THE PATHOBIOLOGY OF COLORECTAL CANCER

结直肠癌的病理学

• 批准号: 3094150
• 负责人: GLENN D STEELE
• 金额: $ 131.86万
• 依托单位: NEW ENGLAND DEACONESS HOSPITAL
• 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 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3094150
• 关键词: colorectal neoplasms; molecular oncology

This program will build on the progress of the past 3 years of interaction among cell biologists, biochemists, molecular biologists and clinicians to provide new postulates to explain key events in human colon cancer etiology and behavior. Experimental questions based on clinical phenomena will focus on the following major themes: (1) What is the function of CEA, particularly in relation to colorectal cancer differentiation and site-specific metastasis? (2) What is the relationship between specific laminin binding proteins, colorectal carcinoma differentiation, and metastasis (3) Is expression of markers of gastrointestinal epithelial differentiation (such as fimbrin, villin, 110K) altered during or after human colorectal cancer transformation? (4) Can genes that influence our candidate differentiation/transformation markers be manipulated in novel, reconstitution models that will allow us to link predicted biochemical and molecular changes in gastrointestinal epithelium to morphologic criteria of premalignant or malignant colonic mucosa? (5) Can the availability of well defined, fresh human tissue samples (normal colon, primary colon cancer, lymph node metastases, or distant metastases from the same patient) allow us to prepare cDNA libraries and to select cDNA clones that will distinguish among various forms of colorectal cancer as well as normal colon, and finally (6) Can the reagents (monoclonal antibodies, oligonucleotide probes) produced against our novel molecular targets be applied directly to fresh and/or archival human tissue in order to enhance our ability to predict the aggressiveness of colon and rectum cancers? The proposed studies will expand the successful investigations of the past 3 years to provide new prognostic criteria for human colon and rectum cancer. Better understanding of mechanisms involved in invasion and site-specific metastasis will allow new therapy avenues to be postulated. Basic science questions derived from strong interaction between clinic and research lab; proven availability of patient resources; establishment of successful tissue and sera bank networks; our record of interaction among Project Leaders as well as Core; involvement of important local medical institutions in the project; and our recent connection with a multi-institutional, national therapy trial group, are the foundations for this revised 5 year renewal request.

该计划将建立在过去 3 年的进展基础上 细胞生物学家、生物化学家、分子生物学家和 临床医生提供新的假设来解释人类结肠的关键事件 癌症的病因学和行为。 基于临床的实验问题 现象将集中于以下几个主题：（1）什么是 CEA 的功能，特别是与结直肠癌相关的功能 分化和位点特异性转移？ (2) 什么是 特定层粘连蛋白结合蛋白、结肠直肠之间的关系 癌的分化和转移（3）是标志物的表达 胃肠道上皮分化（如 fimbrin、villin、 110K）在人类结直肠癌转化期间或之后发生改变？ (4) 基因能否影响我们的候选者分化/转化 在新颖的重构模型中操纵标记，这将允许 我们将预测的生化和分子变化联系起来 胃肠道上皮符合癌前或癌前形态学标准 结肠粘膜恶性？ (5) 能否提供明确、新鲜的信息？ 人体组织样本（正常结肠、原发性结肠癌、淋巴结 转移，或来自同一患者的远处转移）使我们能够 准备 cDNA 文库并选择能够区分的 cDNA 克隆 各种形式的结直肠癌以及正常结肠，以及 最后（6）可以使用试剂（单克隆抗体、寡核苷酸）吗？ 针对我们的新型分子靶标产生的探针）可直接应用 新鲜和/或存档的人体组织，以增强我们的能力 预测结肠癌和直肠癌的侵袭性？ 拟议的研究将扩大对 过去3年为人类结肠癌和结肠癌提供了新的预后标准 直肠癌。 更好地理解入侵机制 特定部位的转移将允许新的治疗途径 假设。 强相互作用衍生的基础科学问题 诊所和研究实验室之间；已证明患者的可用性 资源;建立成功的组织和血清库网络；我们的 项目负责人和核心人员之间互动的记录；参与 项目当地重要医疗机构；以及我们最近的 与多机构、国家治疗试验组的联系 此修订后的 5 年续展请求的基础。