PRE-CLINICAL ANIMAL CORE

临床前动物核心

• 批准号: 8514330
• 负责人: Charles David James
• 金额: $ 16.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514330
• 关键词: Abnormal Cell; Address; Allografting; Animal Euthanasia; Animal Experimentation; Animal Model; Animals; Apoptotic; Archives; Biodistribution; Biological Assay; Biological Markers; Bioluminescence; Blood specimen; Brain; Brain Neoplasms; CD-I; Cell Count; Cell Line; Cells; Collaborations; Data; Data Quality; Development; Engraftment; Euthanasia; Frequencies; Grant; Growth; Human; Immunocompetent; Implant; In Vitro; Instruction; Intraperitoneal Injections; Investigation; Investigational Therapies; Ionizing radiation; Ki-67 Antigen; Length; Life; Luciferases; Malignant - descriptor; Methods; Modeling; Molecular; Monitor; Mus; Neurologic Symptoms; Nude Mice; Operative Surgical Procedures; Oral; Outcome; Pathology; Patients; Pharmaceutical Preparations; Phase; Principal Investigator; Procedures; Process; Protocols documentation; Rattus; Records; Reproduction spores; Research; Research Personnel; Resected; Resources; Rodent; Rodent Model; Source; Specimen; Staining method; Stains; Stem cells; Surrogate Markers; Survival Analysis; Testing; Therapeutic; Therapeutic Effect; Tissue and Organ Harvesting; Tissues; Toxic effect; Training; Tumor Burden; Tumor Cell Line; Tumor Tissue; Vascularization; Xenograft procedure; assay development; base; bioluminescence imaging; caspase-3; design; experience; in vivo; irradiation; mouse model; neoplastic cell; optical imaging; pre-clinical; pre-clinical therapy; research study; response; subcutaneous; therapeutic target; tumor; tumor growth; tumorigenic

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.

由于 SPORE 研究的转化要求，SPORE 研究人员必须具备 获得并协助动物模型进行治疗假设检验。加州大学旧金山分校脑肿瘤 SPORE Animal Core 通过使用 3 种啮齿动物颅内移植模型来满足这一需求，基于 关于细胞来源：1）人类肿瘤细胞； 2)化学诱导的啮齿动物脑肿瘤细胞系； 3) 肿瘤细胞 源自转基因小鼠模型。肿瘤细胞被植入大脑 免疫缺陷和/或免疫功能正常的宿主，其治疗效果由生物发光确定 肿瘤生长监测、动物受试者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，核心还 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 在预定时间点收获组织，检查样本的药物含量和/或指示 获得血液样本时病理异常和/或细胞计数异常。最后，核心服务 作为移植过程产生的肿瘤组织的来源，用于生物标志物研究和测定 开发，以及涉及活组织或细胞转移的情况下的体外研究。 这些活动的开展与以下具体目标相关： 目标 1：传播、分析（组织病理学和分子）、存档并维护所有相关信息的最新记录 用于支持 SPORE 动物模型研究的肿瘤细胞来源和组织。 目标 2：建议和协助所有啮齿动物模型治疗测试，包括光学成像、生存获益 肿瘤治疗反应分析、毒性评估和分子分析。 目标 3：与组织核心结合，利用人类异种移植肿瘤组织来促进 开发可应用于生物制品研究的免疫组织化学和 FISH 检测方法 患者肿瘤的反应指标、治疗靶点和替代标记。 目标 4：在 UCSF 内外处理和分发异种移植肿瘤组织和细胞系以及 从每个中提取，以促进 SPORE 内部和 SPORE 之间的合作，并支持大脑 一般而言，肿瘤研究是通过利用可再生肿瘤细胞资源进行的。 相关性（参见说明）： 动物模型研究是在用于治疗之前测试研究疗法的必要部分 脑肿瘤患者。因此，考虑到 SPORE 研究的转化方向，有一个 SPORE 研究人员持续需要进行动物模型研究。此类研究较多 通过拥有具有动物模型研究专业知识并且随时可以提供帮助的专业人员来提高效率 协助SPORE动物模型研究的设计和实施。