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 will address this need by utilizing serially-passaged human GBM xenografts in conducting in vivo studies using immune-deficient mice and rats. Emphasis will be placed on the use of serially-passaged xenografts since our cumulative experience with this system of tumor propagation indicates that serial in vivo passaging promotes tumor retention of key properties that are lost during cell line establishment. In additon, the Animal Core will emphasize orthotopic (intracranial) therapeutic testing because intracranial tumors established from serially propagated flank xenografts are highly invasive, and therefore present a more rigorous and clinically-relevant test of therapeutic efficacy than would be provided by the well-circumscribed subcutaneous tumors propagated in the flanks of nude mice, or by well-circumscribed intracranial tumors that are produced by injection of established cell lines. In association with this test model philosophy, the objectives of the UCSF Brain Tumor Animal Core are as follows:
Aim 1 : Propagate, analyze (histopathological and molecular), archive, and maintain up-to-date records on all GBM xenografts used in support of SPORE animal model research.
Aim 2 : Coordinate and conduct all immune deficient rodent therapeutics testing, including optical imaging and molecular analyses of intracranial xenograft specimens, in assessing tumor response to therapy.
Aim 3 : In association with the Tissue and Outcome Core, utilize xenograft resources to facilitate interpretation of results from immunohistochemical and FISH analysis of therapeutic targets and/or surrogate markers in patient tumors.
Aim 4 : Collect, process, and distribute, within and outside of UCSF, xenograft tumor tissues and tissue extracts, so as to promote intra- and inter-SPORE collaborations, and utilization of these renewable tumor resources.
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