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  • Title: Roles of thymidylate synthase and dihydropyrimidine dehydrogenase in tumor progression and sensitivity to 5-fluorouracil in human gastric cancer.
    Author: Terashima M, Irinoda T, Fujiwara H, Nakaya T, Takagane A, Abe K, Yonezawa H, Oyama K, Inaba T, Saito K, Takechi T, Fukushima M.
    Journal: Anticancer Res; 2002; 22(2A):761-8. PubMed ID: 12014648.
    Abstract:
    BACKGROUND: The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated. MATERIALS AND METHODS: TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay. RESULTS: There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465). CONCLUSION: These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.
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