在对区域性前列腺癌患者施用前列腺癌根治术之前金雀异黄素的短期干预对前列腺生物标志物表达的影响_巴托

针对病种：前列腺癌

发表时间：2012年12月

发表国家：英国

登载刊物：英国营养学杂志

研究单位：挪威奥斯陆大学附属医院癌症研究所泌尿系等

研究人员：巴托拉泽雷维奇，汉玛斯都木克莱拉，杨进等

主要结论：金雀异黄素的干预大大减少了肿瘤细胞中 KLK4 的mRNA 水平 (P = 0.033)，并且雄激素和细胞周期相关的生物标志物没有显著减少，除了 p27Kip1，其在细胞核中的表达有所增加。金雀异黄素干预调节了可能与PCa预示和进展表达相关的几种生物标志物。本研究认为金雀异黄素可以作为PCa的化学预防药物。需要更大规模和更长时间的研究来进一步调查.

British Journal of Nutrition, 2012, 108(12):1-10.

The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy

Bato Lazarevic, Hammarström Clara, Jin Yang, et al

Department of Urology, Institute of Cancer Research, Oslo University Hospital, The Norwegian Radiumhospital, Montebello, 0310 Oslo, Norway; et al

Nutritionally relevant levels of genistein, the predominant isoflavone in soyabean associated with lower risk of prostate cancer (PCa), may modulate the expression of prostate tissue biomarkers associated with cancer prediction and progression. A phase 2 placebo-controlled, randomised, double-blind clinical trial was conducted in forty-seven Norwegian patients before prostatectomy. Intervention was 30 mg genistein or placebo capsules daily for 3-6 weeks. Luminal cells from malignant and benign glands were isolated with laser capture microdissection and the mRNA levels of androgen-related biomarkers (androgen receptor, NK3 homeobox 1, kallikrein-related peptide 4 (KLK4)) and cell cycle-related genes (p21 Waf1/Cip1 , p27 Kip1 , p53) were analysed with real-time semiquantitative PCR. Immunohistochemistry of androgen-, cell cycle-, proliferative- (Ki67 nuclear antigen), apoptotic- (B-cell CLL/lymphoma 2 (BCL-2) and BCL-2-associated X protein) and neuroendocrine differentiation-related biomarkers (neuron-specific enolase and cytoplasmic chromogranin A) was performed using tissue microarrays containing normal, Gleason grade 3 and grade 4 prostate tissues. There were no significant effects by genistein intervention on proliferation-, cell cycle-, apoptosis- or neuroendocrine biomarkers. Genistein intervention, however, significantly reduced the mRNA level of KLK4 in tumour cells (P = 0·033) and there was a non-significant reduction in androgen and cell cycle-related biomarkers, except for p27Kip1, whose expression in the nuclear compartment was increased. Genistein intervention modulated the expression of several biomarkers which may be related to PCa prediction and progression. The present study supports genistein as a chemopreventive agent in PCa. Further investigation is warranted in larger and longer-duration studies.

英国《英国营养学杂志》，2012年12月

在对区域性前列腺癌患者施用前列腺癌根治术之前金雀异黄素的短期干预对前列腺生物标志物表达的影响

巴托拉泽雷维奇，汉玛斯都木克莱拉，杨进，等

挪威奥斯陆大学附属医院癌症研究所泌尿系等

营养相关水平的金雀异黄素，与降低前列腺癌 (PCa) 的风险有关的大豆的主要异黄酮，可能调节前列腺组织与癌症预示与进展相关的生物标志物的表达。对47个实施前列腺切除术之前的挪威患者进行II期空白剂对照、随机、双盲临床试验。在3-6 周时间段内每日用30 mg金雀异黄素或空白胶囊调节。恶性和良性的腺腔细胞被激光捕获显微切割技术分离，并且与雄激素相关的生物标志物（雄激素受体、 NK3 同源盒 1、激肽释放酶相关肽 4 (KLK4)）的 mRNA 水平以及细胞周期相关基因 (p21 Waf1/Cip1，p27 Kip1， p53) 用实时定量 PCR技术进行分析。雄激素-，细胞周期-，增生性-（Ki67 核抗原），凋亡-(B-细胞慢性淋巴细胞白血病/淋巴瘤 2 (BCL-2) 和 BCL-2 相关的 X 蛋白) 的免疫组织化学和神经内分泌分化相关的生物标记物（神经元特异性烯醇化酶和细胞质嗜铬素 A）使用含有正常、格里森 3 级和 4 级的前列腺组织的微阵列进行测试。金雀异黄素干预对细胞增殖、细胞周期、细胞凋亡或神经内分泌标志物没有显著影响。然而，金雀异黄素的干预大大减少了肿瘤细胞中 KLK4 的mRNA 水平 (P = 0.033)，并且雄激素和细胞周期相关的生物标志物没有显著减少，除了 p27Kip1，其在细胞核中的表达有所增加。金雀异黄素干预调节了可能与PCa预示和进展表达相关的几种生物标志物。本研究认为金雀异黄素可以作为PCa的化学预防药物。需要更大规模和更长时间的研究来进一步调查。