METASTATIC POTENTIAL OF COLORECTAL CARCINOMA

结直肠癌的转移潜力

• 批准号: 3184492
• 负责人: John Milburn Jessup
• 金额: $ 7.95万
• 依托单位: NEW ENGLAND DEACONESS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3184492
• 关键词: T lymphocyte; adenocarcinoma; athymic mouse; cancer registry /resource; gene expression; human tissue; immunofluorescence technique; karyotype; liver neoplasms; lung neoplasms; lymph node neoplasm; metastasis; mixed lymphocyte reaction test; neoplasm /cancer classification /staging; neoplasm /cancer transplantation; neoplastic cell; radiotracer; rectum neoplasms; tumor antigens

Our objective is to examine the possibility that the growth of freshly isolated human colorectal carcinoma cells in appropriate organs of athymic nude mice correlates with the metastatic potential of these neoplasms. The development of metastases in organs distant from the primary neoplasm is the major obstacle to the treatment of human colorectal carcinoma. The treatment of established metastasis may be limited by their biologic heterogeneity, which results from the continuous evolution of tumors, and is responsible for the multiple differences that exist among tumor cells populating primary neoplasms, among different metastases, and even among cells of a single metastasis. Advances in the therapy of human colorectal cancer may occur once we improve our understanding of the basic biology of this disease. To date, most of the data on the biology of metastasis have been derived from studies with rodent neoplasms. It is now necessary to extend our investigations to relevant human tumor systems. We propose to measure the ability of human colorectal carcinoma cells from different sources (primary tumor, lymph node metastasis, distant metastasis) and different stages of disease (early- Dukes A and B, intermediate- Dukes C, and advanced- Dukes D) to grow in mouse liver and lung following intrasplenic and intravenous injection. The human origin of the neoplasms will be verified by karyotypic and isoenzyme analysis. Tumors that grow in the lungs and liver of the nude mouse will be cloned and the clones tested for heterogeneity of metastatic phenotype and organ site preference. The metastatic potential of liver or lung colonies derived from primary tumor cells in nude mice will be compared to the metastatic potential of hepatic or pulmonary metastases from the same patient. Tumor-associated and major histocompatibility antigens of experimental and clinical metastases will be assessed with autologous lymphocytes and T cell clones in proliferative and cytotoxic assays. Our goal is to determine whether measurement of metastatic potential of human colorectal cancers in nude mice improves the ability of the current clinico-pathologic staging system to predict development of metastatic disease.

我们的目标是研究新发现的 在无胸腺的适当器官中分离的人结直肠癌细胞 裸鼠与这些肿瘤的转移潜能相关。 的 远离原发肿瘤的器官发生转移， 这是人类结肠直肠癌治疗的主要障碍。 的 已确定转移的治疗可能受到其生物学特性的限制， 异质性，这是肿瘤不断演变的结果， 负责肿瘤细胞之间存在的多种差异， 在不同的转移瘤之间，甚至在 单个转移的细胞。 人大肠癌的治疗进展 一旦我们提高了对癌症的基础生物学的理解， 这种疾病。 迄今为止，关于转移生物学的大多数数据都是关于转移的。 源自啮齿动物肿瘤研究。 现在有必要 将我们的研究扩展到相关的人类肿瘤系统。 我们建议 测量来自不同来源的人结直肠癌细胞的能力， 来源（原发肿瘤、淋巴结转移、远处转移）和 疾病的不同阶段（早期-DukesA和B，中期-DukesC， 和高级-Dukes D）在小鼠肝脏和肺中生长， 脾内和静脉注射。 肿瘤的人类起源 将通过核型和同工酶分析进行验证。 肿瘤生长在 将克隆裸小鼠的肺和肝脏并对克隆进行测试 转移表型的异质性和器官部位偏好。 的 源自原发性肿瘤的肝或肺集落的转移潜力 将裸鼠中的细胞与肝转移潜能进行比较。 或者是同一个病人的肺转移 肿瘤相关和重大 实验和临床转移的组织相容性抗原将被 用自体淋巴细胞和T细胞克隆评估增殖和 细胞毒性测定。 我们的目标是确定是否测量转移潜力的， 裸鼠中的人结肠直肠癌提高了目前的 临床病理分期系统，以预测转移性 疾病