MECHANISM(S) OF TUMOR PROGRESSION AND METASTASIS

肿瘤进展和转移的机制

• 批准号: 3179221
• 负责人: PHILIP FROST
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1989-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179221
• 关键词: autoradiography; cell mediated cytotoxicity; clone cells; gene expression; genetic strain; host neoplasm interaction; immunogenetics; metastasis; monoclonal antibody; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer invasiveness; neoplasm /cancer transplantation; radiotracer; suppressor T lymphocyte; thymectomy; tumor antigens; tumor promoters

We recently postulated that one mechanism by which tumors progress to a heterogeneous malignant state is via undermethylation of DNA. DNA hypomethylation may result in the expression of genes that were previously not expressed. The treatment of tumor cells with 5-azacytidine has resulted in the selection of clones with varying phenotypes including tumor-immunogenic, nonmetastatic clones from metastatic tumors, metastatic clones from nonmetaststic tumors, and TK+ clones from cell populations that are spontaneously TK-. We continue to investigate the role of under methylation in the generation of the malignant phenotype. The second phase of our study is to assess the usefulness of immunogenic variants in the adoptive immunization of animals bearing metastatic tumors. Our current therapeutic protocol includes surgery, elimination of suppressor cells, adoptive transfer with primed spleen cells, and II-2 administration. These protocols have resulted in considerable prolongation of survival of animals challenged with a tumor considered to be the most aggressive murine tumor known. New experiments will utilize both active and adoptive immunization of animals using both the aggressive tumor and some additional less malignant (metastatic) tumors. Finally, we are also undertaking a series of studies to attempt to identify the antigen expressed by the immunogenic variants using antibodies in the hope of eventually using genetic probes to identify the genes responsible for antigen expression. (IP)

我们最近假设肿瘤进展为一种机制 异质恶性状态是通过 DNA 甲基化不足实现的。 脱氧核糖核酸 低甲基化可能会导致之前的基因表达 没有表达。 5-氮杂胞苷治疗肿瘤细胞 导致选择具有不同表型的克隆，包括 肿瘤免疫原性、来自转移性肿瘤的非转移性克隆、转移性 来自非转移性肿瘤的克隆，以及来自细胞群的 TK+ 克隆 是自发的TK-。 我们继续研究下的作用 恶性表型产生中的甲基化。 第二阶段 我们研究的目的是评估免疫原性变异在 对携带转移性肿瘤的动物进行过继免疫。 我们目前的 治疗方案包括手术、消除抑制细胞、 使用已引发的脾细胞进行过继转移，并进行 II-2 给药。 这些 协议已导致动物的生存时间大大延长 受到被认为是最具侵袭性的小鼠肿瘤的挑战 已知。 新实验将利用主动免疫和过继免疫 使用侵袭性肿瘤和一些其他较少的动物 恶性（转移性）肿瘤。 最后，我们还进行了一系列 试图鉴定免疫原性表达的抗原的研究 使用抗体的变体，希望最终使用基因探针 鉴定负责抗原表达的基因。 （IP）