Hirano Yasuhiro, Takayama Tatsuya, Kageyama Shinji, Ushiyama Tomomi, Suzuki Kazuo, Fujita Kimio
Department of Urology, Hamamatsu University School of Medicine, Handayama Hamamatsu City, Japan.
Urol Res. 2002 May;30(2):112-5. doi: 10.1007/s00240-002-0241-x.
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.
胸苷磷酸化酶（TdR-Pase）是氟尿嘧啶相关药物代谢中的一种关键酶，也是一种强效血管生成因子。我们测定了人肾细胞癌（RCC）中的TdR-Pase活性，以评估TdR-Pase活性与肿瘤恶性程度之间的关系。我们还研究了TdR-Pase活性与对氟尿嘧啶相关药物的化疗敏感性之间的关系。共获得61份RCC组织标本和39份正常肾组织标本。通过酶联免疫吸附测定法测量TdR-Pase活性。还进行了体外组织培养药物反应测定，以检测肿瘤对5-氟尿嘧啶（5-FU）和去氧氟尿苷（5'-DFUR）的敏感性。RCC的TdR-Pase活性是正常组织的13倍。活性随组织学分级增加，在高分期肿瘤（T3或更高）中显著更高。TdR-Pase活性与对5-FU和5'-DFUR的敏感性呈显著正相关。证实人RCC中高TdR-Pase活性可预测高肿瘤分级和分期。具有高TdR-Pase活性的RCC对FU相关药物也敏感。
