AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the im...AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.展开更多
BACKGROUND The infusion of triolein emulsion(TE)induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.AIM To assess changes in doxo...BACKGROUND The infusion of triolein emulsion(TE)induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.AIM To assess changes in doxorubicin concentration according to the percentage of TE infused via a hepatic artery to study the vascular permeability in the rabbit liver.METHODS Thirty-nine healthy rabbits were divided into five groups according to the concentration of emulsified triolein infused into the hepatic arteries:Group 0,saline infusion(control group,n=5);group 1,0.3%TE(n=13);group 2,0.6%TE(n=6);group 3,0.9%TE(n=8);and group 4,1.5%TE(n=6).Doxorubicin(2.4 mg/kg)was infused immediately after TE injection via the hepatic arteries.After 2 h,the livers were harvested,and doxorubicin concentrations were calculated fluorometrically.The doxorubicin concentrations were compared between TE groups and the control group,and the optimal concentrations within the TE groups were calculated.Statistical analysis was performed using the nonparametric Mann-Whitney U test and Kruskal-Wallis test.P<0.05 were considered statistically significant.RESULTS In the liver,doxorubicin concentrations were 2.06,2.07,2.16 and 1.66 times higher in groups 1 through 4,respectively,and significantly higher in the TE groups than in the control group(all P<0.05).However,there were no significant differences in the mean doxorubicin concentrations between the four TE groups(P=0.642).In the lungs,the mean doxorubicin concentrations were not significantly different between the control and TE groups(P>0.05).CONCLUSION TE infusion into the hepatic arteries significantly increased the doxorubicin concentration approximately twofold but was not different between the TE groups.These findings suggest that TE infusion might be a useful adjuvant treatment of liver cancers.展开更多
基金Supported by a faculty research grant of Yonsei University College of Medicine for 2002,No.2002-06
文摘AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.
基金Biomedical Research Institute,Pusan National University Hospital,No.2018B008。
文摘BACKGROUND The infusion of triolein emulsion(TE)induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.AIM To assess changes in doxorubicin concentration according to the percentage of TE infused via a hepatic artery to study the vascular permeability in the rabbit liver.METHODS Thirty-nine healthy rabbits were divided into five groups according to the concentration of emulsified triolein infused into the hepatic arteries:Group 0,saline infusion(control group,n=5);group 1,0.3%TE(n=13);group 2,0.6%TE(n=6);group 3,0.9%TE(n=8);and group 4,1.5%TE(n=6).Doxorubicin(2.4 mg/kg)was infused immediately after TE injection via the hepatic arteries.After 2 h,the livers were harvested,and doxorubicin concentrations were calculated fluorometrically.The doxorubicin concentrations were compared between TE groups and the control group,and the optimal concentrations within the TE groups were calculated.Statistical analysis was performed using the nonparametric Mann-Whitney U test and Kruskal-Wallis test.P<0.05 were considered statistically significant.RESULTS In the liver,doxorubicin concentrations were 2.06,2.07,2.16 and 1.66 times higher in groups 1 through 4,respectively,and significantly higher in the TE groups than in the control group(all P<0.05).However,there were no significant differences in the mean doxorubicin concentrations between the four TE groups(P=0.642).In the lungs,the mean doxorubicin concentrations were not significantly different between the control and TE groups(P>0.05).CONCLUSION TE infusion into the hepatic arteries significantly increased the doxorubicin concentration approximately twofold but was not different between the TE groups.These findings suggest that TE infusion might be a useful adjuvant treatment of liver cancers.
