Hirano Y, Kageyama S, Ushiyama T, Suzuki K, Fujita K
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Anticancer Res. 2000 Nov-Dec;20(6B):4315-8.
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.
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).
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.
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.
胸苷磷酸化酶（TdR-Pase）是氟尿嘧啶相关药物代谢的关键酶，同时也被认为是一种强效血管生成因子。我们检测了人泌尿道移行细胞癌（TCCs）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。此外，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。
获取62例TCC组织和12例正常膀胱组织。采用酶联免疫吸附测定法检测TdR-Pase活性。还进行了体外组织培养药物反应测定，以研究肿瘤对5-氟尿嘧啶（5-FU）和去氧氟尿苷（5'-DFUR）的敏感性。
TCCs的TdR-Pase活性比正常组织高3倍。TdR-Pase活性随组织学分级升高而增加，浸润性癌的TdR-Pase活性显著高于浅表性癌。然而，TdR-Pase与对5-FU或5'-DFUR的敏感性无关。
已证实人TCCs中高TdR-Pase活性可预测高肿瘤分级和分期。然而，氟尿嘧啶相关药物的抗肿瘤作用与TdR-Pase活性无关。
