Molecular Mechanisms ofHelicobacter pyloriPathogenesis

Abstract

Helicobacter pylori infects 50% of mankind. The vast majority of H. pylori infection occurs in the developing countries where up to 80% of the middle-aged adults may be infected. Bacterial infection causes an inflammatory response that proceeds through a series of intermediated stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia). Among infected individuals, approximately 10% develops severe gastric lesions such as peptic ulcer disease, 1-3% progresses to gastric cancer (GC) with a low 5-year survival rate, and 0.1% develops mucosa-associated lymphoid tissue (MALT). GC is one of the most common cancer and the third leading cause of cancer-related deaths worldwide. In this review, we have summarized the most recent papers about molecular mechanisms of H. pylori pathogenesis. The main important steps of H. pylori infection such as adhesion, entry in epithelial gastric cells, activation of intracellular pathways until epigenetic modifications have been described.

Gastric Cancer as Preventable Disease

“…93 An early role in the acquisition of the neoplastic phenotype has also been associated with cyclin E, cyclindependent kinases dysregulations (ie, p15, p16, p21, and p27), alteration of the ras-MAPK pathway, 39,95 and the HER2 gene amplification; the latter in particular has been proposed as promising target of anticancer therapy. 96 H pylori-associated DNA methyltransferases can directly induce gene methylation in epithelial cells 97 ; moreover, infection has been associated to the DNA methylation of key tumor suppressor genes such as CDH1, RUNX3, CDKN2A, and hMLH1. 27,90 Aberrant microRNA expression (including the downregulation of the let-7 family members) is featured by both H pylori gastritis and GC.…”

Stomach development, stem cells and disease

“…For example, such organoid cultures have been used to examine how the H. pylori bacterium affects gastric epithelial cells. H. pylori colonizes the antral mucosa in nearly 50% of humans, inducing chronic tissue damage (De Falco et al, 2015) and hence elevating the risk for gastritis, peptic ulcers and cancer. H. pylori activates NF-κB-mediated inflammation in gastric epithelial cells, eliciting the chemokine interleukin-8 (Keates et al, 1997) and its virulence factor CagA (also known as S100A8) forms a complex with the MET receptor tyrosine kinase, activating epithelial proliferation (Peek et al, 1997;Churin et al, 2003).…”

Influence of vitamin C and E supplementation on the eradication rates of triple and quadruple eradication regimens for Helicobacter pylori infection

“…Moreover, H. pylori leads to the concentration of reactive oxygen intermediates (ROIs), inflammation, and the activation of immune cells (27,28). The mixed toxicity of ROIs and vacuolating cytotoxin A leads to mucosal destruction and slows down mucosal repair (27,29). The expected response of host cells against chronic oxidative stress by increasing the activities of antioxidant enzymes during H. pylori infection is hampered by H. pylori-infected cells (30).…”