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.


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.


CONCLUSIONS
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.
Hirano
Y
Y
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. hirano@hama-med.ac.jp
Kageyama
S
S
Ushiyama
T
T
Suzuki
K
K
Fujita
K
K
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005467:Floxuridine / Q000627:therapeutic use*; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine