胃癌中胸苷酸合成酶和胸苷激酶的活性

Activities of thymidylate synthetase and thymidine kinase in gastric cancer.

作者信息

Konishi T, Miyama T, Sakamoto S, Hirata T, Mafune K, Hiraishi M, Idezuki Y

机构信息

Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.

出版信息

Surg Oncol. 1992 Jun;1(3):215-21. doi: 10.1016/0960-7404(92)90067-u.

DOI:10.1016/0960-7404(92)90067-u

PMID:1341254

Abstract

In a previous clinical study, sequential methotrexate and 5-fluorouracil has shown improved efficacy for treating advanced gastric cancer of the poorly differentiated type. In this study, we investigated whether difference in the levels of thymidylate synthetase (TS) and thymidine kinase (TK) activities in gastric cancer tissue account for selectivity of the treatment. Activity of TS was higher in 19 cases of the poorly differentiated type than in 16 cases of the well differentiated type (P < 0.02), whereas TK activity was lower in the poorly differentiated type than in the well differentiated type (P < 0.01). Thus, the TS/TK ratio was significantly higher in poorly differentiated gastric cancers than in well differentiated cancers (P < 0.001). These results suggest that a greater dependence upon the de novo pathway of pyrimidine synthesis in poorly differentiated gastric carcinomas may enhance the efficacy of sequential methotrexate and 5-fluorouracil treatment.

摘要

在先前的一项临床研究中，序贯使用甲氨蝶呤和5-氟尿嘧啶已显示出对治疗低分化型晚期胃癌有更高的疗效。在本研究中，我们调查了胃癌组织中胸苷酸合成酶（TS）和胸苷激酶（TK）活性水平的差异是否是该治疗具有选择性的原因。19例低分化型胃癌组织中的TS活性高于16例高分化型胃癌组织（P < 0.02），而低分化型胃癌组织中的TK活性低于高分化型胃癌组织（P < 0.01）。因此，低分化型胃癌的TS/TK比值显著高于高分化型胃癌（P < 0.001）。这些结果表明，低分化型胃癌对嘧啶合成的从头途径有更大的依赖性，这可能会提高序贯使用甲氨蝶呤和5-氟尿嘧啶治疗的疗效。