Thymidine phosphorylase activity in transitional cell cancer: Relation to histological parameters and chemosensitivity to fluorouracil-related drugs

Background: Thymidine phosphorylase (TdR-Pase) is an essential enzyme for t he metabolism of fluorouracil-related drugs and it is also recognized as a potent angiogenic factor. We measured the TdR-Pase activity in human transi tional cell cancers (TCCs) of the urinary tract to assess the relationship between TdR-Pase activity and degree of tumor malignancy. Furthermore, we i nvestigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. Materials and Methods: Sixty-two TCC tissue s and 12 normal bladder tissues were obtained. TdR-Pase activity was measur ed with the enzyme-linked immunosorbent assay. The in vitro histoculture dr ug response assay was also performed to investigate armor sensitivity to 5- fluorouracil (5-FU) and doxifluridine (5'-DFUR). Results: The TdR-Pase acti vity of TCCs was three-fold higher than that of normal tissues. The TdR-Pas e activity increased along with the histological grade, and the TdR- Pase a ctivity of invasive cancels was significantly higher than that of superfici al cancers. However, TdR-Pase showed no relationship with the sensitivity t o 5-FU or 5'-DFUR. Conclusion: A high TdR-Pase activity in human TCCs was c onfirmed to predict a high tumor grade and stage. However; the anti-tumor e ffect of fluorouracil-related drugs was independent of the TdR-Pase activit y.