Uracil derivatives. V. Syntheses and growth-inhibitory activity against L-1210 cells of 5-substituted 2'-deoxyuridines and orotidine derivatives.
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Biomedical subjects
Publications and source records attributed to H Miyake.
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The effects of 10 mg/kg and 5 mg/kg intraperitoneally administered triethyl lead on rats were observed through measurement of the following: changes in body weight, passive aggressiveness, wheel running activity, the performance level of Rota-Rod Treadmill, and emotional responses in the open field. The results obtained were as follows: Weight losses of TEL-treated rats were recorded from 2 days after injection to 20 days after injection. Scores of passive aggressiveness were drastically increased following administration of TEL. Maximum passive aggressiveness was observed 4 days after injection and it continued until 13 days after injection. Wheel running activity was decreased for 2 days after injection. It was observed that TEL-treated rats showed extreme reaction on the wheel running activity test for about 30 days after administration. Endurance on the Rota-Rod Treadmill was significantly reduced in the 10 mg/kg group. The amount of defecation, ambulation and rearing of the treated group as measured by covariance analysis did not differ from that of the controls. The whole time course of intoxication and the precise measurement of neurotoxicity due to TEL could be followed using the techniques of behavioral toxicology.
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Fifteen patients with advanced recurrent or metastatic carcinoma of the head and neck were treated with recombinant interferon alpha-2. Cumulative doses for evaluation of at least 1.2 X 10(8) IU were given over a period of 4 weeks. No significant regression was shown in 14 evaluable patients, 6 of which showed no change and 8 progression. Toxicities were minimum and acceptable. All patients had an episode of elevated body temperature. One patient showed transient effects on the central nervous system, which may be a dose-limiting factor. Recombinant interferon alpha-2 was therefore not recommended as a modality for the treatment of recurrent head and neck cancer.
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A Phase II study of UFT for head and neck cancer was conducted in 10 institutions. UFT is a mixture of Futraful and uracil. Eighty-four patients entered this trial, of which 60 were evaluable. UFT was administered orally at a daily dose of 600 mg/day. Eight patients achieved complete response and 10 achieved partial response with an over-all response rate of 30.0 %. Evaluating response according to by histology, the response rate was 30.9% for cases of squamous cell carcinoma. Complete response was observed in one case of undifferentiated carcinoma. Response rate according to primary site was 33 to 40% for the nose & paranasal sinuses, mesopharynx, hypopharynx and larynx. The response rate was 28.9% for the group of patients treated previously, and 33.3% for the group previously untreated. The mean time for 50% or more regression of the tumor was 4.3 weeks. Toxic effects appeared in 40.3% of 67 evaluable cases as anorexia, nausea, vomiting, stomatitis, diarrhea etc. In one case of maxillary carcinoma, severe bone marrow suppression was observed. We concluded that UFT therapy was markedly effective for head and neck cancer.
Chemotherapy with FT-207 suppository (Futraful supo) for head and neck cancer was studied by Six Medical Schools in Kanagawa Prefecture, and its effectiveness and side effects were examined. Seventy-five cases were treated with this drug. However, thirty-four cases were used for the final evaluation, with regard to the given dose etc. Generally, the effectiveness rate was 23.5%. Thyroid cancer, nasal cancer and paranasal sinus cancer gave the best results. All four cases of adenocarcinoma showed an effect. One case, who was given a higher dose, showed an increased effect. Also, cases which has not been treated with any other therapeutic procedure previously, showed a significant effectiveness rate. Side effects were observed in 45.2% of cases. These were largely appetite loss and so on, which concerned the digestive system. On the whole, it has been proved that FT-207 suppository (Futraful Supo) is useful as an induction chemotherapeutic drug for head and neck cancer.
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A case-control study of 80 women with ovarian epithelial carcinoma and 160 individually age-matched controls were conducted to assess various factors associated with the incidence of ovarian cancer in Hokkaido, Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: (1) blood group A; (2) never married or married late in life; (3) more frequent surgery for retroflexion of the uterus; (4) less use of contraceptive appliances; and (5) less daily use of cosmetics. It was inferred from these observations that ovarian cancer patients had a genetic predisposition and dysfunctional ovaries. Gonadal dysfunction among ovarian cancer patients presumably explained not only altered personality and behavior patterns, but also facilitated the pituitary gonadotropin activity which has been suggested as increasing the incidence of the disease experimentally.
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Vascular prostheses with the inner diameter smaller than 1 mm were implanted to the common carotid artery of rats, and their patency was examined. Four types of tubes were prepared for this purpose in Experiment 1: polyethylene (PE), poly-(acrylic acid)-grafted polyethylene (PE-AA), polyacrylamide-grafted polyethylene (PE-AAm), and poly(vinyl alcohol) (PVA) tubes. Comparative studies made using nonsuture anastomosis revealed that the PE-AAm and PVA tubes were antithrombotic, although disconnection was noted at the anastomotic sites within 1 week and 1 month, respectively. Thereafter in Experiment 2, the PVA tubes were implanted to the common carotid artery of 20 rats using conventional anastomosis. Neither anticoagulants nor fibrinolytic agents were used in both series of experiments. Patency of the PVA tubes was 80% after 1 week and 70% after 1 month. In patent cases after 1 month, the luminal surfaces of the prostheses and the host arteries were examined using scanning electron microscopy. The lumen of the arteries and anastomotic sites was covered with endothelial cells, while the lumen of the PVA tubes was free from thrombi and there was no neointima formation. So far, there has been reported no manmade material that has completely antithrombotic property in vivo. However, our studies disclosed that PVA is antithrombotic and one of the most promising materials for the inner surface of small vascular prostheses.
Male ICR mice were either given water containing Cd at a level of 192-200 ppm for 45 days (ingestion group), or were injected subcutaneously once a week with Cd (1 mg/kg) as CdCl2 for 7 weeks (injection group). The control group was given Cd-free water. In both Cd groups, the hematocrit and hemoglobin values did not change markedly. In the ingestion group, the Fe concentration decreased greatly in the liver, kidney, spleen, and duodenum. These decreases may be due to depression of Fe absorption from the intestine. In the injection group, Fe increased in the liver, spleen, and duodenum, although it decreased in the kidney. By Sephadex G-200 gel filtration, Fe-proteins in the hepatic supernatants were located in the void volume region of this gel column in both Cd groups. Apparently, Fe was not a component of metallothionein (MT) protein. The hepatic MT induction by Cd resulted in an increase in hepatic supernatant Cu. Serum Cu and ceruloplasmin (Cp) activity were stimulated only in the injection group. The enhancement of Cp activity may possibly be due to the increase in hepatic Cu which was accompanied by an increase in hepatic Fe, rather than a decrease. Our observations suggest that Fe metabolism is influenced differentially by the administration route of Cd.