinomas (6 gastric, 5 colorectal and 3 other carcinomas) and the clinical effects were evaluated. One PR (partial response) 1 NC (no change) and 9 PD(progressive disease) were obtained among 11 evaluable patients. Response rate was 9.1% (1/11), and overall response rate was 14.3% (2/14). According to Karnofsky's criteria, 2 responders (better than I-A) were obtained and response rate was 15.4% (2/13).

A 59-year-old woman with recurrent malignant melanoma of the vulva has well responded to a combination of immunotherapy and chemotherapy. As an immunotherapy, 10KE OK-432 were injected into the tumor twice a week. Chemotherapeutic regimen consisted of intravenous push of 1 mg vincristine on day 1,100 mg dacarbazine from day 1 through 5 and 50 mg nitrosourea (ACNU) on day 5. This treatment was repeated with 4 week intervals. Before treatment, the patient had a 3 X 3 X 5 cm subcutaneous mass on the left vaginal wall near the introitus. Fifty percent objective reduction of the tumor was achieved 6 weeks after commencement of intralegional immunotherapy and chemotherapy, and the tumor almost disappeared 8 months later. At this time, the treatment was changed to a supportive immunotherapy with intramuscular injection of 1KE OK-432 twice a week. But the tumor began to enlarge 2 months later and the patient is now being treated with the same combination therapy. Major side effects were febrile episodes on the day of intratumor injection of OK-432 and nausea, vomiting during the interval of chemotherapy. Anemia was the main hematologic side effect, but leukocytopenia and thrombocytopenia were not severe. The combination of intratumor injection of OK-432 and chemotherapy seems to be effective for the treatment of malignant melanoma.

Morphological observation was performed to see the effect of bronchial arterial infusion therapy (BAI) of mitomycin C (MMC) and also of the ischemia to the transplanted bronchial carcinoma. Single shot of 2mg/kg of MMC showed destructive changes on the tumor. Single shot of 3mg/kg and repeated administration of MMC brought relatively severe intra-arterial inflammatory changes such as intimal edema, thickening and proliferation which suggested ischemic effect on the tumor due to poor perfusion from stenosis or obstruction of the vessels. On the other hand a simple ligation of the artery also brought about more than moderate destructive changes in the tumor. Therefore, mechanisms of the effect of the BAI of MMC to the lung tumor might involve the secondary effect from ischemia in addition to the effect of MMC itself.

Sakata, et al. has already reported that the combination therapy of mitomycin-C, carboquone, 5-fluorouracil and OK-432 (MQF-OK therapy) which had established from animal experiments, was exceedingly effective for inoperable human gastric cancer. In this paper, the effectiveness of MQF-OK therapy for inoperable gastric cancer was compared with that of MFC therapy. To perform this controlled study, a "large area" co-operative study group of cancer chemotherapy, composed of 14 institutions in Aomori and a part of Akita prefectures, was organized. From April 1977 to April 1980, patients were registered and 61 cases were evaluable; 31 out of 61 were treated with MQF-OK therapy (MQF-OK group) and the others with MFC group. The background of the cases, such as sex, age etc, was not different significantly between two groups statistically. According to the response criteria of Japan Society for Cancer Therapy, 18 cases out of 31 cases of MQF-OK group and 9 of 30 cases of MFC group showed "improvement." According to Karnofsky's criteria 17 cases of MQF-OK group and 8 of MFC group showed effectiveness more than I-A, respectively. There was a statistical significance between the two groups (P less than 0.001). By Kaplan-Meier's method, the MQF-OK group survived longer than the MFC group (P = 0.05). The complications, such as leukocytopenia, thrombocytopenia or gastrointestinal complaints, were more frequently found in MQF-OK-432 group than in MFC group (P less than 0.05). But these complications decreased or resolved spontaneously 1 to 4 weeks after the administration of MQF-OK therapy. On these results, MQF-OK therapy was considered excellent method for treatment of inoperable gastric cancer and will be furthermore attempted against other cancers.

The malignant ovarian cancer cells removed on operation were cultured and exposed to the anticancer drug (either 5-fluorouracil or mitomycin C) for 30 minutes or 24 hours respectively. The activity of the LDH and LDH isozyme in the culture medium was measured. Also the activity of the LDH and its isozyme was determined in the patients undergoing chemotherapy with either 5-fluorouracil or mitomycin C. The results are summarized as follows: 1) The LDH isozyme pattern of the culture medium prior to exposure of malignant cells to the anticancer drugs was classified into 2 types i.e., M type which is characterized by a predominance of LDH4,5 (referred hereinafter to as group M) and H type with a predominance of LDH1,2 (referred to as group H). 2) Of 11 cases studied, 7 were classified as group M and 4 were categorized as group H. there was no distinct relationship between histological type and LDH isozyme pattern. 3) In the group with exposure to anticancer drugs the total LDH activity in both group H and group M was lower than in the control group. Control specimens in group H showed increased total LDH activity. 4) The H/M ratio based on subunits of LDH isozyme was virtually unchanged by exposure to anticancer drugs in group M, while rapidly lowered by the same treatment in group H. 5) The death rate of malignant cells as estimated by dye exclusion methods was higher with exposure to anticancer drugs than without it. 6) The serum LDH was more markedly lowered after treatment in group H than in group M. However, there was no substantial difference between the two groups in M/H ratio before and after treatment.

Serial transplantation in nude mice of human choriocarcinoma showed the drug resistance in clinic was succeeded and experimental chemotherapy has been studied to improve the prognosis of the patients with choriocarcinoma. The experimental tumors were two lines. CC-I-JCK (JCK) and CC-HM-I- (HM). In this paper, single and/or combination chemotherapy with methotrexate (MTX), actinomycin D (ACD), cyclophosphamide (CMP), and vincristine (VCR) were discussed. 1) Effects of the single agent: In JCK, the suppressive effects against tumor growth under administration of CPM or VCR, and some responses in histological finding were obtained. While, in HM, few suppressive effects against tumor growth and some responses in histological findings were obtained. 2) Effects of the combined agents: In JCK, the suppressive effects against tumor growth were as follows; nontreatment group less than MTX + ACD less than MTX + CPM less than MTX + ACD + CPM less than ACD + CPM less than ACD + CPM + VCR. The complete disappearance of tumors were gained under administration of the combination therapy with ACD and CPM. While in in HM, the effects were as follows; nontreatment group less than MTX + ACD less than ACD + CPM less than MTX + ACD + CPM less than MTX + CPM less than MTX + CPM + VRC. But no complete disappearance of tumor was obtained. 3) The good relationship between the results of experimental chemotherapy and the response of clinical patients who provided the tissues could be seen. It has been defined that the experimental chemotherapy with the tumors transplanted to nude mice in useful models for the establishment of rational chemotherapy for drug resistant choriocarcinoma.