Stoner Gary D, Wang Li-Shu, Zikri Nancy, Chen Tong, Hecht Stephen S, Huang Chuanshu, Sardo Christine, Lechner John F
Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Innovation Centre, 2001 Polaris Parkway, Columbus, OH 43240, USA.
Semin Cancer Biol. 2007 Oct;17(5):403-10. doi: 10.1016/j.semcancer.2007.05.001. Epub 2007 May 10.
Our laboratory is developing a food-based approach to the prevention of esophageal and colon cancer utilizing freeze-dried berries and berry extracts. Dietary freeze-dried berries were shown to inhibit chemically induced cancer of the rodent esophagus by 30-60% and of the colon by up to 80%. The berries are effective at both the initiation and promotion/progression stages of tumor development. Berries inhibit tumor initiation events by influencing carcinogen metabolism, resulting in reduced levels of carcinogen-induced DNA damage. They inhibit promotion/progression events by reducing the growth rate of pre-malignant cells, promoting apoptosis, reducing parameters of tissue inflammation and inhibiting angiogenesis. On a molecular level, berries modulate the expression of genes involved with proliferation, apoptosis, inflammation and angiogenesis. We have recently initiated clinical trials; results from a toxicity study indicated that freeze-dried black raspberries are well tolerated in humans when administered orally for 7 days at a dose of 45 g per day. Several Phase IIa clinical trials are underway in patients at high risk for esophagus and colon cancer; i.e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases.
我们的实验室正在研发一种基于食物的方法来预防食管癌和结肠癌,所利用的是冻干浆果和浆果提取物。研究表明,食用冻干浆果可使啮齿动物化学诱导的食管癌发病率降低30%-60%,结肠癌发病率降低达80%。浆果在肿瘤发展的起始阶段和促进/进展阶段均有效果。浆果通过影响致癌物代谢来抑制肿瘤起始事件,从而降低致癌物诱导的DNA损伤水平。它们通过降低癌前细胞的生长速率、促进细胞凋亡、降低组织炎症参数以及抑制血管生成来抑制促进/进展事件。在分子水平上,浆果可调节与增殖、凋亡、炎症和血管生成相关的基因表达。我们最近启动了临床试验;一项毒性研究结果表明,冻干黑莓以每天45克的剂量口服7天时,人体耐受性良好。几项IIa期临床试验正在食管癌和结肠癌高危患者中进行,即巴雷特食管、食管发育异常和结肠息肉患者,以确定浆果是否会调节这些疾病发展的各种组织学和分子生物标志物。