Curcumin chemoprevention in familial adenomatous polyposis

描述(申请人提供)：家族性结肠腺瘤性息肉病(FAP)是一种常染色体显性遗传病，由APC基因的胚系突变引起，其特征是在年轻人中形成数百例结直肠腺瘤性息肉。如果不进行预防性结肠切除术，几乎所有受影响的患者都会患上结直肠癌。目前，对FAP唯一有效的治疗方法是结肠切除术和终生肠道监测。我们的长期目标是为FAP患者发现有效的化学预防性治疗，这是一个可能为普通肠癌中腺瘤-癌序列的分子调控提供见解的模型。姜黄素是从姜黄粉中提取的主要黄色素。姜黄素在亚洲一直被用作调味品，被认为是一种安全的食品添加剂。姜黄素用于治疗5例FAP患者的结直肠和回肠腺瘤，且无副作用。我们的假设是姜黄素可以抑制FAP患者的直肠-回肠生长和相关的上皮细胞过度增殖。我们的具体目标是：a)在一项随机、安慰剂对照的双盲试验中，对FAP患者给予姜黄素，并通过视频内窥镜连续确定直肠-回肠息肉的数量和大小。B)依次检测扁平直肠和息肉直肠回肠黏膜上皮细胞增殖(鸟氨酸脱羧酶、多胺和增殖细胞核抗原免疫组织化学)、细胞凋亡(通过形态学测量和TUNEL法检测细胞凋亡指数)和环氧合酶-2水平(免疫组织化学和qRT-PCR检测COX-2mRNA)的水平。

DESCRIPTION (provided by applicant): Familial adenomatous polyposis coli (FAP) is an autosomal dominant disorder due to germline mutation of the APC gene and characterized by the formation of hundreds of colorectal adenomatous polyps in young adults. Virtually all affected patients will develop colorectal cancer if prophylactic colectomy is not performed. Presently, the only effective therapy for FAP is colectomy and lifelong surveillance of the intestinal tract. Our long term goal is to discover effective chemopreventative therapy for patients with FAP, representing a model which may provide insights into the molecular regulation of the adenoma-carcinoma sequence in ordinary intestinal cancer. Curcumin is the major yellow pigment extracted from turmeric the powdered root of the herb Curcuma longa. Curcumin has long been used as a spice in Asia and is considered a safe food additive. Curcumin has been reported by our group to regress colorectal and ileal adenomas in 5 patients with FAP without side effects. Our hypothesis is that curcumin can decrease growth of rectal-ileal and the associated epithelial hyperproliferation in FAP patients. Our specific aims are to: a) administer curcumin to FAP patients in a randomized, placebo-controlled, double-blinded trial and sequentially determine rectal-ileal polyp number and size by using videoendoscopy. b) Sequentially assess in flat and polypoid rectal-ileal mucosa markers of epithelial proliferation (ornithine decarboxylase, polyamines and immunohistochemistry for proliferating cell nuclear antigen), apoptosis (apoptotic index by morphologic measurement and TUNEL assay), and cyclooxygenase- 2 levels (immunohistochemistry and qRT-PCR assessment of COX-2 mRNA).