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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA097257-11A1
Application #
8514330
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (J1))
Project Start
2013-05-01
Project End
2018-08-31
Budget Start
2013-09-18
Budget End
2014-08-31
Support Year
11
Fiscal Year
2013
Total Cost
$164,864
Indirect Cost
$59,604
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ostrom, Quinn T; Kinnersley, Ben; Wrensch, Margaret R et al. (2018) Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21. Sci Rep 8:7352
Salas, Lucas A; Koestler, Devin C; Butler, Rondi A et al. (2018) An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray. Genome Biol 19:64
Choi, Serah; Yu, Yao; Grimmer, Matthew R et al. (2018) Temozolomide-associated hypermutation in gliomas. Neuro Oncol 20:1300-1309
Jacobs, Daniel I; Liu, Yanhong; Gabrusiewicz, Konrad et al. (2018) Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients. J Neurooncol 136:33-39
Berntsson, Shala G; Merrell, Ryan T; Amirian, E Susan et al. (2018) Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study. J Neurol 265:1432-1442
Goode, Benjamin; Joseph, Nancy M; Stevers, Meredith et al. (2018) Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation. Mod Pathol 31:660-673
Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E et al. (2018) Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas. Neuro Oncol 20:632-641
Ostrom, Quinn T; Kinnersley, Ben; Armstrong, Georgina et al. (2018) Age-specific genome-wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'-like features associated with younger age. Int J Cancer 143:2359-2366
Pekmezci, Melike; Stevers, Meredith; Phillips, Joanna J et al. (2018) Multinodular and vacuolating neuronal tumor of the cerebrum is a clonal neoplasm defined by genetic alterations that activate the MAP kinase signaling pathway. Acta Neuropathol 135:485-488
Behr, Spencer C; Villanueva-Meyer, Javier E; Li, Yan et al. (2018) Targeting iron metabolism in high-grade glioma with 68Ga-citrate PET/MR. JCI Insight 3:

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