AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental pla...AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.展开更多
幽门螺杆菌(Helicobacter pylori,Hp)是引起慢性胃炎、消化性溃疡及胃癌的重要病因,几乎所有胃部 Hp 感染者均可引起不同程度胃部炎症改变,少数发展为慢性萎缩性胃炎(chronic atrophic gastritis,CAG),甚至胃癌.关于 Hp 感染导致 CAG ...幽门螺杆菌(Helicobacter pylori,Hp)是引起慢性胃炎、消化性溃疡及胃癌的重要病因,几乎所有胃部 Hp 感染者均可引起不同程度胃部炎症改变,少数发展为慢性萎缩性胃炎(chronic atrophic gastritis,CAG),甚至胃癌.关于 Hp 感染导致 CAG 的确切发病机制,目前仍不十分清楚.现就 CAG与 Hp 感染关系的研究现状作一综述.展开更多
AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA^+ and VacA^- H pyl...AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA^+ and VacA^- H pylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy. RESULTS: A total of 16 000 cDNA clones were detected. The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA^+ BCS reached 5%, compared with that challenged by VacA^- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels. Most of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton, apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA^+ BCS showed collapsed and disrupted microtubular cytoarchitecture. CONCLUSION: VacA^+ BCS can disrupt cytoskeletal architecture, likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors. VacA^+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.展开更多
To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. ...To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. METHODSSystematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. RESULTSThirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. CONCLUSIONSerological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.展开更多
AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal...AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA.METHODS: Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR.CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindⅢ and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b,s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by χ2test, ttest, and rank sum test.RESULTS: A total of 192 clinical H. pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases,and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P＜0.05)except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P＜0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group,there was a difference between s1a and s1b (P＜0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi′an area isolates.CONCLUSION: The cagA+ vacA type s1 clinical isolates are more in Xi′an area, but this can not serve as an index to predict gastric cancer.展开更多
AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study w...AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study was to investigate the Hpylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan.METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA.RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168,74%) strains in the majority of patients. In patients with gastric cancer, the vacA sla and slc subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P= 0.0001 for sla and 13/66 vs93/168, P<0.0001 for slc). In the middle region, the mlT strain in patients with gastric cancer was more than that of non-cancer patients(23/66 vs 33/168, P = 0.02).CONCLUSION: In Taiwan, H pylori with positive vacA sla,cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and slc subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.展开更多
Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host resp...Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.展开更多
基金Supported by Coordenao de Aperfeioamento de Pessoal de Nível Superior and Federal University of Pará
文摘AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in pa-tients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological exami-nation, rapid urease test and polymerase chain reac-tion (PCR) assays to detect the presence of cagA and vacA polymorphisms.RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR com-pared to histological examination and the rapid ure-ase test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque sam-ples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These viru-lent H. pylori isolates were involved in the severity of clinical outcome.CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth.
文摘幽门螺杆菌(Helicobacter pylori,Hp)是引起慢性胃炎、消化性溃疡及胃癌的重要病因,几乎所有胃部 Hp 感染者均可引起不同程度胃部炎症改变,少数发展为慢性萎缩性胃炎(chronic atrophic gastritis,CAG),甚至胃癌.关于 Hp 感染导致 CAG 的确切发病机制,目前仍不十分清楚.现就 CAG与 Hp 感染关系的研究现状作一综述.
基金Supported by the State Ministry of Educafion Research Foundation for Returned Overseas Chinese Scholars Abroad(2001)498
文摘AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA^+ and VacA^- H pylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy. RESULTS: A total of 16 000 cDNA clones were detected. The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA^+ BCS reached 5%, compared with that challenged by VacA^- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels. Most of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton, apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA^+ BCS showed collapsed and disrupted microtubular cytoarchitecture. CONCLUSION: VacA^+ BCS can disrupt cytoskeletal architecture, likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors. VacA^+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.
基金Supported by the BMBF No.BMBF-0315905D in the frame of ERA-NET Patho Geno Mics to Malfertheiner P
文摘To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. METHODSSystematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. RESULTSThirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. CONCLUSIONSerological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
文摘AIM: To establish stock of clinical Helicobacter pylori (H.pylon) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA.METHODS: Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR.CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindⅢ and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b,s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by χ2test, ttest, and rank sum test.RESULTS: A total of 192 clinical H. pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases,and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P＜0.05)except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P＜0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group,there was a difference between s1a and s1b (P＜0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi′an area isolates.CONCLUSION: The cagA+ vacA type s1 clinical isolates are more in Xi′an area, but this can not serve as an index to predict gastric cancer.
文摘AIM: Helicobacter pylori( H pylori) has been linked to chronic gastritis, peptic ulcer, gastric cancer and MALT-lymphoma.The link of genotypes of Hpylorito gastric cancer remains controversial. The aim of this study was to investigate the Hpylori vacA alleles, cagA and iceA in patients with gastric cancer in Taiwan.METHODS: Patients with gastric cancer, peptic ulcer and chronic gastritis were enrolled in this study. We obtained biopsy specimens from the stomach at least 2 cm away from the tumor margin in patients with gastric cancer, and from the antrum of stomach in patients with peptic ulcer or chronic gastritis. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vacA and iceA.RESULTS: A total of 168 patients (gastric ulcer: 77, duodenal ulcer: 66, and chronic gastritis: 25) were found to have positive PCR results of the biopsy specimens from patients with peptic ulcer and chronic gastritis. We found positive cagA (139/168, 83%), m2 (84/168, 50%) and iceA1 (125/168,74%) strains in the majority of patients. In patients with gastric cancer, the vacA sla and slc subtypes were less commonly found than those in non-cancer patients (35/66 vs 127/168, P= 0.0001 for sla and 13/66 vs93/168, P<0.0001 for slc). In the middle region, the mlT strain in patients with gastric cancer was more than that of non-cancer patients(23/66 vs 33/168, P = 0.02).CONCLUSION: In Taiwan, H pylori with positive vacA sla,cagA and iceA1 strains are found in the majority of patients with gastric cancer or non-cancer patients. In patients with gastric cancer, the vacA s1a and slc subtypes are less and m1T is more than in patients with peptic ulcer and chronic gastritis.
基金Supported by University of Pavia(Fondo d'Ateneo per la Ricercato Ricci V)+1 种基金Second University of Naples(CIRANAD to Romano M)
文摘Helicobacter pylori (H.pylori) has co-evolved with humans to be transmitted from person to person and to colonize the stomach persistently.A well-choreographed equilibrium between the bacterial effectors and host responses permits microbial persistence and health of the host,but confers a risk for serious diseases including gastric cancer.During its long coexistence with humans,H.pylori has developed complex strategies to limit the degree and extent of gastric mucosal damage and in? ammation,as well as immune effector activity.The present editorial thus aims to introduce and comment on major advances in the rapidly developing area of H.pylori/human gastric mucosa interaction (and its pathological sequelae),which is the result of millennia of co-evolution of,and thus of reciprocal knowledge between,the pathogen and its human host.
