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 the metabolism of fluorouracil-related drugs and it is also recognized as a potent angiogenic factor. We measured the TdR-Pase activity in human transitional cell cancers (TCCs) of the urinary tract to assess the relationship between TdR-Pase activity and degree of tumor malignancy. Furthermore, we investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs.

MATERIALS AND METHODS

Sixty-two TCC tissues and 12 normal bladder tissues were obtained. TdR-Pase activity was measured with the enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to investigate tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR).

RESULTS

The TdR-Pase activity of TCCs was three-fold higher than that of normal tissues. The TdR-Pase activity increased along with the histological grade, and the TdR-Pase activity of invasive cancers was significantly higher than that of superficial cancers. However, TdR-Pase showed no relationship with the sensitivity to 5-FU or 5'DFUR.

CONCLUSION

A high TdR-Pase activity in human TCCs was confirmed to predict a high tumor grade and stage. However, the anti-tumor effect of fluorouracil-related drugs was independent of the TdR-Pase activity.