AIM： To test the hypothesis that enhancement of the activity of heine oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-e...AIM： To test the hypothesis that enhancement of the activity of heine oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heine oxygense-1 in a CCl4-induced micronodular cirrhosis model. METHODS： Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated, 1×10^12 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS： Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells （HSCs） in rAAV/ HO-1-transduced livers. CONCLUSIONS： Enhancement of HO activity in the livers suppresses the development of cirrhosis.展开更多
OBJECTIVE: To investigate the immune privilege induced by the Fas ligand (FasL) expressed by cotransplanted testicular Sertoli cells in islet allografts, and the effect of FasL gene transfection on islet cells in panc...OBJECTIVE: To investigate the immune privilege induced by the Fas ligand (FasL) expressed by cotransplanted testicular Sertoli cells in islet allografts, and the effect of FasL gene transfection on islet cells in pancreatic islet allografts. METHODS: Allogeneic islets and testicular cells were cotransplanted into diabetic recipients.Pancreatic islets were infected with the recombinant adenovirus, AdV-FasL, and transplanted into diabetic recipients. Allograft survival, islet function, apoptosis of infiltrative lymphocytes in allografts and gene transfected islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state in a few days (mean survival time 6.3 +/- 0.6 days). When the quantity of testicular cells cotransplanted with islets increased to 1 x 10(7), all animals remained normoglycemic throughout the follow-up period (60 days). FasL expression by cotransplanted Sertoli cells induced apoptosis of activated lymphocytes. Rejection of allografts in the FasL gene transfer group was accelerated and allograft survival was shortened to 3.4 +/- 0.2 days (P展开更多
Objective To study the inhibitory effects of retrovirus-mediated p16 gene on the human ovarian cancer cell line CAOV3.Methods The recombinant eukaryotic expression vector pDOR-p16 containing exogenous human wt-p16 c...Objective To study the inhibitory effects of retrovirus-mediated p16 gene on the human ovarian cancer cell line CAOV3.Methods The recombinant eukaryotic expression vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector with neomycin resistance gene only were introduced into a CAOV3 cell line which does not express p16 endogenously by lipofectamine-mediated gene transfection. By using polymerase chain reaction amplification, mRNA in situ hybridization and immunocytochemistry, the clones obtained were tested for their efficiency of transfection and effects of vector expression. Their biologic behavior was observed further.Results Exogenous wt-p16 was transferred into CAOV3 cells successfully and permanent expression was obtained. The growth rate of the transfected CAOV3 cells in regular medium and soft agar was inhibited, and the tumorigenicity in nude mice showed that two of four mice failed to form tumors, and the others developed tumors 7 to 14 days later than mice of the contrast group. The percentage of phase G1 cells increased and that of phase S cells decreased. Under electron microscope, the ultrastructural changes of the cells revealed necrosis and growth retardation.Conclusions The p16 gene plays an important role in the generation and development of ovarian carcinoma. This study might provide experimental evidence for gene therapy in human ovarian cancer.展开更多
文摘AIM： To test the hypothesis that enhancement of the activity of heine oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heine oxygense-1 in a CCl4-induced micronodular cirrhosis model. METHODS： Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated, 1×10^12 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS： Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells （HSCs） in rAAV/ HO-1-transduced livers. CONCLUSIONS： Enhancement of HO activity in the livers suppresses the development of cirrhosis.
基金ThisstudywassupportedbytheNationalNaturalScienceFundationofChina (No 3 9770 72 6)
文摘OBJECTIVE: To investigate the immune privilege induced by the Fas ligand (FasL) expressed by cotransplanted testicular Sertoli cells in islet allografts, and the effect of FasL gene transfection on islet cells in pancreatic islet allografts. METHODS: Allogeneic islets and testicular cells were cotransplanted into diabetic recipients.Pancreatic islets were infected with the recombinant adenovirus, AdV-FasL, and transplanted into diabetic recipients. Allograft survival, islet function, apoptosis of infiltrative lymphocytes in allografts and gene transfected islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state in a few days (mean survival time 6.3 +/- 0.6 days). When the quantity of testicular cells cotransplanted with islets increased to 1 x 10(7), all animals remained normoglycemic throughout the follow-up period (60 days). FasL expression by cotransplanted Sertoli cells induced apoptosis of activated lymphocytes. Rejection of allografts in the FasL gene transfer group was accelerated and allograft survival was shortened to 3.4 +/- 0.2 days (P
基金ThissubjectwassupportedbyagrantfromtheNaturalScienceFoundationofLiaoningProvince (No 9810 5 0 0 10 5 )
文摘Objective To study the inhibitory effects of retrovirus-mediated p16 gene on the human ovarian cancer cell line CAOV3.Methods The recombinant eukaryotic expression vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector with neomycin resistance gene only were introduced into a CAOV3 cell line which does not express p16 endogenously by lipofectamine-mediated gene transfection. By using polymerase chain reaction amplification, mRNA in situ hybridization and immunocytochemistry, the clones obtained were tested for their efficiency of transfection and effects of vector expression. Their biologic behavior was observed further.Results Exogenous wt-p16 was transferred into CAOV3 cells successfully and permanent expression was obtained. The growth rate of the transfected CAOV3 cells in regular medium and soft agar was inhibited, and the tumorigenicity in nude mice showed that two of four mice failed to form tumors, and the others developed tumors 7 to 14 days later than mice of the contrast group. The percentage of phase G1 cells increased and that of phase S cells decreased. Under electron microscope, the ultrastructural changes of the cells revealed necrosis and growth retardation.Conclusions The p16 gene plays an important role in the generation and development of ovarian carcinoma. This study might provide experimental evidence for gene therapy in human ovarian cancer.
