Furuse Hiroshi, Hirano Yasuhiro, Harada Masaki, Mugiya Soichi, Ushiyama Tomomi, Suzuki Kazuo, Ozono Seiichiro
Dept. of Urology, Hamamatsu University School of Medicine.
Gan To Kagaku Ryoho. 2004 Sep;31(9):1431-3.
5-fluorouracil (5-FU) is an anticancer agent widely used against various tumors including bladder cancer. Orotate phosphoribosyl transferase (OPRT) is one of the key enzymes in metabolic pathways of 5-FU. We examined the possible relationship between OPRT activities of bladder cancer specimens and clinicopathological features. In addition, chemosensitivity to 5-FU was also examined. Bladder cancer specimens were obtained from 36 patients between November 1997 and January 2004. OPRT activity was measured by radioassay. In vitro chemosensitivity to 5-FU was assessed using histoculture drug response assay (HDRA). The mean OPRT activity in bladder cancer specimens was significantly higher than that in normal bladder specimens. In high-grade (G3) and invasive cancer specimens, mean OPRT activities were significantly higher than those in low grade (G1 and G2) and superficial cancer specimens, respectively. There was a significant correlation between OPRT activity and 5-FU sensitivity (r=0.571, p<0.01) in 19 cases whose OPRT activities and 5-FU sensitivities were assessed simultaneously. These results suggest that OPRT activity may be a good indicator of the malignant potential and sensitivity to 5-FU in bladder cancer.
5-氟尿嘧啶(5-FU)是一种广泛用于治疗包括膀胱癌在内的各种肿瘤的抗癌药物。乳清酸磷酸核糖基转移酶(OPRT)是5-FU代谢途径中的关键酶之一。我们研究了膀胱癌标本中OPRT活性与临床病理特征之间的可能关系。此外,还检测了对5-FU的化疗敏感性。1997年11月至2004年1月期间从36例患者获取膀胱癌标本。通过放射分析测定OPRT活性。使用组织培养药物反应测定法(HDRA)评估对5-FU的体外化疗敏感性。膀胱癌标本中的平均OPRT活性显著高于正常膀胱标本。在高级别(G3)和浸润性癌标本中,平均OPRT活性分别显著高于低级别(G1和G2)和浅表性癌标本。在同时评估OPRT活性和5-FU敏感性的19例病例中,OPRT活性与5-FU敏感性之间存在显著相关性(r = 0.571,p <0.01)。这些结果表明,OPRT活性可能是膀胱癌恶性潜能和对5-FU敏感性的良好指标。