Objective:Albumin-globulin ratio(AGR),prognostic nutritional index(PNI),and platelet to-lymphocyte ratio(PLR)have been validated as prognostic factors for gastric cancer(GC).However,significant gender differences exis...Objective:Albumin-globulin ratio(AGR),prognostic nutritional index(PNI),and platelet to-lymphocyte ratio(PLR)have been validated as prognostic factors for gastric cancer(GC).However,significant gender differences exist in albumin levels and inflammatory cell counts,and further research is required to understand how these differences influence GC prognosis.This study aims to investigate the prognostic impact of nutritional and inflammatory indicators on GC patients undergoing radical surgery,as well as the influence of gender on these indicators’prognostic value.Methods:The study included 596 patients with advanced GC hospitalized in the Department of Gastrointestinal Surgery,General Surgery,Xiangya Hospital of Central South University from January 2012 to December 2016.Receiver operating characteristic(ROC)analysis was performed to determine cutoff values for nutritional and inflammatory factors.Univariate analysis was used to identify factors significantly affecting survival in GC patients,while multivariate and Kaplan-Meier analyses determined independent prognostic factors for GC.Results:Multivariate analysis revealed that postsurgical tumor node metastasis(pTNM)stage[stage II:hazard ratio(HR)=3.284,P=0.012;stage III:HR:8.062,P<0.001],low preoperative AGR(HR=1.499,P=0.012),and postoperative PNI(HR=1.503,P=0.008)were risk factors for overall survival in male patients after radical GC surgery.For female patients,pN2-3(HR=3.185,P<0.001),total gastrectomy(HR=2.286,P=0.004),low preoperative PLR(HR=1.702,P=0.027),and postoperative PNI(HR=1.943,P=0.011)were identified as risk factors for overall survival.Conclusion:Postoperative PNI is an independent risk factor for all advanced GC patients.Preoperative PLR is an independent prognostic factor only for female patients,while preoperative AGR is an independent prognostic factor only for male patients.Further research is warranted to investigate the gender-specific differences in GC prognosis.展开更多
OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medic...OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM) as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN(ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear.METHODS CCK-8 assay was used to detect the cell viability.The levels of proteins and mRNA were evaluated using Western blot and q-PCR.Mitochondrial membrane potential was measured by flow cytometry.Depolymerisa.tion of F-actin and translocation of G-actin(gamma-actin) from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay.RESULTS phosphorylated coflin-1(p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP,relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory.lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines.However,ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito.chondria in both SGC7901/DDP and BGC823/DDP cells.This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin,activate mitochondrial dam.age and calcium overloading,and induce the mitochondrial apoptosis pathway.These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer,which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.展开更多
Types and characteristics of gastric dysplasia werestudied histopathologically. Besides the adenomatous,cryptal and globoid dysplasias, regenerative type of gas-tric dysplasia was described, especially about its histo...Types and characteristics of gastric dysplasia werestudied histopathologically. Besides the adenomatous,cryptal and globoid dysplasias, regenerative type of gas-tric dysplasia was described, especially about its histo-pathological features and histogenesis. The peculiarityof this type of gastric dysplasia just coincided with thefindings of gastric mucosal changes found in the inhabitantsliving in Liaodong Panisula-a high incidence area ofgastric cancer. According to the epidemiologic and histo-pathologic studies on the inhabitants of Zhuanghe Countyof Liaodong Panisula, it was found that high salted foodse.g. the salted pork and fish etc. showed strongmutagenecity. The authors detected that these were therisk factors and might be the leading cause of the gastricmucosal erosions and following by epithelial regenerativechanges. Malignant changes were detected in the regene-rative dysplastic lesions in pathologic sections. Therefore,gastric mucosal regeneration should not be oper looked asa precursor of gastric cancer in some cases.展开更多
OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent ...OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition.In this study,several kind of gastric cancer cell lines were used as the research object,and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer.METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823) by using glycolysis inhibitor,2-deoxy-D-glucose(2-DG) and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR) and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences) to deter.mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells.In addition,western blot was used to detect the contribution of AMP-activated protein kinase(AMPK),and anti-apoptotic proteins(Bcl-2 and survivin) to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin.RESULTS In this study,it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L^(-1)(MGC-803) to 15.57 mmol·L^(-1)(BGC-823).MGC-803 was relatively sensitive to 2-DG(IC 50:3.28 mmol·L^(-1)),consumed more glucose and produced more lactate(waste product of glycolysis) than the three other cell lines.Consequently,MGC-803 could be more dependent on glycolysis than other cell lines,which was further confirmed by the fact that glucose(+) FCS(-) medium showed more growth and survival than glucose(-) FCS(+) medium.Alternatively,BGC-823,most resistant to 2-DG(IC50:15.57 mmol · L-1),was most sensitive to oligomycin,and showed more growth and survival in glucose(-) FCS(+) medium than in glucose(+) FCS(-) medium.Thus,we had reasons to think BGC-823 cells depended on oxidative phosphorylation for energy production.In BGC-823,AMPK,which is activated when ATP becomes limiting,was rapidly phosphorylated by 2-DG,and expression of Bcl-2 was augmented,which might result in resistance to 2-DG.Interestingly,AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in MGC-803,which is 2-DG sensitive.CONCLUSION There is a large metabolic difference between gastric cancer cell lines,which will facilitate the future gastric cancer therapy by targeting metabolic pathways.展开更多
基金supported by the National Natural Science Foundation of China(8197103463).
文摘Objective:Albumin-globulin ratio(AGR),prognostic nutritional index(PNI),and platelet to-lymphocyte ratio(PLR)have been validated as prognostic factors for gastric cancer(GC).However,significant gender differences exist in albumin levels and inflammatory cell counts,and further research is required to understand how these differences influence GC prognosis.This study aims to investigate the prognostic impact of nutritional and inflammatory indicators on GC patients undergoing radical surgery,as well as the influence of gender on these indicators’prognostic value.Methods:The study included 596 patients with advanced GC hospitalized in the Department of Gastrointestinal Surgery,General Surgery,Xiangya Hospital of Central South University from January 2012 to December 2016.Receiver operating characteristic(ROC)analysis was performed to determine cutoff values for nutritional and inflammatory factors.Univariate analysis was used to identify factors significantly affecting survival in GC patients,while multivariate and Kaplan-Meier analyses determined independent prognostic factors for GC.Results:Multivariate analysis revealed that postsurgical tumor node metastasis(pTNM)stage[stage II:hazard ratio(HR)=3.284,P=0.012;stage III:HR:8.062,P<0.001],low preoperative AGR(HR=1.499,P=0.012),and postoperative PNI(HR=1.503,P=0.008)were risk factors for overall survival in male patients after radical GC surgery.For female patients,pN2-3(HR=3.185,P<0.001),total gastrectomy(HR=2.286,P=0.004),low preoperative PLR(HR=1.702,P=0.027),and postoperative PNI(HR=1.943,P=0.011)were identified as risk factors for overall survival.Conclusion:Postoperative PNI is an independent risk factor for all advanced GC patients.Preoperative PLR is an independent prognostic factor only for female patients,while preoperative AGR is an independent prognostic factor only for male patients.Further research is warranted to investigate the gender-specific differences in GC prognosis.
基金supported by National Natural Science Foundation of China(81473481)Construct Program of the Key Discipline of State Administration of Traditional Chinese Medicine of People′s Republic of Chinathe Science Foundation for Shanghai Municipal Health and Family Planning Commission(20124065)
文摘OBJECTIVE Despite the status of cisplatin(DDP) as a classical chemotherapeutic agent in the treatment of cancer,the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM) as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN(ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear.METHODS CCK-8 assay was used to detect the cell viability.The levels of proteins and mRNA were evaluated using Western blot and q-PCR.Mitochondrial membrane potential was measured by flow cytometry.Depolymerisa.tion of F-actin and translocation of G-actin(gamma-actin) from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay.RESULTS phosphorylated coflin-1(p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP,relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory.lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines.However,ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito.chondria in both SGC7901/DDP and BGC823/DDP cells.This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin,activate mitochondrial dam.age and calcium overloading,and induce the mitochondrial apoptosis pathway.These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer,which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.
基金This research was supported by the National "7.5" Research Grant on Cancer.
文摘Types and characteristics of gastric dysplasia werestudied histopathologically. Besides the adenomatous,cryptal and globoid dysplasias, regenerative type of gas-tric dysplasia was described, especially about its histo-pathological features and histogenesis. The peculiarityof this type of gastric dysplasia just coincided with thefindings of gastric mucosal changes found in the inhabitantsliving in Liaodong Panisula-a high incidence area ofgastric cancer. According to the epidemiologic and histo-pathologic studies on the inhabitants of Zhuanghe Countyof Liaodong Panisula, it was found that high salted foodse.g. the salted pork and fish etc. showed strongmutagenecity. The authors detected that these were therisk factors and might be the leading cause of the gastricmucosal erosions and following by epithelial regenerativechanges. Malignant changes were detected in the regene-rative dysplastic lesions in pathologic sections. Therefore,gastric mucosal regeneration should not be oper looked asa precursor of gastric cancer in some cases.
基金supported by National Natural Science Foundation of China(81502952)
文摘OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition.In this study,several kind of gastric cancer cell lines were used as the research object,and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer.METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823) by using glycolysis inhibitor,2-deoxy-D-glucose(2-DG) and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR) and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences) to deter.mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells.In addition,western blot was used to detect the contribution of AMP-activated protein kinase(AMPK),and anti-apoptotic proteins(Bcl-2 and survivin) to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin.RESULTS In this study,it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L^(-1)(MGC-803) to 15.57 mmol·L^(-1)(BGC-823).MGC-803 was relatively sensitive to 2-DG(IC 50:3.28 mmol·L^(-1)),consumed more glucose and produced more lactate(waste product of glycolysis) than the three other cell lines.Consequently,MGC-803 could be more dependent on glycolysis than other cell lines,which was further confirmed by the fact that glucose(+) FCS(-) medium showed more growth and survival than glucose(-) FCS(+) medium.Alternatively,BGC-823,most resistant to 2-DG(IC50:15.57 mmol · L-1),was most sensitive to oligomycin,and showed more growth and survival in glucose(-) FCS(+) medium than in glucose(+) FCS(-) medium.Thus,we had reasons to think BGC-823 cells depended on oxidative phosphorylation for energy production.In BGC-823,AMPK,which is activated when ATP becomes limiting,was rapidly phosphorylated by 2-DG,and expression of Bcl-2 was augmented,which might result in resistance to 2-DG.Interestingly,AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in MGC-803,which is 2-DG sensitive.CONCLUSION There is a large metabolic difference between gastric cancer cell lines,which will facilitate the future gastric cancer therapy by targeting metabolic pathways.
