Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the various virulence factors of Helicobacter pylori the role of its heat shock protein 60 (HSP60, HspB) in mucosal inflammation after H. pylori infection was examined. In flow cytometric analysis, the expression of HSP60 on the cell surface was different, depending on the H. pylori strain used. The HSP60 epitope was also detected on the surface of both human gastric cancer cells (MKN45, KATOIII, and MKN28) and human gastric biopsy specimens. The intensity of the expression of HSP60 on the cell surface correlated significantly with the adhesion of H. pylori to MKN45 cells, but not with urease activity and production of vacuolating cytotoxin. A monoclonal antibody to H. pylori HSP60 inhibited the adhesion of H. pylori to MKN45 cells. These results suggest that HSP60 of H. pylori might act as an important virulence factor after H. pylori infection.
 ...
PMID:A virulence factor of Helicobacter pylori: role of heat shock protein in mucosal inflammation after H. pylori infection. 987 96

Helicobacter pylori is a spiral Gram-negative microaerophilic bacterium that causes one of the most common infections in humans; approximately 30-50% of individuals in Western Europe are infected and the figure is nearly 100% in the developing world. It is recognized as the major aetiological factor in chronic active type B gastritis, and gastric and duodenal ulceration and as a risk factor for gastric cancer. H. pylori normally inhabits the mucus-lined surface of the antrum of the human stomach where it induces a mild inflammation, but its presence is otherwise usually asymptomatic. A variety of virulence factors appear to play a role in pathogenesis. These include the vacuolating cytotoxin VacA, cytotoxin-associated proteins, urease and motility. All are under intense study in an attempt to understand how the bacterium colonizes and persists in the gastric mucosa, and how H. pylori infections lead to the disease state. Although an explosion of research on H. pylori has occurred within the past 15 years, most efforts have been directed at aspects of the bacterium and disease process which are of direct clinical relevance. Consequently, our knowledge of many aspects of the physiology and metabolism of H. pylori is relatively poor. This should change rapidly now that the complete genome sequence of a pathogenic strain has been determined. This review focuses attention on these more fundamental areas of Helicobacter biology. Analysis of the genome sequence and some detailed metabolic studies have revealed solute transport systems, an incomplete citric acid cycle and several incomplete biosynthetic pathways, which largely explain the complex nutritional requirements of H. pylori. The microaerophilic nature of the bacterium is of particular interest and may be due in part to the involvement of oxygen-sensitive enzymes in central metabolic pathways. However, the biochemical basis for the requirement for CO2 has not been completely explained and a major surprise is the apparent lack of anaplerotic carboxylation enzymes. Although genes for glycolytic enzymes are present, physiological studies indicate that the Entner-Doudoroff and pentose phosphate pathways are more active. The respiratory chain is remarkably simple, apparently with a single terminal oxidase and fumarate reductase as the only reductase for anaerobic respiration. NADPH appears to be the preferred electron donor in vivo, rather than NADH as in most other bacteria. H. pylori is not an acidophile, and must possess mechanisms to survive stomach acid. Many studies have been carried out on the role of the urease in acid tolerance but mechanisms to maintain the protonmotive force at low external pH values may also be important, although poorly understood at present. In terms of the regulation of gene expression, there are few regulatory and DNA binding proteins in H. pylori, especially the two-component 'sensor-regulator' systems, which indicates a minimal degree of environmentally responsive gene expression.
 ...
PMID:The physiology and metabolism of the human gastric pathogen Helicobacter pylori. 988 78

The Gram-negative bacterium Helicobacter pylori is a widespread human pathogen that colonizes the gastric mucosa and is associated with gastro-intestinal illnesses such as gastritis, peptic ulcer, gastric lymphoma and gastric cancer. Current pharmacological therapies are becoming less reliable for the control of H. pylori due to the elevated costs and to the increasing number of antibiotic resistant strains. New vaccination strategies utilizing H. pylori antigens combined with adjuvants or delivery of antigens by attenuated Salmonella strains have been successful in protecting mice against H. pylori infections. Oral immunization with single doses of urease-expressing Salmonella vaccine strains elicits mucosal and systemic antibody responses and fully protects different mouse strains against challenge infections with H. pylori. The high efficacy in the mouse model, combined with remarkable immunogenicity, safety and low-cost production, makes attenuated live recombinant Salmonella promising vaccine candidates for the control of H. pylori-related diseases in humans.
 ...
PMID:The attenuated Salmonella vaccine approach for the control of Helicobacter pylori-related diseases. 1019 21

Helicobacter pylori is the causative agent of most cases of gastritis. Once acquired, H. pylori establishes chronic persistent infection; it is this long-term infection that, is a subset of patients, leads to gastric or duodenal ulcer, gastric cancer or gastric MALT lymphoma. All fresh isolates of H. pylori express significant urease activity, which is essential to survival and pathogenesis of the bacterium. A significant fraction of urease is associated with the surface of H. pylori both in vivo and in vitro. Surface-associated urease is essential for H. pylori to resist exposure to acid in the presence of urea. The mechanism whereby urease becomes associated with the surface of H. pylori is unique. This process, which we term "altruistic autolysis," involves release of urease (and other cytoplasmic proteins) by genetically programmed autolysis with subsequent adsorption of the released urease onto the surface of neighboring intact bacteria. To our knowledge, this is the first evidence of essential communal behavior in pathogenic bacteria; such behavior is crucial to understanding the pathogenesis of H. pylori.
 ...
PMID:Structure, function and localization of Helicobacter pylori urease. 1037 51

A high-salt diet in humans and experimental animals is known to cause gastritis, has been associated with a high risk of atrophic gastritis, and is considered a gastric tumor promoter. In laboratory rodents, salt is known to cause gastritis, and when coadministered, it promotes the carcinogenic effects of known gastric carcinogens. Because Helicobacter pylori has been associated with a progression from gastritis to gastric cancer, we designed a study to determine whether excessive dietary NaCl would have an effect on colonization and gastritis in the mouse model of H. pylori infection. Seventy-two, 8-week-old female C57BL/6 mice were infected with H. pylori strain Sydney, and 36 control mice were dosed with vehicle only. One-half of the infected and control mice were fed a high-salt diet (7.5% versus 0.25%) for 2 weeks prior to dosing and throughout the entire experiment. Twelve infected and 6 control animals from the high-salt and normal diet groups were euthanized at 4, 8, and 16 weeks. At 8 and 16 weeks postinfection (WPI), the colony-forming units per gram of tissue were significantly higher (P < 0.05) in the corpus and antrum of animals in the high-salt diet group compared with those on the normal diet. Quantitative urease was significantly higher (P < 0.05) at 4 and 8 WPI in the corpus and antrum of animals on the high-salt diet when compared with controls. At 16 WPI, mice in both the normal and the high-salt diet groups developed moderate to marked atrophic gastritis of the corpus in response to H. pylori infection. However, the gastric pits of the corpus mucosa in mice on the high-salt diet were elongated and colonized by H. pylori more frequently than those in mice on the normal diet. The high-salt diet was also associated with a significant increase in proliferation in the proximal corpus and antrum and a multifocal reduction in parietal cell numbers in the proximal corpus, resulting in the elongation of gastric pits. We conclude that excessive NaCl intake enhances H. pylori colonization in mice and in humans and that chronic salt intake may exacerbate gastritis by increasing H. pylori colonization. Furthermore, elevated salt intake may potentiate H. pylori-associated carcinogenesis by inducing proliferation, pit cell hyperplasia, and glandular atrophy.
 ...
PMID:High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. 1051 91

We assessed the sensitivities of several methods for detecting Helicobacter pylori (culture, histology, rapid urease test, and serology), and evaluated the H. pylori positivity considering the degree of atrophy in the background mucosa in 202 gastric cancer patients and 101 controls. The positivity of H. pylori determined by culture (81%) was significantly higher than that determined by serology (62%) in gastric cancer patients (P < 0.001). The positivities of H. pylori determined by biopsy and/or serology in intestinal (84%) and diffuse (95%) types of gastric cancer were higher than that observed in controls (54%) (P < 0.001). Intestinal-type gastric cancer tended to occur in the atrophic mucosa, in which H. pylori positivity was not different from that in controls after adjusting for the degree of atrophy, whereas diffuse-type gastric cancer was observed more often in the nonatrophic mucosa, in which H. pylori positivity was higher than that in controls even after adjusting for the degree of atrophy.
 ...
PMID:Helicobacter pylori and mucosal atrophy in patients with gastric cancer: a special study regarding the methods for detecting Helicobacter pylori. 1054 54

Cytokines have been proposed to play an important role in Helicobacter pylori-associated gastroduodenal diseases, but the exact mechanism of the cytokine induction remains unclear. H. pylori urease, a major component of the soluble proteins extracted from bacterial cells, is considered to be one of the virulence factors for the inflammation in the gastric mucosa that is produced in H. pylori infection. However, the response of human gastric epithelial cells to the stimulation of urease has not been investigated. In the present study, we used human gastric epithelial cells in a primary culture system and examined whether H. pylori urease stimulates the gastric epithelial cells to induce proinflammatory cytokines by reverse transcription-PCR and enzyme-linked immunosorbent assay. First, by using peripheral blood mononuclear cells (PBMC) and a gastric cancer cell line (MKN-45 cells), we confirmed the ability of purified H. pylori urease to induce the production of proinflammatory cytokines. Furthermore, we demonstrated that the human gastric epithelial cells produced interleukin-6 (IL-6) and tumor necrosis factor alpha, but not IL-8, following stimulation with purified urease. The patterns of cytokine induction differed among human PBMC, MKN-45 cells, and human gastric epithelial cells. These results suggest that the human gastric epithelial cells contribute to the induction of proinflammatory cytokines by the stimulation of H. pylori urease, indicating that the epithelial cells were involved in the mucosal inflammation that accompanied H. pylori infection.
 ...
PMID:Cytokine expression and production by purified Helicobacter pylori urease in human gastric epithelial cells. 1063 31

We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.
 ...
PMID:Serological response to Helicobacter pylori recombinant antigens in Chilean infected patients with duodenal ulcer, non-ulcer dyspepsia and gastric cancer. 1066 Jan 36

The bacterium Helicobacter pylori colonises the stomach of man and induces a strong inflammatory response. Differences in the possession of pathogenicity determinants by H. pylori isolates could account in part for the different clinical outcomes of infection. The main H. pylori pathogenic factors, i.e. urease, the cytotoxin VacA, and the genes involved in virulence contained in the pathogenicity island (PAI) cag, may promote tissue damage and ulceration, and could contribute to gastric cancer development. Strains with the mosaic vacA allelic type s1a/m1 and possessing the cag insertion are considered endowed with increased inflammatory potential, and are more likely to be isolated from patients with peptic ulcer and gastric cancer. The presence in H. pylori cag PAI of operons involved in the stimulation of gastric epithelial cells to secrete high levels of inflammatory cytokines, in mobilisation of DNA, and formation of secretory mechanisms and conjugation apparati, could contribute to increase the risk of gastric cancer development in patients infected by this microorganism.
 ...
PMID:Helicobacter pylori determinants of pathogenicity. 1067 5

The finding of II pylori in the gastric mucosa has changed the understanding of the pathogenesis of common diseases of the stomach and duodenum. The bacteria causes acute and chronic gastritis and is the precursor of peptic ulcers, gastric lymphoma and gastric cancer. The most common test used to diagnose the infection is the urease test on a gastric biopsy but an endoscopy must be performed to obtain the biopsy. Determination of serum levels of IgG appears the most suitable test to perform in large population studies. Patients with peptic ulcers, gastric lymphoma and early gastric cancer should be treated. Combinations of antibiotics such as amoxicillin, chlarithromycin and a proton pump inhibitor have yielded the best results in irradicating H pylori. Unfortunately this therapy is expensive and new combinations should be explored. Vaccination should be the treatment of choice for prevention and irradication in countries like Chile with high infection rate. Preliminary results are encouraging.
 ...
PMID:[Helicobacter pylori. The bacteriological revolution]. 1075 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>