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Wang J.J.,Tongji University | Zheng Y.,Xuhui District Central Hospital | Yang F.,Tongji University | Zhao P.,Shanghai University | Li H.F.,Tongji University
International Journal of Gynecological Cancer

Introduction: Small interfering RNA (siRNA) has been used to knock down the expression of specific genes. However, its delivery remains a challenge. Recently, ultrasound combined with microbubbles has been used to deliver plasmid into cells and has shown much superiority. Whether a survivin siRNA transfected with a microbubble contrast agent combined with ultrasound exposure could inhibit survivin expression and induce ovarian cancer cell apoptosis was investigated. Methods: The survivin gene was amplified and inserted into vector pEGFP-N1, resulting in psurvivin-EGFP. Three siRNA expression cassettes (SECs) targeting survivin were obtained by 2-step polymerase chain reaction. The SECs and psurvivin-EGFP were cotrans-fected into 293T cells. A functional SEC was selected and inserted into pMD18T, resulting in the survivin-targeting siRNA expression plasmid, which was transfected into SKOV-3 ovarian carcinoma cells using SonoVue, a microbubble contrast agent, and ultrasound exposure. Survivin expression was monitored by Western blot, and apoptosis was determined by fluorescence-activated cell sorting. Results: One siRNA effectively inhibited survivin expression. SonoVue with ultrasound effectively delivered survivin siRNA to SKOV-3 cells, inhibited survivin expression, and induced apoptosis. Conclusions: Delivery of survivin siRNA using a microbubble contrast agent combined with ultrasound exposure can effectively inhibit survivin expression and induce apoptosis, providing a new promising approach for siRNA delivery in vivo. Source

Bi M.,Xuhui District Central Hospital
Chinese Journal of Gastroenterology

Background: Danshensu is extracted from the dry root of Chinese herb medicine Salvia miltiorrhiza Bge. It has antioxidant properties and cytotoxic activity against many human cancers. Aims: To investigate apoptotic effect of Danshensu on human hepatocellular carcinoma cell line SMMC7721 in vitro and to elucidate its mechanism. Methods: Hepatocellular carcinoma cell line SMMC7721 was incubated with different concentrations of Danshensu (0 mg/L, 10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L) for 24, 48 and 72 hours, respectively. Cell inhibition rate was assessed by MTT assay. Morphological changes were observed under transmission electron microscope. Apoptosis was assessed by Annexin V-FITC/PI double staining after SMMC7721 cells being treated with different concentrations of Danshensu (0-40 mg/L) or with 40 mg/L Danshensu for different time (0-48 hours). mRNA expression of p53 was determined by RT-PCR after SMMC7721 cells being treated with different concentrations of Danshensu (0-40 mg/L) for 24 hours. Results: Proliferation of SMMC7721 cells was obviously inhibited and apoptosis was induced by Danshensu in dose- and time-dependent manners. Characteristic apoptosis was confirmed by transmission electron microscope. mRNA expression of p53 gene enhanced with the increase of Danshensu concentration. Conclusions: Danshensu can inhibit the proliferation and induce apoptosis of SMMC7721 cells in time- and dose-dependent manners, and its mechanism may be related to the up-regulation of p53 expression. Source

Liu L.,Fudan University | Wu N.,Xuhui District Central Hospital | Li J.,Fudan University | Li J.,Shanghai Medical College
Journal of Hematology and Oncology

Contemporary advancements have had little impact on the treatment of gastric cancer (GC), the worlds second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs) and receptor tyrosine kinase inhibitors (TKIs). Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2) gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers. © 2012 Liu et al.; licensee BioMed Central Ltd. Source

Cao M.,Shanghai University | Zhou Z.-W.,Xuhui District Central Hospital | Fang B.-J.,Shanghai University | Zhao C.-G.,Shanghai University | Zhou D.,Shanghai University
Medicine (United States)

A number of studies have been conducted to explore the association between the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and risk of myocardial infarction (MI); however, the results are inconsistent. Therefore, we conducted this meta-analysis to clarify the issue based on all the data available. Eligible studies were retrieved by searching PubMed,Embase,Web of Science, and Google Scholar. We calculated the crude odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) to assess the association between the TaqIB polymorphism and risk of MI. We included 13 studies involving 8733 MI cases and 8573 controls in the meta-analysis. The pooled results from all included studies showed decreased MI risk in the analysis of the B2B2 versus B1B1 (OR=0.78, 95% CI=0.680.91), dominant (OR=0.88, 95% CI=0.770.99), and recessive genetic models (OR=0.84, 95% CI=0.780.91). The frequency of the B2B2 genotype in MI patients was lower (OR=0.87, 95% CI=0.810.94). However, there was no significant association in the B1B2 versus B1B1 analysis (OR=0.92, 95% CI=0.811.05) and no significant difference for the B1B1 genotype (OR=1.04, 95% CI=0.981.11) and B1B2 genotype (OR=1.03, 95% CI=0.97 1.08). Cumulative analysis confirmed these results. Our results suggest that the B2B2 genotype of the CETP TaqIB polymorphism is a protective factor against the development of MI. Source

Chen L.,Xuhui District Central Hospital | Li Q.-Y.,Fudan University | Shi X.-J.,Fudan University | Mao S.-L.,Xuhui District Central Hospital | Du Y.-L.,China Pharmaceutical University
Journal of Agricultural and Food Chemistry

Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARγ) gene expression and PPARγ transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPα) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPα and facilitating the translocation of GLUT4 via the activation of PPARγ, suggesting that 6-HD can be promising in diabetes management. © 2013 American Chemical Society. Source

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