Wang Li-Shu, Burke Carol A, Hasson Henrietta, Kuo Chieh-Ti, Molmenti Christine L Sardo, Seguin Claire, Liu Pengyuan, Huang Tim H-M, Frankel Wendy L, Stoner Gary D
Authors' Affiliations: Division of Hematology and Oncology, Department of Medicine;
Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland;
Cancer Prev Res (Phila). 2014 Jul;7(7):666-74. doi: 10.1158/1940-6207.CAPR-14-0052. Epub 2014 Apr 24.
Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP.
家族性腺瘤性息肉病（FAP）的特征是结肠息肉病发病早且患结直肠癌风险高。FAP的治疗方法是结肠切除术，随后终身切除直肠息肉。本研究确定黑莓（BRB）是否可能使FAP患者的直肠息肉消退。14例FAP患者每天接受BRB治疗9个月。7例患者口服BRB粉末，每晚睡前直肠插入两粒BRB栓剂。另外7例患者接受口服安慰剂加栓剂。在治疗开始时和BRB治疗9个月后获取直肠息肉数量和息肉大小。在两个时间点均收集息肉及相邻正常组织。直肠息肉的负担（P = 0.036）显著降低，但数量（P = 0.069）无显著变化。口服BRB未显示出益处。3例患者无反应。BRB显著降低了反应者直肠息肉（腺瘤）中的细胞增殖、DNA甲基转移酶1蛋白表达和p16启动子甲基化，但未降低Wnt通路拮抗剂SFRP2和WIF1的启动子甲基化，无反应者的直肠息肉未出现上述变化。MBD-seq分析显示，反应者经BRB治疗的腺瘤中有更多去甲基化的转录起始位点（TSS），包括miRNA的转录起始位点。总之，BRB栓剂似乎足以使FAP患者的直肠息肉消退。
