Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy.
Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy.
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原发性结直肠癌中的胸苷磷酸化酶和二氢嘧啶脱氢酶水平与 5-脱氧-5-氟尿苷作为辅助化疗的临床效果有关。
DOI：
10.3892/or.9.3.479
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发表时间：
2002
期刊：
影响因子：
4.2
通讯作者：
K. Miwa
中科院分区：
文献类型：
--
作者：
G. Nishimura;I. Terada;Takashi Kobayashi;I. Ninomiya;H. Kitagawa;S. Fushida;T. Fujimura;M. Kayahara;K. Shimizu;T. Ohta;K. Miwa
胸苷磷酸化酶（TP）将卡培他滨的中间代谢物5 '-脱氧-5-氟尿嘧啶（5'-DFUR，去氧氟尿苷）转化为5-氟尿嘧啶（5-FU）。而二氢嘧啶脱氢酶（DPD）催化5-FU成为无活性分子。我们研究了肿瘤组织中TP和DPD水平，以评估其作为选择结直肠癌患者进行5 '-DFUR辅助化疗的指标的临床意义。共88例结直肠癌患者分为Dukes' B和C组，口服5'-DFUR（800 mg/人/天）治疗2年。在随访期间，88例患者中有20例复发。所有患者均回顾性检查原发肿瘤TP和DPD水平以及对5 '-DFUR的临床反应。结果表明：a）通过酶联免疫吸附测定（ELISA）测量的原发性肿瘤中TP和DPD的中值水平分别为43.6和32.3U/mg蛋白质。20例复发患者的原发肿瘤TP水平低于68例未复发患者（p=0.07）; B）尽管高TP中位数组和低TP中位数组之间的临床病理特征没有显着差异，但高TP组的无病生存率优于低TP组（89%对64%，在第4年）;和c）将患者分为4组，例如高TP/DPD、高TP但低DPD、低TP但高DPD和低TP/DPD，高TP但低DPD的患者具有最好的无病生存期，而低TP但高DPD组具有最差的生存期。这些结果表明，原发性结直肠肿瘤中的TP和DPD水平可能是选择可能对5 '-DFUR辅助化疗和可能对卡培他滨（5'-DFUR的前药）有反应的患者的有用指标。
Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5-FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive molecules. We investigated TP and DPD levels in tumor tissue to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR adjuvant chemotherapy. A total of 88 colorectal cancer patients were classified into Dukes' B and C groups and treated for 2 years with oral 5'-DFUR (800 mg/body/day). During the follow-up period, 20 of the 88 patients developed a recurrence. All the patients were examined retrospectively for primary tumor TP and DPD levels and clinical response to 5'-DFUR. Results showed that: a) median levels of TP and DPD in the primary tumor, measured by enzyme-linked immunosorbent assay (ELISA), were, respectively, 43.6 and 32.3 U/mg protein. Primary tumor TP levels of the 20 patients who had a recurrence were lower than those of the 68 patients with no recurrence (p=0.07); b) although there were no significant differences in clinicopathologic features between high and low median TP level groups, disease-free survival was better in the high TP than in the low TP group (89% vs. 64%, at year 4); and c) of patients classified into 4 groups such as high TP/DPD, high TP but low DPD, low TP but high DPD, and low TP/DPD, patients with high TP but low DPD had the best disease-free survival, whereas the low TP but high DPD group had the worst survival. These results suggest that TP and DPD levels in primary colorectal tumors may be a useful indicator for selecting patients likely to respond to 5'-DFUR adjuvant chemotherapy and probably capecitabine, a prodrug of 5'-DFUR.