Shi-Rong Cai
Washington University in St. Louis
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Featured researches published by Shi-Rong Cai.
Human Gene Therapy | 1999
Cuihua Gao; Rodney Jokerst; Prathima Gondipalli; Shi-Rong Cai; Susan Kennedy; Katherine P. Ponder
Retroviral vectors can result in therapeutic and stable levels of expression of proteins from the liver. However, most retroviral vectors transduce only dividing cells, and hepatocytes are normally quiescent. The goal of this study was to determine if an adenoviral vector could transiently express hepatocyte growth factor (HGF) in order to induce hepatocyte replication and facilitate retroviral vector transduction of the liver. Intramuscular injection of an adenoviral vector that expressed human HGF from the cytomegalovirus promoter (Ad.CMV.HGF) resulted in moderate levels of HGF in blood and liver, and replication of 3 to 12% of hepatocytes. No cytopathic effect was observed in the liver, and a control adenoviral vector induced no or lower levels of replication. When a retroviral vector expressing beta-galactosidase cDNA was injected into a peripheral vein during the peak period of hepatocyte replication induced by intramuscularly administered Ad.CMV.HGF, 8% of hepatocytes were transduced. We conclude that intramuscular injection of Ad.CMV.HGF is a safe and effective way to induce transient systemic expression of HGF and hepatocyte replication, and to facilitate transduction of hepatocytes with a retroviral vector.
Journal of Hepatology | 2000
Shi-Rong Cai; Kentaro Motoyama; Katherine J Shen; Susan Kennedy; M. Wayne Flye; Katherine P. Ponder
BACKGROUND/AIMS Liver insufficiency occurs when the liver cannot perform critical functions such as ammonia metabolism, gluconeogenesis, or production of coagulation factors The hypothesis of this study was that decreased function of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits cholesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver functions, and lovastatin might prevent these changes METHODS Rats received 90% partial hepatectomy (90% PH), and either lovastatin or vehicle alone daily. Survival and liver functions were assessed. RESULTS Lovastatin increased survival to 58% (vs. 6% in controls that received 90% PH without drug), decreased the peak ammonia level to 427 microM (vs. 846 microM in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s in controls), and decreased the peak activated partial thromboplastin time to 29 s (vs. 39 s in controls). The full survival and metabolic benefits were observed when lovastatin was started at 30 min after 90% PH, but lovastatin was less efficacious when started at later times. CONCLUSIONS Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.
Journal of Clinical Investigation | 1998
Shi-Rong Cai; Susan Kennedy; William M. Bowling; Flye Mw; Katherine P. Ponder
Protein C deficiency results in a thrombotic disorder that might be treated by expressing a normal human protein C (hPC) gene in patients. An amphotropic retroviral vector with a liver-specific promoter and the hPC cDNA was delivered to rat hepatocytes in vivo during liver regeneration. Expression of hPC varied from 55 to 203 ng/ml (1.3-5.0% of normal) for 2 wk after transduction. Expression increased to an average of 900 ng/ml (22% of normal) in some rats and was maintained at stable levels for 1 yr. All of these rats developed anti-hPC antibodies and exhibited a prolonged hPC half-life in vivo. The hPC was functional as determined by a chromogenic substrate assay after immunoprecipitation. We conclude that most rats achieved hPC levels that would prevent purpura fulminans, and that hepatic gene therapy might become a viable treatment for patients with severe homozygous hPC deficiency. Anti-hPC antibodies increased the hPC half-life and plasma levels in some rats, but did not interfere with its functional activity. Thus, the development of antibodies against a plasma protein does not necessarily abrogate its biological effect in gene therapy experiments.
Blood | 2003
Lingfei Xu; Cuihua Gao; Mark S. Sands; Shi-Rong Cai; Timothy C. Nichols; Dwight A. Bellinger; Robin A. Raymer; Stephanie McCorquodale; Katherine P. Ponder
Molecular Therapy | 2005
Yuli Liu; Lingfei Xu; Anne K. Hennig; Attila Kovacs; Annabel S. Fu; Sarah Chung; David Lee; Bin Wang; Ramin Herati; Judith Mosinger Ogilvie; Shi-Rong Cai; Katherine P. Ponder
Blood | 1997
MaiThao Le; Torayuki Okuyama; Shi-Rong Cai; Susan Kennedy; William M. Bowling; M. Wayne Flye; Katherine P. Ponder
Hepatology | 2001
Bin Wang; Shi-Rong Cai; Cuihua Gao; Frances M. Sladek; Katherine P. Ponder
Human Gene Therapy | 1996
William M. Bowling; Susan Kennedy; Shi-Rong Cai; James R. Duncan; Cuihua Gao; M. Wayne Flye; Katherine P. Ponder
Hepatology | 1999
Cuihua Gao; Rodney Jokerst; Prathima Gondipalli; Shi-Rong Cai; Susan Kennedy; M. Wayne Flye; Katherine P. Ponder
Archive | 2010
Stephanie McCorquodale; Parker Ponder; Lingfei Xu; Cuihua Gao; Mark S. Sands; Shi-Rong Cai; Timothy C. Nichols