) A hallmark of our laboratory has been the development of novel and innovative in vivo tumor models. These models have allowed us to study barriers to the delivery of therapeutic agents. This has been possible due to the outstanding surgical expertise and unique animal facility available in our lab. The proposed core builds on this foundation. This core will serve two functions: (i) surgical support, and (ii) breeding and maintenance of animals. Both are vital for successful completion of all four project goals. Thus, this core forms the cornerstone of the proposed PPG. The following animal models have been established in our laboratory and will be provided by this core. Transparent window models (all four projects) will enable us to monitor physiological parameters and gene regulation in vivo. The liver tumor (Project 1 and 3) and mammary fat pad tumor (Project 4) models will allow us to study the role of host microenvironment. The micropore chamber model (Project 2) will allow us to collect interstitial fluid. Tissue sample collection, control release pump implantation, vascular line placement, and post surgical care will also be available through this core. The gnotobiotic animal colony in this core will allow 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 uniform quality experimental animals free of murine viruses, pathogenic bacteria, and parasites. This will enable us to carry out surgical procedures without antibiotics. Defined flora C3H (Project 4), SCID (Project 2, 3, 4) mice and RAG-2 knock out (KO)(Project 1, 3, 4) mice are currently available. In addition, GFP transgenic mice developed in Project 1, VEGF conditional KO and bFGF KO mice (Project 1), decorin KO mice (Project 3) and scavenger receptor KO mice (Project 4) will be back crossed with Rag-2 KO mice to obtain immunodeficient background and will be bred and maintained by this Core. Tumors screened and free of mouse pathogens will be serially passaged in vivo and implanted into experimental animals. In vivo tumors are not passaged beyond the fifth generation to avoid changes in tumor characteristics. This assures tight quality control of animals and tumors.
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