BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have show...BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.展开更多
Helicobacter pylori(H.pylori)infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue(MALT).Increasing evidence shows that eradication of H.pylori with anti...Helicobacter pylori(H.pylori)infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue(MALT).Increasing evidence shows that eradication of H.pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission.The eradication of H.pylori is the standard care for patients with gastric MALT lymphoma.Cytotoxin-associated gene A(CagA)protein,one of the most extensively studied H.pylori virulence factors,is strongly associated with the gastric MALT lymphoma.CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races.After being translocated into B lymphocytes via typeⅣsecretion system,CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and-independent manners and/or some other pathways,and thereby promotes lymphomagenesis.A variety of proteins including p53and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA.Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.展开更多
OBJECTIVE： To assess the role of cytotoxin-associated gene-A （CagA） positive strains of Helicobacter pylori （Hp） in ischemic stroke （IS） subtypes. DATA SOURCES： A computer-based online search of PubMed, EMBASE...OBJECTIVE： To assess the role of cytotoxin-associated gene-A （CagA） positive strains of Helicobacter pylori （Hp） in ischemic stroke （IS） subtypes. DATA SOURCES： A computer-based online search of PubMed, EMBASE, the Cochrane Collaboration database, the CNKI database and the VIP database, from January 1997 to July 2010, was performed to find relevant studies. DATA SELECTION： Case-control studies relevant to CagA with IS and IS subtypes were selected. Data regarding related factors in the case group and control group were acquired using the same approach. All patients had been diagnosed as exhibiting IS using skull CT or MRI, and were etiologically typed according to the 1993 TOAST diagnosis criteria. Two investigators independently performed the same search and study selection. Meta-analyses were then performed for the selected studies using RevMan 5.0 software （Cochrane Collaboration） after strict screening. Heterogeneity tests, sensitivity analyses and publication bias assessments were then conducted. MAIN OUTCOME MEASURES： Relationship of CagA with IS and IS subtypes. RESULTS： Eight studies were selected, involving data from 879 patients with IS, and 849 healthy controls. Five out of eight of the selected studies were related to large artery atherosclerosis （461 patients with IS and 497 health controls）. The results of our meta-analysis revealed a significant association between prior infection with CagA-positive strains and increased risk of IS （odds ratio （OR） = 2.31,95% confidence interval （C/）： 1.89-2.82, P 〈 0.01）, In addition, we found an association between infection with CagA-negative strains and IS （OR = 0.57, 95%C1：0.47 0.70, P 〈 0.01）. CagA positive and negative strains were found to correlate with large artery atherosclerosis （CagA-positive strains： OR = 2.87, 95%C/： 2.19-3.77, P 〈 0.01; CagA-negative strains： OR = 0.51, 95%CL 0.39 0.67, P 〈 0.01）. Because of the diversity of etiological factors in the case-control study, we conducted further analyses after correcting for confounding factors, and the overall effects were recalculated. The results revealed significant relationships between CagA-positive strains and IS （OR = 2.36, 95%C1： 1.84-3.02, P 〈 0.01）, and between CagA-positive strains and large artery atherosclerosis （OR = 3.10, 95%C1： 2.29-4.19, P 〈 0.01 ）. A heterogeneity test of CagA-positive strains in IS and its subtypes revealed good homogeneity （f = 0%; f = 0%） and we adopted a fixed-effects model to calculate OR. Sensitivity analysis confirmed that the results of the meta-analysis were reliable. However, the funnel plot suggested that the experimental results may be affected by bias, possibly resulting from a lack of published studies reporting negative outcomes in the meta-analysis. CONCLUSION： Infection with CagA-positive strains is a risk factor for IS, especially the large artery atherosclerosis subtype. However, the evidence from case-control studies is weak, and more prospective studies are required to conclusively determine whether infection by CagA-positive strains should be considered a novel risk factor for IS and its subtypes.展开更多
基金National Natural Science Foundation of China,No.81572350。
文摘BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.
基金Supported by Foundation of Scientific Technology Bureau of Zhejiang Province,No.2010C33118
文摘Helicobacter pylori(H.pylori)infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue(MALT).Increasing evidence shows that eradication of H.pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission.The eradication of H.pylori is the standard care for patients with gastric MALT lymphoma.Cytotoxin-associated gene A(CagA)protein,one of the most extensively studied H.pylori virulence factors,is strongly associated with the gastric MALT lymphoma.CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races.After being translocated into B lymphocytes via typeⅣsecretion system,CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and-independent manners and/or some other pathways,and thereby promotes lymphomagenesis.A variety of proteins including p53and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA.Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.
基金School-level Foundation,No. 200503Ministry Youth Innovation Fund Project,No. 200901
文摘OBJECTIVE： To assess the role of cytotoxin-associated gene-A （CagA） positive strains of Helicobacter pylori （Hp） in ischemic stroke （IS） subtypes. DATA SOURCES： A computer-based online search of PubMed, EMBASE, the Cochrane Collaboration database, the CNKI database and the VIP database, from January 1997 to July 2010, was performed to find relevant studies. DATA SELECTION： Case-control studies relevant to CagA with IS and IS subtypes were selected. Data regarding related factors in the case group and control group were acquired using the same approach. All patients had been diagnosed as exhibiting IS using skull CT or MRI, and were etiologically typed according to the 1993 TOAST diagnosis criteria. Two investigators independently performed the same search and study selection. Meta-analyses were then performed for the selected studies using RevMan 5.0 software （Cochrane Collaboration） after strict screening. Heterogeneity tests, sensitivity analyses and publication bias assessments were then conducted. MAIN OUTCOME MEASURES： Relationship of CagA with IS and IS subtypes. RESULTS： Eight studies were selected, involving data from 879 patients with IS, and 849 healthy controls. Five out of eight of the selected studies were related to large artery atherosclerosis （461 patients with IS and 497 health controls）. The results of our meta-analysis revealed a significant association between prior infection with CagA-positive strains and increased risk of IS （odds ratio （OR） = 2.31,95% confidence interval （C/）： 1.89-2.82, P 〈 0.01）, In addition, we found an association between infection with CagA-negative strains and IS （OR = 0.57, 95%C1：0.47 0.70, P 〈 0.01）. CagA positive and negative strains were found to correlate with large artery atherosclerosis （CagA-positive strains： OR = 2.87, 95%C/： 2.19-3.77, P 〈 0.01; CagA-negative strains： OR = 0.51, 95%CL 0.39 0.67, P 〈 0.01）. Because of the diversity of etiological factors in the case-control study, we conducted further analyses after correcting for confounding factors, and the overall effects were recalculated. The results revealed significant relationships between CagA-positive strains and IS （OR = 2.36, 95%C1： 1.84-3.02, P 〈 0.01）, and between CagA-positive strains and large artery atherosclerosis （OR = 3.10, 95%C1： 2.29-4.19, P 〈 0.01 ）. A heterogeneity test of CagA-positive strains in IS and its subtypes revealed good homogeneity （f = 0%; f = 0%） and we adopted a fixed-effects model to calculate OR. Sensitivity analysis confirmed that the results of the meta-analysis were reliable. However, the funnel plot suggested that the experimental results may be affected by bias, possibly resulting from a lack of published studies reporting negative outcomes in the meta-analysis. CONCLUSION： Infection with CagA-positive strains is a risk factor for IS, especially the large artery atherosclerosis subtype. However, the evidence from case-control studies is weak, and more prospective studies are required to conclusively determine whether infection by CagA-positive strains should be considered a novel risk factor for IS and its subtypes.
