scholarly journals Helicobacter pylori-induced DNA Methylation as an Epigenetic Modulator of Gastric Cancer: Recent Outcomes and Future Direction

Pathogens ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 23 ◽  
Author(s):  
Jibran Muhammad ◽  
Mohamed Eladl ◽  
Ghalia Khoder
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Epigenetic Drugs ◽  
Mesh Terms ◽  
Potential Benefits ◽  
H Pylori ◽  
Future Direction ◽  
Methylating Agents

Gastric cancer is ranked fifth in cancer list and has the third highest mortality rate. Helicobacter pylori is a class I carcinogen and a predominant etiological factor of gastric cancer. H. pylori infection may induce carcinogenesis via epigenetic alterations in the promoter region of various genes. H. pylori is known to induce hypermethylation-silencing of several tumor suppressor genes in H. pylori-infected cancerous and H. pylori-infected non-cancerous gastric mucosae. This article presents a review of the published literature mainly from the last year 15 years. The topic focuses on H. pylori-induced DNA methylation linked to gastric cancer development. The authors have used MeSH terms “Helicobacter pylori” with “epigenetic,” “DNA methylation,” in combination with “gastric inflammation”, gastritis” and “gastric cancer” to search SCOPUS, PubMed, Ovid, and Web of Science databases. The success of epigenetic drugs such as de-methylating agents in the treatment of certain cancers has led towards new prospects that similar approaches could also be applied against gastric cancer. However, it is very important to understand the role of all the genes that have already been linked to H. pylori-induced DNA methylation in order to in order to evaluate the potential benefits of epigenetic drugs.

scholarly journals Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

scholarly journals Helicobacter pylori bacteremia: an unusual finding

2016 ◽  
Vol 8 (3) ◽  
Author(s):  
Concetta De Luca ◽  
Annalisa Mancin ◽  
Maria Calabrò ◽  
Cristina Daleno ◽  
Antonella Ferrario ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Potential Role ◽  
Rare Complication ◽  
Subtotal Gastrectomy ◽  
Blood Cultures ◽  
H Pylori ◽  
Stomach Surgery ◽  
Unusual Finding

We report a case of <em>Helicobacter pylori</em> transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gramnegative bacterium. This isolate was identified as <em>H. pylori</em> and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, <em>H. pylori</em> transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of <em>H</em>. <em>pylori</em> presence in blood.

scholarly journals Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huan Wang ◽  
Nian-Shuang Li ◽  
Cong He ◽  
Chuan Xie ◽  
Yin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Gene Expression Data ◽  
Functional Enrichment ◽  
Expression Data ◽  
H Pylori

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples ( P < 0.05 ). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

scholarly journals Los genes como marcadores de riesgo en cáncer gástrico: revisión de estudios en población colombiana

Respuestas ◽  
2013 ◽  
Vol 18 (2) ◽  
pp. 61-73
Author(s):  
Claudia Marcela Yáñez-Gutiérrez
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gene Polymorphisms ◽  
Genetic Factors ◽  
Human Gene ◽  
Risk Markers ◽  
Different Populations ◽  
H Pylori ◽  
Cáncer Gástrico

 El objetivo de esta revisión, fue identificar el rol de los genes como marcadores de riesgo en cáncer gástrico (CG) en población colombiana. Se revisaron publicaciones de investigaciones realizadas en los últimos diez años, utilizando las bases MEDLINE y LILACS y complementando  la pesquisa con la bibliografía relevante de los artículos. Se encontraron estudios en busca de asociación de CG con polimorfismos de varios genes humanos involucrados en la respuesta inmune, la desintoxicación y el supresor p53. En Colombia al igual que en otros países, las evidencias de asociación de polimorfismos genéticos con CG son aún controversiales, debido a la variación de los resultados que arrojan los estudios en las diferentes poblaciones. El genoma de las cepas de Helicobacter pylori que infectan población colombiana también ha sido investigado en búsqueda de polimorfismos de virulencia. El genotipo cagA/vacAs1m1 identificado como citotóxico en esta bacteria, mostró en la mayoría de las investigaciones, asociación con CG. La evidencia de asociación de CG con factores genéticos en población colombiana no es concluyente. Está lejos aún, la identificación de marcadores genéticos que permitan predecir el riesgo a desarrollar CG. A pesar de ello, algunos polimorfismos de genes humanos como los de IL-1 o los de algunas enzimas desintoxicantes, así como los genes cagA y vacA de Helicobacter pylori podrían ser candidatos a futuros marcadores de riesgo en esta neoplasia.Palabras clave: cáncer gástrico, riesgo, genotipo, Colombia. ABSTRACT  The objective of this review was to identify the role of genes as risk markers in gastric cancer (GC) in Colombian population studies. The study reviewed research publications in the last ten years, using the MEDLINE and LILACS, as well as various literature research of relevant articles. Searching studies found GC association with several human gene polymorphisms involved in the immune response, detoxification and suppressor p53. In Colombia, as in other countries, the evidence of the association of genetic polymorphisms with GC are still controversial because of the variation in results that studies in different populations. The genome of Helicobacter pylori strains that infect Colombian population has also been investigated in search of polymorphisms of virulence. cagA/ vacAs1m1 genotype identified as cytotoxic in this bacterium, demonstrated most of the research associated with GC. Evidence of association of GC with Colombian population genetic factors was inconclusive. It is yet to be determined the exact identification of genetic markers that can predict the risk of developing GC. However, some human gene polymorphisms as IL-1 or some detoxifying enzymes and the vacA and cagA of H. pylori could be candidates for future risk markers in these tumors.Keywords: gastric cancer, risk, genotype, Colombia

scholarly journals The Human Gastric Pathogen Helicobacter pylori and Its Association with Gastric Cancer and Ulcer Disease

Ulcers ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-23 ◽  
Author(s):  
Bianca Bauer ◽  
Thomas F. Meyer
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Peptic Ulcer Disease ◽  
Strain Differences ◽  
Protective Effects ◽  
Ulcer Disease ◽  
Prophylactic Measures ◽  
H Pylori

With the momentous discovery in the 1980's that a bacterium, Helicobacter pylori, can cause peptic ulcer disease and gastric cancer, antibiotic therapies and prophylactic measures have been successful, only in part, in reducing the global burden of these diseases. To date, ~700,000 deaths worldwide are still attributable annually to gastric cancer alone. Here, we review H. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and VacA), immune activation and the challenges posed by resistance to existing therapies. We consider also the important role of host-genetic variants, for example, in inflammatory response genes, in determining infection outcome and the role of H. pylori in other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions that H. pylori has protective effects in GERD and autoimmune diseases, such as asthma, have gained momentum. Therefore, we consider the basis for these suggestions and discuss the potential impact for future therapeutic rationales.

scholarly journals Helicobacter pylori Eradication in Patients Undergoing Gastrectomy: Diagnosis and Therapy

2020 ◽  
Vol 20 (3) ◽  
pp. 204-209
Author(s):  
Youn I Choi ◽  
Jun-Won Chung
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Diagnostic Tests ◽  
Remnant Stomach ◽  
Optimal Timing ◽  
Helicobacter Pylori Eradication ◽  
Metachronous Gastric Cancer ◽  
H Pylori

The role of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend <i>H. pylori</i> eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing <i>H. pylori</i> infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of <i>H. pylori</i> infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for <i>H. pylori</i> infection in the remnant stomach, 2) optimal timing and regimen for <i>H. pylori</i> eradication, and 3) role of <i>H. pylori</i> eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.

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

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.

scholarly journals Helicobacter Pylori Infection And Gastric Cancer: Is It Our National Problem?

2018 ◽  
Vol 36 (2) ◽  
pp. 70-76 ◽  
Author(s):  
M Mizanur Rahman ◽  
Shahjadul Alam ◽  
Abu Mohammad Khaled Iqbal ◽  
Md Monoar Hossain ◽  
Abu Mohammad Kawser Sarker ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Current Knowledge ◽  
Large Body ◽  
High Prevalence ◽  
The World ◽  
Leading Position ◽  
The Common ◽  
H Pylori

Gastric cancer is a leading cause of cancer death worldwide. In Bangladesh it ranks a leading position among the cancers patients. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Scientists throughout the world explored and reached to the understanding about the pathogenesis of their relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains a debate regarding the consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and its role for gastric cancer, present status of Bangladesh and a recommendation for reduction of the infectivity among the common population.J Bangladesh Coll Phys Surg 2018; 36(2): 70-76

scholarly journals Induction and Prevention of Gastric Cancer with Combined Helicobacter Pylori and Capsaicin Administration and DFMO Treatment, Respectively

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 816
Author(s):  
Faisal Aziz ◽  
Mingxia Xin ◽  
Yunfeng Gao ◽  
Abhijit Chakroborty ◽  
Imran Khan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Preventive Measures ◽  
Mucosal Injury ◽  
Lifestyle Changes ◽  
Gastric Cancer Risk ◽  
Hot Peppers ◽  
H Pylori ◽  
Disease Free

Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes, including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e., capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2 g/kg/day) or not. Consequently, tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Moreover, we used 2-difluoromethylornithine (DFMO) in mice to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention by inhibiting IL-6. Accordingly, preventive measures such as reduced capsaicin consumption, H. pylori clearance, and DFMO treatment may lessen gastric cancer incidence.

scholarly journals Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals

2020 ◽  
Vol 21 (17) ◽  
pp. 6451 ◽  
Author(s):  
James W. T. Toh ◽  
Robert B. Wilson
Keyword(s):  
Gastric Cancer ◽  
Ascorbic Acid ◽  
Helicobacter Pylori ◽  
Vitamin C ◽  
Atrophic Gastritis ◽  
Chronic Atrophic Gastritis ◽  
Gastric Carcinogenesis ◽  
Antioxidant Systems ◽  
H Pylori

Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.

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