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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer--in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase.
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Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer--in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase.

机译：二氢嘧啶脱氢酶抑制性氟嘧啶对非小细胞肺癌的作用-与胸苷酸合酶和二氢嘧啶脱氢酶的肿瘤表达相关。

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摘要

5-Fluorouracil (5-FU) and its derivatives have been used worldwide for the treatment of several malignancies in solid organs. The effectiveness of these drugs is well proven in gastrointestinal malignancy, and has been reported upon the inverse correlation with the tumoral expression of dihydropyrimidine dehydrogenase (DPD). However, the significance of DPD expression in 5-FU based chemotherapy has not been well investigated in non-small cell lung cancer (NSCLC). We examined enzymatic activities and immunohistochemical expression of thymidylate synthase (TS) and DPD in 84 cases of NSCLC. In vitro sensitivity for 5-FU was tested in 53 cases of them to evaluate these predictive values for effectiveness of 5-FU. Efficacy of 5-chloro-2,4-dihydroxypyridine (CDHP), potent DPD inhibitor, was also examined in 27 cases of them. There was a reversal correlation between protein expression of DPD and sensitivity to 5-FU (r = -0.65; p < 0.001). Six (33.3%) of 18 cases with strong expression of DPD showed 10% or more increment of the anti-tumor effect by adding CDHP to 5-FU. DPD inhibitory fluoropyrimidine and examination of the tumoral expression of DPD might be a promising chemotherapeutic strategy in NSCLC.
机译：5-氟尿嘧啶（5-FU）及其衍生物已在世界范围内用于治疗实体器官中的多种恶性肿瘤。这些药物在胃肠道恶性肿瘤中的有效性已得到充分证明，并已与二氢嘧啶脱氢酶（DPD）的肿瘤表达呈负相关。但是，尚未在非小细胞肺癌（NSCLC）中很好地研究了基于5-FU的化疗中DPD表达的重要性。我们检查了84例NSCLC患者胸腺嘧啶合酶（TS）和DPD的酶活性和免疫组化表达。测试了53例患者对5-FU的体外敏感性，以评估这些预测值对5-FU的有效性。还对27例有效的DPD抑制剂5-氯-2,4-二羟基吡啶（CDHP）的疗效进行了检查。 DPD的蛋白质表达与对5-FU的敏感性之间存在反向相关性（r = -0.65; p <0.001）。在DPD强烈表达的18例患者中，有6例（33.3％）通过向5-FU中添加CDHP来显示出10％或更高的抗肿瘤作用。 DPD抑制性氟嘧啶和DPD肿瘤表达的检查可能是NSCLC中有希望的化疗策略。

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