Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Met...Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Methods： The data were collected and analyzed by retrieval of 229 published short dsRNAs designed for degradation ofHCV RNA. Results： Statistical analyses showed that the most frequently involved short dsRNAs were directing against 5＇NTR/core and genotype lb, accounting for 64.2% and 69.9%, respectively. Inhibitory efficacy varied with the structural characteristics of short dsRNAs, of which the most potential were those directed against HCV core region with inhibitory efficacy of 70.2%. Moreover, the mean inhibitory efficacy of short dsRNAs with GC contents from 30% to 52% was higher than that of those with GC contents out of this range. Conclusion： Based on this pooled data in a relatively large sample, the present results provided clues to design for short dsRNAs with more potent inhibitory efficacy.展开更多
Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovir...Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovirus carrying the wild-type PTEN gene （Ad-PTEN）. RL95-2 cells, an endometrial carcinoma cell line lacking PTEN function, was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin, decreased proliferation rate, and elevated apoptosis and Go/G1 arrest. Furthermore, the tumorigenicity of these cells was also completely suppressed. These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection, induce apoptosis of tumor cells, and reduce expression of proliferating cell nuclear antigen （PCNA）. Immunohistochemistry analysis also showed that the expression of progesterone receptors （PR） in Ad-PTEN treated tumor cells were induced, while P-glycoproteins （P-gp） and estrogen receptors （ER） decreased significantly. Conclusion： PTEN may play an important role in the development of endometrial carcinoma. Our findings cast new lights for treatment ofendometrial carcinoma.展开更多
Objective: To investigate the effect of adenoviral vector-mediated AT2R gene transfection on neointimal hyperplasia after rat carotid artery balloon injury. Methods :AT2R gene was transferred into rat carotid arteries...Objective: To investigate the effect of adenoviral vector-mediated AT2R gene transfection on neointimal hyperplasia after rat carotid artery balloon injury. Methods :AT2R gene was transferred into rat carotid arteries by recombinant adenovirus pAd-AT2R after the establishment of rat carotid balloon injury restenosis model. The arteries were harvested on the 14th day after gene transfer. The efficiency of trans-gene delivery was measured by the expression of adenovirus-encoding green fluorescent protein (GFP) under fluorescent microscope. The expression of AT2R and PCNA (proliferating cell nuclear antigen) was e-valuated by RT-PCR, immunocytochemistry, immunofluorescence staining, confocal microscopy, respectively. The ratio of intimal to medial area (I/M) was quantified with images and determined by an image analysis system. Results: GFP-positive area in adventitia, media and the forming neointima was about 40%. Adenoviral delivery of rat AT2R gene up-regulated AT2R expression in balloon-injured rat carotid and reduced PCNA expression and I/M significantly in neointima(P<0. 01). Double immunofluorescence labeling of AT2R and PCNA also showed that AT2R gene transfer inhibited VSMCs proliferation in neointima. Conclusion: AT2R gene transfer may be a novel promising therapy to limit neointimal hyperplasia.展开更多
基金Supported by Grants from the Committee of Science and Technology of Shanghai, China (No.10ZR1413100, and No.114119a1400)
文摘Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Methods： The data were collected and analyzed by retrieval of 229 published short dsRNAs designed for degradation ofHCV RNA. Results： Statistical analyses showed that the most frequently involved short dsRNAs were directing against 5＇NTR/core and genotype lb, accounting for 64.2% and 69.9%, respectively. Inhibitory efficacy varied with the structural characteristics of short dsRNAs, of which the most potential were those directed against HCV core region with inhibitory efficacy of 70.2%. Moreover, the mean inhibitory efficacy of short dsRNAs with GC contents from 30% to 52% was higher than that of those with GC contents out of this range. Conclusion： Based on this pooled data in a relatively large sample, the present results provided clues to design for short dsRNAs with more potent inhibitory efficacy.
基金Supported by the National Natural Science Foundation of China(30471676)Shanghai Science and Technology Committee(04DZ19207-2)
文摘Objective： To determine the potential of sustained transgene expression by intratumoral injection of Ad-PTEN in the nude mouse model of endometrial carcinoma. Methods and Results： We constructed recombinant adenovirus carrying the wild-type PTEN gene （Ad-PTEN）. RL95-2 cells, an endometrial carcinoma cell line lacking PTEN function, was infected with Ad-PTEN and showed increased expression of PTEN and chemosensitivity to doxorubicin, decreased proliferation rate, and elevated apoptosis and Go/G1 arrest. Furthermore, the tumorigenicity of these cells was also completely suppressed. These results indicated that gene therapy with Ad-PTEN could significantly inhibit the endometrial carcinoma xenografts growth in nude mice by intratumoral injection, induce apoptosis of tumor cells, and reduce expression of proliferating cell nuclear antigen （PCNA）. Immunohistochemistry analysis also showed that the expression of progesterone receptors （PR） in Ad-PTEN treated tumor cells were induced, while P-glycoproteins （P-gp） and estrogen receptors （ER） decreased significantly. Conclusion： PTEN may play an important role in the development of endometrial carcinoma. Our findings cast new lights for treatment ofendometrial carcinoma.
文摘Objective: To investigate the effect of adenoviral vector-mediated AT2R gene transfection on neointimal hyperplasia after rat carotid artery balloon injury. Methods :AT2R gene was transferred into rat carotid arteries by recombinant adenovirus pAd-AT2R after the establishment of rat carotid balloon injury restenosis model. The arteries were harvested on the 14th day after gene transfer. The efficiency of trans-gene delivery was measured by the expression of adenovirus-encoding green fluorescent protein (GFP) under fluorescent microscope. The expression of AT2R and PCNA (proliferating cell nuclear antigen) was e-valuated by RT-PCR, immunocytochemistry, immunofluorescence staining, confocal microscopy, respectively. The ratio of intimal to medial area (I/M) was quantified with images and determined by an image analysis system. Results: GFP-positive area in adventitia, media and the forming neointima was about 40%. Adenoviral delivery of rat AT2R gene up-regulated AT2R expression in balloon-injured rat carotid and reduced PCNA expression and I/M significantly in neointima(P<0. 01). Double immunofluorescence labeling of AT2R and PCNA also showed that AT2R gene transfer inhibited VSMCs proliferation in neointima. Conclusion: AT2R gene transfer may be a novel promising therapy to limit neointimal hyperplasia.
