Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection

Rivas-Ortiz, Claudia Ivette; López‐Vidal, Yolanda; Arredondo-Hernandez, Luis Jose Rene; Castillo-Rojas, Gonzalo

doi:10.3389/fmed.2017.00047

Cited by 41 publications

(33 citation statements)

References 116 publications

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“…Although hypermethylation of genes involved in SSc pathogenesis has been previously shown to be play a role in fibroblasts,46 little research has been performed within the immune compartment of SSc. The mechanism of RUNX3 downregulation has been most studied in the field of cancer; RUNX3 is one of the most hypermethylated gene in solid tumours, including breast, bladder, colorectal and gastric tumours 47–49. In SSc pDCs, we demonstrated higher methylation level at RUNX3 promoter, with one of the sites next to the transcription start.…”

Section: Discussionmentioning

confidence: 68%

“…We compared the frequency of RUNX3 methylation between men and women as a surrogate marker for oestrogen influence; however, we did not observe any significant difference. The Gram-negative bacteria Helicobacter pylori (HP) is known to induce RUNX3 hypermethylation by production of liposaccharides and nitric oxide 47. HP infection is very common in patients with SSc, with the most aggressive strain of HP being the most prevalent 52.…”

Section: Discussionmentioning

confidence: 99%

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Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

Affandi¹,

Carvalheiro²,

Ottria³

et al. 2019

Ann Rheum Dis

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ObjectivesSystemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy and fibrosis in skin and internal organs. Type I interferon signature found in SSc propelled us to study plasmacytoid dendritic cells (pDCs) in this disease. We aimed to identify candidate pathways underlying pDC aberrancies in SSc and to validate its function on pDC biology.MethodsIn total, 1193 patients with SSc were compared with 1387 healthy donors and 8 patients with localised scleroderma. PCR-based transcription factor profiling and methylation status analyses, single nucleotide polymorphism genotyping by sequencing and flow cytometry analysis were performed in pDCs isolated from the circulation of healthy controls or patients with SSc. pDCs were also cultured under hypoxia, inhibitors of methylation and hypoxia-inducible factors and runt-related transcription factor 3 (RUNX3) levels were determined. To study Runx3 function, Itgax-Cre:Runx3f/f mice were used in in vitro functional assay and bleomycin-induced SSc skin inflammation and fibrosis model.ResultsHere, we show downregulation of transcription factor RUNX3 in SSc pDCs. A higher methylation status of the RUNX3 gene, which is associated with polymorphism rs6672420, correlates with lower RUNX3 expression and SSc susceptibility. Hypoxia is another factor that decreases RUNX3 level in pDC. Mouse pDCs deficient of Runx3 show enhanced maturation markers on CpG stimulation. In vivo, deletion of Runx3 in dendritic cell leads to spontaneous induction of skin fibrosis in untreated mice and increased severity of bleomycin-induced skin fibrosis.ConclusionsWe show at least two pathways potentially causing low RUNX3 level in SSc pDCs, and we demonstrate the detrimental effect of loss of Runx3 in SSc model further underscoring the role of pDCs in this disease.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

Affandi¹,

Carvalheiro²,

Ottria³

et al. 2019

Ann Rheum Dis

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“…Several mechanisms adapted by point mutation could explain the frequent drug resistance and persistence of H. pylori. 18,20,21 1.3 | Helical shape of H. pylori It has always been hypothesized that the morphological advantages in the eminent penetration of the pathogen yields by swimming in a directed way. The helical shape plays a great deal in the pathological process of the bacterium in the invasion of the mucous membrane of the human gut.…”

Section: Adaptation Facilitating To H Pylorimentioning

confidence: 99%

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Gupta

Maurya

Verma

et al. 2019

J of Cellular Biochemistry

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Helicobacter pylori and humans have one of the most complex relationships in nature. How a bacterium manages to live in one of the harshest and hostile environments is a topic of unraveling mysteries. H. pylori is a prevalent species and it colonizes the human gut of more than 50% of the world population. It infects the epithelial region of antrum and persists there for a long period. Over the time of evolution, H. pylori has developed complex strategies to extend the degree of inflammation in gastric mucosa. H. pylori needs specific adaptations for initial colonization into the host environment like helical shape, flagellar movement, chemotaxis, and the production of urease enzyme that neutralizes acidic environment of the stomach. There are several factors from the bacterium as well as from the host that participate in these complex interactions. On the other hand, to establish the persistent infection, H. pylori escapes the immune system by mimicking the host antigens. This pathogen has the ability to dodge the immune system and then persist there in the form of host cell, which leads to immune tolerance. H. pylori has an ability to manipulate its own pathogen‐associated molecular patterns, which leads to an inhibition in the binding with specific pattern recognition receptors of the host to avoid immune cell detection. Also, it manipulates the host metabolic homeostasis in the gastric epithelium. Besides, it has several genes, which may get involved in the acquisition of nutrition from the host to survive longer in the host. Due to the persistence of H. pylori, it causes chronic inflammation and raises the chances of gastric cancer. This review highlights the important elements, which are certainly responsible for the persistence of H. pylori in the human host.

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“…3,4 Genetic alternations, such as mutations, single nucleotide polymorphisms, and DNA methylation, are associated with the development of GC. 5 A family history (FH) of GC is also a strong risk factor for GC. 6 Most GCs are sporadic, and approximately 10% of GC shows familial clustering; however, only approximately 1% to 3% of GCs comes from inherited GC predisposition syndromes, such as hereditary diffuse gastric carcinoma and familial adenomatous polyposis.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Family History on Stage and Survival of Gastric Cancer According to the <i>TGFB1</i> C-509T Polymorphism in Korea

et al. 2020

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Background/Aims: The survival rate of gastric cancer (GC) is known to be higher in patients with a family history (FH) of GC. There is an association between a polymorphism in the transforming growth factor-β1 (TGFB1) gene and the risk of GC in patients with first-degree relatives with GC. This study was performed to investigate whether a FH affects GC outcomes according to the TGFB1 C-509T polymorphism. Methods: TGFB1 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 1,143 GC patients, including 216 patients (18.9%) with firstdegree relatives with GC. Results: The proportion of stage I-II GCs was significantly higher in patients with a FH than in those without a FH of GC (83.8 vs 74.9%, p=0.005). The association between a FH of GC and stage I-II GC was not significant in subgroups divided based on the TGFB1 C-509T polymorphism and sex. A FH did not affect the overall survival rate of GC in patient with all stages and each stage. The overall survival rates were not significantly different between patients with the CC and CT/TT genotypes of the TGFB1-509 polymorphism. Conclusions: Patient with a FH of GC had lower cancer stage (I-II) at diagnosis than those without a FH of GC, but there was no significant difference in overall survival between the patients with and without a FH of GC. A FH did not influence the tumor stage or overall survival in patients stratified by the presence of the TGFB1 C-509T polymorphism. (Gut Liver 2020;14:79-88)

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Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection

Cited by 41 publications

References 116 publications

Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

The Influence of Family History on Stage and Survival of Gastric Cancer According to the <i>TGFB1</i> C-509T Polymorphism in Korea

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