SULINDAC CHEMOPREVENTION IN ADENOMATOUS POLYPOSIS COLI

SULINDAC 化学预防腺瘤性结肠息肉病

• 批准号: 3549720
• 负责人: FRANCIS M GIARDIELLO
• 金额: $ 12.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549720
• 关键词: S adenosylmethionine; adenocarcinoma; adenoma; antiinflammatory agents; autosomal dominant trait; biomarker; biopsy; cancer prevention; cell cycle; colorectal neoplasms; endoscopy; gastrointestinal epithelium; genetic disorder; human subject; human therapy evaluation; hyperplasia; imaging /visualization /scanning; immunocytochemistry; monoclonal antibody; neoplasm /cancer chemotherapy; neoplastic growth; ornithine decarboxylase; placebos; prostaglandin inhibitors; statistics /biometry

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.

家族性腺瘤性结肠息肉病(FAP)是一种常染色体显性遗传病 以形成数百个结直肠腺瘤性息肉为特征 在年轻人身上。几乎所有FAP患者都会发展为结直肠 如果不进行预防性结肠切除术，就会患上癌症。此外，许多患者 有上消化道腺瘤，易发于十二指肠 癌症。目前，对FAP唯一有效的治疗方法是结肠切除术和 对上胃肠道进行终身监测。我们的长期计划 我们的目标是发现有效的化学预防疗法来治疗慢性阻塞性肺疾病 FAP，代表了一个可以提供对分子的基本见解的模型 普通结直肠癌中腺瘤-癌序列的调控。 舒林酸，一种非类固醇抗炎前列腺素抑制剂，已经被 轶事报道解决了15例FAP患者的腺瘤性息肉。我们的 假设舒林酸可以减少结直肠腺瘤的生长和 FAP患者相关的上皮细胞过度增殖。 我们的具体目标是：a)给FAP患者服用舒林酸 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大肠息肉数量，并通过 计算机图像分析。C)对腺瘤进行顺序评估和 非息肉样大肠粘膜鸟氨酸脱羧酶活性及 S-腺苷甲硫氨酸脱羧酶 多胺途径)和上皮细胞增殖指数 增殖细胞核Ki-67抗体的免疫组织化学 抗原。