CALCIUM MODULATION OF COLON CANCER INTERMEDIATE MARKERS

结肠癌中间标志物的钙调节

• 批准号: 3423258
• 负责人: PATRICK M. LYNCH
• 金额: $ 3.46万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-10 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3423258
• 关键词: adenoma; biopsy; bromodeoxyuridine; calcium carbonate; calcium metabolism; cancer prevention; cancer risk; dietary supplements; gastrointestinal epithelium; intestinal mucosa; ornithine decarboxylase; rectosigmoid neoplasm; therapy compliance

A high risk for colon cancer may correlate positively with the, proliferative activity or enzymatic activity in colon mucosa as measured by several assays: tritiated thymidine autoradiography, bromodeoxyuridine immunoperoiddase, and ornithine decarboxylue activity. The proliferative activity of colonic crypt cells has been reported to be suppressed by the administration of oral calcium. Many issues remain to be explored in determining the precise role of calcium in the modulation of colonic cell proliferation and the validity of intermediate markers of proliferation in monitoring this offect. This study proposes to evaluate four high-risk groups for colorectal cancer: a) patients with previous sporadic-type colon cancer, b) patients with a previous colon cancer who are members of a family with hereditary non-polyposis colon cancer (HNPCC); c) asymptomatic individuals at 50% risk of developing colon cancer because of a family history of HNPCC; d) patients with familial polyposis coli (FPC). Following stratification to one of the risk-groups, subjects are randomized to receive either oral calcium (2 g/day) or placebo for 12 weeks, followed by a cross over to the altenate regimen for 12 weeks. Proliferative activity (tritiated thymidine, bromodeoxyuridine labeuing and omithine decarboxylase activity) are measured on rectal biopsy at study entry, and after each of the two study periods (ie placebo or CaCO3). Proliferative and enzymatic activity profiles will be developed for each high risk group and the degree of modulation by oral calcium administration determined. It is anticipated that subject enrolled will be followed prospectively in order to evaluate long-term trends of labelling activity, calcium modulation, and clinical correlation. Issues related to long-term cancer control objectives will be considered. These will include evaluation of subject recruitment, study compliance and drop-out, as well as overall patient acceptance of study requirements.

结肠癌的高风险可能与， 在结肠粘膜中的增殖活性或酶活性 通过几种测定：氚化胸苷放射自显影， 溴脱氧尿苷免疫过氧化物酶和鸟氨酸脱羧活性。 据报道，结肠隐窝细胞的增殖活性 通过口服钙来抑制。许多问题仍然存在 在确定钙在糖尿病中的确切作用时， 结肠细胞增殖的调节和 增殖的中间标志物在监测这种效应。 本研究旨在评估四个结直肠癌高危人群， 癌症：a）先前患有散发型结肠癌的患者，B） 既往患有结肠癌的患者，他们是患有 遗传性非息肉病性结肠癌（HNPCC）; c）无症状 由于家庭原因，50%的人患结肠癌的风险 HNPCC病史; d）家族性结肠息肉病（FPC）患者。 在分层至风险组之一后，受试者 随机接受口服钙剂（2 g/天）或安慰剂， 周，然后交叉到altenate方案12周。 放射活性（氚标记胸苷，溴脱氧尿苷标记 和omithine脱羧酶活性）在直肠活组织检查中测量， 研究入组后，以及两个研究期（即安慰剂或 CaCO3）。 将开发分解和酶活性谱 以及口服钙的调节程度 行政决定。预计入组的受试者将 为了评估长期趋势， 标记活性、钙调节和临床相关性。 与长期癌症控制目标有关的问题将在 考虑了这些将包括评价受试者招募、研究 依从性和脱落，以及患者对研究的总体接受度 要求.