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, Toshiharu Furukawa, H. Tanino, T. H. Kuo, Y. Saikawa, H. Nishibori, K. Ishibiki, M. Kitajima, K. Mabuchi, H. Hirata

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1549-1553
Number of pages5
JournalAnticancer Research
Volume12
Issue number5
Publication statusPublished - 1992

Fingerprint

Leucovorin
Nude Mice
Human Activities
Fluorouracil
Stomach
Colon
Carcinoma
Thymidylate Synthase
Tumor Burden
1-hexylcarbamoyl-5-fluorouracil
Floxuridine
Maximum Tolerated Dose
Heterografts
Cellulose
Weight Loss
Body Weight

Keywords

  • HCFU
  • Leucovorin
  • Thymidylate synthetase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice. / Kubota, T.; Kase, S.; Furukawa, Toshiharu; Tanino, H.; Kuo, T. H.; Saikawa, Y.; Nishibori, H.; Ishibiki, K.; Kitajima, M.; Mabuchi, K.; Hirata, H.

In: Anticancer Research, Vol. 12, No. 5, 1992, p. 1549-1553.

Research output: Contribution to journalArticle

Kubota, T, Kase, S, Furukawa, T, Tanino, H, Kuo, TH, Saikawa, Y, Nishibori, H, Ishibiki, K, Kitajima, M, Mabuchi, K & Hirata, H 1992, 'Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice', Anticancer Research, vol. 12, no. 5, pp. 1549-1553.
Kubota, T. ; Kase, S. ; Furukawa, Toshiharu ; Tanino, H. ; Kuo, T. H. ; Saikawa, Y. ; Nishibori, H. ; Ishibiki, K. ; Kitajima, M. ; Mabuchi, K. ; Hirata, H. / Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice. In: Anticancer Research. 1992 ; Vol. 12, No. 5. pp. 1549-1553.
@article{f5086c4d5b2147ddafd6fa6814bdebac,
title = "Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice",
abstract = "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.",
keywords = "HCFU, Leucovorin, Thymidylate synthetase",
author = "T. Kubota and S. Kase and Toshiharu Furukawa and H. Tanino and Kuo, {T. H.} and Y. Saikawa and H. Nishibori and K. Ishibiki and M. Kitajima and K. Mabuchi and H. Hirata",
year = "1992",
language = "English",
volume = "12",
pages = "1549--1553",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "5",

}

TY - JOUR

T1 - Modulation by l-Leucovorin of 1-Hexylcarbamoyl-5-Fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice

AU - Kubota, T.

AU - Kase, S.

AU - Furukawa, Toshiharu

AU - Tanino, H.

AU - Kuo, T. H.

AU - Saikawa, Y.

AU - Nishibori, H.

AU - Ishibiki, K.

AU - Kitajima, M.

AU - Mabuchi, K.

AU - Hirata, H.

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

KW - HCFU

KW - Leucovorin

KW - Thymidylate synthetase

UR - http://www.scopus.com/inward/record.url?scp=0026496944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026496944&partnerID=8YFLogxK

M3 - Article

C2 - 1444220

AN - SCOPUS:0026496944

VL - 12

SP - 1549

EP - 1553

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 5

ER -