Thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell carcinoma: relationship between histological parameters and chemosensitivity to 5-fluorouracil.
OBJECTIVE
Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathway of 5-fluorouracil (5-FU). Theoretically, cancer cells which have high TdR-Pase activity and/or low DPD activity should be sensitive to 5-FU. TdR-Pase is also known to have angiogenic activity which helps tumor progression and metastasis. On the other hand, little is known concerning the relationship of DPD activity with clinical malignant potential in renal cell carcinoma (RCC). In this study, we measured both TdR-Pase and DPD activities in surgically obtained RCC tissues and examined the relationship between these enzymatic activities and histological parameters. In addition, the results of in vitro chemosensitivity testing were also analyzed to determine whether TdR-Pase and/or DPD activity in carcinoma cells can predict the efficacy of 5-FU.


METHODS
RCC tissues from 53 patients were obtained. TdR-Pase and DPD activities were measured by ELISA and radioenzyme assay, respectively. Sensitivity to 5-FU was assessed by histoculture drug response assay (HDRA), an in vitro chemosensitivity test, for 20 of the 53 specimens.


RESULTS
Both TdR-Pase and DPD activities of RCC increased with histological grade. There was a significant positive correlation between the TdR-Pase activity and 5-FU sensitivity. In addition, a stronger positive correlation was found between TdR-Pase / DPD ratio and 5-FU sensitivity. DPD exhibited no correlation with 5-FU sensitivity.


CONCLUSIONS
The activity of both enzymes increased with malignant potential of RCC. TdR-Pase appeared to be the enzyme regulating activation of 5-FU in RCC.
Hirano
Yasuhiro
Y
Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. flat0726@g02.enjoy.ne.jp
Takayama
Tatsuya
T
Kageyama
Shinji
S
Ushiyama
Tomomi
T
Suzuki
Kazuo
K
Fujita
Kimio
K
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D010088:Oxidoreductases / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; D005472:Fluorouracil