CALCIUM MODULATION OF COLON CANCER INTERMEDIATE MARKERS

结肠癌的高风险可能与 测定结肠粘膜的增殖活性或酶活性 通过几种分析：氚胸苷放射自显影， 溴脱氧尿苷免疫过氧化物酶和鸟氨酸脱羧酶活性。 据报道，结肠隐窝细胞的增殖活性 通过口服钙剂来抑制。许多问题仍然存在 在确定钙在体内的确切作用方面有待探索。 对结肠细胞增殖的调控及其有效性 在监测这一效应中的中间增殖标志物。 这项研究建议评估四个结直肠癌高危人群 癌症：a)既往散发性结肠癌患者，b) 有结肠癌病史的家庭成员患有结肠癌的患者 遗传性非息肉病性结肠癌(HNPCC)；c)无症状 因家庭原因有50%罹患结肠癌风险的个人 HNPCC病史；d)家族性结肠息肉病(FPC)。 在对其中一个风险组进行分层后，受试者为 随机接受口服钙剂(2克/天)或安慰剂治疗12次 几周，然后交叉使用阿魏酸盐疗法，为期12周。 增殖活性(氚胸苷、溴脱氧尿嘧啶核苷 和Omithine脱羧酶活性)在直肠活检中进行测量 进入研究项目，并在两个研究阶段(即安慰剂或 CaCO3)。将开发增殖活性和酶活性分布 对于每个高危人群和口服钙的调节程度 行政当局已决定。预计被录取的科目将 前瞻性地跟踪，以便评估的长期趋势 标记活性、钙调节和临床相关性。 与长期癌症控制目标相关的问题将是 考虑过了。这些将包括对学科招聘、研究的评估 依从性和辍学率，以及患者对研究的总体接受度 要求。

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.