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?”

项目概要 摘要 25 年后，仍然没有足够的卡波西肉瘤 (KS) 动物模型，这是最常见的 全世界艾滋病毒/艾滋病患者的癌症。值得注意的是，即使 HIV 感染者也会出现 KS CD4 计数正常且未检测到 HIV 病毒载量，以及 HIV 阴性者 — 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 基因，我们将整个 138,146 bp KSHV 病毒基因组插入转基因小鼠中。这些发展 血管肉瘤和 KSHV 基因在肿瘤中表达。该提案旨在了解 KS 肿瘤发生机制并研究已知和新型候选药物。该提案回应 NCI 挑衅性问题六：“HIV/AIDS 相关恶性肿瘤的新型体外和体内模型能否 开发用于研究其发展、发病机制和潜在评估 常见的艾滋病毒/艾滋病相关恶性肿瘤的新疗法？”