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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3245-3252
Number of pages8
JournalAnticancer Research
Volume22
Issue number6 A
Publication statusPublished - 2002 Nov

Fingerprint

Thymidylate Synthase
Fluorouracil
RNA
Heterografts
Nude Mice
Neoplasms
Pharmaceutical Preparations
Stomach
Colon
Carcinoma
Drug Therapy
DNA
Enzymes
Therapeutics

Keywords

  • 5-Fluorouracil
  • F-RNA
  • Raltitexed
  • Thymidylate synthetase
  • UFT

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kabeshima, Y., Kubota, T., Watanabe, M., Saikawa, Y., Nishibori, H., Hasegawa, H., & Kitajima, M. (2002). A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed. Anticancer Research, 22(6 A), 3245-3252.

A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed. / Kabeshima, Yasuo; Kubota, Tetsuro; Watanabe, Masahiko; Saikawa, Yoshiro; Nishibori, Hideki; Hasegawa, Hirotoshi; Kitajima, Masaki.

In: Anticancer Research, Vol. 22, No. 6 A, 11.2002, p. 3245-3252.

Research output: Contribution to journalArticle

Kabeshima, Y, Kubota, T, Watanabe, M, Saikawa, Y, Nishibori, H, Hasegawa, H & Kitajima, M 2002, 'A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed', Anticancer Research, vol. 22, no. 6 A, pp. 3245-3252.
Kabeshima Y, Kubota T, Watanabe M, Saikawa Y, Nishibori H, Hasegawa H et al. A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed. Anticancer Research. 2002 Nov;22(6 A):3245-3252.
Kabeshima, Yasuo ; Kubota, Tetsuro ; Watanabe, Masahiko ; Saikawa, Yoshiro ; Nishibori, Hideki ; Hasegawa, Hirotoshi ; Kitajima, Masaki. / A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed. In: Anticancer Research. 2002 ; Vol. 22, No. 6 A. pp. 3245-3252.
@article{6a58ddcce90941388fe328178f28379e,
title = "A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed",
abstract = "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.",
keywords = "5-Fluorouracil, F-RNA, Raltitexed, Thymidylate synthetase, UFT",
author = "Yasuo Kabeshima and Tetsuro Kubota and Masahiko Watanabe and Yoshiro Saikawa and Hideki Nishibori and Hirotoshi Hasegawa and Masaki Kitajima",
year = "2002",
month = "11",
language = "English",
volume = "22",
pages = "3245--3252",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6 A",

}

TY - JOUR

T1 - A potential imortant role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed

AU - Kabeshima, Yasuo

AU - Kubota, Tetsuro

AU - Watanabe, Masahiko

AU - Saikawa, Yoshiro

AU - Nishibori, Hideki

AU - Hasegawa, Hirotoshi

AU - Kitajima, Masaki

PY - 2002/11

Y1 - 2002/11

N2 - 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.

AB - 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.

KW - 5-Fluorouracil

KW - F-RNA

KW - Raltitexed

KW - Thymidylate synthetase

KW - UFT

UR - http://www.scopus.com/inward/record.url?scp=0036827466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036827466&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 3245

EP - 3252

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6 A

ER -