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 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 Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

2019 ◽  
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Worrarat Kongkasame ◽  
Prasit Palittapongarnpim ◽  
Seung-Chul Baik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Gene Polymorphisms ◽  
Inflammatory Responses ◽  
Increased Risk ◽  
Cxc Chemokine ◽  
H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.  

scholarly journals LncRNA H19 induced by helicobacter pylori infection promotes gastric cancer cell growth via enhancing NF-κB-induced inflammation

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yifeng Zhang ◽  
Jin Yan ◽  
Chao Li ◽  
Xiaoyong Wang ◽  
Yu Dong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Growth ◽  
Migration And Invasion ◽  
Cancer Cell Growth ◽  
Protein Levels ◽  
Non Coding Rna ◽  
Healthy Donors ◽  
H Pylori ◽  
Long Non Coding Rna

Abstract Background The aim of this study was to investigate the role of long non-coding RNA (lncRNA) H19 in gastric cancer (GC) with Helicobacter pylori (H. pylori). Methods H19 expression in peripheral blood from H. pylori+/− GC patients and healthy donors (control) as well as in GC tissues and cells were detected by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. The levels of pro-inflammatory cytokines were determined by ELISA. The protein levels of IκBα, p-IκBα and p65 were determined by western blotting. Results H19 expression was upregulated in H. pylori-infected GC tissues and cells. Furthermore, H. pylori promoted GC cell viability, migration, invasion and inflammatory response. Moreover, H19 overexpression promoted the proliferation, migration and invasion of H. pylori-infected GC cells via enhancing NF-κB-induced inflammation. Conclusions LncRNA H19 promotes H. pylori-induced GC cell growth via enhancing NF-κB-induced inflammation.

scholarly journals Association of Helicobacter pylori infection and stomach cancer: our experience

2018 ◽  
Vol 5 (8) ◽  
pp. 2794
Author(s):  
N. G. Javan ◽  
Wormi Sharon
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Stomach Cancer ◽  
Histopathological Examination ◽  
Chronic Atrophic Gastritis ◽  
Helicobacter Pylori Infection ◽  
Future Research ◽  
Gastric Cancer Prevention ◽  
H Pylori

Background: Infection with Helicobacter pylori (H. pylori) has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. There are data on the epidemiology, pathophysiology, and histology of this disease that show that Helicobacter pylori gastritis has an important role in gastric carcinogenesis. However, it has to be considered that only very few of those infected with Helicobacter pylori will develop gastric cancer. Hence, it will be a major target of future research to identify individuals who carry a greater risk for developing gastric cancer, and therefore may benefit from eradication of Helicobacter pylori in terms of gastric cancer prevention. Various studies revealed that approximately more than 50% of the world’s human population is infected by Helicobacter pylori. In underdeveloped countries, this association is shown to be much higher according to different studies.Methods: This study was conducted over a period of 36 months from 1st January 2014 till December 31st, 2016. All patients who underwent Gastrectomy during this period were taken. All specimens were investigated to see presence of helicobacter pylori by histological examination. A total of 50 Gastrectomy was performed by one surgical team over 36-month period.Results: Out of 50 patients, Helicobacter pylori positivity was seen in 33 (66%) cases by histopathological examination (HPE). Gastric cancer is more prevalent among males 31 (62%) as compared to 19 (38%) in females. It is more common among the older age group.Conclusions: Helicobacter pylori infection is higher in prevalence in cases of stomach cancer. Present study also showed that there is significant association of Helicobacter pylori infection with gastric carcinoma. Helicobacter pylori infection could be one of the etiological factors for gastric carcinoma.

scholarly journals Adhesin HpaA of Helicobacter pylori Promoted Migration of AGS Cells via IL-21 Secretion From HpaA-induced CD4+T Cells

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Xianru Xia ◽  
Ying Hua ◽  
Pei Hu ◽  
Jie Li ◽  
Guolin Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Cd4 T Cells ◽  
Cancer Metastasis ◽  
Infection Process ◽  
Ags Cells ◽  
Gastric Carcinoma Cell ◽  
Cell Metastasis ◽  
H Pylori

Background: As known, there is a high correlation between Helicobacter pylori infection and gastric carcinoma. Objectives: Concerning the important role of adhesin HpaA of H. pylori in the infection process, we aimed to explore whether HpaA promotes gastric cancer metastasis. Methods: In this study, the levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection were compared with post-treatment condition. The levels of IL-21 from CD4+ T cells and culture supernatants with the recombinant HpaA treatment were detected, and then the levels of MMP-2, MMP-9, and metastasis were detected and verified via AGS cells co-cultured with aforesaid CD4+ T cells. Results: Our results showed that higher levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection than without H.pylori infection. Adhesin HpaA induced more IL-21 via CD4+ T cells, and IL-21 induced high MMP-2 and MMP-9 via AGS cells. In particular, HpaA caused this serial reaction to improve the migration of AGS cells, and aptamer HA6 (our previous report) and anti-IL-21 mcAb reduced the above phenomenon remarkably. Conclusions: In summary, our research suggested that adhesin HpaA plays a significant role in the process of gastric carcinoma cell metastasis via IL-21 from HpaA-induced T cells, and aptamer HA6 may be a potential therapeutic agent for H. pylori treatment.

scholarly journals Transcriptional Profile of Helicobacter pylori Virulence Genes in Patients with Gastritis and Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Manouchehr Ahmadi Hedayati ◽  
Saeed Salavati
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Clinical Outcomes ◽  
Virulence Genes ◽  
Gastric Biopsy ◽  
Transcriptional Profile ◽  
Statistical Correlations ◽  
H Pylori ◽  
Antral Biopsy

Introduction. Numerous molecular epidemiology studies have been performed about the frequency of Helicobacter pylori virulence genes in patients with H. pylori infection so far. This study was conducted to detect transcriptional profile by cDNA of H. pylori virulence genes in gastric biopsy samples of gastritis and gastric carcinoma patients. Materials and Methods. In a case-control study, based on the prevalence of gastritis and gastric cancer in Sanandaj city during 2018 and 2019, 23 and 11 gastric antral biopsy samples with H. pylori infection were collected from gastritis and gastric carcinoma patients by the consecutive and available sampling method. Pathological characters, including tumor grades and tumor areas for gastric carcinoma biopsy samples prepared from gastric cancer areas, were determined by the pathologist. Total RNA of gastric antral biopsy samples was extracted, and their cDNA was synthesized by TaKaRa kit. H. pylori virulence genes’ cDNA using specific primers and PCR was detected. This study’s results were analyzed by SPSS version 25 and statics chi-square tests for determination of relationship and correlation between cDNAs of H. pylori transcriptional profile and clinical outcomes of H. pylori infection, including gastritis, gastric carcinoma, tumor grades, and tumor area. Results. The positive statistical correlations were observed between transcripts of cagA, cagA-EPIYAC, cagE, and cagY genes and H. pylori infection clinical outcomes ( P < 0.05 ). Conclusion. Detection of the H. pylori virulence genes’ cDNA in gastric biopsy samples can help provide the prognosis of clinical outcomes.

scholarly journals Dangerous Liaison: Helicobacter pylori, Ganglionitis, and Myenteric Gastric Neurons: A Histopathological Study

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Liana Sticlaru ◽  
Florica Stăniceanu ◽  
Mirela Cioplea ◽  
Luciana Nichita ◽  
Alexandra Bastian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Myenteric Plexus ◽  
Morphological Changes ◽  
Neuronal Cell ◽  
Histopathological Study ◽  
Tissue Samples ◽  
H Pylori ◽  
The Impact

Chronic inflammation induced by Helicobacter pylori (H. pylori) infection plays a major role in development of gastric cancer. However, recent findings suggested that progression of inflammation and neoplastic transformation in H. pylori infection are more complex than previously believed and could involve different factors that modulate gastric microenvironment and influence host-pathogen interaction. Among these factors, gastric myenteric plexus and its potential adaptive changes in H. pylori infection received little attention. This study is aimed at identifying the impact of H. pylori-associated gastritis on number and morphology of nerve cells in the stomach. The distribution of density, inflammation, and programmed cell death in neurons was immunohistochemically assessed in full-thickness archival tissue samples obtained from 40 patients with H. pylori infection who underwent surgery for gastric cancer and were compared with findings on samples collected from 40 age- and sex-matched subjects without bacteria. Overall, significant differences were noted between H. pylori-positive and H. pylori-negative patients. The analysis of tissue specimens obtained from those with infection revealed higher density and larger surface of the myenteric nervous plexus, as well as a significant increase in the number of gastric neuronal cell bodies and glial cells compared to controls. A predominant CD3-immunoreactive T cell infiltrate confined to the myenteric plexus was observed in infected subjects. The presence of mature B lymphocytes, plasma cells, and eosinophils was also noted, but to a lesser extent, within the ganglia. Myenteric ganglionitis was associated with degeneration and neuronal loss. Our results represent the first histopathological evidence supporting the hypothesis that H. pylori-induced gastric inflammation may induce morphological changes in myenteric gastric ganglia. These findings could help gain understanding of some still unclear aspects of pathogenesis of H. pylori infection, with the possibility of having broader implications for gastric cancer progression.

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 Helicobacter pylori-Mediated Immunity and Signaling Transduction in Gastric Cancer

2020 ◽  
Vol 9 (11) ◽  
pp. 3699
Author(s):  
Nozomi Ito ◽  
Hironori Tsujimoto ◽  
Hideki Ueno ◽  
Qian Xie ◽  
Nariyoshi Shinomiya
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Intracellular Signaling ◽  
Cellular Proliferation ◽  
Gastric Cancer Cells ◽  
Downstream Signaling ◽  
H Pylori

Helicobacter pylori infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during H. pylori infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon H. pylori stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, H. pylori LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. H. pylori infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in H. pylori infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, H. pylori infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.

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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