Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. Proteomic analysis of the human gastric mucosa from the patients with erosive gastritis, peptic ulcer or gastric cancer, which were either infected or not with H. pylori, was used to determine the differentially expressed proteins by H. pylori in the human gastric mucosa in order to investigate the pathogenic mechanism of H. pylori -induced gastric diseases. Prior to the experiment, the expression of the main 18 proteins were identified in the gastric mucosa and used for a proteome map of the human gastric mucosa. Using two-dimensional electrophoresis of the protein isolated from the H. pylori -infected tissues, Coomassie Brilliant Blue staining and computerized analysis of the stained gel, the expression of eight proteins were altered in the H. pylori -infected tissues compared with the non-infected tissues. MS analysis (matrix-assisted laser desorption/ionization-time of flight MS) of the tryptic fragment and a data search allowed the the identification of the four increased proteins (78 kDa glucose-regulated protein precursor, endoplasmin precursor, aldehyde dehydrogenase 2 and L-lactate dehydrogenase B chain) and the four decreased proteins (intracellular chloride channel protein 1, glutathione S-transferase, heat-shock protein 60 and cytokeratin 8) caused by H. pylori infection in the gastric mucosa. These proteins are related to cell proliferation, carcinogenesis, cytoskeletal function and cellular defence mechanism. The common feature is that these proteins are related to oxidative-stress-mediated cell damage. In conclusion, the established gastric mucosal proteome map might be useful for detecting the disease-related protein changes. The H. pylori -induced alterations in protein expression demonstrate the involvement of oxidative stress in the pathogenesis of H. pylori -induced gastric diseases, including inflammation, ulceration and carcinogenesis.
 ...
PMID:Oxidative-stress-related proteome changes in Helicobacter pylori-infected human gastric mucosa. 1471 73

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.
 ...
PMID:Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. 1473 80

The enzyme inducible nitric oxide synthase (iNOS) is part of the host innate defense system against bacterial infection. During chronic inflammation, like that seen with a Helicobacter pylori infection, constant nitric oxide production may lead to tissue and DNA damage, thus increasing the patient's risk for developing cancer. Several investigations on iNOS expression in H. pylori-associated gastritis have resulted in conflicting data. Therefore, we investigated the association between chronic H. pylori infection and iNOS expression in samples from stomach carcinoma patients as well as in antral biopsies from patients with H. pylori-associated gastritis. iNOS expression was analyzed by means of reverse transcriptase (RT)-PCR and quantified by competitive RT-PCR. To study in situ localization of iNOS in biopsy samples, immunohistochemistry was performed. iNOS enzyme activity was quantified using an arginine/citrulline assay. A significant increase in iNOS mRNA signal was only present in one-third of the analyzed patient biopsies with H. pylori-associated gastritis. These biopsies showed a 90% association with intestinal metaplasia and a 100% association with CagA-positive H. pylori. Intestinal metaplasia is discussed to be one step in the carcinogenesis of stomach cancer. Quantitation of iNOS transcripts and iNOS enzyme activity in non-cancerous mucosa of gastric cancer patients revealed a significant increase in iNOS transcripts and iNOS activity only in the mucosa of patients with stomach cancer of the intestinal type but not in the diffuse type. Our results support the hypothesis that CagA-positive H. pylori strains are associated with the expression and activity of iNOS, and therefore might contribute to the development of intestinal metaplasia leading to gastric cancer of the intestinal type.
 ...
PMID:Up-regulation of inducible nitric oxide synthase in Helicobacter pylori-associated gastritis may represent an increased risk factor to develop gastric carcinoma of the intestinal type. 1476 Sep 71

We report the case of a 72-year-old man with 2 simultaneous gastric carcinomas. The larger, ulcerated mass in the antrum was a conventional infiltrating intestinal-type adenocarcinoma. The associated antral-type mucosa showed moderate chronic gastritis, foci with complete and incomplete intestinal metaplasia, and mild to moderate Helicobacter pylori infection. The second, smaller tumor was found within fundic-type mucosa and was a lymphoepithelioma-like carcinoma associated with Epstein-Barr virus (EBV) infection shown by the EBV-encoded small RNA (EBER) test. The EBER test result was negative in the intestinal type adenocarcinoma. To our knowledge, this is the first report of simultaneous gastric carcinomas with 2 different morphologic phenotypes, in which only one tumor was associated with EBV infection, while the second tumor was related to H pylori-associated chronic gastritis. Our report demonstrates 2 different but simultaneous etiologic pathways of gastric carcinogenesis in the same patient.
 ...
PMID:Simultaneous EBV-positive lymphoepithelioma-like carcinoma and EBV-negative intestinal-type adenocarcinoma in a patient with Helicobacter pylori-associated chronic gastritis. 1498 38

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostanoid biosynthesis, plays a key role in gastrointestinal carcinogenesis. Among various prostanoids, prostaglandin E2 (PGE2) appears to be most responsible for cancer development. To investigate the role of PGE2 in gastric tumorigenesis, we constructed transgenic mice simultaneously expressing COX-2 and microsomal prostaglandin E synthase (mPGES)-1 in the gastric epithelial cells. The transgenic mice developed metaplasia, hyperplasia and tumorous growths in the glandular stomach with heavy macrophage infiltrations. Although gastric bacterial counts in the transgenic mice were within the normal range, treatment with antibiotics significantly suppressed activation of the macrophages and tumorous hyperplasia. Importantly, the antibiotics treatment did not affect the macrophage accumulation. Notably, treatment of the transgenic mice with lipopolysaccharides induced proinflammatory cytokines through Toll-like receptor 4 in the gastric epithelial cells. These results indicate that an increased level of PGE2 enhances macrophage infiltration, and that they are activated through epithelial cells by the gastric flora, resulting in gastric metaplasia and tumorous growth. Furthermore, Helicobacter infection upregulated epithelial PGE2 production, suggesting that the COX-2/mPGES-1 pathway contributes to the Helicobacter-associated gastric tumorigenesis.
 ...
PMID:Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. 1501 33

The biological model of gastric carcinogenesis can be described as a series of sequential phases. The first consists of a chronic active inflammatory response to Helicobacter pylori infection. Infiltration of the gastric mucosa by mucosa-associated lymphoid tissue and polymorphonuclear neutrophils, as well as damage to the epithelial cells, characterize this phase. The second phase is dominated by alterations of the epithelial cell cycle, especially increased rates of apoptosis and cell proliferation. These changes may be responsible for the multifocal atrophy that characterizes the type of gastritis associated with an increased risk of cancer. The third, more advanced phase of the model displays nuclear and architectural abnormalities, which may represent progressive mutational events as expected in classical molecular models of carcinogenesis. The importance of a comprehensive view of the biological model is stressed.
 ...
PMID:The biological model of gastric carcinogenesis. 1505 3

Gastric cancer is the second most common cause of cancer-related mortality world-wide. In most cases, it develops via the pre-malignant stages of atrophic gastritis, intestinal metaplasia and dysplasia, following Helicobacter pylori infection of susceptible individuals. A number of rodent models have recently provided valuable insights into the host, bacterial and environmental factors involved in gastric carcinogenesis. Wild-type rodents do not develop gastric adenocarcinoma, but early studies showed that the disease could be induced in several rodent species by chemical carcinogens. More recently, it has been demonstrated that gastric adenocarcinoma can be induced in Mongolian gerbils by H. pylori infection and in C57BL/6 mice by long-term H. felis infection. These models have allowed the importance of Helicobacter virulence genes, host factors, such as gender, strain and immune response, and environmental factors, such as dietary salt, to be explored. A number of transgenic mice with alterations in various pathways, including the immune response, gastrin biosynthesis, parietal cell development, growth factors and tumour suppressors, have also provided models of various stages of gastric carcinogenesis. One model that has proved to be particularly valuable is the hypergastrinaemic INS-GAS mouse, in which gastric carcinoma develops spontaneously in old animals, but the process is greatly accelerated by Helicobacter infection.
 ...
PMID:Review article: How useful are the rodent animal models of gastric adenocarcinoma? 1508 Aug 46

Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration, and gastric carcinoma. Moreover, H. pylori may induce disease-specific protein expression in gastric epithelial cells. The present study was aimed at determining differentially expressed proteins in H. pylori-infected gastric epithelial AGS cells. AGS cells were treated with H. pylori at a bacterium/cell ratio of 300:1 for 12 h. Altered protein patterns as separated by two-dimensional electrophoresis using pH gradients of 4-7 were conclusively identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the peptide digests. Four differentially expressed proteins, whose expression levels were increased by more than two-fold in H. pylori-infected cells, were analyzed. These proteins (14-3-3 protein alpha/beta, cullin homolog 3, alpha-enolase, ezrin) are known to be related to cell proliferation, cell adhesion, and carcinogenesis, and may be mediated by cellular stress, such as reactive oxygen species. In conclusion, the identification of these differentially expressed proteins provide valuable information for the understanding of the pathophysiologic mechanisms of H. pylori-induced gastric diseases, and may be useful as prognostic indices of H. pylori-related gastric disorders.
 ...
PMID:Cellular stress-related protein expression in Helicobacter pylori-infected gastric epithelial AGS cells. 1514 40

The gastrointestinal peptide hormones gastrin and cholecystokinin (CCK) are well known for their ability to stimulate gastric acid secretion and pancreatic enzyme secretion, respectively. The suggestion that gastrin and CCK might also promote the development of cancers of the gastrointestinal tract has been controversial, but an increasing body of evidence now supports the view that the amidated and non-amidated forms of gastrin act as growth factors via different receptors in different regions of the gut. For example, animal experiments indicate that amidated gastrins are involved in cellular differentiation and repair in the gastric mucosa, and synergize with Helicobacter pylori infection in the development of gastric carcinoma. In contrast, non-amidated gastrins stimulate colonic mucosal growth, accelerate the early steps in colorectal carcinoma formation, and are elevated in the tumour and circulation of patients with colorectal cancer. Although human pancreatic carcinomas express CCK-1 and CCK-2 receptors, the role of gastrins and CCK in pancreatic carcinogenesis is yet to be established. Further investigation of the possible role of the CCK-2 receptor in gastric and pancreatic neoplasia, and of the hypothesis that gastrin precursors act as autocrine growth factors in colorectal carcinoma, is warranted. However, therapies aimed at the gastrins must be targeted to the relevant gastrin/gastrin receptor combination.
 ...
PMID:Gastrins, cholecystokinins and gastrointestinal cancer. 1523 41

Helicobacter pylori infection leads to significant inflammations in the gastric mucosa, which is closely associated with development of gastric cancer. Heat shock protein 90 (HSP 90) has been revealed to be critical for intracellular signaling that participates in inflammatory response as well as carcinogenesis. In this study, we investigated a regulatory role of HSP 90 in H. pylori-induced IL-8 production. Our results showed that H. pylori stimulated significant phosphorylation of HSP 90 and the phosphorylation was diminished by administration of HSP 90 inhibitor, geldanamycin (GA). Treatment of GA completely inhibited H. pylori-induced IL-8 production due to deactivation of ERK1/2 and NF-kappaB. These results subsequently lead to inactivation of AP-1 and NF-kappaB, which are known to be major transcriptional factors of IL-8. Our data provide important insights that HSP 90 is involved as a crucial regulator in H. pylori-induced IL-8 production and its inhibitor could be potentially used for the inhibition of H. pylori-provoked inflammation.
 ...
PMID:Blockage of HSP 90 modulates Helicobacter pylori-induced IL-8 productions through the inactivation of transcriptional factors of AP-1 and NF-kappaB. 1524 Jan 21


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