HUMAN CANCER METASTASIS--BIOLOGY AND TREATMENT

人类癌症转移——生物学和治疗

• 批准号: 3479280
• 负责人: ISAIAH J FIDLER
• 金额: $ 35.34万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479280
• 关键词: antibody dependent killer cell; athymic mouse; basal cell carcinoma; carcinoma; cell growth regulation; cellular oncology; colon neoplasms; combination cancer therapy; disease /disorder model; drug delivery systems; gene expression; human tissue; immunomodulators; kidney neoplasms; laboratory mouse; liposomes; liver neoplasms; macrophage; macrophage activating factor; melanoma; metastasis; model design /development; molecular oncology; monocyte; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer immunotherapy; neoplasm /cancer invasiveness; neoplasm /cancer radiation therapy; neoplasm /cancer therapy; neoplasm /cancer transplantation; neoplastic cell; phagocytosis; skin neoplasms

The emergence of metastases in organs distant from the primary tumor is the most devastating aspect of cancer. The major obstacle for treatment of established metastaes could well be their biologic heterogeneity which results from the continuous evolution of tumors and is responsible for the multiple differences that exist among tumor cells of a single metastasis. To date, most of the data on the biology of metastasis have been derived from studies with rodent neoplasms. It is now necessary extend our investigations into relevant human tumor systems. My long-term goals are to understand the mechanisms that regulate the metastatic spread of human neoplasms and the development of biologic heterogeneity in order to develop new approaches to the prevention and treatment of metastasis in humans. In the coming years, I will investigate the extent of metastatic heterogeneity in freshly isolated human neoplasms. Specific patterns of metastatic spread will also be studied in relation to properties of the neoplastic cells and the nature of the host microenvironment. Metastatic and nonmetastatic subpopulations will be selected from human neoplasms and the genetic and epigenetic mechanisms involved in tumor progression and metastasis will be investigated. The biologic diversity of nepolasms implies that the successful treatment of metastasis will require the total destruction of all cancer cells. The challenge to the oncologist is, therefore, to devise a new approach for the eradication of the few tumor cells that resist conventional therapies. Such an approach would have to circumvent the problem of neoplastic heterogeneity and the emergence of treatment-resistant variant tumor cells. Studies from my laboratory and many others suggest that appropriately activated macrophages can meet these demanding criteria and, thus, provide a biological approach to the destruction of the few but fatal tumor cells that resist or escape conventional therapies. For this reason, the second major goal of my research is to study the role of the macrophage in the pathogenesis of cancer matastasis, to devise methods for systemic activation of macrophages, and to elucidate the mechanisms by which tumoricidal macrophages discriminate between tumorigenic and nontumorigenic cells.

远离原发灶的器官出现转移灶 肿瘤是癌症中最具破坏性的部分。 主要 治疗已确定转移的障碍很可能是 它们的生物异质性， 肿瘤的演变，并负责多种差异， 存在于单个转移的肿瘤细胞中。 到目前为止， 大多数关于转移生物学的数据都是从 啮齿动物肿瘤的研究。 现在有必要扩大 我们对相关人类肿瘤系统的研究。 我的长期目标是了解 调节人类肿瘤的转移扩散， 生物异质性的发展，以开发新的 转移的预防和治疗方法 人类 在未来的几年里，我将调查 新鲜分离的人肿瘤的转移异质性。 转移性扩散的特定模式也将在 与肿瘤细胞的性质和肿瘤细胞的性质的关系 宿主微环境 转移和非转移 亚群将选自人类肿瘤和 肿瘤进展的遗传和表观遗传机制 并将研究转移。 nepolasms的生物多样性意味着成功的 转移的治疗将需要完全破坏所有的 癌细胞 因此，肿瘤学家面临的挑战是， 设计一种新的方法来根除少数肿瘤细胞 抵抗传统疗法的人 这样的做法将 为了避免肿瘤异质性的问题， 出现耐药变异肿瘤细胞。 研究 我的实验室和其他许多人的研究表明， 活化的巨噬细胞可以满足这些苛刻的标准， 因此，提供了一种生物学方法来摧毁少数 而是抵抗或逃避常规疗法的致命肿瘤细胞。 因此，我研究的第二个主要目标是研究 巨噬细胞在癌症发病中的作用 转移，设计系统激活 巨噬细胞，并阐明机制， 杀肿瘤巨噬细胞区分致瘤性和致瘤性 非致瘤细胞。