Biomarkers of Kaposi sarcoma recrudescence in Zambia

赞比亚卡波西肉瘤复发的生物标志物

基本信息

批准号：
10426068
负责人：
Owen Ngalamika
金额：
$ 8万
依托单位：
UNIVERSITY OF ZAMBIA
依托单位国家：
美国
项目类别：
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/10426068
关键词：
AIDS related cancer AIDS with Kaposi&apos s sarcoma Adult Africa South of the Sahara African Anti-Inflammatory Agents Antigens Biological Markers Bleomycin CD8-Positive T-Lymphocytes CXCL10 gene Cell Count Cell physiology Chemotherapy-Oncologic Procedure Clinical Cutaneous Detection Development Disease remission Doxorubicin Effector Cell Etiology Goals HIV HIV-1 Human Herpesvirus 8 Immune response Immunologics Immunotherapeutic agent In complete remission Individual Inflammatory Innate Immune Response Interferon Type II Interleukin-1 Interleukin-10 Interleukin-4 Interleukin-5 Interleukin-6 Intervention Kaposi Sarcoma Lesion Maintenance Therapy Malignant Neoplasms Manuscripts Measures Memory Outcome Pathogenesis Patient Selection Patients Peptides Peripheral Phenotype Plasma Poliomyelitis Population Predictive Value Preparation Prevalence Prospective Studies Recrudescences Recurrence Regimen Regulatory T-Lymphocyte Reporting T cell differentiation T cell response TNF gene Testing Transforming Growth Factor beta Update Vaccines Vincristine Viral Viral Load result Visit Woman Zambia anergy antiretroviral therapy biomarker identification chemokine chemotherapy clinical decision-making cohort cytokine design exhaustion experience follow-up high risk immune reconstitution improved individual response men neutralizing antibody novel pathogen prognostic value programmed cell death protein 1 prospective recruit response scale up senescence sociodemographics success tumor

项目摘要

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。