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首页> 外文期刊>BJU international >The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.
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The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.

机译：二氢嘧啶脱氢酶表达在前列腺癌中的意义。

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OBJECTIVE: To measure dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the metabolism of 5-fluorouracil (5-FU), expression in prostate cancer and determine whether 5-chloro-2,4-dihydroxypyridine (CDHP), a potent inhibitor of DPD, enhances the antitumoral activity of 5-FU against prostate cancer. PATIENTS, MATERIALS AND METHODS: In all, 44 prostate tissue specimens were obtained from men who had a radical prostatectomy alone for prostate cancer, and 38 specimens from men who had had neoadjuvant hormonal therapy. We analysed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry, and determined its prognostic significance. In cultured human prostate cancer lines (DU145 and LNCaP), we compared the cytotoxicity of 5-FU/CDHP with that of 5-FU alone. Finally, in experiments on immunodeficient mice, we studied the effect of oral administration of tegafur, a pro-drug for 5-FU, with or without CDHP on the growth of tumours introduced by injection of DU145 cells. RESULTS: The expression of DPD was significantly higher in cancerous than normal prostate tissue; 36 of 44 (82%) specimens of prostate cancer expressed DPD, whereas only 25 of 44 (57%) specimens of normal prostate tissue expressed DPD. For men with prostate cancer who had radical prostatectomy alone, men with negative DPD expression tended to have a longer recurrence-free survival than those with positive expression; there were no recurrences in men with prostate cancer and negative DPD expression in the 5-year follow-up. DPD expression was significantly lower in men with prostate cancer who received neoadjuvant hormonal therapy. In vitro treatment of human prostate cancer cell lines with 5-FU/CDHP showed more cytotoxicity than with 5-FU treatment alone. Finally, DU145 tumours in mice treated with tegafur and CDHP were significantly smaller than in mice given tegafur alone. CONCLUSION: The present study showed that DPD expression is elevated in prostate cancer, and indicate that DPD inhibitors might enhance the antitumour activity of 5-FU against prostate cancer.
机译：目的：测定二氢嘧啶脱氢酶（DPD），一种参与5-氟尿嘧啶（5-FU）代谢的酶，在前列腺癌中的表达，并确定5-氯-2,4-二羟基吡啶（CDHP）是否是一种有效的抑制作用。 DPD增强了5-FU对前列腺癌的抗肿瘤活性。患者，材料和方法：总共从单独进行前列腺癌根治性前列腺切除术的男性获得44份前列腺组织标本，并从接受新辅助激素治疗的男性获得38份标本。我们使用免疫组织化学分析了癌组织和正常前列腺组织中DPD的表达，并确定了其预后意义。在培养的人前列腺癌株系（DU145和LNCaP）中，我们比较了5-FU / CDHP和单独的5-FU的细胞毒性。最后，在针对免疫缺陷小鼠的实验中，我们研究了口服或不注射CDHP的5-FU前药替加氟对通过注射DU145细胞引入的肿瘤生长的影响。结果：癌组织中DPD的表达明显高于正常前列腺组织。前列腺癌的44个样本中有36个（82％）表达了DPD，而正常前列腺组织的44个样本中只有25个（57％）表达了DPD。对于仅进行根治性前列腺切除术的前列腺癌男性，DPD表达阴性的男性往往比阳性表达的男性更长的无复发生存期。在5年的随访中，前列腺癌和DPD表达阴性的男性均未复发。在接受新辅助激素治疗的前列腺癌男性中，DPD表达明显降低。与单独使用5-FU治疗相比，使用5-FU / CDHP体外治疗人前列腺癌细胞系显示出更高的细胞毒性。最后，用替加氟和CDHP治疗的小鼠中的DU145肿瘤明显小于单独给予替加氟的小鼠。结论：本研究表明DPD在前列腺癌中表达升高，并表明DPD抑制剂可能增强5-FU对前列腺癌的抗肿瘤活性。

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