Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice

T. Kubota, S. Kase, T. Furukawa, H. Tanino, T. H. Kuo, Yoshirou Saikawa, H. Nishibori, K. Ishibiki, M. Kitajima, K. Mabuchi, H. Hirata

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Experimental biochemical modulation of l-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5, 10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity.

本文言語English
ページ(範囲)1549-1553
ページ数5
ジャーナルAnticancer research
12
5
出版ステータスPublished - 1992 1月 1

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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