Animal Core

动物核心

• 批准号: 8588580
• 负责人: JOHN F DE GROOT
• 金额: $ 24.27万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8588580
• 关键词: Animal Experiments; Animals; Brain; Brain Neoplasms; Breeding; Cell Line; Cells; Data; Evaluation; Experimental Designs; Funding; Genes; Genetically Engineered Mouse; Glial Fibrillary Acidic Protein; Glioma; Harvest; Health; Human; Human Resources; Immunocompetent; Immunodeficient Mouse; Implant; Injection of therapeutic agent; Intraperitoneal Injections; Laboratory Technicians; Leadership; Malignant neoplasm of brain; Mediating; Mesenchymal; Modeling; Monitor; Mus; Oral; Patients; Principal Investigator; Process; Protocols documentation; Reporting; Research Infrastructure; Research Personnel; Resistance; Services; Solid Neoplasm; Stem cells; System; Techniques; Tetanus Helper Peptide; Therapeutic; TimeLine; Tissues; U251; Virus; Work; Writing; Xenograft Model; Xenograft procedure; cell type; experience; glioma cell line; human disease; implantation; interest; meetings; member; mouse model; nestin protein; relating to nervous system; research study; tumor; tumorigenesis

In next 5-year funding period, investigators in Brain Tumor SPORE will continue to utilize the expert services provided by the Animal Core. The majority of projects in the SPORE rely on intracranial (orthotopic) implantation of established, adherent glioma cell lines, which are molecularly well characterized. Improvements in modeling the human disease will be achieved through the use of orthotopic xenografts of human glioma stem cells (GSCs), which are an important component of solid tumors, better replicate the human disease, and may mediate treatment resistance. These patient-derived GSC cell lines (N>50 to date) have been molecularly characterized into proneural, mesenchymal, classical and neural subtypes. In addition, genetically engineered mouse models of glioma (GEMMs) such as the RCAS/Ntv-a system are utilized by SPORE investigators. Specific genes of interest important for tumorigenesis can be evaluated in this model in a cell-type specific manner. Other GEMMs available within the Animal Core include: hGFAP-Cre*;p5S '¿'^¿'';Pten '¿^^ and Nestin-CreERT2 clnk4a/Arf UL cPTEN UL GFAP-tta tet- EGFRviil. Importantly, tumors generated in immunocompetent mice allow for better evaluation of interactions between tumor and the native microenvironment. Finally, we will continue to maintain and provide assistance with the establishment of traditional xenograft models from standard glioma cell lines (e.g. U87, U251, LN229, etc.). The Specific Aims of the Animal Core are: Aim 1: Provide support for animal experiments using patient derived glioma stem cell lines (GSCs) as orthotopic xenografts in immunodeficient mice. Aim 2: Provide support for animal experiments using Genetically Engineered Mouse Models (GEMMs). Aim 3: Maintain working stocks of cell lines. Aim 4: Provide support for xenografts of standard glioma cell lines. RELEVANCE: DO NOT EXCEED THE SPACE PROVIDED. Three of the four Brain Turiior SPORE projects are expected to use significant numbers of mice for their experiments. The Brain Tumor Animal Core will provide expert oversight of the animal experiments. Experienced personnel will execute the experimental plans.

在接下来的 5 年资助期内，Brain Tumor SPORE 的研究人员将继续利用该专家 动物核心提供的服务。 SPORE 中的大部分项目都依赖于颅内 （原位）植入已建立的、贴壁的神经胶质瘤细胞系，其分子结构良好 特点。人类疾病建模的改进将通过使用原位技术来实现 人类神经胶质瘤干细胞（GSC）是实体瘤的重要组成部分，其异种移植效果更好 复制人类疾病，并可能介导治疗耐药性。这些源自患者的 GSC 细胞系 （迄今为止 N> 50）已被分子表征为原神经、间充质、经典和神经 亚型。此外，基因工程小鼠神经胶质瘤模型（GEMM），例如 RCAS/Ntv-a 系统由 SPORE 调查员使用。对肿瘤发生重要的特定基因可以是 在此模型中以细胞类型特定的方式进行评估。动物核心中提供的其他 GEMM 包括：hGFAP-Cre*;p5S '¿'^¿'';Pten '¿^^ 和 Nestin-CreERT2 clnk4a/Arf UL cPTEN UL GFAP-tta tet- EGFRviil。重要的是，在免疫活性小鼠中产生的肿瘤可以更好地评估 肿瘤与天然微环境之间的相互作用。最后，我们将继续维护和 协助建立标准神经胶质瘤细胞系的传统异种移植模型 （例如U87、U251、LN229等）。动物核心的具体目标是： 目标 1：为使用患者来源的胶质瘤干细胞系 (GSC) 作为动物实验提供支持 免疫缺陷小鼠的原位异种移植。 目标 2：为使用基因工程小鼠模型 (GEMM) 的动物实验提供支持。 目标 3：维持细胞系的工作库存。 目标 4：为标准神经胶质瘤细胞系的异种移植提供支持。 相关性：请勿超出所提供的空间。 四个 Brain Turiior SPORE 项目中的三个预计将使用大量小鼠 实验。脑肿瘤动物核心将为动物实验提供专家监督。 经验丰富的人员将执行实验计划。