Significance of 5-fluorouracil-related enzyme activities in predicting sensitivity to 5-fluorouracil in bladder carcinoma.

Background: The association between 5-fluorouracil (5-FU)-related enzyme activity and the sensitivity of bladder urothelial carcinoma (BUC) to 5-FU were investigated, and methods to improve 5-FU sensitivity were analyzed.

Materials And Methods: Tumor specimens were obtained from 127 patients. Orotate phosphoribosyl transferase (OPRT) activity was analyzed by the paper disc method and thymidine phosphorylase and dihydropyrimidine dehydrogenase (DPD) activities were measured by ELISA. 5-FU sensitivity was assessed in 99 cases by an in vitro chemosensitivity test.

Results: A significant positive correlation between OPRT activity level and the sensitivity of BUC to 5-FU was identified. Moreover, the combination of 5-FU and 5-chloro-2,4-dihydroxypyrimidine significantly enhanced 5-FU sensitivity in BUC, particularly in cases showing higher DPD activity.

Conclusion: OPRT was the most important enzyme in predicting sensitivity to 5-FU in BUC. These results may have implications for tailor-made medication using 5-FU-related compounds as postoperative adjuvant chemotherapy in BUC patients.