Kosaka Takeo, Usami Kazuo, Ueshige Nobuo, Sugaya Junichi, Nakano Yasuharu, Takashima Shigeki
Department of General and Gastrointestinal Surgery, School of Medicine, Kanazawa Medical University, Ishikawa-ken 920-0293, Japan.
Oncol Rep. 2004 Dec;12(6):1279-86.
Due to the contradictory roles that thymidine phosphorylase (TP) plays in both tumor aggressiveness and fluoropyrimidine activation, its impact on drug responses has yet to be clearly established. Therefore, the present study was performed to clarify the effects of TP levels on the prognosis of gastric cancer patients treated postoperatively with different fluoropyrimidines. A total of 52 gastric cancer patients who underwent gastrectomy from January 1997 to March 1998 were enrolled in the present study. The TP levels in the specimens were assayed by enzyme-linked immunosorbent assay (ELISA). Survival was significantly poorer for the 27 patients with high normal tissue TP activity than for the 25 with low normal tissue TP activity. Normal tissue TP level showed different effects on survival according to the chemotherapy regimen used. While the survival rate was significantly poorer in patients with high normal TP level than in those with low normal TP in the 5-FU group, the rate was almost the same in the 5'-DFUR group. Cox's proportional hazard model revealed that tumor TP was an independent prognostic factor in gastric cancer patients. Since activating and catabolizing enzymes for fluoropyrimidines differ from each other, alterations in gene expression of these enzymes should be useful predictive factors.
由于胸苷磷酸化酶（TP）在肿瘤侵袭性和氟嘧啶激活过程中发挥着相互矛盾的作用，其对药物反应的影响尚未明确。因此，本研究旨在阐明TP水平对接受不同氟嘧啶类药物术后治疗的胃癌患者预后的影响。本研究纳入了1997年1月至1998年3月期间接受胃切除术的52例胃癌患者。通过酶联免疫吸附测定（ELISA）法检测标本中的TP水平。27例正常组织TP活性高的患者的生存率明显低于25例正常组织TP活性低的患者。正常组织TP水平根据所使用的化疗方案对生存率有不同影响。在5-氟尿嘧啶组中，正常TP水平高的患者的生存率明显低于正常TP水平低的患者，而在5'-去氧氟尿苷组中，两者的生存率几乎相同。Cox比例风险模型显示，肿瘤TP是胃癌患者的独立预后因素。由于氟嘧啶类药物的激活酶和分解代谢酶各不相同，这些酶基因表达的改变应是有用的预测因素。
