Terashima M, Irinoda T, Fujiwara H, Nakaya T, Takagane A, Abe K, Yonezawa H, Oyama K, Inaba T, Saito K, Takechi T, Fukushima M
Department of Surgery 1, Iwate Medical University, Morioka, Japan.
Anticancer Res. 2002 Mar-Apr;22(2A):761-8.
The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated.
TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay.
There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465).
These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.
评估胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）的酶活性在肿瘤进展及对5-氟尿嘧啶（5-FU）敏感性中的作用。
测定81例胃癌临床样本中的TS和DPD活性。TS活性通过5-氟脱氧尿苷单磷酸结合试验测定，DPD活性分别通过放射酶法测定。通过体外ATP试验确定对5-FU的敏感性。
TS活性与对5-FU的敏感性之间无相关性。然而，发现DPD活性与对5-FU的敏感性之间存在弱相关性。在未接受辅助化疗的患者亚组中，TS活性高的患者总生存期较差（p = 0.0265）。相反，在接受以5-FU为基础的辅助化疗的患者亚组中，DPD活性高的患者总生存期较差（p = 0.0465）。
这些结果表明TS在肿瘤进展中起重要作用，而DPD可能是胃癌中5-FU敏感性的主要预测指标。
