Hamaji Masayasu, Nishida Toshiroh, Miyazaki Satoru, Nishida Yukihiro
Dept. of Surgery, Higashiosaka City General Hospital.
Gan To Kagaku Ryoho. 2002 Jun;29(6):889-93.
Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) in cancer are considered to play key roles in the sensitivity to 5-FU-based chemotherapy. We measured DPD activities and TS content in cancer and normal mucosa obtained from 59 patients with colorectal carcinomas and examined their relationship and clinicipathological relevance. DPD activity was significantly decreased in cancer compared to that in adjacent mucosa, irrespective of the clinicopathological parameters (p < 0.0001), while TS content was significantly increased in cancer (p < 0.0001). DPD activity in cancer correlated with that of the normal mucosa (r = 0.57, p < 0.001), but no correlation was found between TS content of normal mucosa and cancer. The DPD activity difference between cancer and normal mucosa was significantly correlated with difference in TS content (r = 0.70, p < 0.0001). These results suggest that the reduction of DPD activity is associated with the elevation of TS content, which may be connected with the development of 5-FU resistance and the effectiveness of biochemical modulation through the stabilization of TS inhibition with folic acid in colon carcinoma.
癌症中的二氢嘧啶脱氢酶（DPD）和胸苷酸合成酶（TS）被认为在基于5-氟尿嘧啶（5-FU）的化疗敏感性中起关键作用。我们测定了59例结直肠癌患者癌组织和正常黏膜中的DPD活性及TS含量，并研究了它们之间的关系及其临床病理相关性。与相邻黏膜相比，癌组织中的DPD活性显著降低，与临床病理参数无关（p<0.0001），而癌组织中的TS含量显著升高（p<0.0001）。癌组织中的DPD活性与正常黏膜中的DPD活性相关（r = 0.57，p<0.001），但正常黏膜和癌组织的TS含量之间未发现相关性。癌组织与正常黏膜之间的DPD活性差异与TS含量差异显著相关（r = 0.70，p<0.0001）。这些结果表明，DPD活性降低与TS含量升高有关，这可能与5-FU耐药性的发展以及通过叶酸稳定TS抑制作用在结肠癌中进行生化调节的有效性有关。
