Carcinogenic Strains Selectively Dysregulate the Gastric Proteome, Which May Be Associated with Stomach Cancer Progression.

is the strongest risk factor for gastric cancer. Initial interactions between and its host originate at the microbial-gastric epithelial cell interface, and contact between and gastric epithelium activates signaling pathways that drive oncogenesis. One microbial constituent that increases gastric cancer risk is the pathogenicity island, which encodes a type IV secretion system that translocates the effector protein, CagA, into host cells.

genetic diversification in the Mongolian gerbil model.

requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed genetic adaptation in the Mongolian gerbil model. This model is of particular interest because -infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration.

Pan-genomic analyses identify key pathogenic loci modified by carcinogenic host microenvironments.

Objective: is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of to in vivo carcinogenic microenvironments results in genetic modification important for disease.

Draft Genome Sequences of 13 Colombian Strains Isolated from Pacific Coast and Andean Residents.

We present here the draft genomes of 13 strains isolated from Colombian residents on the Pacific coast ( = 6) and in the Andes mountains ( = 7), locations that differ in gastric cancer risk. These 13 strains were obtained from individuals with diagnosed gastric lesions.

Draft Genome Sequence of Gerbil-Adapted Carcinogenic Helicobacter pylori Strain 7.13.

We report here the draft genome sequence of Helicobacter pylori strain 7.13, a gerbil-adapted strain that causes gastric cancer in gerbils. Strain 7.

Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells.

Objective: Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H.

Berberine inhibits proliferation and down-regulates epidermal growth factor receptor through activation of Cbl in colon tumor cells.

Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter.

Effect of Helicobacter pylori cdrA on interleukin-8 secretions and nuclear factor kappa B activation.

Aim: To investigate genetic diversity of Helicobacter pylori (H. pylori) cell division-related gene A (cdrA) and its effect on the host response.

Methods: Inactivation of H.

Cell-associated hemolysis induced by Helicobacter pylori is mediated by phospholipases with mitogen-activated protein kinase-activating properties.

Pathogenic Helicobacter pylori strains can selectively activate epithelial mitogen-activated protein kinase (MAPK) signaling pathways linked with disease. We now demonstrate that H. pylori-induced hemolysis is strain specific and is mediated by phospholipases PldA1 and PldD.

Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice.

Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections.

Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA.

Background & Aims: Helicobacter pylori-induced gastric carcinogenesis has been linked to the microbial oncoprotein cytotoxin-associated gene A (CagA). Spermine oxidase (SMO) metabolizes the polyamine spermine into spermidine and generates H(2)O(2), which causes apoptosis and DNA damage. We determined if pathogenic effects of CagA are attributable to SMO.

β-Catenin and p120 mediate PPARδ-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia.

Background & Aims: Colonization of gastric mucosa by Helicobacter pylori leads to epithelial hyperproliferation, which increases the risk for gastric adenocarcinoma. One H pylori virulence locus associated with cancer risk, cag, encodes a secretion system that transports effectors into host cells and leads to aberrant activation of β-catenin and p120-catenin (p120). Peroxisome proliferator-activated receptor (PPAR)δ is a ligand-activated transcription factor that affects oncogenesis in conjunction with β-catenin.

Helicobacter pylori induction of eosinophil migration is mediated by the cag pathogenicity island via microbial-epithelial interactions.

The host immune response directed against Helicobacter pylori is ineffective in eliminating the organism and strains harboring the cag pathogenicity island augment disease risk. Because eosinophils are a prominent component of H. pylori-induced gastritis, we investigated microbial and host mechanisms through which H.

Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk.

Background And Aims: Helicobacter pylori colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with H pylori prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (∼90%) prevalence of H pylori in the two locations.

Surreptitious manipulation of the human host by Helicobacter pylori.

Microbial pathogens contribute to the development of more than 1 million cases of cancer per year. Gastric adenocarcinoma is the second leading cause of cancer-related death in the world, and gastritis induced by Helicobacter pylori is the strongest known risk factor for this malignancy. H.

Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori-infected mice.

Helicobacter pylori-induced gastritis is the strongest singular risk factor for gastric adenocarcinoma. Matrix metalloproteinase-7 (MMP-7) is a proteolytic enzyme that can modify the intestinal microbial replicative niche as well as affect tumorigenesis, and H. pylori stimulates expression of MMP-7 in gastric epithelial cells in vitro.

Delineation of a carcinogenic Helicobacter pylori proteome.

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons ever develop cancer. The extensive genetic diversity inherent to this pathogen has precluded comprehensive analyses of constituents that mediate carcinogenesis. We previously reported that in vivo adaptation of a non-carcinogenic H.

Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential.

Helicobacter pylori cagA-positive strains exert population-specific risks for gastric cancer. We determined whether variations in CagA phosphorylation motifs were associated with carcinogenic or proinflammatory epithelial phenotypes induced by strains from regions with divergent cancer risks (Colombia and Nashville, TN). Motif number was significantly related to levels of CagA phosphorylation and cytoskeletal abnormalities.

Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling.

Helicobacter pylori is the strongest identified risk factor for gastric adenocarcinoma. One H. pylori virulence constituent that augments cancer risk is the cag secretion system, which translocates CagA and peptidoglycan into host cells, eventuating in activation of signal transduction pathways.

Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer.

Background: Persistent colonization of the human stomach by Helicobacter pylori is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of H. pylori strains from patients with gastritis or duodenal ulcer disease have been analyzed.

Standardized ginger (Zingiber officinale) extract reduces bacterial load and suppresses acute and chronic inflammation in Mongolian gerbils infected with cagAHelicobacter pylori.

Previous investigations demonstrated that a standardized extract of ginger rhizome inhibited the growth of Helicobacter pylori in vitro with a minimum inhibitory concentration in the range 0.78 to 12.5 mug/mL.

Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation.

Background & Aims: Helicobacter pylori-induced gastritis predisposes to the development of gastric cancer. Increased epithelial tight junction permeability and alterations in apical-junctional complexes are also associated with an increased risk of carcinogenesis. Phosphorylation of myosin regulatory light chain (MLC) by MLC kinase (MLCK) regulates tight junction function.

p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells.

Regulation of the Helicobacter pylori cellular receptor decay-accelerating factor.

Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulceration and distal gastric cancer, and adherence of H. pylori to gastric epithelial cells is critical for induction of inflammation. One H.

Regulation of gastric carcinogenesis by Helicobacter pylori virulence factors.

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, and strains that possess the cag secretion system, which translocates the bacterial effector CagA into host cells, augment cancer risk. H. pylori strains that express the vacuolating cytotoxin or the outer membrane protein OipA are similarly associated with severe pathologic outcomes.