Takabayashi A, Iwata S, Kawai Y, Kanai M, Taki Y, Takechi T, Fukushima M
Department of Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Kita-ku, Osaka 530-8480, Japan.
Int J Oncol. 2000 Nov;17(5):889-95. doi: 10.3892/ijo.17.5.889.
Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradation and inactivation of 5-fluorouracil (5-FU). The amount of its expression in a tumor is thought to be a factor determining the response of the tumor to 5-FU therapy. We compared DPD activity and DPD mRNA expression in resected tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAC) and surgery and a group of 24 patients with advanced gastric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. In the surgery alone group, DPD activity decreased significantly as the tumor stage advanced. This change was not observed in the NAC plus surgery group. Neither tumor depth (T factor) nor lymph node metastasis was found to correlate with DPD activity. Patients who responded to preoperative chemotherapy had lower DPD mRNA levels. Based on these results, we anticipate that measurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.
二氢嘧啶脱氢酶（DPD）是一种参与5-氟尿嘧啶（5-FU）降解和失活的酶。肿瘤中其表达量被认为是决定肿瘤对5-FU治疗反应的一个因素。我们比较了两组患者切除肿瘤中的DPD活性和DPD mRNA表达，一组是14例接受术前化疗（新辅助化疗；NAC）及手术的晚期胃癌患者，另一组是24例未接受术前化疗而接受手术的晚期胃癌患者。发现肿瘤DPD活性与肿瘤DPD mRNA表达密切相关。在单纯手术组中，随着肿瘤分期进展，DPD活性显著降低。在NAC加手术组中未观察到这种变化。未发现肿瘤深度（T因子）和淋巴结转移与DPD活性相关。对术前化疗有反应的患者DPD mRNA水平较低。基于这些结果，我们预计在临床标本中检测DPD表达可能对晚期胃癌的治疗具有临床应用价值。
