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

Hypertension is the leading risk for premature death in the world. High dietary sodium is an important contributor to increased blood pressure and is strongly associated with other important diseases (e.g., gastric cancer, calcium containing kidney stones, osteoporosis, asthma and obesity). The average dietary sodium intake in Canada is approximately 3400 mg/day. It is estimated that 30% of hypertension, more than 10% of cardiovascular events and 1.4 billion dollars/year in health care expenses are caused by this high level of intake in Canada. Since 2006, Canada has had a focused and evolving effort to reduce dietary sodium based on actions from Non Governmental Organizations (NGO), and Federal and Provincial/Territorial Government actions. NGOs initiated Canadian sodium reduction programs by developing a policy statement outlining the health issue and calling for governmental, NGO and industry action, developing and disseminating an extensive health care professional education program including resources for patient education, developing a public awareness campaign through extensive media releases and publications in the lay press. The Federal Government responded by striking a Intersectoral Sodium Work Group to develop recommendations on how to implement Canada's dietary reference intake values for dietary sodium and by developing timelines and targets for foods to be reduced in sodium, assessing key research gaps with funding for targeted dietary sodium based research, developing plans for public education and for conducting evaluation of the program to reduce dietary sodium. While food regulation is a Federal Government responsibility Provincial and Territorial governments indicated reducing dietary sodium needed to be a priority. Federal and Provincial Ministers of Health have endorsed a target to reduce the average consumption of sodium to 2300 mg/day by 2016 and the Deputy Ministers of Health have tasked a joint committee to review the recommendations of the Sodium Work Group and report back to them.
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PMID:Canadian initiatives to prevent hypertension by reducing dietary sodium. 2225 22

Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori-specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell-driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN(+)HLA-DR(hi)CD80(lo)CD86(lo) phenotype. Mechanistically, the tolerogenic activity of H. pylori-experienced DCs was shown to require IL-18 in vitro and in vivo; DC-derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4(+)CD25(+) Tregs from infected wild-type mice but not Il18(-/-) or Il18r1(-/-) mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18.
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PMID:DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. 2230 23

The genome of the bacterium Helicobacter pylori has evolved over the millennia since its migration out of Africa along with its human host approximately 60,000 years ago. Human migrations, after thousands of years of permanent settlement in those lands, resulted in seven prototypes of genetic populations of H. pylori with distinct geographical distributions. In all continents, present day isolates of H. pylori have molecular markers that reflect population migrations. The colonization of the Americas as well as the slave trade introduced European and African strains to the New World. The relationship between H. pylori genome and gastric cancer rates is linked to the presence of the cagA gene, but the knowledge on this subject is incomplete because other genes may be involved in certain populations. A new situation for Homo sapiens is the absence of H. pylori colonization in certain, mostly affluent, populations, apparently brought about by improved home sanitation and widespread use of antibiotics during the last decades. The disappearance of H. pylori from the human microbiota may be linked to emerging epidemics of esophageal adenocarcinoma, some allergic diseases such as asthma and some autoimmune disorders.
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PMID:Evolutionary History of the Helicobacter pylori Genome: Implications for Gastric Carcinogenesis. 2237 67

Helicobacter pylori infects about 50% of the world's population and inevitably results in the development of gastritis. Of those infected, about 10% develop peptic ulcer disease and roughly 1% develop gastric cancer. Conversely, some take the view that H. pylori infection provides some protection against gastro-esophageal reflux disease and possibly asthma. This review aims to explore the case for and against eradication of the bacterium using a "test and treat" approach amongst the general population.
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PMID:Helicobacter pylori: Eradication or Preservation. 2250 Jan 91

The bacterial pathogen Helicobacter pylori is predominantly known for its tight association with peptic ulcer disease and gastric cancer. However, recent evidence suggests that chronic infection with H. pylori may also be beneficial to the host by conferring protection against allergies, asthma and inflammatory bowel diseases. The protective effects of H. pylori depend on highly suppressive regulatory T-cells. In this addendum, we summarize results showing that H. pylori infection efficiently re-programs dendritic cells (DCs) toward a tolerance-promoting phenotype; their "tolerogenic" activity requires inflammasome activation and the secretion of interleukin-18. H. pylori-experienced DCs fail to induce T-cell effector functions, but efficiently induce FoxP3 expression in naive T-cells in vitro and in vivo. The experimental depletion of DCs breaks tolerance and results in improved infection control, but also in aggravated T-cell-driven immunopathology. In summary, we propose that H. pylori evades adaptive immune responses by re-programming DCs in favor of tolerance over immunity.
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PMID:Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma. 2289 83

Chronic infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high risk of developing gastric and duodenal ulcers, gastric cancer, and gastric lymphoma, but has also recently been shown to protect against certain allergic and chronic inflammatory disorders. The immunomodulatory properties that allow the bacteria to persist for decades in infected individuals in the face of a vigorous, yet ultimately non-protective, innate, and adaptive immune response may at the same time confer protection against allergies, asthma, and inflammatory bowel diseases. Experimental evidence from mouse models suggests that H. pylori has evolved to skew the adaptive immune response toward immune tolerance rather than immunity, which promotes persistent infection on the one hand, and inhibits auto-aggressive and allergic T-cell responses on the other. Regulatory T-cells mediating peripheral immune tolerance have emerged as key cellular players in facilitating persistent infection as well as protection from allergies, in both observational studies in humans and experimental work in mice. Recent data suggest that H. pylori actively targets dendritic cells to promote tolerance induction. The findings discussed in this review raise the possibility of harnessing the immunomodulatory properties of H. pylori for the prevention and treatment of allergic and auto-immune diseases, and also provide new insights relevant for H. pylori-specific vaccine development.
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PMID:The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. 2291 2

Metastable epialleles (MEs) are mammalian genomic loci where epigenetic patterning occurs before gastrulation in a stochastic fashion leading to systematic interindividual variation within one species. Importantly, periconceptual nutritional influences may modulate the establishment of epigenetic changes, such as DNA methylation at MEs. Based on these characteristics, we exploited Infinium HumanMethylation450 BeadChip kits in a 2-tissue parallel screen on peripheral blood leukocyte and colonic mucosal DNA from 10 children without identifiable large intestinal disease. This approach led to the delineation of 1776 CpG sites meeting our criteria for MEs, which associated with 1013 genes. The list of ME candidates exhibited overlaps with recently identified human genes (including CYP2E1 and MGMT, where methylation has been associated with Parkinson disease and glioblastoma, respectively) in which perinatal DNA methylation levels where linked to maternal periconceptual nutrition. One hundred 18 (11.6%) of the ME candidates overlapped with genes where DNA methylation correlated (r > 0.871; p < 0.055) with expression in the colon mucosa of 5 independent control children. Genes involved in homophilic cell adhesion (including cadherin-associated genes) and developmental processes were significantly overrepresented in association with MEs. Additional filtering of gene expression-correlated MEs defined 35 genes, associated with 2 or more CpG sites within a 10 kb genomic region, fulfilling the ME criteria. DNA methylation changes at a number of these genes have been linked to various forms of human disease, including cancers, such as asthma and acute myeloid leukemia (ALOX12), gastric cancer (EBF3), breast cancer (NAV1), colon cancer and acute lymphoid leukemia (KCNK15), Wilms tumor (protocadherin gene cluster; PCDHAs) and colorectal cancer (TCERG1L), suggesting a potential etiologic role for MEs in tumorigenesis and underscoring the possible developmental origins of these malignancies. The presented compendium of ME candidates may accelerate our understanding of the epigenetic origins of common human disorders.
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PMID:Human metastable epiallele candidates link to common disorders. 2332 99

Half of the world's population is infected with Helicobacter pylori and approximately 20% of infected individuals develop overt clinical disease such as ulcers and stomach cancer. Paradoxically, despite its classification as a class I carcinogen, H. pylori has been shown to be protective against development of asthma, allergy, and esophageal disease. Given these conflicting roles for H. pylori, researchers are attempting to define the environmental, host, and pathogen interactions that ultimately result in severe disease in some individuals. From the bacterial perspective, the toxins, CagA and VacA, have each been shown to be polymorphic and to contribute to disease in an allele-dependent manner. Based on the notable advances that have recently been made in the CagA field, herein we review recent studies that have begun to shed light on the role of CagA polymorphism in H. pylori disease. Moreover, we discuss the potential interaction of CagA and VacA as a mediator of gastric disease.
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PMID:Polymorphism in the Helicobacter pylori CagA and VacA toxins and disease. 2338 Jun 46

Matrix Metalloproteinases (MMPs) play an important role in gastric cancer (GC). Accumulated evidence suggests that functional MMP-1 and MMP-7 gene polymorphisms are associated with several tumors. The aim of this study was to investigate two single nucleotide polymorphisms, MMP-1 -1607 1G/2G and MMP-7 -181 A/G, and their potential relationship with GC. We examined 246 GC patients and 252 age-and sex-matched controls from Sichuan province in China. Genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism strategy and DNA sequencing. We also performed a meta-analysis of relevant studies, involving 1084 cases and 1721 controls, to place our findings in a broader context. No significant relationship was observed between the MMP-1 -1607 1G/2G alleles and genotypes and the risk of GC. There were significant differences in the genotypes and allele distributions of the -181 A/G polymorphism of the MMP-7 gene between cases and controls. The -181 A allele carriers had a significantly increased risk of GC compared with -181 G allele carriers (OR=3.051, 95% CI, 1.475-6.310, P=0.002), and the AA genotype of -181 A/G was associated with an increased risk of GC compared with the AG genotype (OR=3.189, 95% CI, 1.523-6.676, P=0.001). A meta-analysis of six studies also showed a significant risk of GC associated with MMP-7 polymorphism.
Iran J Allergy Asthma Immunol 2013 Jul 09
PMID:Genetic polymorphisms in Matrix Metalloproteinases -1 and -7 and susceptibility to gastric cancer: an association study and meta-analysis. 2389 3

Various clinical presentations have been ascribed to Helicobacter (H.) pylori. Most importantly, H. pylori is considered the leading cause of gastric cancer worldwide and because of that, in adult population, it is listed as a number one carcinogen. However, children are less prone to develop H. pylori related serious diseases such as peptic ulcer disease (PUD) and cases of malignancy are only sporadically reported. On the other hand, there is an increasing level of evidence suggesting that H. pylori in children could also have a beneficial effect. Recently, several data confirmed previously described inverse relationship of H. pylori infection and gastroesophageal reflux disease. Furthermore, it has been hypothesized that an increased prevalence of allergic diseases could be, at least partially, explained by the decreased incidence of H. pylori infection. H. pylori can, to some degree, influence immunological response. It has an ability to promote high proinflammatory cytokine expression in the gastric mucosa shifting immunity towards Th1 response, which could be a plausible explanation for the down-regulated clinical expression of allergies (including asthma) in patients with H. pylori gastritis. Based on these findings the aim of this review is to present "pros and cons" for H. pylori eradication in children.
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PMID:Is Helicobacter pylori always a "bad guy"? 2418 Apr 9


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