[Choice of chemotherapeutic drugs for colorectal cancers by DPD and OPRT activities in cancer tissues].
[Choice of chemotherapeutic drugs for colorectal cancers by DPD and OPRT activities in cancer tissues].
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根据癌组织中DPD和OPRT活性选择结直肠癌化疗药物[J].
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
H. Iwasaki
中科院分区：
文献类型：
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作者：
M. Takemura;H. Osugi;Shigeru Lee;M. Kaneko;Yoshinori Tanaka;Y. Fujiwara;S. Nishizawa;H. Iwasaki
5-FU是用于消化系统癌症的最广泛使用的抗癌药物，并且最近已经报道5-FU的效果随着癌症组织中参与药物代谢的酶的量而变化。本文通过对正常大肠粘膜和大肠癌组织中DPD和OPRT活性的测定，并与临床病理因素进行比较，探讨大肠癌化疗方案的选择。对我科1999年至2003年3月间手术切除的46例大肠癌患者（结肠癌28例，直肠癌18例）进行了检查。正常组织和癌组织中DPD活性无显著差异，而OPRT在癌组织中显示出显著较高的活性。虽然我们没有发现DPD活性与临床病理因素之间的关系，但OPRT活性在性别和肿瘤分类之间存在显著差异，粘液腺癌的OPRT活性显著低于分化腺癌。粘液腺癌DPD活性与5-FU磷酸化的相关性与腺癌相当，而OPRT活性与5-FU磷酸化的主要途径相关性显著降低。因此，结肠粘液腺癌比分化腺癌对5-FU更耐药。因此，粘液腺癌的化疗应选择5-FU以外的抗癌药物。
5-FU is the most widely used anticancer drug for digestive system cancers, and it has been recently reported that the effect of 5-FU varies with the amount of enzymes that are involved in the drug metabolism in the cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of chemotherapy for colorectal cancers. Forty-six patients with colorectal carcinoma (28 colon and 18 rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and cancer tissues, whereas OPRT showed significantly higher activity in the cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of tumor, and mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated adenocarcinoma. The DPD activity of mucinous adenocarcinoma is related to catabolism of 5-FU is equal to that of adenocarcinoma, however, the OPRT activity is related to a main pathway of 5-FU phosphorylation is significantly lower. Thus, mucinous adenocarcinoma of the colon was more resistant to 5-FU than the differentiated adenocarcinoma. Therefore, for chemotherapy of mucinous adenocarcinoma, anticancer agents other than 5-FU should be selected.