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)

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the the role of NO in the human lower esophageal sphincter (LES), enteric nerve responses in lower esophageal tissue specimens obtained from patients with esophageal cancer (n = 7) and patients with gastric cancer (n = 6) were investigated. A mechanographic technique was used to evaluate in vitro LES muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including NG-nitro-L-arginine (L-NNA) and L-arginine. Findings were: (1) Cholinergic nerves were those mainly involved in the regulation of enteric- nerve responses to EFS in the steady state, and NANC inhibitory nerves acted on the LES; (2) L-NNA concentration-dependently inhibited the relaxation in response to EFS in the LES; and (3) this inhibitory effect in the LES was reversed by L-arginine. These findings suggest that cholinergic and NANC inhibitory nerves play important roles in regulating contraction and relaxation of the human LES, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human LES.
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PMID:Relationship between nitric oxide and non-adrenergic non-cholinergic inhibitory nerves in human lower esophageal sphincter. 905 87

Helicobacter pylori can utilise amino acids as the sole carbon energy source. The present study demonstrated that H. pylori grown in continuous culture in a defined medium containing glucose and amino acids utilised alanine, arginine, asparagine, aspartate, glutamine, glutamate, proline and serine. Specific asparaginase and glutaminase enzymes deaminated asparagine and glutamine respectively to aspartate and glutamate, with the production of ammonia. The glutaminase activity was inhibited by 6-diazo-5-oxo-L-norleucine. All the 13 strains of H. pylori tested produced both glutaminase and asparaginase activities. Glutamine is important in the health of the gastric and intestinal mucosa and is a primary energy source for lymphocytes. Depletion of glutamine at the site of H. pylori infection may be of significance in the pathogenesis of H. pylori-associated diseases such as peptic ulcer and gastric cancer.
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PMID:Amino acid utilisation and deamination of glutamine and asparagine by Helicobacter pylori. 929 92

The paper presents the results of study on polymorfisms of xenobiotic biotransformation enzymes (CYP1A1, glutathione S-transferase MI and N-acetyltransferase 2) and p53 tumor suppressor protein in patients with lung, stomach and intestine cancer. The frequency of CYP1A1-Val allele in all studied cancer groups was 3 to 5 times higher than in healthy control group. The carriers of homozygous glutathione S-transferase M1 gene deletion and slow acetylator phenotype were also of higher lung cancer risk. The substantial increase in slow acetylator phenotype frequency was shown also in the group of intestine cancer patients. The p53 Arg/Pro polymorphism study revealed the elevated frequency of Arg allele in lung and stomach cancer groups. The risk of lung cancer for the carriers of susceptible alleles depended on the age and smoking status of the patients. The results testify to a high possibility of studied polymorphic genes to be the markers of susceptibility to oncopathologies.
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PMID:[Genes and enzymes of the xenobiotic-metabolizing system in cancer pathology]. 944 23

DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh8Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser326 vs. hOGG1-Cys326) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys326 allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.
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PMID:Infrequent mutations of the hOGG1 gene, that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer. 976 18

We have isolated a gene from stomach fibroblasts encoding novel proteins containing two follistatin modules which might bind TGF-beta-related growth factors and a single epidermal growth factor (EGF)-like domain which is closely related to EGF/Neuregulin (NRG) family growth factors. Sequence analysis revealed novel cDNA clones, the protein products of which were designated tomoregulin (TR) and consisted of at least three isoforms which were distinguished by their cytoplasmic domains. The cytoplasmic domains in all isoforms were short and contained potential G-protein activating motifs. Precursors of TR (Pro-TR) are glycosylated transmembrane proteins. Two secreted soluble forms resulting from proteolytic cleavage were distinguished by the presence or absence of the EGF-like domain. The EGF-like domain of TR was highly conserved compared to EGF/NRG family growth factors with the exception of an arginine to histidine substitution at position 39 (Arg --> His 39). Soluble TR stimulated erbB-4 tyrosine phosphorylation in MKN 28 gastric cancer cells, although it was weak compared to neuregulin-induced erbB-4 tyrosine phosphorylation; this suggests that TR might be a ligand for erbB-4- or erbB-4-related receptor tyrosine kinase. TR may have important roles in normal development of middle to late stages of embryos and maintenance of adult central nervous system tissues as high expression of TR mRNAs was observed in these tissues. The modular features suggest multiple roles for TR; these include functioning as a ligand for erbB- receptor, a regulator of TGF-beta-related growth factor signaling by direct interaction through the follistatin modules, and a G-protein-coupled receptor.
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PMID:A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells. 1060 May 48

p53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the p53 codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis (H. pylori-CG). We, therefore, examined the polymorphism in 117 gastric cancer patients (72 intestinal type and 45 diffuse type) with H. pylori-CG and 116 H. pylori-CG patients without gastric cancer as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to analyze the p53 codon 72 polymorphism. The crude genotypic frequencies in the gastric cancer patients were similar to those of the controls. However, when gastric cancers were classified by histologic subtype, the Pro/Pro was more frequent in the patients with diffuse type gastric cancer than in the controls (22.2% of cases vs. 12.1% of controls). The Pro/Pro genotype was associated with a 2.98-fold higher risk of diffuse-type cancer compared to the Arg/Arg genotype (95% confidence interval [CI] 1.07-8.32, p = 0.038). These results suggest that the Pro/Pro genotype at p53 codon 72 contributes to susceptibility for diffuse-type gastric cancer in patients with H. pylori-CG. The p53 codon 72 polymorphism may serve as the genetic marker for the risk assessment of the diffuse-type gastric cancer development in patients with H. pylori-CG.
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PMID:p53 Codon 72 polymorphism in gastric cancer susceptibility in patients with Helicobacter pylori-associated chronic gastritis. 1211 45

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.
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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

The p53 gene plays an important role in cell cycle control in response to DNA damage, which may increase the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg right curved arrow Pro polymorphism has been suggested to be associated with risk for different kind of cancers, but the data on gastric cancer (GC) is very limited. To evaluate the association between this polymorphism and risk of GC, we performed genotype analysis by using a polymerase chain reaction-based restriction fragment length polymorphism assay in a population-based case-control study of 324 GC patients and 317 cancer-free controls in a Chinese population. The controls were frequency-matched to the cases by age, sex and smoking status. The frequency of the p53 Arg allele was 57.4% in the cases and 54.9% in the controls, and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 29.6%, 55.6%, and 14.8%, respectively, in the cases, and 29.6%, 50.5%, and 19.9%, respectively, in the controls (p=0.207). Logistic regression analysis revealed that the p53 Arg allele (Arg/Pro and Arg/Arg genotype) was associated with a borderline significantly increased risk of gastric cancer (adjusted OR=1.44, 95% CI=0.95-2.18), particularly non-cardia gastric cancer (adjusted OR=1.67, 95% CI=1.00-2.77), compared with p53 homozygous Pro allele (Pro/Pro genotype), and the risk was significantly more evident among alcohol drinkers (adjusted OR=2.85, 95% CI=1.37-5.95). While the results suggest that the p53 codon 72 polymorphism may contribute to gastric cancer susceptibility, further larger studies are needed to substantiate our findings and to explore a possible interaction between p53 codon 72 polymorphism and alcohol in the etiology of gastric cancer.
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PMID:P53 codon 72 polymorphism and risk of gastric cancer in a Chinese population. 1506 55

Gastric ulcer is positively, and duodenal ulcer negatively, associated with the risk of gastric cancer. The relationship between a common p53 polymorphism at codon 72 and gastric cancer risk in patients with gastric and duodenal ulcer was examined in 397 Caucasian patients using PCR-RFLP. Noncardiac cancer patients had a distribution pattern of codon 72 genotypes similar to that of other non-cancer patient groups, though the frequency of the Pro/Pro genotype looks higher in duodenal ulcer. However, patients with cancer of the cardiac region had a significantly higher frequency of the Arg/Arg genotype than patients with chronic gastritis, duodenal ulcer, and noncardiac cancer. There was no significant difference in the distribution patterns between gastric ulcer and noncardiac or cardiac cancer or between gastric and duodenal ulcer. These findings may be a reflection of differences in the interaction between p53 codon 72 polymorphism and local factors in the stomach.
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PMID:A comparison study of gastric cancer risk in patients with duodenal and gastric ulcer: roles of gastric mucosal histology and p53 codon 72 polymorphism. 1510 66

Helicobacter pylori infects approximately half the human population. The outcomes of the infection range from gastritis to gastric cancer and appear to be associated with the immunity to H. pylori. Patients developing nonatrophic gastritis present a Th1 response without developing protective immunity, suggesting that this bacterium may have mechanisms to evade the immune response of the host. Several H. pylori proteins can impair macrophage and T cell function in vitro through mechanisms that are poorly understood. We tested the effect of H. pylori extracts and live H. pylori on Jurkat cells and freshly isolated human normal T lymphocytes to identify possible mechanisms by which the bacteria might impair T cell function. Jurkat cells or activated T lymphocytes cultured with an H. pylori sonicate had a reduced proliferation that was not caused by T cell apoptosis or impairment in the early T cell signaling events. Instead, both the H. pylori sonicate and live H. pylori induced a decreased expression of the CD3zeta-chain of the TCR. Coculture of live H. pylori with T cells demonstrated that the wild-type strain, but not the arginase mutant rocF(-), depleted L-arginine and caused a decrease in CD3zeta expression. Furthermore, arginase inhibitors reversed these events. These results suggest that H. pylori arginase is not only important for urea production, but may also impair T cell function during infection.
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PMID:Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta). 1521 Aug 20


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