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: 9919022
• 负责人: Owen Ngalamika
• 金额: $ 8万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9919022
• 关键词: AIDS related cancer; AIDS with Kaposi' 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

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！ 卡波西氏肉瘤(KS)在撒哈拉以南非洲地区仍然是一种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 KS在美国HIV感染人群中的流行率，但抗逆转录病毒疗法对撒哈拉以南地区KS的影响 非洲则不那么明朗。在赞比亚，即使扩大了抗逆转录病毒治疗的规模，KS仍然是第二常见的 成年男性罹患癌症。对于女性来说，这是第三常见的。此外，治疗与治疗 化疗加抗逆转录病毒治疗与复发率高达50%有关。 完整的回应。此应用程序的总体目标是识别流行性KS的标记 最初完全消退的患者的复发和/或持续缓解 化疗后的病变。我们假设所有完全回归的个体 化疗后的病变在免疫和病毒因素上会有所不同 对预测KS复发和/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来提出假说 KSHV，并将复发患者与未复发患者进行比较。身份的鉴定 这些缓解后预后的生物标志物将使选择需要更长时间的患者成为可能 随访期，需要维持治疗的和需要二线治疗的 化疗。通过我们提议的活动，我们将改善艾滋病毒+的长期成果 以前有过KS的人，因此复发的风险很高。这最终会让我们知道 努力更好地了解KS的发病机制并开发新的干预策略。