This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This is a pilot program to create a new model for liver cancer research and therapy. We will create a baboon model of liver cancer for use in new technologies involving advanced diagnostics and therapies using sophisticated imaging techniques to visualize and treat the tumor. Currently no large animal model of liver cancer is available to develop and perfect these methods. Liver cancer is the 4th leading cause of cancer death worldwide. Because it is a fast-growing tumor that is rarely diagnosed in the early stages, liver cancer is typically fatal within a year of diagnosis. In this program we will clone the genes involved in liver cancer from the baboon, such that all genes involved are homologous to the host. We will introduce genetic modifications to convert the genes into cancer inducing genes or oncogenes. We will use gene therapy vectors (Lentivirus vectors) to introduce multiple modified genes into liver cells (hepatocytes) growing in our well established hepatocyte culture system for baboon hepatocytes. Cells with tumorigenic properties will first be selected in the SCID mouse model and then introduced into the liver of baboon that was the original donor of the cells (autologous cell transplant). Once perfected, the model will be used to advance new therapies for liver cancer.
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