AAV-DJ is an artificial chimeric AAV vector containing hybrid capsid sequences from three naturally occurring AAV serotypes (AAV2, 8, and 9).28 This and other chimeric AAV vectors are currently being used because of their improved tissue tropism and transduction frequencies.28, 34, 38 However, understanding of the

factors that influence AAV gene targeting are still incomplete and more work in this area will likely improve our ability in the future to modify genes in primary somatic cells. According to the annual report of the American Liver Foundation, hepatitis, cirrhosis, and HCC affect 25 million Americans. However, research in the area of Romidepsin nmr liver disease lags behind other well-studied prominent disorders because of the lack of appropriate animal models. The HT1 pig will potentially address several significant needs, including serving as the first large-animal model of HCC arising

spontaneously in the background of cirrhosis. In addition, the Fah-null mouse has proven an invaluable model for cell and gene therapy work, including its use for hepatocyte and bone marrow transplantation studies, as well as both viral and non-viral-mediated gene therapy approaches.39-42 We anticipate BMN 673 chemical structure that the pig model will also be extensively used for similar gene and cell therapy studies. Finally, we recently developed a method whereby primary human hepatocytes were efficiently expanded MCE in immune-deficient mice mutant for Fah.43 In these mice, transplanted Fah+/+ primary human hepatocytes were able to engraft and expand to greater than 90% repopulation of the mouse liver. These hepatocytes were fully functioning adult primary hepatocytes capable of performing all the necessary metabolic and synthetic functions that are required in the normal liver. However, a limitation in the repopulated FAH-deficient mouse is related to its small size. The absolute number of primary human hepatocytes that can be obtained from these animals is low, making a large animal

model of FAH deficiency highly desirable. We thank Mark Kay and Leszek Lisowski (Stanford University, Stanford, CA) for supplying the AAV-DJ capsid and helper plasmids, as well as the AAV-DJ GFP virus. We also thank Angela Major of the NIDDK-sponsored Digestive Disease Core Laboratory of the Texas Medical Center (DK56338) for histology support. “
“In 1991 this journal published the report of an international working party to the World Congress of Gastroenterology regarding the clinicopathological staging of colorectal cancer. Since that time staging has continued to evolve as further prognostic factors in colorectal cancer have been elucidated in studies of increasingly large databases in several countries. This review summarizes several of the key issues that have arisen during this evolutionary process and raises matters which still remain controversial in staging at the present time.