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.


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.


CONCLUSIONS
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.
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. furuseh@hama-med.ac.jp
Hiroshi
H
Furuse
Yasuhiro
Y
Hirano
Masaki
M
Harada
Liu Hong
LH
Ming
Takahiro
T
Aoki
Yutaka
Y
Kurita
Soichi
S
Mugiya
Tomomi
T
Ushiyama
Seiichiro
S
Ozono
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D011237:Predictive Value of Tests; D001743:Urinary Bladder / Q000201:enzymology / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil