Biomarkers of Kaposi sarcoma recrudescence in Zambia

赞比亚卡波西肉瘤复发的生物标志物

• 批准号: 10652768
• 负责人: Owen Ngalamika
• 金额: $ 4.1万
• 依托单位: UNIVERSITY OF ZAMBIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-16 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652768
• 关键词: AIDS with Kaposi' s sarcoma; Adult; Africa South of the Sahara; Biological Markers; Development; Disease remission; HIV; Human Herpesvirus 8; Immune response; Immunologics; In complete remission; Individual; Intervention; Kaposi Sarcoma; Lesion; Maintenance Therapy; Malignant Neoplasms; Outcome; Pathogenesis; Patient Selection; Patients; Population; Predictive Value; Prevalence; Recrudescences; Recurrence; Testing; Viral; Woman; Zambia; antiretroviral therapy; biomarker identification; chemotherapy; cohort; experience; follow-up; high risk; immune reconstitution; improved; men; novel; prognostic value; prospective; scale up

ABSTRACT Kaposi's sarcoma (KS) remains a highly prevalent malignancy in sub-Saharan Africa. Antiretroviral therapy (ART) and associated immune reconstitution has been correlated with a dramatic decline in the prevalence of KS in the US HIV infected population, but the impact of ART on KS in sub-Saharan Africa is less clear. In Zambia, even with the scale up of ART, KS remains the second most common cancer among adult men. For women, it is the third most common. Furthermore, treatment with chemotherapy plus ART is associated with recurrence rates of up to 50 percent in those that have a complete response. The overall objective of this application is to identify markers of epidemic KS recurrence and/or sustained remission in individuals that have an initial complete regression of lesions upon chemotherapy. We hypothesize that individuals with complete regression of all the lesions after chemotherapy will have differences in immunological and viral factors that have prognostic value for predicting KS re-development and/or sustained remission. We will test our hypothesis by longitudinally characterizing innate, humoral, and cellular immune responses against KSHV and comparing individuals that experience recurrence to those who do not. The identification of these biomarkers of outcome after remission will enable the selection of patients that require a longer follow up period, those that require maintenance therapy, and those that require second line chemotherapy. From our proposed activities, we will improve the long-term outcomes of HIV+ individuals that have had KS before and hence at high risk of recurrence. This will ultimately inform efforts to better understand KS pathogenesis and develop novel interventional strategies.

抽象的 在撒哈拉以南非洲，卡波西的肉瘤（KS）仍然是一个非常普遍的恶性肿瘤。抗逆转录病毒 治疗（ART）和相关的免疫重构与急剧下降有关 美国艾滋病毒感染人群的KS的流行率，但艺术对撒哈拉以南KS的影响 非洲不太清楚。在赞比亚，即使是艺术的规模，KS仍然是第二常见的 成年男性的癌症。对于女性来说，这是第三大常见的。此外，处理 化学疗法加艺术与具有高达50％的复发率有关 完全回应。该应用的总体目的是确定流行病的标记 具有初始完全回归的个人的复发和/或持续缓解 化学疗法的病变。我们假设所有人完全回归的人 化学疗法后的病变将在具有的免疫和病毒因素上存在差异 预测KS重新开发和/或持续缓解的预后价值。我们将测试我们的 通过纵向表征先天，体液和细胞免疫反应的假设 KSHV和比较经历复发的个人与那些没有的人。识别 缓解后结果的这些生物标志物将使需要更长的患者选择 后续期，需要维护治疗的那些以及需要第二行的人 化学疗法。根据我们提出的活动，我们将改善HIV+的长期结果 以前有KS的人，因此有很高的复发风险。这最终将告知 更好地理解KS发病机理并制定新颖的介入策略的努力。