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）：癌症已成为美国最常见的长期HIV感染并发症之一，由于萨哈拉以南非洲的威胁可能会成为更大的威胁，因为对抗逆转录病毒疗法的延迟和不完整的机会，病毒性毒素的高普遍性，病毒性肿瘤的高度患者可能会导致更大的年龄以及更大的年龄造成造成癌症的风险。在该地区，包括Kaposi Sarcoma（KS），非霍奇金淋巴瘤（NHL）和侵入性宫颈癌（ICC）在内的三种“艾滋病定义癌症”仍然是整个人群中最常见的癌症之一。在过去的十年中，弗雷德·哈钦森癌症研究中心（Fred Hutchinson Cancer Research Center）与乌干达癌症研究所（Uganda Cancer Institute）合作，对感染相关的癌症进行合作研究和培训。并定义了与HLV相关的恶性肿瘤（HIVAM）的自然史，生物学和治疗。这项工作表明，与类似的HIV阴性患者相比，感染了HIV感染的癌症患者死亡风险显着增加，并且对治疗的反应在三种ADC的HIV感染者中差异很大。在当前的提案中，我们试图通过以下特定目的了解乌干达ADC差异自然历史的生物学基础：1）表征两个病毒性毒素，人类疱疹病毒8（HHV-8）（HHV-8）和人类乳头瘤病毒（HPV）的病毒遗传多样性，并开始探索属于遗传的历史，并探索属于kiss and kity and kisiant and kistiant and kistiant and Ictial sistial and kistiant and kistiant and kistiant and kistiant and kistiant and Sertialt and Sertiant and Sertiant and Sertiant and Sertiant＆Ictim and Sertialt and Sertiant; 2）描述启动抗逆转录病毒疗法和化学疗法的ALDS恶性肿瘤患者中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，维持乌干达的独特且非凡的生物疾病，以扩大乌干达艾滋病研究，将ADC招募到ADC的自然历史研究中，以扩大乌干达培训的乌干达人的科学领导力，以扩大乌干达培训的科学领导力，从而扩大了乌干达培训的科学领导力，从 他们的恶性肿瘤，并为两个大洲的合作生物医学研究提供了行政支持。