Orotate Phosphoribosyl Transferase (OPRT), Dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. In this study, we measured the activities of OPRT, DPD and TS. We also investigated the correlation between these 3 enzymatic activities and the clinical pathologic factors (Histological typing, extent of tumor invasion,extent of metastasis to the lymph nodes,stage, lymphatic invasion and venous invasion). We had surveyed 79 cases of colorectal cancers surgically removed. Poorly-differentiated adenocarcinoma showed a tendency to lower OPRT and higher DPD, as compared to moderately or well-differentiated adenocarcinomas. In case with metastasis to lymph nodes, OPRT showed a tendency to lower activities, but a significant difference was not noticed. TS showed no relation to any of these pathologic factors. In each application of 5-FU, measuring the activities of these three enzymes is important for estimation of the antitumoral effect. With poorly-differentiated adenocarcinoma, it is estimated that many cases would show high DPD and if the enzyme activities can not be measured, so administration of TS-1, which includes DPD inhibitor, may be considered.

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