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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection by bacteria, parasites or viruses and tissue inflammation such as gastritis, hepatitis and colitis are recognized risk factors for human cancers at various sites. Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development. A similar mechanism could apply to other suspected and known cancer-causing agents including Helicobacter pylori infection (stomach cancer) or asbestos exposure (lung mesothelioma). Studies on the type of tissue and DNA damage produced by NO and by other reactive oxygen species are shedding new light on the molecular mechanisms by which chronic inflammatory processes may initiate or enhance carcinogenesis in humans.
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PMID:Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. 751 36

Investigation of urinary markers as indices of endogenous nitrosation and of gastric cancer etiology has been a major focus of our work. As part of this effort, studies have been carried out on a Colombian population at high risk for gastric cancer. In this group, nitrosoproline excretion was highly correlated with nitrate excretion in the subpopulation with advanced gastric pathology, but not in control subpopulations with more normal stomachs. Neither urinary 7-methylguanine nor 3-methyladenine was strongly related to gastric pathology or to urinary nitrate or nitrosoproline levels. More recently, as evidence has accumulated concerning the importance of nitric oxide as a cellular messenger, we have begun research toward developing markers for the presence of nitric oxide and for endogenous nitrosation via this compound. Nitric oxide is formed from arginine by activated endothelial cells as a messenger for vasodilation. We have shown that prolonged exercise leads to increased urinary nitrate and that when 15N-arginine is ingested by humans, 15N-nitrate levels increase in 24-hr urine collections. Nitrosohydroxyethylglycine and 3-nitrotyrosine were evaluated as indices for the formation of N-nitrosomorpholine and for the nitration of protein, respectively, under experimental conditions (e.g., immunostimulation) expected to enhance nitric oxide formation. Nitrotyrosine has not proved useful as a biomarker for nitration/nitrosation reactions in immunostimulated rats. Immunostimulation of rats following administration of morpholine led to increases in urinary nitrate and nitrosohydroxyethylglycine. This procedure, however, would not be appropriate for humans due to the toxicity of morpholine and the carcinogenicity of N-nitrosomorpholine.
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PMID:Urinary markers for exposures to alkylating or nitrosating agents. 831 14

Intact Helicobacter pylori cells, as well as cellular components, stimulated nitric oxide (NO) synthesis in an in vitro murine macrophage system by the L-arginine-nitric oxide pathway. Macrophage-mediated NO formation was dependent on the presence of H. pylori and exhibited a dose-dependent increase at H. pylori concentrations between 10(6) and 5 and 10(7) cells/ml. H. pylori mediated NO synthesis also required L-arginine and was inhibited by NG-monomethyl-L-arginine (NMMA), a selective inhibitor of nitric oxide synthase. NO synthesis was induced by whole H. pylori cells. H. pylori media filtrate, extracted membrane proteins, and H. pylori lipopolysaccharide (LPS). Maximal NO synthesis was induced by viable H. pylori cells with media filtrate and membrane protein extracts inducing significant NO responses. NO stimulation by media filtrate and membrane protein extracts support secreted H. pylori products as potential activators of inflammatory cell NO synthesis in vivo. NO synthesis in response to H. pylori suggests that chronic H. pylori infection may increase endogenous formation of NO. Elevated NO exposure may represent an etiologic factor explaining the epidemiologic association between long-term H. pylori infection and gastric cancer.
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PMID:Induction of nitric oxide synthesis in murine macrophages by Helicobacter pylori. 860 78

Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4-12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with beta-carotene (30 mg every day for 4-12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4-12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or beta-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with beta-carotene and ascorbic acid may prevent the formation of these potential carcinogens.
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PMID:Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. 876 15

Helicobacter pylori is a major pathogenic factor in gastritis, ulcer disease and gastric cancer. Helicobacter pylori associated gastritis is of complex pathogenesis which is only partially elucidated. In the present study we investigated by immunohistochemical BSA method the expression of inducible nitric oxide synthase in the gastric wall and in vitro in Helicobacter pylori. In the gastric wall nitric oxide synthase immunoreactivity was found in macrophages, in endothelial cells and in neural elements. In Helicobacter pylori nitric oxide synthase was also expressed. In conclusion, we postulate a possibility of a direct toxic effect of Helicobacter pylori to gastric epithelial cells through the nitric oxide radical.
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PMID:Helicobacter pylori from duodenal ulcer patients expresses inducible nitric oxide synthase immunoreactivity in vivo and in vitro. 877 93

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

A selection of landmark articles for a given year in any subject risks being somewhat subjective, and subjectivity is best avoided in scientific endeavor. However, the very nature of such a selection process invites judgment. Like most judges, I, too, claim to avoid conscious bias, but no one who has ever graced the bench can claim that at the subconscious level personal bias has never crept into a decision. Similarly, deep down in the vault of my subconscious, I love a maverick. That perhaps explains why so many articles that challenge long-held beliefs have especially found favor. Among them are those that question the strength of the association of Helicobacter pylori with gastric cancer, the usefulness of surveillance endoscopy in patients with Barrett's esophagus, a randomized trial that casts doubt on the preeminence of laparoscopic cholecystectomy, and a metaanalysis that concludes that corticosteroids may not be nearly as good for alcoholic hepatitis as we were once told. I have tried to resist the temptation to be too laudatory of technologic advancement, unless the benefit to the patient of such technology has been defined clearly. Thus, of all of the new technologies (endoscopic retrograde choledochopancreatography is no longer a new technology), only endoscopic ultrasonography finds a place. Articles that assess preventive strategies and are in the realm of epidemiology have received mention. All in all, 1996 was not a spectacular year for major therapeutic advances. In contrast, some notable advances have been made in the laboratory, and perhaps the most important has to do with the role of nitric oxide both in the regulation of normal function and in the genesis of disease.
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PMID:Oxides, onions, and other matters gastrointestinal--1996--a perspective. 917 30

Recent progress in the field of infectious diseases involving carcinogenesis has been striking. Extensive studies of Helicobacter pylori, and hepatitis type B and C virus showed that they are the primary cause of gastric cancer and hepatoma, respectively. Also some parasites such as Opistorchis viverrini and Schistosoma haematobium are also putative causes of cholangiocarcinoma and urinary bladder cancer, respectively. All of them require a chronic infection of more than 15 years. More than 50% of Japanese cancers are thus considered to be caused by chronic infection. The classic theory of carcinogenesis is radiation, chemicals and viral infection. Recent studies in free radical and biochemical research in our infectious diseases show all carcinogenesis involves free radical generation such as superoxide (O2.-), nitric oxide (NO), and their adducts peroxynitrite (ONOO-), H2O2 hydrooxyl radical (.OH), HClO, and NO2Cl as well as alkylperoxy radicals. All these molecular species are capable of modifying nucleic acid and DNA or RNA; furthermore a strand break is frequently observed, and hence potent mutagenicity and a probable cause of cancer. Thus, the unifying theory of carcinogenesis may most likely involve the mechanism of free radicals. This means a paradigm shift is needed in the public health policy for the tactics of cancer prevention.
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PMID:[Carcinogenesis via microbial infection]. 972 37

The importance of tumour angiogenesis in the process of tumour growth and progression in solid tumours has been widely accepted. Among many angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a major role in the development and dissemination of the malignant tumours. Nitric oxide (NO) production was also observed in solid tumour tissues. NO has been reported to play an important role for the mitogenic effect of VEGF in the angiogenic process. However, little is known about the correlation between VEGF and NO in circulating levels. Therefore, we investigated serum VEGF and NO concentrations in human gastric cancers as well as healthy individuals, and examined the influence of tumour stage on circulating level of VEGF. The study consisted of 11 healthy individuals and 37 patients with primary gastric cancer who did not receive any prior therapy. Patients were categorized into four groups according to TNM classification. The level of VEGF165 in preoperative sera of gastric cancer patients and healthy donors was assayed using the quantitative sandwich enzyme immunoassay technique. NO concentration was estimated indirectly from serum nitrite. The ANOVA test showed a significant difference in serum VEGF165 concentrations between tumour stages (P < 0.001). A striking relationship was found between serum NO levels and tumour stage (P < 0.001). A significant difference was also seen between healthy individuals and patients with stage 1 disease. The present study suggested that large tumour burden was associated with significantly increased levels of VEGF165 and NO.
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PMID:Serum concentrations of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer. 1040 10

Nitric oxide, a gaseous free radical, is poorly reactive with most biomolecules but highly reactive with other free radicals. Its ability to scavenge peroxyl and other damaging radicals may make it an important antioxidant in vivo, particularly in the cardiovascular system, although this ability has been somewhat eclipsed in the literature by a focus on the toxicity of peroxynitrite, generated by reaction of O2*- with NO* (or of NO- with O2). On balance, experimental and theoretical data support the view that ONOO- can lead to hydroxyl radical (OH*) generation at pH 7.4, but it seems unlikely that OH* contributes much to the cytotoxicity of ONOO-. The cytotoxicity of ONOO- may have been over-emphasized: its formation and rapid reaction with antioxidants may provide a mechanism of using NO* to dispose of excess O2*-, or even of using O2*- to dispose of excess NO*, in order to maintain the correct balance between these radicals in vivo. Injection or instillation of "bolus" ONOO- into animals has produced tissue injury, however, although more experiments generating ONOO- at steady rates in vivo are required. The presence of 3-nitrotyrosine in tissues is still frequently taken as evidence of ONOO- generation in vivo, but abundant evidence now exists to support the view that it is a biomarker of several "reactive nitrogen species". Another under-addressed problem is the reliability of assays used to detect and measure 3-nitrotyrosine in tissues and body fluids: immunostaining results vary between laboratories and simple HPLC methods are susceptible to artefacts. Exposure of biological material to low pH (e.g. during acidic hydrolysis to liberate nitrotyrosine from proteins) or to H2O2 might cause artefactual generation of nitrotyrosine from NO2- in the samples. This may be the origin of some of the very large values for tissue nitrotyrosine levels quoted in the literature. Nitrous acid causes not only tyrosine nitration but also DNA base deamination at low pH: these events are relevant to the human stomach since saliva and many foods are rich in nitrite. Several plant phenolics inhibit nitration and deamination in vitro, an effect that could conceivably contribute to their protective effects against gastric cancer development.
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PMID:Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies. 1063 Jun 88


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