Prediction of 5-fluorouracil Sensibility by Measurement of Thymidylate Synthase Activity and Dihydropyrimidine Dehydrogenase Activity against Gastric Cancer

Takashi Irinoda, Masanori Terashima, Hidenobu Kawamura and Akinori Takagane

Department of Surgery 1, Iwate Medical University

In order to evaluate prediction of therapeutic efficacy by intracellular enzyme activity in gastric cancer, we investigated the role of thymidilate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activity in tumor sensitivity to 5-fluorouracil (5-FU). We measured TS and DPD activities in 8 human gastric cancer cell lines, 4 human gastric cancer xenografts and 40 clincal samples from gastric cancer. TS and DPD activities were determined by [³H]-FdUMP binding assay and thin-layer chromatography protocol, respectively. Sensitivity to 5-FU was determined by MTT assay in cell lines and by in vitro ATP assay in clinical samples. In cell lines and tumor xenografts, strong correlations between TS activity or DPD activity and 5-FU sensitivity were found. In clinical samples, a statistically significant correlation between DPD activity and in vitro senstivity to 5-FU also was found. These results suggest that senstivity to 5-FU is predictable by measurement of both TS activity and DPD activit.

Key words
5-fluorouracil, thymidylate synthase, dihydropyrimidine dehydrogenase, gastric cancer, drug sensitivity

Reprint requests
Takashi Irinoda Department of Surgery 1, Iwate Medical University 19-1 Uchimaru, Morioka, 020-8505 JAPAN

Accepted
February 24, 1999

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