A hallmark of our laboratory is the development of novel and innovative in vivo tumor models that allow us to study barriers in the delivery of therapeutic agents. This is only possible because of the outstanding surgical expertise and unique animal facility available in the Steele Laboratory since its inception in 1975. This Core will continue to serve two major functions: (i) the surgical support, including novel animal model development, and (ii) the breeding and maintenance of mice, including genetically engineered mice (GEM). Both are vital for successful completion of all Program Project Grant (PPG) goals. Thus, Core C is a cornerstone of this PPG. This Core will continue to develop or improve and provide sophisticated orthotopic tumor models - syngeneic tumor grafts (all four Projects) - as well as cranial window (Projects 1), lung window (Project 2), liver tumor preparation (Project 2, 3) and abdominal window (Project 4). These will enable in vivo time-course monitoring of molecular, cellular, anatomical, and functional parameters in the orthotopic organ environment of brain, colon, liver and pancreatic tumors and their metastases. In addition, this Core will significantly expand maintenance and provision of GEM models in this revised PPG in order to meet a surge of GEM demand from all 4 Projects to study the role of the host microenvironment in response to treatment in spontaneous tumors. Through his leadership of the operation of Cox-7 gnotobiotic animal facility. Dr. Huang will continue to ensure that all experimental animals are of uniform quality and free of murine viruses, pathogenic bacteria, and parasites. This will enable the PPG team to carry out all experimental procedures without the use of antibiotics. These studies are extremely difficult and more costly elsewhere. Currently 26 defined-flora genetically engineered mouse lines are available in the Cox-7 facility. Based on the need of all 4 Projects, additional mouse lines will also be engineered or rederived, bred, and produced 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 continue to provide standard animal procedures such as controlled-release pump implantation, vascular line placement, post-surgical care and tissue collection.

Public Health Relevance

The overall goal of the proposed Program Project Grant is to develop strategies to overcome barriers to effective treatment of brain, colorectal, liver and pancreatic cancers. Preclinical models, which resemble the clinical features of these tumors, are absolutely essential. This core continues to provide outstanding surgical expertise and high quality and quantity of genetically engineered mice to all four Projects. Thus, Core C forms a cornerstone of this Program Project.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-O)
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Massachusetts General Hospital
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