TUMOR PROGRESSION AND THE IMMUNOBIOLOGY OF METASTASIS

肿瘤进展和转移的免疫生物学

• 批准号: 3179224
• 负责人: PHILIP FROST
• 金额: $ 11.77万
• 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/3179224
• 关键词: DNA methylation; athymic mouse; azacitidine; carcinogenesis; clone cells; difluoromethylornithine; disease /disorder model; drug resistance; host neoplasm interaction; immunogenetics; isozymes; laboratory mouse; molecular genetics; mouse leukemia; mutant; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer transplantation; neoplastic growth; radiotracer; suppressor T lymphocyte; tissue /cell culture; tumor antigens; tumor promoters

The primary goal of this proposal is to define (at least in part) the mechanism(s) of tumor progression. To achieve this, we plan to further analyse the role of DNA hypomethylation in the progression of tumors from the benign to the malignant state. Because it is possible that hypomethylation in itself may be insufficient to achieve this transition (i.e., secondary agents likely play a role), the central focus of this proposal is to study the role of genomic destabilization in tumor progression. We believe that agents such as 5-aza-d-Cyd and DFMO, which respectively cause DNA hypomethylation and polyamine depletion, can broadly destabilize DNA and result in augmented genomic injury induced by secondary agents. The agents which we have chosen to provide 'secondary' injury are MNNG (a monofunctional alkylating agent) and m-AMSA, an intercalating agent. The key factor in these studies is that the effects of each of these agents, 5-aza-d-Cyd, DFMO, MNNG and m-AMSA, can be quantitated biochemically. In addition, we have chosen to study tumor cell lines with known characteristics so that specific phenotypic changes induced by each agent alone or in defined combinations can be readily assessed. Four phenotypic characteristics will be analyzed including the generation of drug resistant mutants, metastatic variants, immunogenic variants, and changes in isozymes. Chromosomal rearrangements will also be assessed. These protocols will therefore allow for a systematic analysis (using the parameters outlined) of the role of genomic instability in the generation of phenotypic diversity. A secondary goal of these studies is to address the role of DNA hypomethylation in carcinogenesis. Both an in vivo and in vitro model for potential murine lymphoma/leukemia generation are outlined.

本建议的主要目标是定义（至少部分地）

项目成果

Metastatic potential and spontaneous mutation rates: studies with two murine cell lines and their recently induced metastatic variants.

转移潜力和自发突变率：对两种小鼠细胞系及其最近诱导的转移变体的研究。

• 发表时间: 1986
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Kendal,WS;Frost,P
• 通讯作者: Frost,P

Modulation of cisplatin resistance by 2'-deoxy-5-azacytidine in human ovarian tumor cell lines.

• 发表时间: 1994
• 期刊: Anticancer research
• 影响因子: 2
• 作者: R. Lenzi;P. Frost;J. Abbruzzese

Spontaneous mutation rates in cloned murine tumors do not correlate with metastatic potential, whereas the prevalence of karyotypic abnormalities in the parental tumors does.

克隆鼠肿瘤的自发突变率与转移潜力无关，而亲代肿瘤中核型异常的发生率却与转移潜力相关。

• DOI: 10.1002/ijc.2910400321
• 发表时间: 1987
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Kendal,WS;Wang,RY;Frost,P
• 通讯作者: Frost,P

Selection of metastatic variants with identifiable karyotypic changes from a nonmetastatic murine tumor after treatment with 2'-deoxy-5-azacytidine or hydroxyurea: implications for the mechanisms of tumor progression.

用 2-脱氧-5-氮杂胞苷或羟基脲治疗后，从非转移性小鼠肿瘤中选择具有可识别核型变化的转移性变异：对肿瘤进展机制的影响。

• 发表时间: 1987
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Frost,P;Kerbel,RS;Hunt,B;Man,S;Pathak,S
• 通讯作者: Pathak,S

Rate of generation of major karyotypic abnormalities in relationship to the metastatic potential of B16 murine melanoma.

主要核型异常的发生率与 B16 小鼠黑色素瘤的转移潜力相关。

• 发表时间: 1987
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Kendal,WS;Wang,RY;Hsu,TC;Frost,P
• 通讯作者: Frost,P