Interaction of Schistosomiasis mansoni and hepatitis B virus infections on hepatocellular carcinoma

曼氏血吸虫病和乙型肝炎病毒感染对肝细胞癌的相互作用

• 批准号: 10084616
• 负责人: David L Thomas
• 金额: $ 28.27万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10084616
• 关键词: Advocate; Affect; Africa; Africa South of the Sahara; African; Aftercare; Age; Animal Model; Antigens; Blood Circulation; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cancer Etiology; Chronic; Chronic Care; Chronic Hepatitis B; Clinical; Collaborations; Country; DNA Double Strand Break; Data; Eligibility Determination; Genes; Genetic; Goals; HBV Genotype; HIV; HIV Infections; Hepatic; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Virus; Hepatitis C virus; Hepatocyte; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Immune response; Immunity; Immunologics; Immunology; In Vitro; Income; Infection; Inflammation; Inflammatory; Intercept; Interruption; Investigation; JUN gene; Light; Liver; Malignant Neoplasms; Measures; Medical; Mentors; Mesentery; Oncogenes; Oncogenic; Pathway interactions; Patients; Persons; Physiological; Plasma; Praziquantel; Primary carcinoma of the liver cells; Proto-Oncogenes; Public Health; Research; Residual state; Risk; Risk Factors; Schistosoma mansoni; Schistosoma mansonii infection; Senegal; Site; System; T cell response; Testing; Time; Tissues; Treatment Efficacy; Uganda; Universities; Venous; Virus Diseases; Virus Replication; carcinogenicity; chronic infection; cytokine; egg; improved; inflammatory milieu; insight; liver biopsy; macrophage; mortality; novel; response; standard of care; viral DNA

Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live longer, the HCC burden may increase. In prior studies, our team identified chronic infection with hepatitis B and C viruses (HBV, HCV), HIV and Schistosomiasis mansoni (Sm) as independent risk factors for HCC. Compared to the US, HCC in sub-Saharan Africa occurs at younger age and more advanced stage with survival of only months. Proposed is an East and West African partnership between colleagues at Makerere University in Uganda, Fann University in Senegal and Johns Hopkins University focused on HIV and hepatocellular carcinoma (HCC) in Africa: The H2A Consortium. Building on long-standing collaborative research, mentoring and clinical activities in both countries, our overarching goal is to reduce the heavy burden of HCC in sub-Saharan Africa. We advocate investigating cancer interception strategies using appropriate medical treatments to interrupt or reverse the impact of HCC-causing infections. To understand our data demonstrating synergistic interaction between chronic HBV and Sm infections, we will examine HBV clinical and immunological responses in the periphery and the liver in response to Sm treatment with praziquantel. Over time, liver Sm-related inflammation transitions from a Th1 to Th2 bias, and we hypothesize this transition may promote HBV replication. We will evaluate the dynamics of plasma HBV DNA during Sm treatment and correlate these with contemporaneous changes in plasma cytokines to characterize Th1 shifted inflammation. We also concurrently examine HBV specific CD4+ and CD8+ T cell responses, and measures of Sm treatment efficacy. Through investigation of liver biopsies on patients before and after SM treatment as well as with HCC, we anticipate confirming in humans that Sm is pro-carcinogenic and that Sm treatment only partially diminishes expression of pro-carcinogenic genes. HIV will be evaluated as a modifier of each relationship. Given our strong record, the proposed research has a high likelihood for successful contribution to reducing the burden and improving understanding of chronic infections and HCC in Africa.

肝细胞癌（HCC）是非洲非常普遍且致命的癌症，随着HIV患者的活力 更长的时间，HCC负担可能会增加。在先前的研究中，我们的团队确定了乙型肝炎的慢性感染 和C病毒（HBV，HCV），HIV和血吸虫病Mansoni（SM）作为HCC的独立危险因素。 与美国相比，撒哈拉以南非洲的HCC发生在年轻时，并且更高级的阶段 仅几个月的生存。拟议的是Makerere同事之间的东非和西非伙伴关系 乌干达的大学，塞内加尔的范恩大学和约翰·霍普金斯大学专注于艾滋病毒和 非洲的肝细胞癌（HCC）：H2A财团。基于长期合作 两国的研究，指导和临床活动，我们的总体目标是减轻负担 撒哈拉以南非洲的HCC。我们主张使用适当的 医疗治疗以中断或扭转引起HCC引起的感染的影响。了解我们的数据 证明慢性HBV与SM感染之间的协同相互作用，我们将检查HBV临床 以及外围和肝脏中的免疫反应，以响应用praziquantel治疗的SM治疗。 随着时间的流逝，肝脏SM相关的炎症从Th1到Th2偏见，我们假设这种过渡 可能会促进HBV复制。我们将在SM处理过程中评估血浆HBV DNA的动力学和 将这些与血浆细胞因子的同时变化相关，以表征Th1转移的炎症。 我们还同时检查HBV特异性CD4+和CD8+ T细胞反应以及SM处理的度量 功效。通过调查SM治疗前后对患者的肝活检以及HCC的患者 我们预计在人类中确认SM是亲和致癌的，而SM治疗只会部分减少 促癌基因的表达。艾滋病毒将作为每种关系的修饰符进行评估。鉴于我们 良好的记录，拟议的研究很有可能成功地减轻负担 并提高对非洲慢性感染和HCC的了解。