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)

In the years that followed the issuance in 2000 of the Guidelines for the Management of Helicobacter pylori Infection in Japan by the Japanese Society for Helicobacter Research (JSHR), a number of major issues arose, including the emergence of H. pylori strains resistant to clarithromycin as part of primary eradication therapy, and this led to the Guidelines being revised by the JSHR in 2003. While the JSHR aimed in the 2000 Guidelines to prepare clinicians for the task ahead in view of H. pylori eradication therapy becoming available, the JSHR went a step further in the 2003 Guidelines to include more evidence-based recommendations to address clinical and institutional challenges and issues of interest in the management of H. pylori infection in Japan. Thus, a number of diseases were upgraded to either class A or B indications for H. pylori eradication, including mucosa-associated lymphoid tissue lymphoma (class A), and after endoscopic mucosal resection for early gastric cancer, atrophic gastritis, and gastric hyperplastic polyp (all class B), with further diseases such as extragastric disease also included as class C indications requiring further examination. Concern was expressed over reliance on a single diagnostic test for H. pylori infection, which is in place due to institutional constraints. Metronidazole was also recommended for use in the place of clarithromycin as part of a second-line eradication regimen in light of increasing clarithromycin resistance, although metronidazole remains to be approved for health insurance coverage. Finally, areas requiring further clinical research and endeavors, including establishment of second-line eradication therapy, were also proposed in the 2003 Guidelines to point the way for the future.
 ...
PMID:Guidelines for the management of Helicobacter pylori infection in Japan: current status and future prospects. 1723 17

Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IkappaB kinase-dependent nuclear factor-kappaB activation pathway. H. pylori-mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.
 ...
PMID:Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. 1741 70

There are geographic and ethnic differences in the incidence of gastric cancer around the world as well as with its trends for each population over time. The incidence patterns observed among immigrants change according to where they live. All of these factors serve to indicate the close association of gastric cancer with modifiable factors such as diet. This review presents epidemiological evidence on the association between dietary factors and gastric cancer based on previous systematic reviews and subsequent updates. Infection with Helicobacter pylori is a strong and established risk factor of gastric cancer but is not a sufficient cause for its development. Substantial evidence from ecological, case-control, and cohort studies strongly suggests that the risk may be increased with a high intake of various traditional salt-preserved foods and salt per se and decreased with a high intake of fruit and vegetables, particularly fruit. However, it remains unclear which constituents in fruit and vegetables play a significant role in gastric cancer prevention. Among them, vitamin C is a plausible candidate supported by a relatively large body of epidemiological evidence. Consumption of green tea is possibly associated with a decreased risk of gastric cancer, although the protective effects have been, for the most part, identified in Japanese women, most of whom are nonsmokers. In contrast, processed meat and N-nitroso compounds may be positively associated with the risk of gastric cancer. In conclusion, dietary modification by reducing salt and salted food intake, as well as by increasing intake of fruit and vitamin C, represents a practical strategy to prevent gastric cancer.
Gastric Cancer 2007
PMID:Diet and the risk of gastric cancer: review of epidemiological evidence. 1757 15

Bacterial resistance to antibiotics is a major public health problem around the world causing high rates of morbi-mortality and economic problems in hospital settings. Major bacterial causing nosocomial infections are: extended-spectrum beta-lactameses (ESBL) producing enterobacteria, methicillin resistance Staphylococcus aureus, coagulase negative Staphylococcus, metallo fl-lactamases (MBL) producing Pseudomonas aeruginosa, Streptococcus pneumoniae, Enterococcus spp, Acinetobacter baumani. This last bacteria is not very often isolated in hospital settings yet, but it is multi-resistance pathogen causing high mortality. Helicobacter pylori, which is not a nosocomial pathogen but is associated to gastric diseases (from gastritis to gastric cancer). Infections prevention, to obtain an accuracy diagnostic and effective treatment, use antibiotic wisely and pathogen dissemination prevention (hand washing), are important steps to control the bacterial resistance.
 ...
PMID:[Resistance to antibiotics]. 1757 81

Helicobacter infection is the leading cause of gastric cancer worldwide. Infection with this ubiquitous bacterium incites a chronic active immune response that persists for the life of the host, in the absence of antibiotic-induced eradication. It is the combination of bacterial factors, environmental insults, and the host immune response that drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer. Although it may seem intuitively obvious that removing the offending organism would negate the cancer risk, this approach is neither feasible (half of the world harbors this infection) nor is it straightforward. Most patients are infected in childhood, and present with various degrees of mucosal damage before any therapy. This review outlines the histologic progression of human Helicobacter infection from the early stages of inflammation through the development of metaplasia, dysplasia, and, finally, cancer. The effects of dietary and bacterial eradication therapy on disease progression and lesion reversibility are reviewed within the context of population studies and compared between study designs and populations tested. Eradication studies in the mouse model of infection prevents the formation of gastric cancer, and allows regression of established lesions, providing a useful model to study interaction between bacterium, environment, and host, without the difficulties inherent in human population studies. Recent advances in identifying the bone marrow-derived stem cell as the cell of origin of Helicobacter-induced gastric cancer in the murine model are discussed and interpreted in the context of human disease, and implications for future treatment are discussed.
 ...
PMID:Carcinogenesis of Helicobacter pylori. 1832 6

Infection with Helicobacter pylori has been shown to be at the origin of various gastric pathologies. However, it has not yet been established whether the etiology of such diseases, particularly of gastric cancer, is related to the production of free radicals or to mutagenesis. The aim of this study was to determine whether a six-month infection with Helicobacter pylori increased the amount of lipid peroxidation, nitric oxide, and DNA damage in Mongolian gerbils (Meriones unguiculatus). H. pylori was characterized genotypically and administered orally to the animals. Four tests were applied to identify the presence of bacteria at one, two, four, and six months after the inoculation, namely, isolation and identification in culture, the urease test, the ELISA assay, and immunohistochemical staining of gastric biopsies. The infection was considered to be successful when three of the above-mentioned tests were positive. The infection occurred in 30% of the animals in the first month after the H. pylori inoculation and in 60-70% of the animals in the later stages. Levels of malondialdehyde, nitric oxide, and DNA damage (using the "comet" assay) were determined in the gastric tissue of the animals at one, two, four, and six months. We found statistically significant increases in malondialdehyde and nitric oxide levels from the second month on. The comet assay in animals infected with H. pylori showed a significant increase in the mean tail length throughout the observation period. We conclude that our results support the assumption that oxidative damage and DNA breakage produced by the infection with H. pylori are some of the initial alterations occurring in the development of gastric diseases.
 ...
PMID:Genotoxic and oxidative damage induced by Helicobacter pylori in Meriones unguiculatus. 1772 29

Helicobacter pylori is a human-specific gastric pathogen that colonizes over half the world's population. Infection with this bacterium is associated with a spectrum of gastric pathologies ranging from mild gastritis to peptic ulcers and gastric cancer. A strong predictor of severe disease outcome is infection with a bacterial strain harbouring the cag (cytotoxin associated gene) pathogenicity island (PAI), a 40 kb stretch of DNA that encodes homologues of several components of a type IV secretion system (TFSS). One gene within the cag PAI, cagA, has been shown to encode a substrate for the TFSS which is translocated into host cells, inducing the dephosphrylation of host cell proteins and leading to changes in the morphology or shape of AGS gastric epithelial cells. Furthermore, the TFSS is involved in the induction of proinflammatory cytokines. It appeears to play a key role in H. pylori pathogenesis. Very little is known about the H. pylori cag PAI-encoded TFSS, the expression of Cag proteins in H. pylori, and the functions of individual proteins encoded by the cag PAI. Only by exploring the mechanistic details of the interplay between H. pylori and eukaryotic cells can we endeavour to understand how these cellular interactions play out at the tissue and organismal level during the lifelong coexistence of bacterium and host.
 ...
PMID:[The type IV secretion system encoded by the cag PAI of Helicobacter pylori]. 1794 86

Infection with Helicobacter pylori is linked to inflammation and is the main cause of peptic ulcer, gastritis, and gastric malignancies. To examine associations between gastric cancer risk and the erythrocyte composition of docosahexaenoic acid (DHA), a fatty acid with anti-inflammatory and apoptosis-inducing effects, here we conducted a case-control study of 179 incident gastric cancer cases and 357 noncancer controls (matched by age, sex, and season of sample collection). Dietary information and blood samples were collected from all subjects, and erythrocyte fatty acid levels were measured using accelerated solvent extraction and gas-liquid chromatography. Gastric cancer risk did not seem to be directly associated with dietary intake of fish and n-3 highly unsaturated fatty acids (HUFAs), such as DHA, derived from fish. However, risk was inversely associated with erythrocyte compositions of n-3 HUFAs [the highest to the lowest tertile, odds ratio (OR), 0.39; 95% confidence interval (95% CI), 0.23-0.68; P(trend)<0.005] and DHA (OR, 0.47; 95% CI, 0.28-0.79; P(trend)<0.01). Particularly strong associations were noted for well-differentiated type lesions and n-3 HUFAs (OR, 0.10; 95% CI, 0.03-0.35; P(trend)=0.0005) as well as DHA (OR, 0.20; 95% CI, 0.07-0.58; P(trend)<0.01) values. In conclusion, the erythrocyte composition of DHA was found to be negatively linked to risk of gastric cancer, especially of well-differentiated adenocarcinoma. Further studies are needed to investigate mechanisms of action of DHA relevant to antitumor effects in the stomach.
 ...
PMID:Gastric cancer risk and erythrocyte composition of docosahexaenoic acid with anti-inflammatory effects. 1800 30

Infection with Helicobacter pylori cagA-positive strains is associated with gastritis, ulcerations, and gastric cancer. CagA is translocated into infected epithelial cells by a type IV secretion system and can be tyrosine phosphorylated, inducing signal transduction and motogenic responses in epithelial cells. Cellular cholesterol, a vital component of the membrane, contributes to membrane dynamics and functions and is important in VacA intoxication and phagocyte evasion during H. pylori infection. In this investigation, we showed that cholesterol extraction by methyl-beta-cyclodextrin reduced the level of CagA translocation and phosphorylation. Confocal microscope visualization revealed that a significant portion of translocated CagA was colocalized with the raft marker GM1 and c-Src during infection. Moreover, GM1 was rapidly recruited into sites of bacterial attachment by live-cell imaging analysis. CagA and VacA were cofractionated with detergent-resistant membranes (DRMs), suggesting that the distribution of CagA and VacA is associated with rafts in infected cells. Upon cholesterol depletion, the distribution shifted to non-DRMs. Accordingly, the CagA-induced hummingbird phenotype and interleukin-8 induction were blocked by cholesterol depletion. Raft-disrupting agents did not influence bacterial adherence but did significantly reduce internalization activity in AGS cells. Together, these results suggest that delivery of CagA into epithelial cells by the bacterial type IV secretion system is mediated in a cholesterol-dependent manner.
 ...
PMID:Cholesterol depletion reduces Helicobacter pylori CagA translocation and CagA-induced responses in AGS cells. 1844 91

Despite the progress in cancer therapeutics and chemotherapy development with the introduction of new drugs, advanced gastric cancer continues to have an extremely poor prognosis and with limited treatment options. The introduction of new antitarget drugs has introduced a new perspective in cancer treatment in general and gastric cancer in particular. Nevertheless, few studies have been developed with this generation of drugs. The monoclonal antibody antiepidermal growth factor receptor (EGFR) cetuximab and the antiangiogenic bevacizumab have been used in phase I and II studies with good results, which need to be confirmed in new phase III studies. The carcinogenesis of this tumor provides information regarding two transcription and signaling pathways of great interest and with therapeutic potential. Infection by Helicobacter pylori is recognized as the cause of gastric cancer development, and there are two elements that play an important role in this process: the CagA gene, whose protein is introduced in the cell by H. pylori initiates the process; and the hedgehog signaling pathway, which regulates the gastric mucosa and is very frequently activated in gastric cancer. Taking action on these agents may be a new and effective method of treating gastric cancer, and therefore must be researched.
 ...
PMID:New drugs in the treatment of gastric tumors. 1849 Feb 41


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