BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of t...BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I^(2)statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I^(2)=72.6%,P<0.001)and PFS(I^(2)=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.展开更多
AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepi...AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.展开更多
AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE ce...AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).展开更多
Derived from enteroendocrine cells(EECs),glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic peptide(GIP)are pivotal incretin hormones crucial for blood glucose regulation.Medications of GLP-1 analogs a...Derived from enteroendocrine cells(EECs),glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic peptide(GIP)are pivotal incretin hormones crucial for blood glucose regulation.Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes(T2D)and obesity.However,there are currently no agents to stimulate endogenous incretin secretion.Here,we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion.Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance.Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion,particularly GIP.Furthermore,KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin,especially GIP secretion upon nutrient stimulation.Mechanistically,KCNH2 knockdown in EECs leads to reduced K+currents,prolonged action potential duration,and elevated intracellular calcium levels.Finally,we found that dofetilide,a KCNH2-specific inhibitor,could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo.These findings elucidate,for the first time,the mechanism and application of KCNH2 in regulating incretin secretion by EECs.Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management,this study advances our understanding of incretin regulation,paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.展开更多
基金Supported by Sichuan Science and Technology Program,No.2022YFS0625。
文摘BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I^(2)statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I^(2)=72.6%,P<0.001)and PFS(I^(2)=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.
基金the Natural Science Foundation of Shaanxi Province(No.2022JM-521)the Science and Technology Plan Project of Xi’an(No.21YXYJ0031).
文摘AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.
基金Supported by the Natural Science Foundation of Shaanxi Province,China(No.2022JM-521).
文摘AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).
基金supported by grants from the National Natural Science Foundation of China(81930019)to Jin-Kui Yangsupported by grants from Beijing Municipal Natural Science Foundation(7232232)to Hao Wang。
文摘Derived from enteroendocrine cells(EECs),glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic peptide(GIP)are pivotal incretin hormones crucial for blood glucose regulation.Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes(T2D)and obesity.However,there are currently no agents to stimulate endogenous incretin secretion.Here,we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion.Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance.Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion,particularly GIP.Furthermore,KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin,especially GIP secretion upon nutrient stimulation.Mechanistically,KCNH2 knockdown in EECs leads to reduced K+currents,prolonged action potential duration,and elevated intracellular calcium levels.Finally,we found that dofetilide,a KCNH2-specific inhibitor,could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo.These findings elucidate,for the first time,the mechanism and application of KCNH2 in regulating incretin secretion by EECs.Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management,this study advances our understanding of incretin regulation,paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.
