Animal Core

在接下来的5年资助期内，脑瘤孢子研究人员将继续使用该专家 由动物核心组织提供的服务。孢子中的大多数项目都依赖于颅内 (原位)移植已建立的、黏附的胶质瘤细胞系，这些细胞系分子状态良好 特色化的。在模拟人类疾病方面的改进将通过使用正位模型来实现 作为实体瘤重要组成部分的人脑胶质瘤干细胞(GSCs)异种移植效果更好 复制人类疾病，并可能介导治疗耐药。这些患者来源的GSC细胞系 (n&gt；50)迄今已被分子表征为神经原、间充质、经典和神经 子类型。此外，基因工程小鼠胶质瘤模型(GEMM)，如RCAS/NTV-a 系统被孢子调查人员利用。对肿瘤发生很重要的特定感兴趣的基因可能是 在此模型中以特定于细胞类型的方式进行评估。动物核心中可获得的其他GEMM 包括：hGFAP-Cre*；P5s‘�’^�‘；Pten’�^^和Nestin-Creert2clnk4a/arf UL cPTEN UL GFAP-tta tet- EGFRviil。重要的是，免疫活性小鼠产生的肿瘤可以更好地评估 肿瘤与自然微环境的相互作用。最后，我们将继续维护和 协助从标准胶质瘤细胞系建立传统的异种移植模型 (例如U87、U251、LN229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(GSCs)进行动物实验提供支持 免疫缺陷小鼠的原位异种移植。 目的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：维持细胞系的正常库存。 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。 四个脑部孢子项目中的三个预计将使用大量的小鼠进行他们的 实验。脑瘤动物核心中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。

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.