Application of Biopsy Samples Used for Helicobacter pylori Urease Test to Predict Epstein–Barr Virus-Associated Cancer

Persistent gastric mucosal damage caused by Helicobacter pylori infection is a major risk factor for gastric cancer (GC). The Epstein–Barr virus (EBV) is also associated with GC. Most patients with EBV-associated GC are infected with H. pylori in East Asia. However, very few reports have described where and when both H. pylori and EBV infect the gastric mucosa. To clarify this, old biopsy samples used for the rapid urease test (RUT) were applied to count EBV genomic DNA (gDNA) copies using DNA probe quantitative polymerase chain reaction. DNA extracted from the gastric biopsy samples of 58 patients with atrophic gastritis was used to analyze the correlation between the degree of atrophic gastritis and the copy number of EBV gDNA. EBV was detected in 44 cases (75.9%), with viral copy numbers ranging from 12.6 to 4754.6. A significant correlation was found between patients with more than 900 copies of EBV gDNA and those with a more severe grade of atrophic gastritis (p = 0.041). This study shows that EBV can be detected in RUT samples in a manner that reduces patient burden.

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Epstein-Barr virus detection using gastric biopsy specimens after rapid urease test for Helicobacter pylori

Endoscopy International Open ◽

10.1055/a-0859-7233 ◽

2019 ◽

Vol 07 (04) ◽

pp. E431-E432 ◽

Cited By ~ 1

Author(s):

Hideo Yanai ◽

Hisashi Iizasa ◽

Daisuke Chihara ◽

Tomoyuki Murakami ◽

Jun Nishikawa ◽

...

Keyword(s):

Helicobacter Pylori ◽

Epstein Barr Virus ◽

Virus Detection ◽

Gastric Biopsy ◽

Rapid Urease Test ◽

Barr Virus ◽

Biopsy Specimens ◽

Urease Test ◽

Epstein Barr

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Epstein–Barr Virus and Helicobacter Pylori Co-Infection in Non-Malignant Gastroduodenal Disorders

Pathogens ◽

10.3390/pathogens9020104 ◽

2020 ◽

Vol 9 (2) ◽

pp. 104 ◽

Cited By ~ 2

Author(s):

Ramsés Dávila-Collado ◽

Oscar Jarquín-Durán ◽

Le Thanh Dong ◽

J. Luis Espinoza

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Infection Rate ◽

Epstein Barr Virus ◽

Barr Virus ◽

Ebv Infection ◽

Pubmed Database ◽

Epstein Barr ◽

H Pylori ◽

Gastroduodenal Disorders

Epstein–Barr virus (EBV) and Helicobacter pylori (H. pylori) are two pathogens associated with the development of various human cancers. The coexistence of both microorganisms in gastric cancer specimens has been increasingly reported, suggesting that crosstalk of both pathogens may be implicated in the carcinogenesis process. Considering that chronic inflammation is an initial step in the development of several cancers, including gastric cancer, we conducted a systematic review to comprehensively evaluate publications in which EBV and H. pylori co-infection has been documented in patients with non-malignant gastroduodenal disorders (NMGDs), including gastritis, peptic ulcer disease (PUD), and dyspepsia. We searched the PubMed database up to August 2019, as well as publication references and, among the nine studies that met the inclusion criteria, we identified six studies assessing EBV infection directly in gastric tissues (total 949 patients) and three studies in which EBV infection status was determined by serological methods (total 662 patients). Due to the substantial methodological and clinical heterogeneity among studies identified, we could not conduct a meta-analysis. The overall prevalence of EBV + H. pylori co-infection in NMGDs was 34% (range 1.8% to 60%). A higher co-infection rate (EBV + H. pylori) was reported in studies in which EBV was documented by serological methods in comparison with studies in which EBV infection was directly assessed in gastric specimens. The majority of these studies were conducted in Latin-America and India, with most of them comparing NMGDs with gastric cancer, but there were no studies comparing the co-infection rate in NMGDs with that in asymptomatic individuals. In comparison with gastritis caused by only one of these pathogens, EBV + H. pylori co-infection was associated with increased severity of gastric inflammation. In conclusion, only relatively small studies testing EBV and H. pylori co-infection in NMGDs have been published to date and the variable report results are likely influenced by geographic factors and detection methods.

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Prevalence of Helicobacter pylori Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer

Journal of Global Oncology ◽

10.1200/jgo.19.00122 ◽

2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Carlos A. Castaneda ◽

Miluska Castillo ◽

Iván Chavez ◽

Fernando Barreda ◽

Nancy Suarez ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Chronic Gastritis ◽

Epstein Barr Virus ◽

Quantitative Polymerase Chain Reaction ◽

Geographic Location ◽

Clinicopathological Features ◽

Barr Virus ◽

Virulent Strains ◽

Epstein Barr

PURPOSE Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. PATIENTS AND METHODS A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. RESULTS Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC ( P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate ( P < .001) and multivariate ( P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. CONCLUSION Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.

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Helicobacter pylori and Epstein-Barr Virus Coinfection Stimulates Aggressiveness in Gastric Cancer through the Regulation of Gankyrin

mSphere ◽

10.1128/msphere.00751-21 ◽

2021 ◽

Author(s):

Dharmendra Kashyap ◽

Budhadev Baral ◽

Shweta Jakhmola ◽

Anil Kumar Singh ◽

Hem Chandra Jha

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Epstein Barr Virus ◽

Synergistic Effects ◽

Gastric Epithelial Cells ◽

Content Type ◽

Barr Virus ◽

Epstein Barr ◽

H Pylori

In the present study, we evaluated the synergistic effects of EBV and H. pylori infection on gastric epithelial cells in various coinfection models. These coinfection models were among the first to depict the exposures of gastric epithelial cells to EBV followed by H. pylori ; however, coinfection models exist that narrated the scenario upon exposure to H. pylori followed by that to EBV.

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Gastric Cancer and Associated Pathogens: Is There Any Association in Moroccan Region?

10.21203/rs.3.rs-1169749/v1 ◽

2021 ◽

Author(s):

Samia Alaoui Boukhris ◽

Mounia El khadir ◽

Safae Karim ◽

Tiatou Souho ◽

Dafr-Allah Benajah ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Retrospective Study ◽

Epstein Barr Virus ◽

University Hospital ◽

Cancer Development ◽

Barr Virus ◽

Epstein Barr ◽

H Pylori

Abstract Purpose: Helicobacter pylori, Epstein-Barr virus and human papillomavirus are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in Moroccan population Methods: For this, a retrospective study has been conducted on participants attending the gastroenterology department of Hassan II University Hospital of Fez. A total of 279 participants were enrolled. H. pylori, EBV and HPV were detected and genotyped by PCR.Results: A significant association has been established between H. pylori, EBV and gastric cancer. 93.4% and 43.3% of gastric cancer cases are related to H. pylori and EBV respectively (p≤0.01). H. pylori-EBV co-infection is responsible of 31.6% of gastric cancer cases (p<0.01). Correlation between pathogens genotypes and gastric cancer shows 55.6% of GC EBV positives are carrying the 30bp deletion in LMP1gene, while 16% of gastric cancers cases are carrying high-risk genotypes of HPV (p=0.21). Conclusion: The obtained results highlight the possible role of co-infection in gastric cancer development.

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Helicobacter pylori and Epstein-Barr virus coinfection stimulates the aggressiveness in gastric cancer through the regulation of gankyrin

10.1101/2020.11.19.390807 ◽

2020 ◽

Author(s):

Dharmendra Kashyap ◽

Budhadev Baral ◽

Nidhi Varshney ◽

Anil Kumar Singh ◽

Hem Chandra Jha

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Molecular Mechanism ◽

Epstein Barr Virus ◽

Gastric Epithelial Cells ◽

Carcinogenic Activity ◽

Barr Virus ◽

Epstein Barr ◽

H Pylori

AbstractPersistent coinfection of Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) promotes aggressive gastric carcinoma. The molecular mechanisms underlying the aggressiveness in H. pylori and EBV coinfected gastric cancer is not well characterized. In the current study, we investigated the molecular mechanism involved in the cooperation of H. pylori and EBV-driven proliferation of gastric epithelial cells. Results showed that the coinfections are significantly more advantageous to the pathogens to create a microenvironment that favors the higher pathogen-associated gene expression. The EBV latent genes EBNA1 and EBNA3C are highly overexpressed in the coinfections compared to individual EBV infection at different time points (12 and 24 hrs). The H. pylori-associated genes 16s rRNA, CagA, and BabA has also been highly overexpressed in coinfections compared to H. pylori alone. Gankyrin is a small protein of 25 KDa involved in multiple biological and physiological processes. The upregulation of gankyrin modulates the various cell signaling pathways, leading to oncogenesis. The gankyrin shows a similar expression pattern as EBNA3C at both transcript and protein levels, suggesting a possible correlation. Further EBV and H. pylori create microenvironments that induce cell transformation and oncogenesis by dysregulation of the cell-cycle regulator, GC marker, cell migration, DNA response, and antiapoptotic genes in infected gastric epithelial cells by enhancing the expression of gankyrin. Our study provides new insights into the molecular mechanism where the interplay between two oncogenic agents (H. pylori and EBV) leads to the enhanced carcinogenic activity of gastric epithelial cells through overexpression of oncoprotein gankyrin.ImportanceIn the present study, we have evaluated the synergistic effect of EBV and H. pylori infection on gastric epithelial cells in various coinfection models. These coinfection models depict the first exposures of gastric epithelial cells with EBV and then the H. pylori. While other coinfection models narrated the first exposures of H. pylori followed by the infection of EBV. This led to an enhanced oncogenic phenotype in gastric epithelial cells. We determined the coinfection of EBV and H. pylori enhanced the expression of oncogenic protein gankyrin. The interplay between EBV and H. pylori promotes the oncogenic properties of AGS cells through the newly discovered oncoprotein gankyrin. EBV and H. pylori mediated upregulation of gankyrin further dysregulates various cancer-associated hallmarks of genes such as cell-migratory, gastric cancer marker, tumor suppressor, DNA damage response, and proapoptotic genes.

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Helicobacter pylori-associated oxidant monochloramine induces reactivation of Epstein–Barr virus (EBV) in gastric epithelial cells latently infected with EBV

Journal of Medical Microbiology ◽

10.1099/jmm.0.46580-0 ◽

2006 ◽

Vol 55 (7) ◽

pp. 905-911 ◽

Cited By ~ 32

Author(s):

Junko Minoura-Etoh ◽

Kazuyo Gotoh ◽

Ryugo Sato ◽

Masao Ogata ◽

Naomi Kaku ◽

...

Keyword(s):

Helicobacter Pylori ◽

Epstein Barr Virus ◽

Lytic Infection ◽

Gastric Epithelium ◽

Human Pathogens ◽

Ags Cells ◽

Barr Virus ◽

Latently Infected ◽

Epstein Barr ◽

H Pylori

To investigate the possibility of an interaction between two ubiquitous human pathogens, Helicobacter pylori and Epstein–Barr virus (EBV), the effect of monochloramine (NH2Cl), locally produced by H. pylori infection, on gastric epithelium latently infected with EBV was examined, by assessing the induction of EBV lytic infection. AGS cells harbouring latently infected EBV were used as the indicator of lytic change caused by NH2Cl treatment. Lytic infection, determined by morphological change and EA-D antigen expression, occurred immediately after treatment with in vitro-synthesized NH2Cl. Analysis of EBV infection in human gastric tissue revealed that out of 48 H. pylori-positive patients, 24 were positive for EBER-1, and 18 and 13 were positive for EBNA1 and LMP-1 antigen, respectively. The results suggest that H. pylori-associated NH2Cl induces EBV lytic conversion in gastric epithelium latently infected with EBV.

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Status of kinases in Epstein-Barr virus and Helicobacter pylori Coinfection in gastric Cancer cells

BMC Cancer ◽

10.1186/s12885-020-07377-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Charu Sonkar ◽

Tarun Verma ◽

Debi Chatterji ◽

Ajay Kumar Jain ◽

Hem Chandra Jha

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Helicobacter Pylori ◽

Epstein Barr Virus ◽

Morphological Changes ◽

Ags Cells ◽

Barr Virus ◽

Apoptotic Genes ◽

Epstein Barr ◽

H Pylori

Abstract Background Helicobacter pylori (H. pylori) and Epstein - Barr virus (EBV) plays a significant role in aggressive gastric cancer (GC). The investigation of genes associated with these pathogens and host kinases may be essential to understand the early and dynamic progression of GC. Aim The study aimed to demonstrate the coinfection of EBV and H. pylori in the AGS cells through morphological changes, expression of the kinase and the probable apoptotic pathways. Methods Genomic DNA isolation of H. pylori and its characterization from clinical samples were performed. RT-qPCR of kinases was applied to scrutinize the gene expression of kinases in co-infected GC in a direct and indirect (separated through insert size 0.45 μm) H. pylori infection set up. Morphological changes in co-infected GC were quantified by measuring the tapering ends of gastric epithelial cells. Gene expression profiling of apoptotic genes was assessed through RT-qPCR. Results An interleukin-2-inducible T-cell kinase (ITK) showed significant upregulation with indirect H. pylori infection. Moreover, Ephrin type-B receptor six precursors (EPHB6) and Tyrosine-protein kinase Fyn (FYN) showed significant upregulation with direct coinfection. The tapering ends in AGS cells were found to be extended after 12 h. A total of 24 kinase genes were selected, out of which EPHB6, ITK, FYN, and TYK2 showed high expression as early as 12 h. These kinases may lead to rapid morphological changes in co-infected gastric cells. Likewise, apoptotic gene expression such as APAF-1 and Bcl2 family genes such as BAD, BID, BIK, BIM, BAX, AND BAK were significantly down-regulated in co-infected AGS cells. Conclusion All the experiments were performed with novel isolates of H. pylori isolated from central India, for the functional assessment of GC. The effect of coinfection with EBV was more profoundly observed on morphological changes in AGS cells at 12 h as quantified by measuring the tapering of ends. This study also identifies the kinase and apoptotic genes modulated in co-infected cells, through direct and indirect approaches. We report that ITK, EPHB6, TYK2, FYN kinase are enhanced, whereas apoptotic genes such as APAF-1, BIK, FASL, BAX are significantly down-regulated in AGS cells coinfected with EBV and H. pylori.

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