[Histopathological studies on antitumor effect of tegafur administered by continuous intravenous infusion].
The effects of preoperative treatment by continuous intravenous infusion of Tegafur, the antagonist of DNA synthesis, were histopathologically studied in 34 patients with gastric cancer. Histologically the treatment was found to be effective in 41.2% of patients with cancer invasion in the mucosa, 58.8% in the submucosa, 61.3% in the muscularis propria, 59.3% in the subserosa and 86.9% of those with metastatic lymph nodes. The treatment was effective, when assessed in terms of the histological type of cancer, in 90.9% of cancers of the differentiated type (papillary adenocarcinoma, well differentiated tubular adenocarcinoma and moderately differentiated tubular adenocarcinoma) and 47.8% of those of the poorly differentiated type (poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet-ring cell carcinoma), showing a higher rate of efficacy in the differentiated type cancers. Meanwhile, even among patients with cancer of poorly differentiated type, a high efficacy rate (90.0%) was found in those with metastatic cancer of the lymph nodes. No relationship was found between the total doses of Tegafur and histological effects. There was a tendency, however, for a higher frequency of a good response in patients administered more than 4,000 mg of Tegafur. In the patients with a histologically positive effect, 5-FU concentration in the tumor tissue was higher than 0.071 microgram/g. However, some patients showed no response despite a high concentration. This finding suggested that sensitivity to 5-FU and 5-FU metabolism vary depending on the tumor. The inhibitory effect of Tegafur on DNA synthesis is produced through inhibition of thymidylate synthase (TS) by the Tegafur metabolite FdUMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Yagawa
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A
Department of Gastrointestinal Surgery, Tokyo Women's Medical College.
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D005641:Tegafur; D013940:Thymidylate Synthase