scholarly journals Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Surface Receptor ◽  
Tumor Promoter ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α ◽  
Surface Receptor ◽  
H Pylori ◽  
Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

scholarly journals Tumor necrosis factor-α polymorphism in helicobacter pylori associated gastric carcinoma

2019 ◽  
Vol 45 (3) ◽  
pp. 170-174
Author(s):  
Rita Rani Barua ◽  
Sushanta Barua ◽  
Hena Rani Barua ◽  
Ajoy Kishore Barua ◽  
M.A. Jalil Ansari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Chronic Inflammation ◽  
High Risk Group ◽  
Predisposing Factor ◽  
Asian Patients ◽  
Tnf Α ◽  
H Pylori ◽  
Factor Α ◽  
Asian People

Background: Gastric cancer (GC) is the leading cause of cancer death in the world. Chronic inflammation is a predisposing factor of gastric carcinogenesis. TNF-α is a key pro-inflammatory cytokine secreted by macrophages and causes development of malignant diseases. It also plays an important role in chronic inflammation caused by Helicobacter Pylori. Therefore, TNF-α polymorphisms is studied in Helicobacter Pylori infected gastric cancer. Objective: To find out the high risk group of Helicobacter Pylori infected gastric cancer cases in Asian and Caucasian people. Methods: A total of 130 GC cases and 103 healthy controls from Jichi Medical School, Japan were studied. TNF-α genotype and allele frequency were studied by Restriction Fragment Length Polymorphism (RFLP). Results: Among the study population TNFa-308A was less frequent in Asian people than those of Caucasian. TNFa-238G allele was more frequent in H. pylori positive GC (p<0.036) cases. Conclusion: Findings of the study suggest that TNF-238G polymorphism of TNF-α gene may be closely associated with susceptibility to Helicobacter Pylori infected gastric cancer in Asian patients.  This might be due to high cytokine production by TNF-238G allele.

Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori

2012 ◽  
Vol 322 (2) ◽  
pp. 133-138 ◽  
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Kensei Yamaguchi ◽  
Atsushi Takahashi ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α

scholarly journals Transcriptome Analysis of the Inhibitory Effect of Astaxanthin on Helicobacter pylori-Induced Gastric Carcinoma Cell Motility

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 365 ◽  
Author(s):  
Suhn Hyung Kim ◽  
Hyeyoung Kim
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Cell Motility ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Human Gastric Cancer ◽  
Gastric Carcinoma Cell ◽  
H Pylori

Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are differently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified differentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLCγ1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the effects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLCγ. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLCγ1, Cdc42, and ROCK1.

scholarly journals Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains

Gut ◽  
1997 ◽  
Vol 41 (4) ◽  
pp. 442-451 ◽  
Author(s):  
Y Yamaoka ◽  
M Kita ◽  
T Kodama ◽  
N Sawai ◽  
K Kashima ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Expression Patterns ◽  
Mucosal Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Biopsy Specimens ◽  
Tnf Α ◽  
Polymerase Chain ◽  
H Pylori ◽  
Factor Α ◽  
Necrosis Factor

Background—Helicobacter pyloristrains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8.Aims—To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA).Patients and methods—In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1β, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor α (TNF-α) in antral biopsy specimens were measured by ELISA.Results—Mucosal levels of IL-1β, IL-6, IL-8, and TNF-α were significantly higher in H pyloripositive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1β and IL-8 were significantly higher in specimens infected with cagApositive strains than in those infected with cagAnegative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1β (p<0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-α (p<0.0001).Conclusion—These findings suggest that the ability to induce cytokines differs among the strains;cagA+ strains induce various kinds of cytokines and may cause severe inflammation, whereascagA− strains induce IL-8 and IL-1β only weakly and may cause only mild inflammation. However, as most patients infected with the cagA+ strains have gastritis, these strains may not be equivalent to ulcerogenic strains.

scholarly journals Interleukin-6, Tumor Necrosis Factor-α, and High-sensitivity C-reactive Protein in Diabetic Patients with Helicobacter pylori in Kosovo

2020 ◽  
Vol 8 (B) ◽  
pp. 172-175
Author(s):  
Greta Begolli-Stavileci ◽  
Gramos Begolli ◽  
Luljeta Begolli
Keyword(s):  
Helicobacter Pylori ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Tnf Α ◽  
H Pylori ◽  
Factor Α ◽  
Necrosis Factor

Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects from 30% to 50% of the world’s population and it is one of the most important in dyspeptic syndrome causes of gastritis and peptic ulcer. H. pylori is one of the most common chronic bacterial infections especially in the development countries because the socioeconomic contribute to chronic disease. The infection induces an acute polymorphonuclear infiltration in the gastric mucosa. Infection with H. pylori has been epidemiologically linked to some extra digestive conditions, including ischemic heart disease, diabetes mellitus (DM), and others. The patients with DM are at risk for H. pylori infection, since they have coupled susceptibility of to a wide range of infections as a result of chronic elevation of blood glucose level and impairment of immune functions. Chronic inflammation is a risk factor for coronary heart disease, because inflammation, vascular injury and thrombosis are considered to cause atherosclerosis. The risk of cardiovascular events is associated with increased levels of the acute phase proteins, C-reactive protein (CRP), and pro-inflammatory cytokines. Interleukin 6 (IL-6), a major pro-inflammatory cytokine is produced in a variety of tissues, including activated leukocytes, adipocytes, and endothelial cells. CRP is the principal downstream mediator of the acute phase response and is primarily derived through IL-6-dependent hepatic biosynthesis. Tumor necrosis factor-α (TNF-α), as an important inflammatory factor, has been shown to play a central role in the pathogenesis of diabetes. CRP and IL-6 were determinant of risk for the development of type 2 DM in apparently healthy middle-aged women. Since the prevalence of infected persons with H. pylori in Kosovo is high, the aim of this study was the evaluation of cytokines (IL1, TNF-α) and CRP in diabetic type 2 patients with positive H. pylori.

scholarly journals Relationship Between Mucosal TNF-α Expression and Th1, Th17, Th22 and Treg Responses in Helicobacter Pylori Infection

2021 ◽  
Author(s):  
Ghorbanali Rahimian ◽  
Milad Shahini Shams Abadi ◽  
Reza Ahmadi ◽  
Mohammedhadi Shafigh ◽  
Fatemeh Azadegan-Dehkordi
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Treg Cells ◽  
Infected Group ◽  
Ulcer Disease ◽  
Tnf Α ◽  
H Pylori ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background: Helicobacter pylori (H. pylori) -induced gastric inflammation in the gastric mucosa and significantly increases the risk of developing gastritis and peptic ulcer disease (PUD). The objective of this research is to determine the role of tumor necrosis factor-α (TNF-α) expression in the gastric mucosa of patients with H. pylori –associated gastritis and PUD compared to uninfected patients, and we determined the relation between TNF-α expression and Th1/Th17/Th22, and Treg cells.Methods: Fifty-five patients with H. pylori –associated gastritis, 47 patients with H. pylori –associated PUD, and 48 uninfected patients were in this research. Antrum biopsy was used to detect H. pylori, virulence factors and histopathological assessments.Results: Expression of TNF-α in the infected group was significantly higher than the uninfected group. Also, cagA/oipA-positive infected patients induce significantly more TNF-α expression than do cagA/oipA-negative infected patients. Expression of TNF-α was significantly increased in the PUD group than the gastritis group. Notably, TNF-α expression had a significant positive correlation with the frequency of Th1/Th17/Th22 lymphocytes in the PUD group.Conclusion: These findings indicate the importance of increasing TNF-α with Th1, Th17, Th22 responses increase as an important risk factor for PUD in context of H. pylori infection.

scholarly journals Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients

2021 ◽  
Vol 22 (11) ◽  
pp. 5624
Author(s):  
Piotr Deptuła ◽  
Łukasz Suprewicz ◽  
Tamara Daniluk ◽  
Andrzej Namiot ◽  
Sylwia Joanna Chmielewska ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mechanical Properties ◽  
Helicobacter Pylori ◽  
Mechanical Response ◽  
Cellular Level ◽  
Cancer Development ◽  
Tissue Samples ◽  
Diagnostic Measures ◽  
Gastric Cells ◽  
H Pylori

Background: the molecular mechanism of gastric cancer development related to Helicobacter pylori (H. pylori) infection has not been fully understood, and further studies are still needed. Information regarding nanomechanical aspects of pathophysiological events that occur during H. pylori infection can be crucial in the development of new prevention, treatment, and diagnostic measures against clinical consequences associated with H. pylori infection, including gastric ulcer, duodenal ulcer, and gastric cancer. Methods: in this study, we assessed mechanical properties of children’s healthy and H. pylori positive stomach tissues and the mechanical response of human gastric cells exposed to heat-treated H. pylori cells using atomic force microscopy (AFM NanoWizard 4 BioScience JPK Instruments Bruker). Elastic modulus (i.e., the Young’s modulus) was derived from the Hertz–Sneddon model applied to force-indentation curves. Human tissue samples were evaluated using rapid urease tests to identify H. pylori positive samples, and the presence of H. pylori cells in those samples was confirmed using immunohistopathological staining. Results and conclusion: collected data suggest that nanomechanical properties of infected tissue might be considered as markers indicated H. pylori presence since infected tissues are softer than uninfected ones. At the cellular level, this mechanical response is at least partially mediated by cell cytoskeleton remodeling indicating that gastric cells are able to tune their mechanical properties when subjected to the presence of H. pylori products. Persistent fluctuations of tissue mechanical properties in response to H. pylori infection might, in the long-term, promote induction of cancer development.

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-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 479 ◽  
Author(s):  
Chung-Jung Liu ◽  
Yao-Kuang Wang ◽  
Fu-Chen Kuo ◽  
Wen-Hung Hsu ◽  
Fang-Jung Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Tumor Cell ◽  
Critical Role ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
H Pylori

Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori (H. pylori) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinoma-associated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Mesenchymal stem cells (MSCs) are reported to promote tumor malignance through differentiation of MSCs toward CAFs. In the present study, we demonstrated that H. pylori infection promotes HDGF expression in human gastric cancer cells. HBMMSCs treated with HDGF assume properties of CAF-like myofibroblastic phenotypes, including expression of myofibroblast markers (α-smooth muscle actin (α-SMA), procollagen α1, tropomyoson I, desmin, fibroblast activation protein (FAP)), and fibroblast markers (prolyl-4-hydroxylase A1 (PHA1) and fibroblast specific protein-1 (FSP-1)/S100A4). HDGF recruits HBMMSCs, and then HBMMSCs further contributes to cell survival and invasive motility in human gastric cancer cells. Treatment of HDGF neutralizing antibody (HDGF-NAb) and serum significantly inhibit HDGF-regulated differentiation and recruitment of HBMMSCs. These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to myofibroblast-like cells.

scholarly journals Predictive Effect of Helicobacter pylori in Gastric Carcinoma Development: Systematic Review and Quantitative Evidence Synthesis

Medicines ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 1
Author(s):  
Laurens Holmes ◽  
Jasmine Rios ◽  
Betyna Berice ◽  
Jacqueline Benson ◽  
Nastocia Bafford ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Cancer Development ◽  
Causative Role ◽  
Quantitative Evidence ◽  
H Pylori

Helicobacter pylori (H. pylori) is a bacterial pathogen implicated in gastritis, gastric ulceration, and gastric carcinoma. This study aimed to synthesize literature in providing evidence on the causative role of H. pylori in gastric carcinoma development. This study is based on assessing public literature using an applied meta-analysis, namely, quantitative evidence synthesis (QES). The analytic procedure uses DerSimonian-Laird, including assessing heterogeneity. The QES also utilizes meta-regression and the environmental effect associated with H. pylori in gastric cancer development. Eighteen studies are included in the QES. There is increased prevalence of H. pylori exposure among the cases. The heterogeneity between the CES and individual effect sizes is also significant. Despite controlling for the confoundings, there is increased exposure to H. pylori among the gastric cancer cases, regardless of the differences in the geographic location. H. pylori in this synthesized literature illustrates the contributory role of this microbe in gastric carcinoma. Additionally, regardless of geographic locale, namely, South Korea or Spain, H. pylori is implicated in gastric cancer development.

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