Background Hepatitis B virus encoded X protein (HBx) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBx that participate in this process have been ident...Background Hepatitis B virus encoded X protein (HBx) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBx that participate in this process have been identified. We screened, by comparative proteomics method, effectors of HBx associated with hepatocarcinogenesis.Methods HBx positive and negative HepG2 cells were constructed and expression patterns of cellular proteins were obtained by high resolution, two dimensional electrophoresis. Comprehensive analyses of proteins associated with hepatocellular carcinoma (HCC) were focused on the differently expressed proteins (more than two-fold increase or decrease, P 〈0.05) from HBx positive and negative HepG2 cells. For peptide mass fingerprinting, protein spots with different intensity between HBx positive and negative HepG2 cells were directly cut out of gels and processed for matrix assisted, laser desorption/ionization, time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) analysis.Results The mean number of protein spots for HBx negative and HBx positive HepG2 cells were 2095±137 and 2188±105, respectively. The analysis of paired cells showed 75 spots with significant differences in expression between HBx negative and HBx positive cells: 37 spots corresponding to 32 different proteins; 25 proteins were upregulated, 7 downregulated. We found 7 proteins not previously reported differentially expressed in HBx positive HepG2 cells. Variations in protein accumulation were confirmed for four (HSP90AB1, BCL2 associated athanogene 2. nucleophosmin and chloride intracellular channel 1) by Western blotting in HBx positive HepG2 cells.Conclusions Numerous effectors of HBx that may promote the development of HCC are identified, of which 7 are newly noted in HepG2 cells. Several of these effectors of HBx may help in elucidating the roles of HBx in hepatocarcinogenesis and diagnostics or targets for therapeutic intervention.展开更多
Background Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta...Background Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to etuc(date this issue. Methods The electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated. Results Eleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95% CI: 2.15-3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95% CI: 0.62-0.71) and overall survival (OS) (HR: 0.84, 95% CI: 0.78-0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95% CI: 4.61-9.01). Conclusion In patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.展开更多
文摘Background Hepatitis B virus encoded X protein (HBx) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HBx that participate in this process have been identified. We screened, by comparative proteomics method, effectors of HBx associated with hepatocarcinogenesis.Methods HBx positive and negative HepG2 cells were constructed and expression patterns of cellular proteins were obtained by high resolution, two dimensional electrophoresis. Comprehensive analyses of proteins associated with hepatocellular carcinoma (HCC) were focused on the differently expressed proteins (more than two-fold increase or decrease, P 〈0.05) from HBx positive and negative HepG2 cells. For peptide mass fingerprinting, protein spots with different intensity between HBx positive and negative HepG2 cells were directly cut out of gels and processed for matrix assisted, laser desorption/ionization, time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) analysis.Results The mean number of protein spots for HBx negative and HBx positive HepG2 cells were 2095±137 and 2188±105, respectively. The analysis of paired cells showed 75 spots with significant differences in expression between HBx negative and HBx positive cells: 37 spots corresponding to 32 different proteins; 25 proteins were upregulated, 7 downregulated. We found 7 proteins not previously reported differentially expressed in HBx positive HepG2 cells. Variations in protein accumulation were confirmed for four (HSP90AB1, BCL2 associated athanogene 2. nucleophosmin and chloride intracellular channel 1) by Western blotting in HBx positive HepG2 cells.Conclusions Numerous effectors of HBx that may promote the development of HCC are identified, of which 7 are newly noted in HepG2 cells. Several of these effectors of HBx may help in elucidating the roles of HBx in hepatocarcinogenesis and diagnostics or targets for therapeutic intervention.
文摘Background Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to etuc(date this issue. Methods The electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated. Results Eleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95% CI: 2.15-3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95% CI: 0.62-0.71) and overall survival (OS) (HR: 0.84, 95% CI: 0.78-0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95% CI: 4.61-9.01). Conclusion In patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.