Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of C6 and 9L glioma cells into Wistar and Fisher 344 rats, respectively. Chemotherapy of these models and in vitro chemosensitivity assay for these cell lines were studied with ACNU, BCNU and VM-26. In vitro chemosensitivity assay revealed that 9L cells were sensitive to all of the anticancer drugs above, and that C6 cells were resistant to ACNU and BCNU, but not to VM-26. In vivo experiment, the survival time of the rats inoculated with 9L glioma cells (9LMG) was prolonged by both ACNU and BCNU but not by VM-26. None of these drugs were effective against the rats inoculated with C6 glioma cells (C6MG). It is concluded that the result of in vitro chemosensitivity assay is not always correlative with that of in vivo. This implies that an in vivo chemosensitivity assay system including MG models is indispensable in researching into chemotherapy of brain tumor.

We have previously reported the leukocyte migration inhibition (LMI) factor in cancer patients, which is one of the specific parameters of cell mediated immunity. Since interpretation of these results was sometimes difficult in human cancer because of the unknown participation in the reaction, the inbred mouse strains were used as an experimental animal. We studied how the LMI factor of murine spleen cells changed with immunization of tumor cells, and intraperitoneal injection of protein polysaccharide (PSK) and/or cyclophosphamide (CPA). Method. LMI was performed by Clausen's method. Mouse strain; C3H/Heston. Tumors; C3M2 (methylcholanthrene induced tumor) and MAC (spontaneous mammary tumor). Result. Migration cells of murine spleen cells were almost granulocytes. Migration inhibition was maximum in 2 to 3 weeks after immunization of tumor cells. In vivo studies as well as in vitro studies revealed that C3M2 and MAC were not crossreactive. Migration was accelerated with CPA and inhibited with PSK. Leukocyte migration was inhibited by injection of PSK after treatment of CPA at a dose of 50 mg/kg, while in the case of CPA at a dose of 200 mg/kg, preinjection of PSK inhibited leukocyte migration.

Estracyt is a new drug for treatment of prostatic cancer, which is a molecule combining estradiol and nornitrogen mustard by a carbamate link. Estracyt is completely dephosphorylated prior to reaching the peripheral circulation after oral administration of the drug to men. Estramustine, i. e. dephosphorylated Estracyt, appears to be metabolized in liver as follows: Estramustine leads to estromustine leads to nitrogen mustard + estrone. There is a large amount of estramustine binding protein (EMBP) in the cytosol 3.5 S fraction of human prostatic cancer tissue, which is involved with the selective uptake and long term retention of both estramustine and estromustine in prostate. The anticancer action of Estracyt appears to be the sum of the direct prostatic action of estramustine and estromustine and the indirect prostatic action of free estradiol-17 beta and estrone via the inhibition of hypothalamo-pituitary axis. Estracyt Research Group in Japan concluded that Estracyt was effective in 38% of reactivated prostatic cancer patients (15% (I-C, I-B), 23% (I-A, O-B, O-C]. Side effects of this drug at the time of 3 months treatment is as follows: gastrointestinal disturbance in 36%, edema in 15%, and hepatic disorder in 7%.

For the analysis of the mechanism of cancer metastasis, effects of anticancer agents on the NK activity of spleen cells and on the artificial metastasis of B-16 melanoma cells were comparatively studied. The inhibitory effect of these anticancer agents on the growth of B-16 melanoma inoculated to foot pad of C57/BL6 mice was also examined. The growth of B-16 melanoma was inhibited by intravenous administration of 6 mg/kg of MMC, 18 mg/kg of KW-2083 and 5 mg/kg of CDDP, but not of 6 mg/kg of KW-2083. The NK activities in spleen cells of C57/BL6 mice administered with 6 mg/kg of MMC and 18 mg/kg of KW-2083 were decreased, but they were not decreased in mice administered with 6 mg/kg of KW 2083 and 5 mg/kg of CDDP. Significant increases in the number of artificial pulmonary and liver metastasis were observed in mice administered with 6 mg/kg of MMC and 18 mg/kg of KW-2083. It is suggested that the depression of NK activity induced by anticancer agents results in the promotion of metastatic disease.

Clinical study of UFT which was a mixture of FT and uracil, was conducted on 16 patients with urogenital malignancies. Seven patients had renal cell carcinoma, 5 patients had bladder cancer and 4 patients had prostatic cancer. UFT was continuously administrated at doses of 300 mg or 600 mg per day. One of the patients with renal cell carcinoma and 1 of the patients with bladder cancer showed a complete response, and 1 patient with each cancer showed a partial response, but none of the 4 patients with prostatic cancer responded. In total, complete or partial responses were obtained in 4 of the 16 patients, given an effective rate of 25.0%. Concerning side effects, 3 of the 16 patients complained of anorexia, nausea and vomiting, and stomatitis, but no hepatic or renal disorders, or marrow depression was observed.

Sixty patients with adult acute lymphocytic leukemia (ALL) and 40 patients with blastic crisis of chronic myeloid leukemia (CML . BC) were randomly allocated by envelope method to receive either vindesine (VDS; 2 mg/m2 i.v., twice or once weekly) or vincristine (VCR; 1.2 mg/m2 i.v., once weekly) in combination with prednisolone (Pred; 40 mg/m2 p.o., daily). Out of 100 patients entered, 53 patients with ALL and 34 patients with CML . BC were evaluable. Remissions for ALL were seen in 20 of 25 patients (80.0%; 12 CRs and 8 PRs) treated with VDS regimen, and in 17 of 28 patients (60.7%; 7 CRs and 10 PRs) treated with VCR regimen, respectively. For CML . BC, however, remission rates for VDS regimen (42.1%; 5 CRs and 3 PRs in 19 patients) and for VCR regimen (40.0%; 2 CRs and 4 PRs in 15 patients) were equivalent. Overall remission rates of VDS regimen for both diseases, twice weekly regimen (65.5%; 11 CRs and 8 PRs in 29 patients) and once weekly regimen (60.0%; 6 CRs and 3 PRs in 15 patients) were similar. Patients treated with either regimen experienced high incidence of neurotoxicity. Neurotoxic disturbance appeared severer in patients treated with VCR regimen. Incidence of leukopenia and alopecia was high in patients treated with VDS regimen. These data suggest that VDS in combination with Pred is comparable-rather superior-to VCR in combination with Pred for adult ALL and CML . BC. Less neurotoxic and sufficiently effective dosage of VDS is considered to be 2 mg/m2, once weekly.

Small charcoal particles adsorbing Mitomycin C (MMC-CH) were used in the treatment of lymphnode metastasis of gastric cancer. Immediately after injection of MMC-CH into the gastric wall, lymph capillaries and regional lymphnodes were stained in black and the high concentration of MMC was delivered with charcoal particles. MMC-CH was injected preoperatively using endoscope into the gastric wall of 20 patients with gastric cancer. MMC-CH was observed in 70% of metastatic regional lymphnodes. Systemic side effect was not noted at all. Erosion and shallow ulcers were observed at the site of injection but no perforation occurred.

To evaluate the time response of anticancer drugs, we observed the morphological changes of solid tumor cells using a new simple method of cytologic examination. Mitomycin C and Bleomycin were administered to nude mice transplanted with human uterine cervical carcinoma of the Yumoto strain. The cancer cells were classified as follows: A, uniform, pyknotic nuclei with indistinct nucleoli; B, pyknotic nucleus with distinct nucleoli; C, pale-stained nuclei and cytoplasm; D, condensation of nuclei and cytoplasm. Three hours after MMC administration the destruction of the nuclei of A type cancer cells and shrinkage of B type cells was observed. Pyknosis of B type cells and destruction of C type cells was seen 7 hours after BLM administration. These characteristic changes which occurred at a very early period appear to be available as a marker for the evaluation of the oncostatic effect and for the anticancer drug selection in patients with malignancy.