Thymidine phosphorylase activity in renal cell carcinoma: relationship between histological parameters and chemosensitivity to fluorouracil-related drugs.
Thymidine phosphorylase (TdR-Pase) is an essential enzyme in the metabolism of fluorouracil-related drugs and is also a potent angiogenic factor. We measured the TdR-Pase activity in human renal cell carcinomas (RCCs) to assess the relationship between TdR-Pase activity and the degree of tumor malignancy. We also investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. A total of 61 RCC tissue specimens and 39 normal kidney tissue specimens were obtained. TdR-Pase activity was measured by enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to examine tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). The TdR-Pase activity of RCCs was 13-fold that of the normal tissues. Activity increased with histological grade, and,was significantly higher in high-stage tumors (T3 or higher). TdR-Pase activity exhibited a significant positive correlation with sensitivity to 5-FU and 5'-DFUR. High TdR-Pase activity in human RCC was confirmed to predict high tumor grade and stage. RCCs with high TdR-Pase activity were also sensitive to FU-related drugs.
Hirano
Yasuhiro
Y
Department of Urology, Hamamatsu University School of Medicine, Handayama Hamamatsu City, Japan. hirano@hama-med.ac.jp
Takayama
Tatsuya
T
Kageyama
Shinji
S
Ushiyama
Tomomi
T
Suzuki
Kazuo
K
Fujita
Kimio
K
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D005467:Floxuridine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D012016:Reference Values; D013939:Thymidine Phosphorylase / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine