PQ6: Transgenic Mouse Model for Kaposi Sarcoma

PQ6：卡波西肉瘤转基因小鼠模型

• 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
• 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

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，最常见的卡波西肉瘤(KS)仍然没有合适的动物模型 世界范围内艾滋病毒/艾滋病感染者的癌症。值得注意的是，KS即使在HIV感染者中也会发生 CD4计数正常，没有检测到艾滋病毒病毒载量，以及艾滋病毒阴性的人--所谓的经典 KS.KS相关疱疹病毒(KSHV)是KS所必需的。而不是专注于一种特定的病毒 我们将KSHV病毒全长138,146个碱基的基因组插入转基因小鼠体内。这些都会发展 血管肉瘤和KSHV基因在肿瘤中表达。这项提议试图理解 KS肿瘤发生机制及已知和新药候选药物的研究。这项提议回应了 NCI挑衅性问题六：新的艾滋病毒/艾滋病相关恶性肿瘤的体外和体内模型是否可以 旨在研究它们的发展、发病机制和潜在的评估 常见的艾滋病毒/艾滋病相关恶性肿瘤的新治疗方法？