The Animal Research Core is an integral unit for the SPORE - Bay Area Breast Cancer Translational Research Program. The translational nature of the research involved in this program frequently requires animal studies prior to clinical application. The centralized nature of the Core and interaction with all SPORE investigators allows maximal usage of this valuable research asset of an animal model for human breast cancer. The use of a single facility for this research reduces equipment duplication and costs and allows coordination of animal work to achieve volume discounts. The primary goal of the Animal Research Core is maintenance and refinement of the xenogeneic animal model for human breast cancer. Immune deficient mice, hormone supplemented if required, are inoculated with human breast cancer cell lines in Matrigel. Tumor-bearing mice are then supplied to investigators in the SPORE Projects and Developmental Projects. Animals are treated within the Core at the direction of the investigator. Animals or harvested tumor or tissues are then supplied to the investigator for analysis. Project 1 will utilize animals with HER2/neu expressing tumors from BT474, MDA453, MKN7 and transfected MCF7 (clone 18) cell lines to determine the efficacy and toxicity of immunoliposomes encapsulating specific chemotherapy agents. Project 2 will use doxorubicin chemoresistant tumors developed in animals for analysis using comparative genomic hybridization (CGH) to determine copy number abnormalities at one or a few chromosomal regions associated with chemoresistance. Project 4 will use cell lines transfected with the Luciferase reporter gene to sensitively examine the effect of urokinase plasminogen activator inhibitors on metastatic activity. The Animal Research Core has conducted one extensive study through a SPORE Developmental Project (In vivo drug resistance of breast cancer cell lines due to HER2/neu oncogene) and has consulted on several other projects awaiting funding. Refinement of the animal model system occurs continuously in the Core and pilot studies are conducted as necessary to support the SPORE Projects and Developmental Projects. In addition to growth of breast cancer cell lines as tumors, the Animal Research Core is growing primary human breast cancers in the mouse model system. In vitro culture of these tissues has been difficult and has routinely resulted in selection of the diploid population of tumor cells, very different from the original aneuploid tumor. Recent inoculations and serial passages of animal tumors from primary human breast tumors have yielded tumor tissue for analysis and studies are pending for use of this new tissue source.
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