PRE-CLINICAL ANIMAL CORE

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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.