A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed

Yasuo Kabeshima, Tetsuro Kubota, Masahiko Watanabe, Yoshiro Saikawa, Hideki Nishibori, Hirotoshi Hasegawa, Masaki Kitajima

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Background: Because thymidylate synthetase (TS) is a key enzyme in DNA synthesis, it has been used as a target for cancer chemotherapy. Materials and Methods: We investigated the combined antitumor activity of raltitexed, 5-FU and UFT on human tumor xenografts in nude mice and examined changes in TS activity and 5-FU-bound RNA (F-RNA) levels. Human gastric (SC-1-NU) or colon (HT-29) carcinoma xenografts were transplanted subcutaneously into nude mice, and drugs administered intraperitoneally (raltitexed and 5-FU) or perorally (UFT) daily for 5 days, and repeated once after a 2-day interval. Results: The antitumor effects were mostly equivalent between the treatment groups despite the different drugs and sequence orders. TS inhibition rates correlated with the tumor inhibition rate, which was statistically significant, while F-RNA levels did not correlate with antitumor activity. Conclusion: Our results indicated that the combination of fluoropyrimidine-related agents should be directed towards increased TS inhibition rather than increased F-RNA levels.

本文言語English
ページ(範囲)3245-3252
ページ数8
ジャーナルAnticancer research
22
6 A
出版ステータスPublished - 2002 11月 1

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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