Pancreatic cancer is usually a fatal disease with 5-year survival rates of only 1-4%. We have developed fluorescent orthotopic models of human pancreatic cancer in the nude mouse by transforming the tumors with green-fluorescent protein (GFP) gene and red fluorescent protein (RFP) to enable visualization of primary tumor growth angiogenesis, and metastasis in live animals in real time. The unique advantages of GFP and RFP-expressing tumor cells are that no preparative procedures, contrast agents, substrates, anesthesia, or light-tight boxes are required for whole-body imaging. We are proposing to test the following hypotheses: #1 The model can replicate and predict the clinical course of individual pancreatic cancer patient tumor growth and metastases. Tumors from pancreatic cancer patients will be orthotopically implanted in the model using nude and SClD mice and transfected with GFP or RFP in vivo. GFP and RFP imaging will be compared to traditional tumor imaging techniques of ultrasound, computed tomography, and magnetic resonance imaging. #2 These improved mouse models of pancreatic cancer can be used to facilitate translational drug discovery in a preclinical setting. We will assess the feasibility of in vivo drug-screening to inhibit tumor growth and metastatic spread in the OFF and RFP orthotopic models of human patient pancreatic cancer. Real-time tumor and metastatic growth inhibition by representative standard and experimental agents will be imaged and quantified to demonstrate feasibility of use of the models as a rapid anti-tumor and anti-metastatic drug screen. #3 Dual-color fluorescence imaging can distinguish tumor cells from induced host angiogenic vessels and stromal cells. This method clearly images implanted tumors and adjacent stroma, distinguishing the host and tumor-specific components of the malignancy by using RFP-expressing tumors growing in GFP expressing transgenic mice. Using such dual-colored imaging techniques, a better characterization of the tumor-host interactions in pancreatic cancer can be made.
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