A hallmark of our laboratory is the development of novel and innovative in vivo tumor models that allow us to study barriers to the delivery of therapeutic agents. This is possible due to the outstanding surgical expertise and unique animal facility available in our lab, for which this Core serves as its foundation. This Core will continue to serve two functions: (i) surgical support which includes novel animal model development, and (ii) breeding and maintenance of animals. Both are vital for successful completion of all project goals. Thus, this Core forms a cornerstone of the competing renewal of our PPG. This Core will continue to establish and provide animal models to all Projects of this PPG. Transparent window models - the mammary fat pad window (all three Projects), the cranial window (Projects 1, 2) and the dorsal skin chamber (Project 3)- enable in vivo time-course monitoring of molecular, cellular, anatomical, and functional parameters in orthotopic organ environments for breast, brain and skin cancers, respectively. In addition, spontaneous tumors allow us to study the role of the host microenvironment in tumor development and treatment. The Cox-7 gnotobiotic animal colony maintained by this Core allows us to carry out longitudinal physiological studies in immunodeficient mice. These studies are extremely difficult and more costly elsewhere. This facility will continue to provide us with experimental animals of uniform quality that are free of murine viruses, pathogenic bacteria, and parasites. This enables us to carry out surgical procedures without the use of antibiotics. Defined flora C3H, FVB,C57BL/6, Nude, SCID, rag-T'' rag-T'-, VTGFP-GFP/(FVB, C3H, rag-Z'' background), Tie2p-GFP/(FVB, rag-T'- background), EFlcf- GFP/FVB, and ACTbp-GFP/C57VL/6 mice are currently available in the Cox-7 facility. Additional transgenic and knock-out mice for all Projects will also be engineered or rederived, bred, and maintained for all Projects within the facility. Tumors that are screened and free of mouse pathogens will be serially passaged in vivo and implanted into experimental animals within the colony. In vivo tumors will not be passaged beyond the fifth generation (F5) to avoid changes in tumor characteristics. This assures tight control of the quality of animals and tumors. Core C will also continue to provide controlled-release pump implantation, tissue sample collection, vascular line placement, and post-surgical care.
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