The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo

Suguru Kase; Tetsuro Kubota; Masahiko Watanabe; Tetsuya Takahara; Tooru Takeuchi; Hiroshi Yamaguchi; Toshiharu Furukawa; Tatsuo Teramoto; Susumu Kodaira; Kyuya Ishibiki; Masaki Kitajima

doi:10.1007/BF00311910

The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo

Suguru Kase, Tetsuro Kubota, Masahiko Watanabe, Tetsuya Takahara, Tooru Takeuchi, Hiroshi Yamaguchi, Toshiharu Furukawa, Tatsuo Teramoto, Susumu Kodaira, Kyuya Ishibiki, Masaki Kitajima

Law School

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m², this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.

Original language	English
Pages (from-to)	615-620
Number of pages	6
Journal	Surgery today
Volume	23
Issue number	7
DOIs	https://doi.org/10.1007/BF00311910
Publication status	Published - 1993 Jul

Keywords

5-fluorouracil
L-leucovorin
human colon carcinoma

ASJC Scopus subject areas

Surgery

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10.1007/BF00311910

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title = "The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo",

abstract = "We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.",

keywords = "5-fluorouracil, L-leucovorin, human colon carcinoma",

author = "Suguru Kase and Tetsuro Kubota and Masahiko Watanabe and Tetsuya Takahara and Tooru Takeuchi and Hiroshi Yamaguchi and Toshiharu Furukawa and Tatsuo Teramoto and Susumu Kodaira and Kyuya Ishibiki and Masaki Kitajima",

year = "1993",

month = jul,

doi = "10.1007/BF00311910",

language = "English",

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T1 - The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo

AU - Kase, Suguru

AU - Kubota, Tetsuro

AU - Watanabe, Masahiko

AU - Takahara, Tetsuya

AU - Takeuchi, Tooru

AU - Yamaguchi, Hiroshi

AU - Furukawa, Toshiharu

AU - Teramoto, Tatsuo

AU - Kodaira, Susumu

AU - Ishibiki, Kyuya

AU - Kitajima, Masaki

PY - 1993/7

Y1 - 1993/7

N2 - We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.

AB - We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 μg/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.

KW - 5-fluorouracil

KW - L-leucovorin

KW - human colon carcinoma

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The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo

Abstract

Keywords

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