PATHOBIOLOGY OF COLORECTAL CANCER

结直肠癌的病理学

• 批准号: 2330740
• 负责人: Arthur M Mercurio
• 金额: $ 147.42万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-06-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2330740
• 关键词: colorectal neoplasms; molecular oncology; molecular pathology

This application is a revision which we believe is completely responsive to the recent review of our competitive renewal. Additional progress since the previous submission and Site Visit are emphasized. Rationale for a five (rather than four) year budget is emphasized. Key themes in the revision maintain program interactions among cell biologists, biochemists, molecular biologists and clinicians, that have extended key postulates in our investigations of the pathobiology of human colorectal cancer during the past five years. Broad experimental questions are still based on clinical phenomena: (l) What are the structure/function relationships in integrin laminin receptors and other adhesion molecules that may help to explain the unique biology of poorly differentiated or highly mucin producing colorectal carcinoma? Can these determinants of aggressive behavior predict bad outcome among the bore prevalent and heterogeneous moderate-to-well differentiated morphologies? (2) Can potential "founder genes" such as MSH2 and MLH1 be functionally defined in new model systems that help to explain their effects not only in HNPCC but also possibly "sporadic" colorectal carcinoma? (3) Can reconstitution models allow us to link many of the genetic changes found to be associated with gastrointestinal epithelial transformation to function and phenotype in premalignant or malignant mucosa? (4) Can information from our cDNA subtractive libraries be defined more elegantly by palindromic PCR driven differential DNA display in searching for significant mRNA differences between primary human colorectal carcinoma and adjacent epithelium and between primary and metastatic colorectal carcinoma? Finally, (5) Can markers studied during the last four years such as sucrase-isomaltase, DF3, Mac-2, CD44, and alpha6beta4 integrin be applied in archival tissues and in our prospective tissue bank to predict better the biologic aggressiveness of colorectal carcinoma?

这个应用程序是一个修订，我们相信是完全响应 最近对我们竞争性续约的审查 补充进度 因为强调了以前的提交和实地考察。 理由 五年（而不是四年）预算。 的关键主题 该修订保持了细胞生物学家之间程序交互， 生物化学家，分子生物学家和临床医生， 假设在我们的研究人类结直肠癌的病理生物学 癌症在过去的五年里。 广泛的实验问题仍然是 基于临床现象：（l）结构/功能是什么 整合素层粘连蛋白受体和其他粘附分子的关系 这可能有助于解释低分化或低分化的独特生物学， 高粘蛋白大肠癌 这些决定因素 攻击性行为预示着在普遍的无聊人群中会有糟糕的结果， 异质的中度至高度分化的形态？ (2)可以 潜在的“创始基因”如MSH 2和MLH 1在功能上是确定的。 新的模型系统，有助于解释其影响不仅在HNPCC， 也可能是“散发性”结肠直肠癌 (3)罐头复溶 模型使我们能够将许多发现的相关遗传变化联系起来， 胃肠道上皮细胞功能和表型的转变 在癌前病变或恶性粘膜中？ (4)我们的cDNA中的信息 通过回文PCR驱动的消减文库可以更好地定义 差异DNA显示在寻找显着的mRNA差异 原发性人结肠直肠癌和邻近上皮之间的关系， 原发性和转移性结直肠癌之间的关系 （5）可以 在过去四年中研究的标记物如蔗糖酶-异麦芽糖酶， DF 3、Mac-2、CD 44和α 6 β 4整联蛋白应用于档案组织 在我们未来的组织库中， 大肠癌的侵袭性