Animal Core

在接下来的5年资助期内，脑瘤孢子的研究人员将继续利用专家 动物中心提供的服务。SPORE中的大多数项目依赖于颅内 （原位）植入已建立的粘附性胶质瘤细胞系，其在分子水平上良好地 表征了人类疾病建模的改进将通过使用原位 人胶质瘤干细胞（GSC）是实体瘤的重要组成部分， 复制人类疾病，并可能介导治疗耐药性。这些患者来源的GSC细胞系 （迄今为止N>50）已被分子表征为前神经的、间质的、经典的和神经的 亚型此外，神经胶质瘤的基因工程小鼠模型（GEMM），如RCAS/Ntv-a， SPORE调查人员使用了这些系统。对于肿瘤发生重要的感兴趣的特定基因可以是 在该模型中以细胞类型特异性方式进行评估。Animal Core中可用的其他GEMM 包括：hGFAP-Cre*; p5 S“突变”;Pten“突变”和Nestin-CreERT 2 clnk 4a/Arf UL cPTEN UL GFAP-tta泰特。 EGFRviil.重要的是，在免疫活性小鼠中产生的肿瘤允许更好地评估肿瘤的生物学特性。 肿瘤与天然微环境之间的相互作用。最后，我们将继续保持和 协助从标准神经胶质瘤细胞系建立传统异种移植模型 (e.g. U87、U251、LN 229等）。动物核心的具体目标是： 目的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 免疫缺陷小鼠中的原位异种移植物。 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：维持细胞系的工作储备。 目的4：为标准胶质瘤细胞系的异种移植提供支持。 相关性：不要超过所提供的空间。 四个Brain Turior SPORE项目中的三个预计将使用大量的小鼠进行研究。 实验脑肿瘤动物中心将提供动物实验的专家监督。 有经验的人员将执行实验计划。

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.