Helicobacter pylori and gastric cancer

Gastric cancer is a worldwide cancer especially frequent in Japan and South America. This cancer affects 10 to 70 people per 100,000 according to the countries. Since the end of the Second World War, the incidence of gastric cancer has been decreasing in France and accounts for less than 10 % of mortality. Helicobacter pylori infection, host genetic background, food regimen are known to be involved in this cancer. Helicobacter pylori should be eradicated in selected patients, such as patients' relatives with documented gastric cancer as well as patients having another gastrointestinal cancer.     

Distribution of Helicobacter pylori in a Mongolian gerbil gastric ulcer model

BACKGROUND AND PURPOSE: To the authors' knowledge, histopathologic changes associated with early H. pylori infection and ulceration have not been established. We examined presence of H. pylori infection in an acetic acid-induced gastric ulcer (AAU) model in Mongolian gerbils. METHODS: Sixty Mongolian gerbils were used as an AAU model, and another 60 gerbils were studied as a control (non-AAU) group. All animals were orally administered H. pylori, then were evaluated by use of histologic and bacteriologic examinations. RESULTS: Helicobacter pylori were scattered on the surface mucous gel layer and in the pyloric gland gastric were pits; inflammation seen at the early stages later extended to the mucosa of the fundic gland area. The organisms were predominantly observed in the AAU model, but findings were comparable to those in controls at 1, 3, 7, 14, 28, or 56 days. Evaluation with regard to viable bacterial numbers reflected the histologic aspects, that the pyloric gland area had more viable counts than did the fundic gland area. Carbohydrate composition of mucin differed between pyloric and fundic gland areas. These findings shed light on L-fucose related to the H. pylori adhesive factor abundant in mucin of the pyloric gland area. CONCLUSIONS: Findings for this ulcer model of Helicobacter pylori infection make it useful for the study of onset of infection and screening of anti-ulcer agents.     

Helicobacter pylori antibodies and gastric cancer: a gender-related difference

Helicobacter pylori has been proposed as a causative agent of gastric cancer. The aim of this study was to define serum antibodies response against different H. pylori antigens in patients with gastric cancer. Serum samples were collected from 115 Lithuanian patients with non-cardia gastric cancer and 110 age- and sex-matched controls without cancer. Heat-stable, low-molecular-mass, and outer membrane proteins were used as antigens to analyze serum IgG antibody response against H. pylori by enzyme-linked immunosorbent assay. Seroprevalence of H. pylori using low-molecular-mass antigen was significantly higher in gastric cancer patients, compared to controls (77% versus 57%, p<0.05). Significant differences in the prevalence of H. pylori infection between gastric cancer patients and controls were found in females using all three studied antigens: heat-stable (98% versus 84%, p<0.05), low-molecular-mass (88% versus 48%, p<0.05) and outer membrane proteins (78% versus 57%, p<0.05). In males, no significant differences were revealed between gastric cancer patients and controls. There may be other cofactors in addition to H. pylori that are important for the development of gastric cancer. H. pylori seems, however, to be a more important for development of gastric cancer in females than in males or males may have more confounding risk factors for gastric cancer than females.     

Phagocytosis and persistence of Helicobacter pylori

Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram-negative bacterium that colonizes the gastric epithelium of humans. All persons infected with H. pylori have gastritis, and some will develop severe disease such as peptic ulcers or gastric cancer. A characteristic feature of this infection is the pronounced accumulation of phagocytes, particularly neutrophils, in the gastric mucosa. H. pylori thrives in a phagocyte-rich environment, and we describe here how this organism uses an array of novel virulence factors to manipulate chemotaxis, phagocytosis, membrane trafficking and the respiratory burst as a means to evade elimination by the innate immune response.     

Some mechanisms of Helicobacter pylori persistence

The mechanisms of the pathogenesis of Helicobacter pylori infection, ensuring the prolonged survival of these bacteria in the aggressive medium (gastric mucosa), are considered. A new approach to the systematization of the mechanisms of H. pylori persistence is proposed: the mechanisms ensuring the stability of H. pylori in the presence of aggressive physical and chemical factors, the mechanisms ensuring antagonistic effects in biocenosis and the mechanisms ensuring resistance to the protective factors of the host. Data on the persistence potential of H. pylori in accordance with the proposed classification are presented.     

Statistical model of the interactions between Helicobacter pylori infection and gastric cancer development

Background. The bacterium Helicobacter pylori is associated with a number of gastrointestinal diseases, such as gastric ulcer, duodenal ulcer and gastric cancer. Several histological changes may be observed during the course of infection; some may influence the progression towards cancer. The aim of this study was to build a statistical model to discover direct interactions between H. pylori and different precancerous changes of the gastric mucosa, and in what order and to what degree those may influence the development of the intestinal type of gastric cancer. Methods. To find direct and indirect interactions between H. pylori and different histological variables, log‐linear analyses were used on a case–control study. To generate mathematically and biologically relevant statistical models, a designed algorithm and observed frequency tables were used. Results. The results show that patients with H. pylori infection need to present with proliferation and intestinal metaplasia to develop gastric cancer of the intestinal type. Proliferation and intestinal metaplasia interacted with the variables atrophy and foveolar hyperplasia. Intestinal metaplasia was the only variable with direct interaction with gastric cancer. Gender had no effect on the variables examined. Conclusion. The direct interactions observed in the final statistical model between H. pylori, changes of the mucosa and gastric cancer strengthens and supports previous theories about the progression towards gastric cancer. The results suggest that gastric cancer of the intestinal type may develop from H. pylori infection, proliferation and intestinal metaplasia, while atrophy and foveolar hyperplasia interplay with the other histological variables in the disease process.     

幽门螺杆菌相关miRNA与胃癌关系的研究进展

微小核糖核酸(microRNA,miRNA)是一种由内源基因编码长度约为22个核苷酸的非编码RNA,其能抑制靶基因蛋白质表达,有多种生物学功能。越来越多的研究表明,miRNA在多种肿瘤中异常表达,参与肿瘤发生、发展过程。幽门螺杆菌(Helicobacter pylori,Hp)作为胃癌的主要致病因素,可通过调节miRNA的表达,在胃癌中起促进或抑制作用。现就Hp相关miRNA在胃癌中的作用作一概述。     

Epigenetic changes in gastric cancer induction by Helicobacter pylori

Epigenetic disorder mechanisms are one of the causes of cancer. The most important of these changes is the DNA methylation, which leads to the spread of Helicobacter pylori and inflammatory processes followed by induction of DNA methylation disorder. Mutations and epigenetic changes are the two main agents of neoplasia. Epithelial cells infection by H. pylori associated with activating several intracellular pathways including: MAPK, NF-κB, Wnt/β-catenin, and PI3K are affects a variety of cells and caused to an increase in the production of inflammatory cytokines, changes in apoptosis, proliferation, differentiation, and ultimately leads to the transformation of epithelial cells into oncogenic. The arose of free radicals impose the DNA cytosine methylation, and NO can increase the activity of DNA methyltransferase. H. pylori infection causes an environment that mediates inflammation and signaling pathways that probably caused to stomach tumorigenicity. The main processes that change by decreasing or increasing the expression of various microRNAs expressions include immune responses, apoptosis, cell cycle, and autophagy. In this review will be describe a probably H. pylori roles in infection and mechanisms that have contribution in epigenetic changes in the promoter of genes.     

Helicobacter pylori infection and gastric cardia cancer in Chaoshan region

Helicobacter pylori (H. pylori) infection represents the most important risk factor for gastric cancer, while its association with gastric cardia cancer (GCC) has not been recognized yet. In this current study, we aim to investigate the status of H. pylori infection in the gastric cardia tissue samples from high-risk populations in Chaoshan littoral region, and the relationship between H. pylori infection and chronic inflammation as well as the proliferative activity of the gastric cardia epithelial cells. A total of 706 gastric cardia biopsy specimens were obtained from 372 GCC cases and 334 tumor-free controls in Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. Immunohistochemistry and Giemsa staining were employed for the verification of H. pylori infection. H. pylori infection rate was significantly higher in GCC (81.5%, P < 0.01) and gastric carditis (80.1%, P < 0.01) in comparison with that in the healthy group (34.8%). A significant higher prevalence of chronic inflammation was found in H. pylori+ samples (96.9%) than that in H. pylori− specimens (80.5%) (P < 0.01). To explore the possible role of H. pylori infection-related chronic inflammation in the GCC, we found that the expression of Ki-67 was progressively increased in tissues with chronic inflammation degrees from normal to severe inflammation (P < 0.01). Collectively, these results suggest that persistent H. pylori infection and the related chronic inflammation may contribute to the high incidence of GCC in Chaoshan littoral.     

Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer

Gastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (-) GC that can sensitively and efficiently predict the prognostic. The RNA-seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (-) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven-mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (-) GC. The seven-mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high-risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low-risk scores (P < .0001). In this study, we developed a seven-mRNA signature related to G2/M checkpoint from H. pylori (-) GCs that as an independent biomarker potentially with a good performance in predicting OS and might be valuable for the clinical management for patients with GC.     

Helicobacter pylori and gastric autoimmunity

Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry.     

A stain for demonstrating Helicobacter pylori in gastric biopsies

Helicobacter pylori continues to be a significant health care problem. It is associated with a variety of stomach disorders such as gastritis, gastric ulcer disease, gastric carcinoma and B-cell gastric lymphoma. One common method diagnosing an infection by this bacterium is microscopic examination of routine processed gastric or duodenal biopsies. With this type of specimen, it is necessary to demonstrate visually the presence of H. pylori using an appropriate staining technique. This paper presents a simple staining technique for demonstrating H. pylori in gastric biopsy specimens using carbol fuchsin staining against a contrasting background of light green.