Biologic Determinants of the Natural History of AIDS-Defining Cancers in Uganda

乌干达艾滋病定义癌症自然史的生物决定因素

• 批准号: 8929189
• 负责人: Corey Casper
• 金额: $ 83.07万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-18 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8929189
• 关键词: Biologic; Determinants; Natural; History; AIDS

DESCRIPTION (provided by applicant): Cancer has become one of the most common complications of long-term HIV infection in the US, and may come to be an even greater threat in sub-Saharan Africa because of the delayed and incomplete access to antiretroviral therapy, the high prevalence of viral oncogens, and a larger number of years a person may be at risk for developing cancer due to pediatric HIV infection. In this region, the three "AIDS-Defining Cancers", including Kaposi sarcoma (KS), non-Hodgkin Lymphoma (NHL), and invasive cervical cancer (ICC), remain among the most common cancers in the entire population. Over the past decade, the Fred Hutchinson Cancer Research Center has collaborated with the Uganda Cancer Institute to conduct collaborative research and training on infection-related cancers; and define the natural history, biology and treatment of HlV-associated malignancies (HIVAM). This work has revealed HIV-infected individuals with cancer are at significantly increased risk of death when compared with similar HIV-negative persons with cancer, and that the response to therapy varies dramatically within HIV-infected persons with the three ADCs. In the current proposal, we seek to understand the biologic basis for the differential natural history of ADCs in Uganda through the following Specific Aims: 1) To characterize the viral genetic diversity among two viral oncogens, human herpesvirus-8 (HHV-8) and human papillomavirus (HPV), and begin to explore the relationship between genetic variants and the natural history of KS and ICC, respectively; 2) To describe the evolution of the cellular immune response among persons with AlDS-defining malignancies who initiate antiretroviral therapy and chemotherapy; 3) To expand the capacity to conduct state-of-the-art translational research in HIVAM in Uganda through optimizing scientific leadership among Ugandans who have been trained in HIVAM research, maintaining a unique and extraordinary biorepository for the study of HIVAM in Uganda, expanding the enrollment of patients with ADCs into translational studies of the natural history of their malignancies, and providing the administrative support for collaborative biomedical research across two continents.

描述（由申请人提供）：在美国，癌症已成为长期艾滋病毒感染最常见的并发症之一，并且由于抗逆转录病毒治疗的延迟和不完全，可能成为撒哈拉以南非洲地区更大的威胁病毒致癌物的高患病率，以及一个人可能因儿童艾滋病毒感染而面临罹患癌症的风险的年数更长。在该地区，三种“艾滋病定义的癌症”，包括卡波西肉瘤（KS）、非霍奇金淋巴瘤（NHL）和浸润性宫颈癌（ICC），仍然是整个人口中最常见的癌症之一。过去十年，Fred Hutchinson癌症研究中心与乌干达癌症研究所合作，针对感染相关癌症开展合作研究和培训；并定义 HIV 相关恶性肿瘤 (HIVAM) 的自然史、生物学和治疗。这项工作表明，与类似的 HIV 阴性癌症患者相比，HIV 感染者的癌症死亡风险显着增加，并且 HIV 感染者对三种 ADC 治疗的反应存在显着差异。在当前的提案中，我们试图通过以下具体目标来了解乌干达 ADC 差异自然史的生物学基础：1) 表征两种病毒致癌原人类疱疹病毒 8 (HHV-8) 和人乳头瘤病毒（HPV），并开始分别探索基因变异与KS和ICC自然史之间的关系； 2) 描述患有 AlDS 定义的恶性肿瘤并开始抗逆转录病毒治疗和化疗的人的细胞免疫反应的演变； 3) 通过优化接受过 HIVAM 研究培训的乌干达人的科学领导力、维持乌干达独特而非凡的 HIVAM 研究生物样本库、扩大乌干达 HIVAM 领域最先进转化研究的能力，将 ADC 患者纳入自然史转化研究 他们的恶性肿瘤，并为跨两大洲的生物医学合作研究提供行政支持。