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：
10454491
负责人：
Owen Ngalamika
金额：
$ 8.03万
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 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10454491
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 virology

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.

抽象的卡波西肉瘤（KS）仍然是撒哈拉以南非洲地区高度流行的恶性肿瘤。抗逆转录病毒治疗（ART）和相关的免疫重建与美国 HIV 感染人群中 KS 的患病率，以及 ART 对撒哈拉以南地区 KS 的影响非洲则不太清楚。在赞比亚，即使扩大了 ART 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，这是第三常见的。此外，治疗用化疗加 ART 的复发率高达 50% 完整的回应。该应用程序的总体目标是识别流行性 KS 的标记物最初完全消退的个体复发和/或持续缓解化疗时出现病变。我们假设所有能力完全退化的个体化疗后的病灶会出现免疫和病毒因素的差异，预测 KS 再发展和/或持续缓解的预后价值。我们将测试我们的通过纵向描述先天、体液和细胞免疫反应的假设 KSHV 并将经历复发的个体与未经历复发的个体进行比较。鉴定这些缓解后结果的生物标志物将有助于选择需要更长时间的患者随访期、需要维持治疗的患者以及需要二线治疗的患者化疗。从我们提议的活动中，我们将改善艾滋病毒+的长期结果以前患有 KS 且因此复发风险较高的个体。这最终将告知努力更好地了解 KS 发病机制并制定新的干预策略。