MARKERS OF COLLOID & POORLY-DIFFERENTIATED COLON CANCER

胶体标记

基本信息

批准号：
3191257
负责人：
YOUNG S KIM
金额：
$ 15.88万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-04-01 至 1991-03-31
项目状态：
已结题

项目摘要

Colorectal cancers are biologically and histologically diverse. Two histological types that have a poor clinical outcome are those with extensive mucin production (colloid carcinomas) and those with poor cellular differentiation. A well-characterized patient population will be used to focus on these two unique subsets of colorectal cancers in order to identify markers and mechanisms that may later be applicable to improving diagnosis, staging, and treatment of the broader class of moderately- to well- differentiated adenocarcinomas. Although colloid carcinomas and poorly-differentiated adenocarcinomas are biologically distinct, the same patient population and many of the same methods will be used to study both. The broad goals of this proposal are to identify markers for colon cancers of the colloid carcinoma and poorly-differentiated types and to develop experimental models for studying the biological effects and molecular mechanisms of mucin production. The specific aims include: 1) Establishment of an adequate data base through close follow-up of analytic colorectal cancer cases; 2) Identification of markers for colloid carcinomas using histochemistry, lectin-binding, and new and existing mucin- reactive antibodies; 3) Establishment of cell lines from colloid and signet ring cell carcinomas and evaluation of the biological behavior of these experimental models; 4) Elucidation of the molecular mechanisms for synthesis and secretion of mucin by identification of precursors, inhibitors, and secretagogues, by structural comparison of colloid carcinoma and adenocarcinoma mucins, by quantitation of glycosyltransferases, and by isolation and characterization of mucin cDNA; 5) Identification of markers and evaluation of models for poorly-differentiated adenocarcinomas by surveying antigen expression immunohistochemically, by producing monoclonal antibodies to poorly-differentiated cells, by examining the biological properties of poorly-differentiated cell lines, and by investigating nuclear and proliferative parameters by flow cytometry and image analysis; 6) Correlation of the results of these laboratory studies with clinical outcome and with histopathological data.

结直肠癌在生物学和组织学上具有多样性。临床结果较差的两种组织学类型是具有大量粘蛋白产生（胶体癌）和那些细胞分化差。一位特征明确的患者人口将被用来关注这两个独特的子集结直肠癌以确定标记物和机制以后可能适用于改善诊断、分期和治疗更广泛类别的中度至良好患者分化型腺癌。尽管胶体癌和低分化腺癌在生物学上是不同的，相同的患者群体和许多相同的方法将可以用来研究两者。该提案的主要目标是确定结肠标记物胶体癌和低分化型癌症并开发研究生物的实验模型粘蛋白产生的影响和分子机制。这具体目标包括： 1) 建立充足的数据库通过对结直肠癌病例分析的密切跟踪； 2）胶体癌标记物的鉴定组织化学、凝集素结合以及新的和现有的粘蛋白反应性抗体； 3) 胶体细胞系的建立印戒细胞癌及其生物学评价这些实验模型的行为； 4) 说明粘蛋白合成和分泌的分子机制前体、抑制剂和促分泌素的鉴定胶体癌与腺癌的结构比较粘蛋白，通过糖基转移酶的定量和分离和粘蛋白 cDNA 的表征； 5) 标记物的识别低分化模型的评估和评估通过检测抗原表达来检测腺癌免疫组织化学，通过产生单克隆抗体低分化细胞，通过检查生物学特性低分化细胞系，并通过研究核通过流式细胞仪和图像检测增殖参数分析; 6) 这些实验室研究结果的相关性具有临床结果和组织病理学数据。