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)

Gastric cancer is the commonest malignant neoplasm in Southwest Korea. The possibility of carcinogenic dietary factors led to the investigation of exposure to N-nitroso compound precursors among residents of the City of Chonju and of two outlying rural townships in North Cholla Province. Two traditional and widely consumed home-prepared food products, salted pickled cabbage (kimchi) and salted seafood sauce (chut-kal) were analysed (a) for nitrite, nitrate, total secondary amines and pH in these food products prior to nitrite incubation and (b) for volatile nitrosamines and total N-nitroso compounds before and after incubation with nitrite in simulated human stomach conditions. Nitrate levels were significantly higher in kimchi (median 1550 mg/kg) than in chut-kal (median 140 mg/kg) (P < 0.001). Secondary amine levels in non-nitrosated samples of kimchi (median 5.5 mg/kg) were significantly lower than secondary amine levels in non-nitrosated chut-kal (median 56 mg/kg) (P = < 0.001). Analyses of nitrite-incubated kimchi revealed high levels of total N-nitroso compounds (median 1173 micrograms/kg); the increase with nitrosation was significant (P = 0.001). The concentration of N-nitroso compounds in nitrite-incubated kimchi was significantly greater than that found in nitrite-incubated chut-kal (P = 0.015). The combination of high levels of nitrate in the kimchi, the demonstration of high levels of total N-nitroso compounds in this food after nitrosation, and the volume of kimchi consumed in the traditional diet suggest that salted pickled cabbage may play a role in gastric carcinogenesis in Southwest Korea.
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PMID:N-nitroso compounds in two nitrosated food products in southwest Korea. 781 83

Gastric cancer is the world's overall second most common cancer, and carries a bad prognosis. In the Correa model of gastric carcinogenesis, environmental factors (salt, nitrate, a lack of vitamin C and beta-carotene, bile reflux, bacterial overgrowth in atrophic gastritis with nitrosamine formation) are related to the evolution from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma. The incidence of H. pylori decreases with progressing preneoplastic lesions. In several studies, the prevalence of H. pylori was elevated in patients with gastric cancer, with a trend for a higher prevalence in intestinal type gastric cancer vs diffuse type. Family members of patients with gastric adenocarcinoma have a higher H. pylori prevalence than controls; patients infected with H. pylori have more family members with gastric cancer. Several epidemiological studies showed a higher H. pylori prevalence in regions or populations with high gastric cancer risk vs low-risk populations. Large-scale studies in China and Europe showed a correlation between H. pylori seroprevalence and gastric cancer incidence and mortality. Three prospective nested case-control studies showed that infection with H. pylori increased the risk of further development of gastric adenocarcinoma, showing that H. pylori infection precedes the development of gastric cancer. Several pathways can be identified explaining the association between H. pylori and gastric adenocarcinoma. We showed that gastric cell proliferation is increased in parallel with inflammation. The ascorbic acid concentrating mechanism is abolished in gastritis. Ammonia, generated by H. pylori's urease, gives rise to gastric mucosal atrophy. We showed that salt increases the gastric cell proliferation only in H. pylori-infected individuals. The organism's toxin may play a role in gastric cancer. Besides H. pylori, other environmental factors are important in determining the gastric cancer risk. For instance, we showed that in Belgium, Maghreb immigrants have a high prevalence of H. pylori infection but a low prevalence of intestinal metaplasia and gastric cancer. Gastric lymphoma is rare (about 5% of all gastric tumours), but its incidence is steadily increasing. It was shown that H. pylori also increases the risk for low-grade as well as high-grade gastric lymphoma. Eradication of H. pylori has been shown to cure several cases of unequivocally proven gastric low-grade lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Helicobacter pylori: the link with gastric cancer. 806 90

Nitrogen compounds occur in excess in the air, water, soil and food, which unfavourably affects human's health, causing a number of diseases. Toxic effect of nitrates and nitrites ought to be mentioned here in the first place. Nitrates and nitrites cause intoxications, specially of infants and of children, manifesting themselves by methemoglobinemia, anaemia and decreased content of vitamin A in the liver. Besides, nitrates and nitrites participate in the formation of strong nitrogen carcinogenic compounds, which may lead to stomach cancer. Due to big harmfulness of nitrogen compounds one should strive after lowering, minimizing their presence in the environment.
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PMID:[Nitrogen compounds and their role in the contamination of the environment]. 853 51

The mutagenic activity of glycine upon nitrosation was studied in the Ames tester strains TA98, TA100, TA102, and TA104. The results obtained show that glycine at acidic pH values and in the presence of Cl- can react with nitrite giving rise to genotoxic compounds to the tester strains used. When these experiments were carried out in the presence of gastric juice the genotoxicity observed was associated with the Cl- concentration in the different gastric juice samples. The nature and the mechanism of genetic lesion induced by the ultimate genotoxicant arising from the nitrosation of glycine are not fully understood. Primary amines (e.g., amino acids) have been described as potential alkylating agents after nitrosation. However, in our experimental conditions these alkylating activities were not detected, suggesting that other mechanisms could be involved in the genetic lesion induced by nitrosated glycine. The influence of Cl- in the genotoxic activity of glycine and other primary amines upon nitrosation and its possible involvement in the etiology of gastric cancer are discussed.
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PMID:Mutagenic activity of glycine upon nitrosation in the presence of chloride and human gastric juice: a possible role in gastric carcinogenesis. 912 93

To create cytotoxic hybrid analogs of somatostatin (SST), octapeptides RC-160 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Trp-NH2) and RC-121 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Thr-NH2) were linked to doxorubicin (DOX) or its superactive derivative, 2-pyrrolino-DOX (AN-201). The conjugation was performed by coupling N-9-fluorenylmethoxycarbonyl (N-Fmoc)-DOX-14-O-hemiglutarate or 2-pyrrolino-DOX-14-O-hemiglutarate to the amino terminus of [Lys(Fmoc)5]RC-160 yielding AN-163 and AN-258, respectively, after deprotection. The respective cytotoxic conjugates of RC-121 (AN-162 and AN-238) were prepared similarly. In vitro tests on human cancer cell lines-MKN-45 gastric cancer, MDA-MB-231 breast cancer, PC-3 prostate cancer, and MIA PaCa-2 pancreatic cancer-demonstrated that the antiproliferative activity of the cytotoxic radicals in these conjugates was virtually retained. In H-345 human small cell lung carcinoma cell line, conjugates of RC-121 preserved the cytotoxic activity of their radicals, but the hybrids with RC-160 showed approximately 10 times lower activity. The ability of the carriers and the hybrids to inhibit the binding of 125I-labeled RC-160 to receptors for SST on rat pituitary membrane preparation was also determined. The cytotoxic conjugates inhibited 50% of the specific binding of the radioligand in the nanomolar concentration range (IC50 < 80 nM). When SST-like activities of AN-238 and its carrier, RC-121, were compared in the rat pituitary superfusion system, both compounds were found to suppress a stimulated growth hormone release at nanomolar concentrations. Preliminary studies in animal models of breast and prostate cancers showed that AN-238 is less toxic than AN-201 and more potent in inhibiting tumor growth. These highly active cytotoxic analogs of SST have been designed as targeted antitumor agents for the treatment of various cancers expressing receptors for SST octapeptides.
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PMID:Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin. 946 96

Many putative virulence determinants of Helicobacter pylori are believed to trigger and worsen the gastroduodenal mucosa damage observed in infected patients. H. pylori urease reacts with the gastric urea and generates ammonia; ammonia combines with water and yields ammonium hydroxide, which is cytotoxic. Ammonia may also inhibit cell proliferation and cause indirect mucosal injury by stimulating neutrophils. Phospholipases may damage the gastric mucosa by degrading phospholipids and generating precursors of ulcerogenic components. Other enzymes, such as protease, neuraminidase, fucosidase, and alcohol dehydrogenase, can contribute to damage of the gastric epithelium by destroying the integrity of mucus or by inducing lipid peroxidation. Infection by vacuolating cytotoxic (VacA+) H. pylori strains is considered to constitute increased risk for development of peptic ulcer and gastric cancer. Exploration of the vacA gene structure has shown the existence of strongly toxigenic strains, and has confirmed at the molecular level the increased ulcerogenic potential of VacA+ H. pylori strains. A pathogenicity island called cag has been recently described in Type 1 H. pylori strains (VacA+/CagA+).cag contains the cagA gene (whose expression is associated with toxigenicity) and many genes, some of which are highly homologous to virulence genes of other virulent bacteria, that account for the enhanced pathogenic potential of CagA+ organisms.
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PMID:Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration. 947 42

Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.
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PMID:Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. 953 64

Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, Tcf, and E-cad defects in gastrointestinal cancers, we assessed gastric and pancreatic cancers for constitutive Tcf transcriptional activity (CTTA). Two of four gastric and two of eight pancreatic cancer lines showed CTTA. One gastric and one pancreatic cancer had mutations in the NH2-terminal phosphorylation sites of beta-cat. The other gastric cancer with CTTA had a missense mutation at serine 28 of gamma-cat, a potential phosphorylation site in this beta-cat-related protein. Although E-cad is an important binding partner for beta-cat and gamma-cat, E-cad inactivation did not result in CTTA. The beta-cat and gamma-cat mutant proteins identified in our studies strongly activated Tcf transcription in vitro, whereas beta-cat mutant proteins with large NH2-terminal deletions had only modest effects on Tcf. Our results suggest a role for Tcf deregulation in gastric and pancreatic cancer, resulting from beta-cat and gamma-cat mutations in some cases and, in others, from yet to be defined defects. Furthermore, these data imply that the consequences of APC and beta-cat mutations are distinct from the effects of E-cad inactivation.
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PMID:Beta- and gamma-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. 1039 98

Mouse Nkd is a Dishevelled-binding protein, functioning as a negative regulator of WNT - beta-catenin - TCF signaling pathway. Here, human NKD1 and NKD2 were cloned and characterized. NKD1 and NKD2 were predicted to encode 470- and 451-amino-acid polypeptide, respectively. NKD1 and NKD2, showing 43.8% total amino-acid identity, were more homologous in the NH1, NH2, NH3, and NH4 domains. The NH2 domain of NKD1 and NKD2 contained the EF-hand motif. Exon-intron structures of NKD1 and NKD2 genes, consisting of 10 exons, were well conserved. NKD1 was highly expressed in fetal kidney, while NKD2 was moderately expressed in fetal kidney, lung, and adult lung. NKD1 was up-regulated in colorectal cancer cell line SW480, gastric cancer cell line TMK1, and pancreatic cancer cell line Hs700T. NKD2 was up-regulated in gastric cancer cell line MKN45, pancreatic cancer cell line BxPC-3, and esophageal cancer cell lines TE6, and TE13. NKD1 and NKD2 were up-regulated together in 1 case of primary gastric cancer out of 10 cases, and were down-regulated together in 2 cases. Up-regulation of NKD1 or NKD2 might be due to a negative feed-back mechanism. Alternatively, genetic alteration of NKD1 or NKD2 might lead to activation of the WNT - beta-catenin - TCF signaling pathway.
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PMID:Molecular cloning, gene structure, and expression analyses of NKD1 and NKD2. 1160 95

AIM:To further investigate the effect of cyclin D1 on the biologic behavior of cancer cells and its potential role in gene therapy of tumor.METHODS:A cyclin D1 subcloning plasmid termed BKSD1 was constructed by subcloning the human cyclin D1 cDNA into Bluescript-KS, a plasmid vector with a pair of T7 and T3 promoters, with recombinant DNA technology of molecular biology. So,it is easy to generate digoxigenin (DIG)-labeled RNA probes of antisense and sense to cyclin D1 using RKSD1 as a template vector. PDORD1AS, an eukaryotic expression vector containing the full-length human cyclin D1 cDNA in its antisense orientation cloned into the retroviral vector pDOR-neo, was successfully constructed with BKSD1 to change restriction sites. A gastric cancer cell line, SGC7901/VCR, was transfected with pDORD1AS by Lipofect Amine-mediated introduction and a subline termed SGC7901/VCRD1AS, which had stable overexpression of antisense RNA to cyclin D1, was obtained by selection in G418. The subline, control subline transfected pDOR-neo and SGC7901/VCR were evaluated by methods of immunohistochemistry, flow cytometry, molecular hybridization, morphology and cell biology.RESULTS:Compared with control cell lines, SGC7901/VCRD1AS had a reduced expression of cyclin D1 (inhibition rate was about 36%), increased cell size and cytoplasm to nucleus ratio, increased doubling time (42.2h to 26.8h and 26.4h), decreased saturation density (18.9X10(4) to 4.8X10(5) and 4.8X10(5)), increased percentage of cells in the G(1)/G(0) phase (80.9%-64.6% and 63.8%), reacquired serum dependence, and a loss of tumorigenicity in nude mice (0/4 to 4/4 and 4/4).CONCLUSION: Stable overexpression of antisense RNA to cyclin D1 can reverse the transformed phenotype of human gastric cancer cells and may provide an approach of gene therapy for gastric cancer.
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PMID:Antisense to cyclin D1 reverses the transformed phenotype of human gastric cancer cells. 1181 76


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