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首页> 外文期刊>Clinical cancer research: an official journal of the American Association for Cancer Research >Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study.
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Modulation of genetic and epigenetic biomarkers of colorectal cancer in humans by black raspberries: a phase I pilot study.

机译：黑莓对人类大肠癌遗传和后生生物标志物的调节：I期试验研究。

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PURPOSE: This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis, and expression of Wnt pathway genes. EXPERIMENTAL DESIGN: Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60 g/d) for 1-9 weeks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured. RESULTS: The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks, but not in all 20 patients with 1-9 weeks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis, and angiogenesis in a protective direction. CONCLUSIONS: These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted.
机译：目的：本研究评估了黑莓（BRBs）对人结肠和直肠肿瘤发展的生物标志物的影响，包括相关肿瘤抑制基因的甲基化，细胞增殖，凋亡，血管生成和Wnt通路基因的表达。实验设计：从20例口服BRB粉末（60 g / d）1-9周前后，对邻近的正常组织和结直肠腺癌进行活检。量化了五个抑癌基因启动子区域的甲基化状态。测量了DNA甲基转移酶1（DNMT1）的蛋白质表达以及与细胞增殖，凋亡，血管生成和Wnt信号传导相关的基因。结果：三种Wnt抑制剂SFRP2，SFRP5和WIF1（Wnt途径的上游基因）和PAX6a（一种发育调节剂）的甲基化仅在接受了BRB的患者中受到正常组织和结直肠肿瘤中BRB的保护方向的调节。治疗时间平均为4周，但并非所有20例接受1-9周BRB治疗的患者。这与DNMT1的表达降低有关。 BRB在保护方向上调节与Wnt途径，增殖，凋亡和血管生成相关的基因的表达。结论：这些数据提供了BRB在人类结肠和直肠中使抑癌基因去甲基化并调节肿瘤发展的其他生物标志物的能力的证据。尽管所有接受治疗的患者的大肠组织中均未发生基因脱甲基，但次要终点的阳性结果表明，现在有必要对BRBs进行其他预防人类大肠癌的研究。

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