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Dos Santos Pereira E, Magalhães Albuquerque L, de Queiroz Balbino V, da Silva Junior WJ, Rodriguez Burbano RM, Pordeus Gomes JP, Barem Rabenhorst SH. Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer. INFECTION GENETICS AND EVOLUTION 2020; 84:104477. [PMID: 32736040 DOI: 10.1016/j.meegid.2020.104477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 01/15/2023]
Abstract
It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.
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Affiliation(s)
- Eliane Dos Santos Pereira
- Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Valdir de Queiroz Balbino
- Department of Genetics, Biomedical Center, Federal University of Pernambuco, Recife, Pernambuco, Brazil
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Bakhti SZ, Latifi-Navid S, Zahri S, Yazdanbod A. Inverse association of Helicobacter pylori cagPAI genotypes with risk of cardia and non-cardia gastric adenocarcinoma. Cancer Med 2019; 8:4928-4937. [PMID: 31273955 PMCID: PMC6712521 DOI: 10.1002/cam4.2390] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 06/19/2019] [Accepted: 06/19/2019] [Indexed: 12/17/2022] Open
Abstract
Iran is a high‐risk country for cardia gastric adenocarcinoma (CGA) in Central Asia, with an incidence rate five times the average global rate, and shows a high infection rate for Helicobacter pylori (69%). The aim was to examine the associations of multiple H. pylori cagPAI genotypes (ie cagH, cagL, cagG, and orf17) with the risk of CGA, non‐CGA, and different histological types of GA in Iran. A large number of H. pylori strains (N = 336) were successfully cultured and genotyped. Histopathological evaluations were performed. The analysis showed an inverse association between the cagH+ genotype and the risk of CGA and intestinal‐type gastric adenocarcinoma (IGA) (adjusted ORs; 0.312 and 0.283, respectively), where the controls were nontumors. The orf17+ genotype decreased the risk of non‐CGA and diffuse‐type gastric adenocarcinoma (DGA)(adjusted ORs; 0.310 and 0.356, respectively). When the controls were those with nonatrophic gastritis, the cagG+ genotype was negatively associated with the risk of CGA, non‐CGA, IGA, and DGA (adjusted ORs; 0.324, 0.366, 0.306, and 0.303, respectively). We did not find such a significant association for the cagL+ genotype in multiple logistic regression analysis. Combination of the vacA c2 and cagPAI genotypes further decreased the risk estimates for GAs. This study showed the reverse association of H. pylori cagPAI genotypes—cagH+ and cagG+—with the risk of CGA in male patients aged ≥ 55 in Iran. Presence of the vacA c2 genotype in combination with cagPAI genotypes showed strong inverse associations with the risk of CGA and non‐CGA. These findings may reveal a coordinated relationship between the vacA c2 and cagPAI genotypes.
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Affiliation(s)
- Seyedeh Zahra Bakhti
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saber Zahri
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Abbas Yazdanbod
- Digestive Diseases Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
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Mihara H, Suzuki N, Muhammad JS, Nanjo S, Ando T, Fujinami H, Kajiura S, Hosokawa A, Sugiyama T. Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium. Helicobacter 2017; 22:e12361. [PMID: 27687509 PMCID: PMC5363345 DOI: 10.1111/hel.12361] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 08/22/2016] [Accepted: 09/04/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP-infected gastric epithelium, we evaluated HP infection-dependent changes in TRPV4 expression in gastric epithelium. MATERIALS AND METHODS Human gastric biopsy samples, a human gastric cancer cell line (AGS), and a normal gastric epithelial cell line (GES-1) were used to detect TRPV4 mRNA and protein expression by RT-PCR and Western blotting, respectively. Ca2+ imaging was used to evaluate TRPV4 ion channel activity. TRPV4 methylation status was assessed by methylation-specific PCR (MSP). ATP release was measured by a luciferin-luciferase assay. RESULTS TRPV4 mRNA and protein were detected in human gastric biopsy samples and in GES-1 cells. MSP and demethylation assays showed TRPV4 methylation silencing in AGS cells. HP coculture directly induced methylation silencing of TRPV4 in GES-1 cells. In human samples, HP infection was associated with TRPV4 methylation silencing that recovered after HP eradication in a time-dependent manner. CONCLUSION HP infection-dependent DNA methylation suppressed TRPV4 expression in human gastric epithelia, suggesting that TRPV4 methylation may be involved in HP-associated dyspepsia.
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Affiliation(s)
- Hiroshi Mihara
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan,Center for Medical Education and Career DevelopmentUniversity of ToyamaToyamaJapan
| | - Nobuhiro Suzuki
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Jibran Sualeh Muhammad
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan,Department of Biological and Biomedical SciencesFaculty of Health SciencesThe Aga Khan UniversityKarachiPakistan
| | - Sohachi Nanjo
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Takayuki Ando
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Haruka Fujinami
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Shinya Kajiura
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Ayumu Hosokawa
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Toshiro Sugiyama
- Department of GastroenterologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
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Raei N, Latifi-Navid S, Zahri S. Helicobacter pylori cag Pathogenicity Island cagL and orf17 Genotypes Predict Risk of Peptic Ulcerations but not Gastric Cancer in Iran. Asian Pac J Cancer Prev 2016; 16:6645-50. [PMID: 26434889 DOI: 10.7314/apjcp.2015.16.15.6645] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is the third most common cancer regarding mortality in the world. The cag pathogenicity island (PAI) of Helicobacter pylori which contains genes associated with a more aggressive phenotype may involve in the pathogenesis of gastrointestinal disease. We here aimed to examine the associations of cagH, cagL, orf17, and cagG genotypes of H. pylori cag PAI with severe gastrointestinal disease. MATERIALS AND METHODS A total of 242 H. pylori strains were genotyped. Histopathological examination and classification of subjects were performed. RESULTS The frequencies of the cagH, cagL, cagG, and orf17 genotypes were 40/54 (74.1%), 53/54 (98.1%), 38/54 (70.4%), and 43/54 (79.6%), respectively, in patients with peptidic ulceration (PU),while in the control group, the frequencies were 87/147 (59.6%) for cagH, 121/146 (82.9%) for cagL, 109/146 (74.7%) for cagG, and 89/146 (61.0%) for orf17. The results of simple logistic regression analysis showed that the cagL and orf17 genotypes were significantly associated with an increased risk of PU not GC; the ORs (95% CI) were 10.950 (1.446-82.935), and 2.504 (1.193-5.253), respectively. No significant association was found between the cagH and cagG genotypes and the risk of both the PU and the GC in Iran (P>0.05). Finally, multiple logistic regression analysis showed that the cagL genotype was independently and significantly associated with the age- and sex-adjusted risk for PU; the OR (95% CI) was 9.557 (1.219-17.185). CONCLUSIONS We conclude that the orf17 and especially cagL genotypes of H. pylori cag PAI could be factors for risk prediction of PU, but not GC in Iran.
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Affiliation(s)
- Negin Raei
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran E-mail :
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Muhammad JS, Zaidi SF, Zhou Y, Sakurai H, Sugiyama T. Novel epidermal growth factor receptor pathway mediates release of human β-defensin 3 fromHelicobacter pylori-infected gastric epithelial cells. Pathog Dis 2016; 74:ftv128. [DOI: 10.1093/femspd/ftv128] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/26/2015] [Indexed: 12/11/2022] Open
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Salih BA, Guner A, Karademir A, Uslu M, Ovali MA, Yazici D, Bolek BK, Arikan S. Evaluation of the effect of cagPAI genes of Helicobacter pylori on AGS epithelial cell morphology and IL-8 secretion. Antonie van Leeuwenhoek 2013; 105:179-89. [PMID: 24170115 DOI: 10.1007/s10482-013-0064-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 10/23/2013] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori cagPAI genes play an important role in pathogenesis, however little is known about their functions in isolates from Turkish patients. We aimed to evaluate the intactness and the effect of the cagPAI genes (cagT, cagM, cagE, cagA) and cagA EPIYA motifs on the AGS morphological changes and IL-8 induction. Of 53 patients 38 were found infected with H. pylori. PCR amplification of the cagPAI genes showed 42.1 % intact, 39.5 % partially deleted and 18.4 % with complete deletions. Isolates from gastritis, duodenal and gastric ulcer patients with intact and partially deleted cagPAI genes induced higher IL-8 secretion than those with complete deletions. Isolates from gastritis patients had higher deletion frequencies of the cagT and cagM genes than the other two genes. Infection of AGS cells with isolates that possess intact cagPAI and EPIYA-ABC resulted in the formation of the hummingbird phenotype. The cagA positive isolates induced higher IL-8 secretion than cagA negative isolates. Isolates from DU patients with more than one EPIYA-C motif induced higher concentrations of IL-8 than those with EPIYA-ABC. In conclusion, the intactness of the cagPAI in our isolates from different patients was not conserved. An intact cagPAI was found to play an important role in the pathogenesis of DU but not GU or gastritis. The cagA gene, but not other cagPAI genes, was associated with the induction of IL-8 and the morphological changes of the AGS cells. An increase in the number of EPIYA-C motifs had noticeable effect on the formation of the hummingbird phenotype.
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Affiliation(s)
- Barik A Salih
- Department of Biology, Faculty of Science and Literature, Fatih University, B. Cekmece, Istanbul, Turkey,
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Cendron L, Zanotti G. Structural and functional aspects of unique type IV secretory components in the Helicobacter pylori cag-pathogenicity island. FEBS J 2011; 278:1223-31. [PMID: 21284804 DOI: 10.1111/j.1742-4658.2011.08038.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Helicobacter pylori cytotoxin-associated gene-pathogenicity island (cagPAI) is responsible for the secretion of the CagA effector through a type IV secretion system (T4SS) apparatus, as well as of peptidoglycan and possibly other not yet identified factors. Twenty-nine different polypeptide chains are encoded by this cluster of genes, although only some of them show a significant similarity with the constitutive elements of well characterized secretion systems from other bacteria. The other cagPAI components represent almost unique proteins in this scenario. The majority of the T4SS include approximately fifteen components, taking into account either the transmembrane complex subunits, ATPases or substrate factors. The composition of the cagPAI is very complex: it includes proteins most likely involved at different levels in the pilus assembly, stabilization and processing of secreted substrate, as well as regulatory particles possibly involved in the control of the entire apparatus. Despite recent findings with respect to components that play a role in the interaction with the host cell, the function of several cagPAI proteins remains unclear or unknown. This is particularly true for those that represent unique members with no clear similarity to those of other T4SS and no obvious evidence of involvement in the secretion of CagA or induction of pro-inflammatory responses. We summarize what is known about these accessory components, both from a molecular and structural point of view, as well as their putative physiological role.
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Affiliation(s)
- Laura Cendron
- Department of Biological Chemistry, University of Padua, Padua, Italy
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Tomimori K, Uema E, Teruya H, Ishikawa C, Okudaira T, Senba M, Yamamoto K, Matsuyama T, Kinjo F, Fujita J, Mori N. Helicobacter pylori induces CCL20 expression. Infect Immun 2007; 75:5223-32. [PMID: 17724069 PMCID: PMC2168315 DOI: 10.1128/iai.00731-07] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
CCL20 attracts immature dendritic cells and memory T cells and plays a role on mucosal surfaces in inflammation. However, whether Helicobacter pylori infection induces CCL20 in human gastric epithelial cells remains to be determined. The aim of this study was to analyze the molecular mechanism of H. pylori-induced CCL20 expression. Expression of CCL20 mRNA was assessed by reverse transcription-PCR. Five normal and five H. pylori-infected gastric tissue samples were stained immunohistochemically for CCL20. A luciferase assay was used to monitor activation of the CCL20 gene promoter, and an electrophoretic mobility shift assay was used to explore the binding of transcription factors to this promoter. The CCL20 expression in epithelial cells of H. pylori-positive tissues was higher than that in H. pylori-negative tissues. H. pylori induced CCL20 expression in gastric epithelial cell lines, and the induction was dependent on an intact cag pathogenicity island. Activation of the CCL20 promoter by H. pylori occurred through the action of NF-kappaB. Transfection of IkappaB kinase and NF-kappaB-inducing kinase dominant negative mutants inhibited H. pylori-mediated activation of CCL20. Treatment with an inhibitor of Hsp90 suppressed H. pylori-induced CCL20 mRNA due to deactivation of NF-kappaB. Collectively, these results suggest that H. pylori activates NF-kappaB through an intracellular signaling pathway that involves IkappaB kinase and NF-kappaB-inducing kinase, leading to CCL20 gene transcription, and that Hsp90 is a crucial regulator of H. pylori-induced CCL20 expression, presumably contributing to the immune response in H. pylori.
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Affiliation(s)
- Koh Tomimori
- Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
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Tamura A, Kumai H, Nakamichi N, Sugiyama T, Deguchi R, Takagi A, Koga Y. Suppression of Helicobacter pylori-induced interleukin-8 production in vitro and within the gastric mucosa by a live Lactobacillus strain. J Gastroenterol Hepatol 2006; 21:1399-406. [PMID: 16911683 DOI: 10.1111/j.1440-1746.2006.04318.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Accumulating evidence indicates that interleukin-8 (IL-8) plays a major role in the mucosal inflammation caused by Helicobacter pylori infection. The purpose of the present study was to examine whether Lactobacillus gasseri OLL2716 (LG21) can inhibit the H. pylori-induced production of IL-8. METHODS A coculture system including MKN45 cells, H. pylori, and LG21 was established for an in vitro analysis. Biopsy specimens were obtained from H. pylori-infected human subjects consisting of 19 men and six women. RESULTS When LG21 was 1/100 less than H. pylori in a coculture system, LG21 significantly suppressed both the IL-8 mRNA and protein generation in the coculture. Live, but not heat- or UV-treated LG21, could exert the suppressive effect. However, this amount of LG21 could not suppress either the adhesion of H. pylori to the cell surface or the IL-8 production by tumor necrosis factor-alpha, which induces IL-8 generation through the activation of the transcription. These results thus suggest that LG21 suppresses an event leading to IL-8 production, which is specific for H. pylori-induced IL-8 generation, and this event is located upstream from the IL-8 transcription but downstream from the adhesion. The measurement of the IL-8 level using gastric biopsy specimens from H. pylori-infected subjects demonstrated that LG21 also suppresses the production of IL-8 in the gastric mucosa. CONCLUSIONS Live LG21 were found to suppress H. pylori-induced IL-8 production in both a gastric cell line and within gastric mucosa.
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Affiliation(s)
- Akira Tamura
- Laboratory for Infectious Diseases, Tokai University Medical School, Bohseidai, Isehara, Japan
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Liu HY, Fang PC, Jiang YS, Tao R, Chen J. Gene distribution of cagII in Helicobacter pylori-infected patients of Zhejiang Province. World J Gastroenterol 2004; 10:2060-2. [PMID: 15237434 PMCID: PMC4572333 DOI: 10.3748/wjg.v10.i14.2060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To determine the prevalence of genotypes of cagII in Helicobacter pylori (H pylori)-infected patients in Zhejiang Province and investigate the relationship between these genotypes and the types of gastroduodenal diseases.
METHODS: One hundred and seventy one clinical isolates were collected from 70 chronic superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21 duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma patients. Polymerase chain reaction assays were performed for analysis of cagT, ORF13 and ORF10 genes in the cagII region.
RESULTS: Of 171 H pylori isolates from Zhejiang patients, 159 (93.0%) were positive for all the three loci. One isolate (0.6%) was negative for all the three loci, and 11 (6.4%) were partially deleted in cagII. The positive rates of cagT, ORF13 and ORF10 genes were 97.1%, 94.7% and 99.4%, respectively. In the strains isolated from the patients with diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and duodenal ulcer, the sitive rates of cagT were 95.7%, 100.0%, 95.1% and 100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and 100.0%, respectively. The sitive rates of ORF10 were 98.6%, 100.0%, 100.0% and 100.0%, respectively. The three genes were all positive in the three H pylori strains isolated from the patients with both gastric and duodenal ulcer. In the five strains isolated from the patients with gastric adenocarcinoma, only one isolate was negative for ORF13. There were no significant differences of the cagT, ORF13 and ORF10 genes among the different gastroduodenal diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer, duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma (χ2 = 3.098, P > 0.05 for cagT; χ2 = 3.935, P > 0.05 for ORF13 and χ2 = 6.328, P > 0.05 for ORF10).
CONCLUSION: The cagII is not a uniform and conserved entity. Although the genes in cagII are highly associated with the gastroduodenal diseases, the clinical outcome of H pylori infection is not reliably predicted by the three genes in cagII in patients from Zhejiang Province.
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Affiliation(s)
- Hai-Yan Liu
- Department of Medical Microbiology and Parasitology, School of Medicine, Zhejiang University, 353 Yanan Road, Hangzhou 310031, Zhejiang Province, China
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Xu C, Li ZS, Tu ZX, Xu GM, Gong YF, Man XH. Distribution of cagG gene in Helicobacter pylori isolates from Chinese patients with different gastroduodenal diseases and its clinical and pathological significance. World J Gastroenterol 2003; 9:2258-60. [PMID: 14562388 PMCID: PMC4656473 DOI: 10.3748/wjg.v9.i10.2258] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the distribution of cagG gene of Helicobacter pylori (H pylori) isolates cultured from patients with various digestive diseases and its relationship with gastroduodenal diseases.
METHODS: cagG was amplified by polymerase chain reaction in 145 H pylori isolates cultured from patients with chronic gastritis (n = 72), duodenal ulcer (n = 48), gastric ulcer (n = 17), or gastric and duodenal ulcer (n = 8), and the relationship between cagG status and the grade of gastric mucosal inflammation was determined.
RESULTS: cagG was present in 91.7% of the 145 H pylori isolates, with the rates were 90.3%, 93.8%, 88.2% and 100.0%, respectively, in those from patients with chronic gastritis, duodenal ulcer, gastric ulcer, and gastric and duodenal ulcer. There was no significant difference among the four groups (P > 0.05). The average grade of gastric mucosal inflammation in the antrum and corpus was 1.819 ± 0.325 and 1.768 ± 0.312, respectively in cagG positive patients, whereas the average inflammation grade was 1.649 ± 0.297, 1.598 ± 0.278 respectively in cagG negative cases (P > 0.05).
CONCLUSION: cagG gene of H pylori was quite conservative, and most H pylori strains in Chinese patients were cagG positive. cagG status was not related to clinical outcome or the degree of gastric mucosal inflammation. Therefore, cagG can not be used as a single marker for discrimination of H pylori strains with respect to a specific digestive disease.
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Affiliation(s)
- Can Xu
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
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Nagasako T, Sugiyama T, Mizushima T, Miura Y, Kato M, Asaka M. Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by Helicobacter pylori infection. J Biol Chem 2003; 278:4821-5. [PMID: 12473652 DOI: 10.1074/jbc.m211143200] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The gastric pathogen Helicobacter pylori activates epithelial cell signaling pathways, and its infection induces changes in the expression of several genes in infected human gastric tissues. Recent studies have indicated that the ability of H. pylori to regulate epithelial cell responses depends on the presence of an intact cag pathogenicity island (cagPAI). We investigated altered mRNA expression of gastric epithelial cells after infection with H. pylori, both cagPAI-positive and cagPAI-negative strains, by cDNA microarray, reverse transcription PCR, and Northern blot analysis. Our results indicated that cagPAI-positive H. pylori strains (ATCC 43504 and clinical isolated strains) significantly activated Smad5 mRNA expression of human gastric epithelial cells (AGS, KATOIII, MKN28, and MKN45). We further examined whether the up-regulated Smad5 was related to apoptosis of gastric epithelial cells induced by H. pylori. Smad5 RNA interference completely inhibited H. pylori-induced apoptosis. These results suggest that Smad5 is up-regulated in gastric epithelial cells through the presence of cagPAI of H. pylori and that Smad5 mediates apoptosis of gastric epithelial cells induced by H. pylori infection.
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Affiliation(s)
- Tomokazu Nagasako
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan
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