PRE-CLINICAL ANIMAL CORE

由于孢子研究的翻译要求，孢子研究人员必须具备 获得并协助动物模型进行治疗性假设检验。加州大学旧金山分校的脑瘤 孢子动物核心通过使用3种类型的啮齿动物颅内植入模型来满足这一需求，基于 细胞来源：1)人肿瘤细胞；2)化学诱导鼠脑肿瘤细胞系；3)肿瘤细胞 源自转基因小鼠模型。肿瘤细胞被植入人的大脑 免疫缺陷和/或免疫活性宿主，其治疗效果由生物发光确定 肿瘤生长监测、动物生存分析和肿瘤免疫组织化学分析 生物反应指标，特别是增殖和凋亡反应。此外，酷睿还 进行研究以评估治疗毒性和生物分布。这些研究通常涉及器官和 在预定的时间点采集组织，并检查标本的药物含量和/或适应症 当采集血样时，病理异常和/或细胞计数异常。最后，核心服务于 作为植入过程中产生的肿瘤组织的来源，用于生物标记物的研究和分析 发展，以及在涉及转移活组织或细胞的情况下进行体外研究。 这些活动是结合以下具体目标开展的： 目标1：传播、分析(组织病理学和分子学)、存档和维护所有 用于支持孢子动物模型研究的肿瘤细胞来源和组织。 目标2：建议并协助所有啮齿动物模型疗法测试，包括光学成像、生存益处 肿瘤治疗反应的分析、毒性评估和分子分析。 目的3：结合组织核心，利用人异种移植瘤组织促进 应用于生物调查的免疫组织化学和FISH方法的研究进展 患者肿瘤的反应指标、治疗靶点和替代标记物。 目标4：在加州大学旧金山分校、异种移植瘤组织和细胞系内外加工和分布 每种植物的提取物，以促进孢子内和孢子间的协作，以及支持大脑 肿瘤研究一般是通过利用可再生的肿瘤细胞资源。 相关性(请参阅说明)： 动物模型研究是在将研究疗法用于治疗之前测试研究疗法的必要部分 脑瘤患者。因此，考虑到孢子研究的翻译方向，有一个 目前需要孢子研究人员进行动物模型研究。这样的研究被做得更多 通过拥有具有动物模型研究专业知识的专业人员以及随时可以联系到的人员来提高效率 协助设计和实施孢子动物模型研究。

Because of the translational requirement of SPORE research, it is essential that SPORE investigators have access to and assistance with animal models for therapeutic hypothesis testing. The UCSF Brain Tumor SPORE Animal Core addresses this need by using 3 types of rodent intracranial engraftment models, based on cell of origin: 1) human tumor cells; 2) chemically induced rodent brain tumor cell lines; and 3) tumor cells derived from genetically modified mouse models. Tumor cells are implanted in the brains of immunodeficient, and/or immunocompetent hosts, with therapeutic effect determined by bioluminescence monitoring of tumor growth, animal subject survival analysis, and immunohistochemical analysis of tumor biologic response indicators, especially proliferation and apoptotic response. In addition, the Core also conducts studies to assess therapeutic toxicity and biodistribution. These studies typically involve organ and tissue harvests at pre-determined timepoints, with specimens examined for drug content, and/or indication of abnormal pathology, and/or abnormal cell counts when blood samples are obtained. Finally, the Core serves as a source of tumor tissues, resulting from engraftment procedures, for biomarker investigation and assay development, and for in vitro investigation in instances involving the transfer of viable tissues or cells. These activities are carried out in association with the following specific aims: Aim 1: Propagate, analyze (histopathological and molecular), archive, and maintain up-to-date records on all tumor cell sources and tissues used in support of SPORE animal model research. Aim 2: Advise and assist all rodent model therapeutics testing, including optical imaging, survival benefit analysis, toxicity assessment, and molecular analyses of tumors for response to therapy. Aim 3: In association with the Tissue Core, utilize human xenograft tumor tissues to facilitate the development of immunohistochemical and FISH assays that can be applied to the investigation of biologic response indicators, therapeutic targets, and surrogate markers in patient tumors. Aim 4: Process, and distribute, within and outside of UCSF, xenograft tumor tissues and cell lines, as well as extracts from each, so as to promote intra- and inter-SPORE collaborations, as well as to support brain tumor research in general, through utilization of renewable tumor cell resources. RELEVANCE (See instructions): Animal model research is a required part of testing investigational therapies prior to their being used to treat brain tumor patients. As such, and given the translational orientation of SPORE research, there is an ongoing need of SPORE investigators to perform animal model studies. Such studies are made more efficient by having specialized staff with animal model research expertise, and who are readily available to assist in the design and implementation of SPORE animal model research.