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.

由于孢子研究的翻译要求，孢子研究人员必须 用于治疗假设检验的动物模型的访问和协助。 UCSF脑肿瘤 孢子动物核心通过使用3种类型的颅内植入模型来满足这种需求 关于原始细胞：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 源自转基因的小鼠模型。肿瘤细胞植入 免疫缺陷和/或免疫能力宿主，具有生物发光确定的治疗作用 监测肿瘤生长，动物受试者生存分析和肿瘤的免疫组织化学分析 生物反应指标，尤其是增殖和凋亡反应。另外，核心也 进行研究以评估治疗性毒性和生物分布。这些研究通常涉及器官和 在预定的时间点上收获组织，并检查了标本是否有药物含量和/或指示 当获得血液样本时，异常病理和/或异常细胞计数。最后，核心服务 作为生物标志物研究和测定的肿瘤组织的来源 在涉及生存组织或细胞转移的情况下进行开发，并进行体外研究。 这些活动与以下特定目的进行： 目标1：传播，分析（组织病理学和分子），存档并保持所有人的最新记录 用于支持孢子动物模型研究的肿瘤细胞源和组织。 目标2：建议和协助所有啮齿动物模型疗法测试，包括光学成像，生存益处 分析，毒性评估和肿瘤的分子分析，以应对治疗。 目标3：与组织核有关，利用人异种移植肿瘤组织促进 可以应用于生物学研究的免疫组织化学和鱼类测定法的开发 患者肿瘤中的反应指标，治疗靶标和替代标记。 AIM 4：过程，并在UCSF内外分布，异种移植肿瘤组织和细胞系以及 从每种摘录中提取，以促进内部和跨间的合作，并支持大脑 通常，通过利用可再生肿瘤细胞资源来研究肿瘤研究。 相关性（请参阅说明）： 动物模型研究是测试研究疗法之前所需的一部分 脑肿瘤患者。因此，鉴于孢子研究的转化取向，有一个 持续需要孢子研究人员进行动物模型研究。这样的研究更多 通过拥有动物模型研究专业知识的专业员工而有效，并且很容易获得 协助设计和实施孢子动物模型研究。