PQ6: Transgenic Mouse Model for Kaposi Sarcoma

PQ6：卡波西肉瘤转基因小鼠模型

基本信息

批准号：
10115683
负责人：
Dirk P Dittmer
金额：
$ 52.16万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10115683
关键词：
AIDS related cancer AIDS/HIV problem Age Animal Model Animals Anniversary Antiviral Agents Bypass CD4 Lymphocyte Count CRISPR/Cas technology Cell Line Cells Cellular Structures DNA Damage Data Development Doxorubicin Doxorubicin Hydrochloride Liposome Drug Modelings Evaluation FRAP1 gene Frequencies Ganciclovir Gene Expression Profile Generations Genes Genetic Transcription Genome HIV HIV Seronegativity Hemangiosarcoma Herpesviridae Human Human Herpesvirus 8 Immune Immunocompetent In Vitro Incidence Kaposi Sarcoma Knowledge Lesion Lymphoma Lytic Malignant Neoplasms Maps Modeling Molecular Molecular Target Mus Neoplasm Transplantation Pathogenesis Pathway interactions Persons Pharmaceutical Preparations Phase Platelet-Derived Growth Factor Proteins Regimen Research Safety Signal Transduction Structure Study models Testing Tissues Transcript Transgenic Mice Transgenic Model Transplantation Tumor-Derived Vaccines Vascular Endothelial Growth Factors Viral Viral Genes Viral Genome Viral Load result Viral Oncogene Virus Latency antiretroviral therapy cell type cohort common treatment drug candidate drug development drug testing human fetus tissue in vivo in vivo Model mTOR Inhibitor mouse model neoplastic cell novel novel therapeutics pomalidomide prevent preventive intervention response targeted treatment tumor tumorigenesis vaccine development vaccine evaluation

项目摘要

Project Summary Abstract After 25 years there is still is no adequate animal model for Kaposi Sarcoma (KS), which is the most common cancer in people living with HIV/AIDS world-wide. Notably, KS develops even in HIV-infected person with normal CD4 counts and no detectable HIV viral load, as well as in HIV-negative persons – so called classic KS. The KS-associated herpesvirus (KSHV) is necessary for KS. Rather than focusing on one specific viral gene, we inserted the entire 138,146 bp KSHV viral genome into transgenic mice. These develop angiosarcoma and the KSHV genes are expressed in the tumor. This proposal seeks to understand the mechanism of KS tumorigenesis and to study known and novel drug candidates. This proposal responds to NCI provocative question six: “Can novel in vitro and in vivo models of HIV/AIDS-associated malignancies be developed to study their development, pathogenesis, and the potential evaluation of novel treatments for common HIV/AIDS-associated malignancies?”

项目摘要摘要 25年后，Kaposi肉瘤（KS）仍然没有足够的动物模型，这是最常见的全世界患艾滋病毒/艾滋病的人的癌症。值得注意的是，即使是在感染的HIV感染者中，KS也会发展正常的CD4计数，无可检测的HIV病毒载荷以及HIV阴性人 - 所谓的经典 KS。 KS相关的疱疹病毒（KSHV）对于KS是必需的。而不是专注于一种特定的病毒基因，我们将整个138,146 bp kshv病毒基因组插入转基因小鼠。这些发展血管肉瘤和KSHV基因在肿瘤中表达。该提议试图了解 KS肿瘤发生的机制，并研究已知和新的候选药物。此提案回应 NCI挑衅性的问题6：“艾滋病毒/艾滋病相关的恶性肿瘤的体外和体内模型都可以开发旨在研究其发育，发病机理和潜在评估常见艾滋病毒/艾滋病相关恶性肿瘤的新型治疗方法？”