SULINDAC CHEMOPREVENTION IN ADENOMATOUS POLYPOSIS COLI

家族性腺瘤性结肠息肉病是一种常染色体显性遗传疾病 以数百个结直肠腺瘤性息肉的形成为特征 在年轻的成年人。几乎所有患有FAP的人都会发展成结直肠癌。 如果不进行预防性结肠切除术，则为癌症。此外，许多患者 有上消化道腺瘤，易患十二指肠 carcinoma.目前，FAP的唯一有效疗法是结肠切除术， 上消化道的终身监测。我们的长期 目的是发现有效的化学预防疗法， FAP，代表了一个模型，可以提供基本的见解，分子 调节普通结直肠癌中的腺瘤-癌序列。 舒林酸是一种非甾体类前列腺素抑制剂， 据报道，15例FAP患者的腺瘤性息肉消退。我们 假设舒林酸可以减少结肠直肠腺瘤的生长， FAP患者相关的上皮过度增殖。 我们的具体目标是：a）在一个特定的时间内向FAP患者给予舒林酸， 随机安慰剂对照双盲试验。B）按顺序 通过视频内窥镜检查确定结肠直肠息肉数量， 计算机图像分析c）在腺瘤中进行顺序评估， 非息肉样结直肠粘膜的鸟氨酸脱羧酶活性， S-腺苷甲硫氨酸脱羧酶（在调节 多胺途径）和上皮细胞增殖指数 增殖细胞核Ki-67抗体免疫组化 抗原的

Familial adenomatous polyposis coli (FAP) is an autosomal dominant disorder characterized by the formation of hundreds of colorectal adenomatous polyps in young adults. Virtually all individuals with FAP will develop colorectal cancer if prophylactic colectomy is not performed. Moreover, many patients have upper gastrointestinal adenomas which predispose to duodenal carcinoma. Presently, the only effective therapy for FAP is colectomy and lifelong surveillance of the upper gastrointestinal tract. Our long term goal is to discover effective chemopreventative therapy for patients with FAP, representing a model which may provide basic insights into molecular regulation of the adenoma-carcinoma sequence in ordinary colorectal cancer. Sulindac, a nonsteroidal antiinflammatory prostaglandin inhibitor, has been reported anecdotally to resolve adenomatous polyps in 15 FAP patients. Our hypothesis is that sulindac can decrease growth of colorectal adenomas and the associated epithelial hyperproliferation in FAP patients. Our specific aims are to: a) Administer sulindac to FAP patients in a randomized, placebo-controlled, double-blinded trial. b) Sequentially determine colorectal polyp number by video endoscopy and polyp volume by computerized image analysis. c) Sequentially assess in adenomas and nonpolypoid colorectal mucosa the activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase (enzymes important in the regulation of the polyamine pathway), and epithelial proliferation index by immunohistochemistry with Ki-67 antibody to proliferating cell nuclear antigen.