Sample records for gastric antisecretory activity

  1. Role of antisecretory agents for gastric endoscopic submucosal dissection.

    PubMed

    Fujishiro, Mitsuhiro; Chiu, Philip W Y; Wang, Hsui-Po

    2013-03-01

    Gastric endoscopic submucosal dissection (ESD) causes artificial gastric ulcers and there is no consensus regarding the optimal perioperative management in terms of prevention of intra- or postoperative bleeding and promotion of healing. Traditionally, 8-week administration of proton pump inhibitors (PPI) and mucosal protective agents were used in the same way as for peptic ulcer management. However, recent studies have revealed that prior use of PPI might reduce intraoperative bleeding or early-phase postoperative bleeding, and combination of histamine-2 receptor antagonist (H2RA), and second-look endoscopy might have a similar effect on postoperative bleeding to PPI. Additionally, the advantage of PPI over H2RA is not proven and the optimal duration of PPI may be shortened until 2 weeks when the deteriorating factors for ESD ulcer are excluded. Furthermore, mucosal protective agents may facilitate ulcer healing. Further studies are needed to determine the optimal treatment protocol before and after ESD for both prevention of bleeding complication and promotion of ulcer healing, by using available antisecretory agents and mucosal protective agents. PMID:23368844

  2. Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats.

    PubMed

    Sibilia, Valeria; Pagani, Francesca; Bulgarelli, Ilaria; Tulipano, Giovanni; Possenti, Roberta; Guidobono, Francesca

    2012-04-01

    TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg, intraperitoneally) TLQP-21 administration on gastric acid secretion in pylorus-ligated rats. The mechanisms involved in such activity were also examined. Central TLQP-21 injection significantly reduced gastric acid volume and dose-dependently inhibited total acid output (ED(50) = 2.71 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 antisecretory activity was prevented by cysteamine (300 mg/kg, subcutaneously), a depletor of somatostatin, by indomethacin (0.25 mg/rat, intracerebroventricularly), a non-selective cyclooxygenase inhibitor, and by functional ablation of sensory nerves by capsaicin. We conclude that TLQP-21 could be considered a new member of the large group of regulatory peptides affecting gastric acid secretion. The central inhibitory effect of TLQP-21 on gastric acid secretion is mediated by endogenous somatostatin and prostaglandins and requires the integrity of sensory nerve fibres. PMID:21132337

  3. Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.

    PubMed

    Singh, Rohit; Mishra, Vaibhav; Pandeti, Sukanya; Palit, Gautam; Barthwal, Manoj K; Pandey, Haushila Prasad; Narender, Tadigoppula

    2015-06-01

    Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in-vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25851068

  4. A mini review on biological activities of pyridazinone derivatives as antiulcer, antisecretory, antihistamine and particularly against histamine H3R.

    PubMed

    Asif, Mohammad

    2015-01-01

    Pyridazinone derivatives and their related analoges were introduced for gastric antiulcer and antisecretory activities. Selected compounds were applied to ulcer models and showed their antiulcer and anti secretary activities. Some pyridazinone compounds are recently reported as H3R antagonists. Some amine analogs of pyridazinones, pyridazinone- phenethylamines and 4,5-fused pyridazinones showed histamine H3R antagonist activity with significant affinity for rat and human H3R. These pyridazinone analogs also showed excellent selectivity and metabolic stability, with adequate pharmacokinetics. PMID:25429662

  5. Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers.

    PubMed

    Singh, Vinay Kumar; Mishra, Vaibhav; Tiwari, Sriniwas; Khaliq, Tanvir; Barthwal, Manoj Kumar; Pandey, Haushila Prasad; Palit, Gautam; Narender, Tadigoppula

    2013-10-15

    Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47?g/ml as compared to the IC50 value of omeprazole (30.24?g/ml) confirming its anti-secretory activity. PMID:23880327

  6. Evaluation of the gastric antiulcer activity of fixed oil of Ocimum sanctum (Holy Basil).

    PubMed

    Singh, S; Majumdar, D K

    1999-04-01

    The fixed oil of Ocimum sanctum L. (Labiatae) was found to possess significant antiulcer activity against aspirin-, indomethacin-, alcohol-, histamine-, reserpine-, serotonin- and stress-induced ulceration in experimental animal models. Significant inhibition was also observed in gastric secretion and aspirin-induced gastric ulceration in pylorus ligated rats. The lipoxygenase inhibitory, histamine antagonistic and antisecretory effects of the oil could probably have contributed towards antiulcer activity. O. sanctum fixed oil may be considered to be a drug of natural origin which possesses both anti-inflammatory and antiulcer activity. PMID:10350365

  7. An Experimental Study and a Randomized, Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Antisecretory Activity of Lactobacillus acidophilus Strain LB Against Nonrotavirus Diarrhea

    Microsoft Academic Search

    Vanessa Lievin-Le Moal; Luis E. Sarrazin-Davila; Alain L. Servin

    OBJECTIVE.Previous studies have shown that selected strains of Lactobacillus have the capacity to antagonize rotavirus-induced diarrhea. However, only a few reports have documented their efficacy against nonrotavirus diarrhea. This study involved an experimental investigation and a clinical trial of the antisecretory activity of Lactobacillus acidophilus strain LB in the context of nonrotavirus diarrhea. METHODS.The activity of a culture of L

  8. Tetrahydrochromenoimidazoles as potassium-competitive acid blockers (P-CABs): structure-activity relationship of their antisecretory properties and their affinity toward the hERG channel.

    PubMed

    Palmer, Andreas M; Chiesa, Vittoria; Schmid, Anja; Münch, Gabriela; Grobbel, Burkhard; Zimmermann, Peter J; Brehm, Christof; Buhr, Wilm; Simon, Wolfgang-Alexander; Kromer, Wolfgang; Postius, Stefan; Volz, Jürgen; Hess, Dietmar

    2010-05-13

    Potassium-competitive acid blockers (P-CABs) constitute a new therapeutic option for the treatment of acid-related diseases that are widespread and constitute a significant economical burden. Enantiomerically pure tetrahydrochromenoimidazoles were prepared using the readily available candidate 4 (BYK 405879) as starting material or the Noyori asymmetric reduction of ketones as key reaction. A comprehensive SAR regarding the influence of the 5-carboxamide and the 8-aryl residue on in vitro activity, acid-suppression in the Ghosh Schild rat, and affinity toward the hERG channel was established. In addition, efficacy and duration of the antisecretory action was examined for the most promising target compounds by 24 h pH-metry in the fistula dog and a significantly different SAR was observed as compared to the Ghosh Schild rat. Several tetrahydrochromenoimidazoles were identified that possessed a comparable profile as the candidate 4. PMID:20380432

  9. Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication)

    Microsoft Academic Search

    Martin J. Collen; Valerie J. Stanczak; Cecelia A. Ciarleglio

    1989-01-01

    To evaluate possible differences between patients with refractory duodenal ulcers and those with duodenal ulcers that respond to standard doses of antisecretory medications, we determined basal acid outputs by nasogastric suction and daily smoking histories in 75 patients with endoscopically documented active duodenal ulcers. Patients were treated for at least eight weeks with standard doses of antisecretory medications and endoscopic

  10. Gastric myoelectrical activity in patients with cervical spinal cord injury

    Microsoft Academic Search

    Ching-Liang Lu; Pam Montgomery; Xiaoping Zou; William C Orr; J D Z Chen; F. A. C. G

    1998-01-01

    Objective:Dyspeptic symptoms are common in patients with cervical spinal cord injury (SCI). The supraspinal control of sympathetic innervation to the stomach is interrupted in these patients. Gastric emptying has been reported to be delayed in some patients with cervical SCI. Gastric myoelectrical activity is known to regulate gastric motility and is correlated with gastric emptying. The change in gastric myoelectrical

  11. The gastric acid conundrum in peptic ulcer.

    PubMed

    Dobrilla, G; Steele, A; Comberlato, M; Amplatz, S

    1990-06-01

    According to the traditional view, gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanism of action antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents-thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing, yield contradictory clinical results; morning and bedtime single administration of H2-antagonists prove equiactive on ulcer healing, leading to a appraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby reapparently under-mining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the proton-pump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility. PMID:2131944

  12. Hydrogen potassium adenosine triphosphatase activity inhibition and downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum burmannii in gastric parietal cells

    PubMed Central

    Tjandrawinata, Raymond R; Nailufar, Florensia; Arifin, Poppy F

    2013-01-01

    This study assessed the gastric acid antisecretory effect of DLBS2411 fractionated from Cinnamomum burmannii. Hydrogen potassium adenosine triphosphatase (H+/K+ ATPase) activity and its gene expression were observed, and the antioxidant activity of DLBS2411 was also investigated. Treatment of DLBS2411 decreased the level of H+/K+ ATPase messenger RNA expression on human embryonic kidney 293 cells and rat gastric parietal cells in a dose-dependent manner, in vitro and ex vivo. DLBS2411 also acted as a competitive inhibitor by showing inhibition in gastric H+/K+ ATPase activity at various pHs. In gastric ulcer animal models induced with indomethacin and ethanol, DLBS2411showed a reduction in the number of petechiae, suggesting that the fraction also confers gastroprotective activity. Moreover, DLBS2411 was also found to have potent antioxidant activity. Taken together, DLBS2411 is a promising novel agent for the management of dyspepsia, a condition of hyperacidity and diseases in the stomach requiring gastroprotection. PMID:24101879

  13. Involvement of the opioid system in the central antisecretory action of alpha-2 adrenoceptor agonists in rat.

    PubMed

    Müllner, K; Gyires, K; Furst, S

    2001-01-01

    The aim of the present study was to analyse the role of the central alpha-2 adrenoceptors in the regulation of gastric acid secretion in pylorus ligated rats. It was found that the intracerebroventricularly (icv.) injected presynaptic alpha-2 adrenoceptor agonist clonidine and the alpha-2A adrenoceptor subtype selective stimulant oxymetazoline exerted a dose dependent inhibition on gastric acid secretion. The antisecretory ED(50) values for clonidine and oxymetazoline were 20 and 7.5 nmol/rat icv., respectively. The antisecretory effect of these compounds was antagonised by the presynaptic adrenoceptor antagonist yohimbine (50 nmol/rat icv.) indicating that the action is mediated through central presynaptic alpha-2 adrenoceptors. Moreover, naloxone (50 nmol/rat icv.)--non-selective opioid antagonist--and naltrindole (0.5 nmol/rat icv.)--delta-opioid receptor selective antagonist--also decreased the antisecretory effect of clonidine and oxymetazoline suggesting that the endogenous opioid system is likely to be involved in the central antisecretory action of alpha-2 adrenoceptor stimulants. PMID:11595439

  14. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity.

    PubMed

    Al-Said, M S; Ageel, A M; Parmar, N S; Tariq, M

    1986-03-01

    The effect of mastic, a concrete resinous exudate obtained from the stem of the tree Pistacia lentiscus, has been studied on experimentally-induced gastric and duodenal ulcers in rats. Mastic at an oral dose of 500 mg/kg produced a significant reduction in the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint + cold stress. It produced a significant decrease of free acidity in 6-h pylorus-ligated rats and a marked cytoprotective effect against 50% ethanol in rats which could be reversed by prior treatment with indomethacin. The protective effect was not seen when it was given intraperitoneally in phenylbutazone and restraint + cold stress models. The reduction in the intensity of ulceration in cysteamine-induced duodenal ulcers was not found to be statistically significant in mastic-pretreated rats. The results suggest that mild antisecretory and a localized adaptive cytoprotectant action may be responsible for its anti-ulcer activity. These observations support the results of an earlier study on the clinical effectiveness of mastic in the therapy of duodenal ulcer. PMID:3724207

  15. Magnetogastrographic detection of gastric electrical response activity in humans

    Microsoft Academic Search

    Andrei Irimia; William O Richards; L Alan Bradshaw

    2006-01-01

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is

  16. Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats

    SciTech Connect

    Tariq, M.; Parmar, N.S.; Ageel, A.M.

    1987-05-01

    Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

  17. Changes in gastric myoelectric activity during space flight

    NASA Technical Reports Server (NTRS)

    Harm, Deborah L.; Sandoz, Gwenn R.; Stern, Robert M.

    2002-01-01

    The purpose of the present study was to examine postprandial myoelectric activity of the stomach and gastric activity associated with space motion sickness using electrogastrography. Three crewmembers participated in this investigation. Preflight, subjects exhibited normal postprandial responses to the ingestion of a meal. Inflight, crewmembers exhibited an abnormal decrease in the power of the normal gastric slow wave after eating on flight day 1, but had a normal postprandial response by flight day 3. Prior to and during episodes of nausea and vomiting, the electrical activity of the stomach became dysrhythmic with 60-80% of the spectral power in the bradygastric and tachygastric frequency ranges. These findings indicate that gastric motility may be decreased during the first few days of space flight. In addition, changes in the frequency of the gastric slow wave associated with space motion sickness symptoms are consistent with those reported for laboratory-induced motion sickness.

  18. Gastric mesenchymal myofibroblasts maintain stem cell activity and proliferation of murine gastric epithelium in vitro.

    PubMed

    Katano, Takahito; Ootani, Akifumi; Mizoshita, Tsutomu; Tanida, Satoshi; Tsukamoto, Hironobu; Ozeki, Keiji; Kataoka, Hiromi; Joh, Takashi

    2015-03-01

    Stem cells are influenced by a microenvironmental niche that includes mesenchymal cells. We established a novel long-term method for primary mouse glandular stomach culture with mesenchymal myofibroblasts to investigate gastric epithelial-mesenchymal interactions. A gastric mesenchymal myofibroblast (GMF) cell line was established from mouse glandular stomach. Glandular stomach cells from neonatal mice and GMF cells were co-cultured in a collagen gel. Cultured stomach cells yielded expanding sphere-like structures. In the GMF co-culture system, the number and size of gastrospheres were increased compared with control cultures (P = 0.009 and 0.008, respectively). Immunohistochemistry showed cells positive for human gastric mucin, HIK1083, and chromogranin A, indicating differentiation into surface mucous cells, mucous neck cells, and enteroendocrine cells, respectively. RNA in situ hybridization for Lgr5 showed Lgr5(+) stem cells in the cultured gastrospheres. Lgr5(+) cells were observed persistently in the epithelium of gastrospheres in the GMF co-culture system for 2 months. GMFs allowed the cultured gastric epithelium to maintain active proliferation similar to that seen in vivo. Real-time quantitative RT-PCR showed that Gas1 expression was higher in GMFs (P = 0.0445), and Hoxc8, Notch1, and Sox10 expressions were higher in intestinal mesenchymal myofibroblasts (P = 0.0003, 0.0143, and 0.0488, respectively). We show the potential role of GMFs in sustaining Lgr5(+) stem cell activity and affecting normal gastric epithelial differentiation and proliferation. PMID:25546442

  19. Antisecretory Action of the Extract of the Aerial Parts of Eremomastax speciosa (Acanthaceae) Occurs through Antihistaminic and Anticholinergic Pathways.

    PubMed

    André Perfusion, Amang; Tan, Paul V; Ernestine, Nkwengoua; Barthélemy, Nyasse

    2014-01-01

    Objective. The objective of this study was to find out the possible antiulcer mechanism of action of Eremomastax speciosa. Method. Carbachol- and histamine-induced hypersecretion, associated with the pylorus ligation technique, were used in rats. Gastric mucosal ulceration, mucus production, pH, gastric volume, and acidity were measured. Results. Histamine and carbachol raised gastric acidity to 86.50 and 84.80?mEq/L, respectively, in the control rats, and the extracts (200?mg/kg) reduced gastric acidity to 34.60 and 39.00?mEq/L, respectively. Intraduodenal aqueous extract (400?mg/kg) in histamine- and carbachol-treated rats produced significant (P < 0.001) decreases in acid secretion to 28.50 and 28.80?mEq/L, respectively, and 100 percent inhibition of gastric ulceration. Augmented histamine-induced gastric acid secretion (90.20?mEq/L) was significantly reduced to 52.60 and 27.50?mEq/L by the 200 and 400?mg/kg doses of the aqueous extract, respectively. The extract significantly reduced (P < 0.001) the volume of gastric secretion and significantly increased mucus production. The ulcer inhibition potential of the extract significantly dropped to 25-44% (oral extract) and to 29-37% (duodenal extract) in carbachol/indomethacin-treated rats. Conclusion. The aqueous extract of E. speciosa has both cytoprotective and antisecretory effects. The antisecretory effect may involve a mechanism common to both cholinergic and histaminergic pathways. PMID:24695819

  20. Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats.

    PubMed

    Asmari, Abdulrahman Al; Omani, Saud Al; Otaibi, Malfi Al; Abdulaaly, Abdul-Aziz Al; Elfaki, Ibrahim; Yahya, Khalid Al; Arshaduddin, Mohammed

    2014-01-01

    Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action. PMID:24753752

  1. Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats.

    PubMed

    Asmari, Abdulrahman Al; Arshaduddin, Mohammed; Elfaki, Ibrahim; Kadasah, Saeed; Robayan, Abdulrahman Al; Asmary, Saeed Al

    2014-01-01

    The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels. PMID:25232384

  2. Discovery and Development of Antisecretory Drugs for Treating Diarrheal Diseases

    PubMed Central

    Thiagarajah, Jay R.; Ko, Eun-A; Tradtrantip, Lukmanee; Donowitz, Mark; Verkman, A.S.

    2014-01-01

    Diarrheal diseases constitute a significant global health burden and are a major cause of childhood mortality and morbidity. Treatment of diarrheal disease has centered on the replacement of fluid and electrolyte losses using oral rehydration solutions (ORS). Although ORS has been highly successful, significant mortality and morbidity due to diarrheal disease remains. Secretory diarrheas, such as those caused by bacterial and viral enterotoxins, result from activation of cyclic nucleotide and/or Ca2+ signaling pathways in intestinal epithelial cells, enterocytes, which increase the permeability of Cl? channels at the lumen-facing membrane. Additionally, there is often a parallel reduction in intestinal Na+ absorption. Inhibition of enterocyte Cl? channels, including the cystic fibrosis transmembrane conductance regulator (CFTR) and Ca2+-activated Cl? channels, represents an attractive strategy for antisecretory drug therapy. High-throughput screening of synthetic small molecule collections has identified several classes of Cl? channel inhibitors that show efficacy in animal models of diarrhea but remain to be tested clinically. In addition, several natural-product extracts with Cl? channel inhibition activity have shown efficacy in diarrhea models. However, a number of challenges remain to translate the promising bench science into clinically useful therapeutics, including efficiently targeting orally administered drugs to enterocytes during diarrhea, funding development costs, and carrying out informative clinical trials. Nonetheless, Cl? channel inhibitors may prove to be effective adjunctive therapy in a broad spectrum of clinical diarrheas, including acute infectious and drug-related diarrheas, short-bowel syndrome, and congenital enteropathies. PMID:24316107

  3. Gastroprotective Effect of an Aqueous Suspension of Black Cumin Nigella sativa on Necrotizing Agents-Induced Gastric Injury in Experimental Animals

    PubMed Central

    Al Mofleh, Ibrahim A; Alhaider, Abdulqader A.; Mossa, Jaber S.; Al-Sohaibani, Mohammed O.; Al-Yahya, Mohammed A; Rafatullah, Syed; Shaik, Shaffi A.

    2008-01-01

    Background/Aim Previous studies on “Black seed” or “Black Cumin” Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners. Materials and Methods The study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically. Results An aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcer effect was further confirmed histopathologically. Conclusion These findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities. PMID:19568521

  4. The acetone soluble fraction from bark extract of Stryphnodendron adstringens (Mart.) coville inhibits gastric acid secretion and experimental gastric ulceration in rats.

    PubMed

    Martins, D T O; Lima, J C S; Rao, V S N

    2002-08-01

    The acetone soluble fraction from a crude methanol extract of Stryphnodendron adstringens stem bark (AFSAB) was evaluated in acute (ethanol, indomethacin and hypothermic restraint-stress) and chronic (acetic acid) models of gastric ulceration and on basal and bethanechol-stimulated gastric acid secretion in rats. Rats pretreated orally with AFSAB at doses of 400 and 800 mg/kg showed significant decreases of gastric lesion scores in ethanol (62% and 98%) and hypothermic restraint-stress (89% and 88%) models but exerted no significant influence on indomethacin-induced acute or acetic acid-induced chronic ulceration. In pylorus-ligated rats, AFSAB significantly decreased the basal as well as bethanechol-stimulated gastric secretory volume and the total acidity with an elevated pH value. AFSAB failed to modify the gastric mucus and the gastric wall nonprotein-sulphydryl content. These results point to a possible antisecretory effect of AFSAB which account for the observed antiulcer activity in ethanol and hypothermic restraint-stress induced models of acute gastric ulceration. PMID:12203261

  5. Crofelemer, an Antisecretory Antidiarrheal Proanthocyanidin Oligomer Extracted from Croton lechleri, Targets Two Distinct Intestinal Chloride Channels

    PubMed Central

    Tradtrantip, Lukmanee; Namkung, Wan

    2010-01-01

    Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signaling processes involved in intestinal fluid transport. Using cell lines and measurement procedures to isolate the effects on individual membrane transport proteins, crofelemer at 50 ?M had little or no effect on the activity of epithelial Na+ or K+ channels or on cAMP or calcium signaling. Crofelemer inhibited the cystic fibrosis transmembrane regulator (CFTR) Cl? channel with maximum inhibition of ?60% and an IC50 ?7 ?M. Crofelemer action at an extracellular site on CFTR produced voltage-independent block with stabilization of the channel closed state. Crofelemer did not affect the potency of glycine hydrazide or thiazolidinone CFTR inhibitors. Crofelemer action resisted washout, with <50% reversal of CFTR inhibition after 4 h. Crofelemer was also found to strongly inhibit the intestinal calcium-activated Cl? channel TMEM16A by a voltage-independent inhibition mechanism with maximum inhibition >90% and IC50 ?6.5 ?M. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl? channels may account for its intestinal antisecretory activity. PMID:19808995

  6. The effect of autonomic nervous system activity on gastric myoelectrical activity: does the spectral reserve hypothesis hold for the stomach?

    Microsoft Academic Search

    Eric R. Muth; Julian F. Thayer; Robert M. Stern; Bruce H. Friedman; Christopher Drake

    1998-01-01

    Previous studies have associated changes in gastric myoelectrical activity during motion sickness, as indexed using the electrogastrogram (EGG), with changes in autonomic nervous system (ANS) activity. Subjects who did not report nausea in a rotating optokinetic drum were characterized by normal 3 cycles per minute (cpm) gastric myoelectrical activity, strong parasympathetic nervous system (PNS) activity, and low sympathetic nervous system

  7. Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer

    Microsoft Academic Search

    M Nojima; H Suzuki; M Toyota; Y Watanabe; R Maruyama; S Sasaki; Y Sasaki; H Mita; N Nishikawa; K Yamaguchi; K Hirata; F Itoh; T Tokino; M Mori; K Imai; Y Shinomura

    2007-01-01

    Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (?-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in

  8. Inhibition of gastric H,K-ATPase activity and gastric epithelial cell IL-8 secretion by the pyrrolizine derivative ML 3000

    PubMed Central

    Smolka, Adam J; Goldenring, James R; Gupta, Sandeep; Hammond, Charles E

    2004-01-01

    Background ML 3000 ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid) is an inhibitor of both cyclooxygenase and 5-lipoxygenase in vitro, and shows promise as a novel non-steroidal anti-inflammatory drug (NSAID). Unlike conventional NSAIDs which are associated with gastric ulcerogenic effects, ML 3000 causes little or no damage to the gastric mucosa, even though it significantly depresses gastric prostaglandin synthesis. Methods As part of an effort to clarify mechanisms underlying the gastric sparing properties of ML 3000, we studied the effects of ML 3000 on H,K-ATPase activity in vitro, on acid accumulation in isolated gastric parietal cells, and on IL-8 secretion by gastric epithelial cells in culture. Results SCH28080-sensitive H,K-ATPase activity in highly-purified pig gastric microsomes was dose-dependently inhibited by ML 3000 (IC50 = 16.4 ?M). Inhibition was reversible, and insensitive to ML 3000 acidification in the pH range 2.0–8.0. In rabbit gastric parietal cells, ML 3000 dose-dependently inhibited histamine-stimulated acid accumulation (IC50 = 40 ?M) and forskolin-stimulated acid accumulation (IC50 = 45 ?M). Lastly, in human gastric adenocarcinoma (AGS) cells, ML 3000 dose-dependently inhibited both baseline and IL-1?-stimulated (20 ng/ml) IL-8 secretion with IC50s of 0.46 ?M and 1.1 ?M respectively. Conclusion The data indicate that ML 3000 affects acid-secretory mechanisms downstream of cAMP mobilization induced by histamine H2 receptor activation, that it directly inhibits H,K-ATPase specific activity, and that baseline gastric epithelial cell IL-8 secretory inhibition may be mediated by ML 3000 inhibition of 5-lipoxygenase activity. We conclude that these gastric function inhibitory data may underlie the gastric sparing properties of ML 3000. PMID:15028114

  9. [Contact transendoscopic thermometry via a tube in active gastric and duodenal ulcer].

    PubMed

    Tenev, T

    1982-01-01

    The temperature of the gastric and duodenal mucosa was taken by a contact method in 473 patients with active ulcer disease, 118 of them being with gastric ulcers and 355--with duodenal ulcers. Sixty four of the gastric ulcers were with superficial gastritis, 54 gastric ulcers were with atrophic gastritis, 298 duodenal ulcers--with superficial inflammatory process and 57 duodenal ulcers with atrophic inflammatory process. The control group consisted of 31 healthy subjects without ulcer niche. In all patients, the temperature of the gastric and duodenal mucosa and in the periulcer niche was transendoscopically taken, at 6 separate levels. Four determinations were performed at each level (at the lesser curvature, greater curvature, anterior and posterior walls). A higher temperature, as compared with the control group, was found in the presence of ulcer defect in the region of duodenum and stomach. In case of superficial inflammatory process no temperature change developed in the mucosa, thus maintaining a statistically significant discrepancy in the region of the ulcer niche. The atrophic process reduced the temperature in the gastric zone in case of active gastric ulcer. The atrophic inflammatory process, in case of active duodenal ulcer, had no statistically significant effect on the higher temperature in the zones of duodenum and pylorous (T1 and T2) in the sites of the ulcer and around it, very likely due to the less manifested atrophic process in the duodenal mucosa as compared with the gastric one. PMID:7113182

  10. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

    PubMed

    da Silva, Luisa Mota; Allemand, Alexandra; Mendes, Daniel Augusto G B; Dos Santos, Ana Cristina; André, Eunice; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Dartora, Nessana; Marques, Maria Consuelo Andrade; Baggio, Cristiane Hatsuko; Werner, Maria Fernanda

    2013-01-01

    We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms. PMID:23036453

  11. Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin.

    PubMed Central

    Richter, C; Tanaka, T; Yada, R Y

    1998-01-01

    The gastric aspartic proteinases (pepsin A, pepsin B, gastricsin and chymosin) are synthesized in the gastric mucosa as inactive precursors, known as zymogens. The gastric zymogens each contain a prosegment (i.e. additional residues at the N-terminus of the active enzyme) that serves to stabilize the inactive form and prevent entry of the substrate to the active site. Upon ingestion of food, each of the zymogens is released into the gastric lumen and undergoes conversion into active enzyme in the acidic gastric juice. This activation reaction is initiated by the disruption of electrostatic interactions between the prosegment and the active enzyme moiety at acidic pH values. The conversion of the zymogen into its active form is a complex process, involving a series of conformational changes and bond cleavage steps that lead to the unveiling of the active site and ultimately the removal and dissociation of the prosegment from the active centre of the enzyme. During this activation reaction, both the prosegment and the active enzyme undergo changes in conformation, and the proteolytic cleavage of the prosegment can occur in one or more steps by either an intra- or inter-molecular reaction. This variability in the mechanism of proteolysis appears to be attributable in part to the structure of the prosegment. Because of the differences in the activation mechanisms among the four types of gastric zymogens and between species of the same zymogen type, no single model of activation can be proposed. The mechanism of activation of the gastric aspartic proteinases and the contribution of the prosegment to this mechanism are discussed, along with future directions for research. PMID:9794784

  12. Ulcer healing activity of Mumijo aqueous extract against acetic acid induced gastric ulcer in rats

    PubMed Central

    Shahrokhi, Nader; Keshavarzi, Zakieh; Khaksari, Mohammad

    2015-01-01

    Objective: Gastric ulcer is an important clinical problem, chiefly due to extensive use of some drugs. The aim was to assess the activity of Mumijo extract (which is used in traditional medicine) against acetic acid induced gastric ulcer in rats. Materials and Methods: The aqueous extract of Mumijo was prepared. Animals were randomly (n = 10) divided into four groups: Control, sham-operated group (received 0.2 ml of acetic acid to induce gastric ulcer), Mumijo (100 mg/kg/daily) were given for 4 days postacetic acid administration, and ranitidine group (20 mg/kg). The assessed parameters were pH and pepsin levels (by Anson method) of gastric contents and gastric histopathology. Ranitidine was used as reference anti-ulcer drug. Results: The extract (100 mg/kg/daily, p.o.) inhibited acid acetic-induced gastric ulceration by elevating its pH versus sham group (P < 0.01) and decreasing the pepsin levels compared to standard drug, ranitidine (P < 0.05). The histopathology data showed that the treatment with Mumijo extract had a significant protection against all mucosal damages. Conclusion: Mumijo extract has potent antiulcer activity. Its anti-ulcer property probably acts via a reduction in gastric acid secretion and pepsin levels. The obtained results support the use of this herbal material in folk medicine. PMID:25709338

  13. Gastrin — active participant or bystander in gastric carcinogenesis?

    Microsoft Academic Search

    Anna M. Grabowska; Mohamad El-Zaatari; Arjun Takhar; Susan A. Watson

    2006-01-01

    Gastrin is a pro-proliferative, anti-apoptotic hormone with a central role in acid secretion in the gastric mucosa and a long-standing association with malignant progression in transgenic mouse models. However, its exact role in human gastric malignancy requires further validation. Gastrin expression is tightly regulated by two closely associated hormones, somatostatin and gastrin-releasing peptide, and aspects of their interaction may be

  14. ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

    PubMed Central

    Chen, Xia; Fu, Xiang-Sheng; Li, Chang-Ping; Zhao, Hong-Xian

    2014-01-01

    AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum (ER) stress in rats with diabetic gastroparesis. METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells (SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78 (GRP78), and the ER-specific apoptosis mediator, caspase-12 protein, was determined by immunohistochemistry. RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk (40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P < 0.05). Swollen and distended ER with an irregular shape was observed in gastric SMCs in diabetic rats. Apoptosis of gastric SMCs increased in the diabetic rats in addition to increased expression of GRP78 and caspase-12 proteins. CONCLUSION: ER stress and ER stress-mediated apoptosis are activated in gastric SMCs in diabetic rats with gastroparesis. PMID:25009401

  15. Proliferative activity of epithelium of the surface and pits of the gastric mucosa after aspirin injury

    Microsoft Academic Search

    G. V. Tsodikov; V. V. Klimenko; S. N. Laz'kova

    1979-01-01

    The proliferative activity of the surface epithelium of the gastric mucosa and the epithelium of the gastric pits in albino mice was studied after injury by aspirin (200 mg\\/kg). An intraperitoneal injection of3H-thymidine was given to all the animals 1 h before sacrifice. The mitotic index and index of labeled nuclei were counted on autoradiographs 3, 10, and 20 days

  16. Alkylating activity of processed fish products treated with sodium nitrite in simulated gastric juice.

    PubMed

    Yano, K

    1981-06-01

    The alkylating activity of extracts from several fish products with or without sodium nitrite in simulated gastric juice has been investigated. Some of the extracts had strong alkylating potency which may be due to the action of the formed N-nitrosamides. These compounds were not derived from nitrosation of methylguanidine and agmatine or from pyrolysis products of the processed fish. The results suggest an urgent need for a comprehensive investigation of nitrosation of various foods in simulated gastric juice. PMID:7319202

  17. Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats.

    PubMed

    Sakat, S S; Tupe, Preeti; Juvekar, Archana

    2012-01-01

    The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers. PMID:23204622

  18. Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats

    PubMed Central

    Sakat, S. S.; Tupe, Preeti; Juvekar, Archana

    2012-01-01

    The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers. PMID:23204622

  19. The role of plasminogen activator inhibitor-1 in gastric mucosal protection

    PubMed Central

    Kenny, Susan; Steele, Islay; Lyons, Suzanne; Moore, Andrew R.; Murugesan, Senthil V.; Tiszlavicz, Laszlo; Dimaline, Rod; Pritchard, D. Mark; Varro, Andrea

    2013-01-01

    Gastric mucosal health is maintained in response to potentially damaging luminal factors. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt protective mechanisms leading to bleeding and ulceration. The plasminogen activator system has been implicated in fibrinolysis following gastric ulceration, and an inhibitor of this system, plasminogen activator inhibitor (PAI)-1, is expressed in gastric epithelial cells. In Helicobacter pylori-negative patients with normal gastric histology taking aspirin or NSAIDs, we found elevated gastric PAI-1 mRNA abundance compared with controls; the increase in patients on aspirin was independent of whether they were also taking proton pump inhibitors. In the same patients, aspirin tended to lower urokinase plasminogen activator mRNA. Immunohistochemistry indicated PAI-1 localization to epithelial cells. In a model system using MKN45 or AGS-GR cells transfected with a PAI-1 promoter-luciferase reporter construct, we found no evidence for upregulation of PAI-1 expression by indomethacin, and, in fact, cyclooxygenase products such as PGE2 and PGI2 weakly stimulated expression. Increased gastric PAI-1 mRNA was also found in mice following gavage with ethanol or indomethacin, but plasma PAI-1 was unaffected. In PAI-1?/? mice, gastric hemorrhagic lesions in response to ethanol or indomethacin were increased compared with C57BL/6 mice. In contrast, in PAI-1-H/K? mice in which PAI-1 is overexpressed in parietal cells, there were decreased lesions in response to ethanol and indomethacin. Thus, PAI-1 expression is increased in gastric epithelial cells in response to mucosal irritants such as aspirin and NSAIDs probably via an indirect mechanism, and PAI-1 acts as a local autoregulator to minimize mucosal damage. PMID:23494120

  20. Helicobacter pylori Induces Plasminogen Activator Inhibitor 2 in Gastric Epithelial Cells through Nuclear Factor-B and RhoA: Implications for Invasion and Apoptosis

    Microsoft Academic Search

    Andrea Varro; M. Noble; D. Mark Pritchard; Susan Kennedy; C. Anthony Hart; Rod Dimaline; Graham J. Dockray

    2004-01-01

    The gastric pathogen Helicobacter pylori is associated with a progres- sion to gastric cancer. The specific targets of H. pylori that might influence this progression are still unclear. Previous studies indicated that the gastric hormone gastrin, which may be increased in H. pylori infection, stimulates gastric expression of plasminogen activator inhibitor (PAI)-2, which is an inhibitor of the urokinase plasminogen

  1. Inhibitory Activities of Palmatine from Coptis chinensis Against Helicobactor pylori and Gastric Damage

    PubMed Central

    Jung, Joohee; Choi, Jae Sue

    2014-01-01

    Helicobacter pylori (H. pylori) is the most important factor of gastric disease in clinical practice. Moreover, smoking, stress and a poor diet may be additive factors for gastric damage. With these factors, increasing infection of H. pylori triggers gastritis, gastric ulcers and gastric cancer. To develop a new protective agent, we are concerned with plant-derived extract. The extract of Coptis chinensis (C. chinensis) and its constituents were investigated to assess their protective activities against gastric damage. The C. chinensis extract showed a scavenging effect against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, inhibition of H. pylori colonization and antiulcerogenic activities in rat. In particular, palmatine derived from C. chinensis was found to be the novel protective agent. It is better than the C. chinensis extract, berberine, a well-known constituent of C. chinensis. We suggest that palmatine from the root cortex of C. chinensis may be a good candidate for the development of new pharmaceuticals to prevent gastric disease. PMID:24795799

  2. KCl Depolarization Increases HIF-1 Transcriptional Activity via the Calcium-Independent Pathway in SGC7901 Gastric Cancer Cells

    Microsoft Academic Search

    Mei Lan; Yongquan Shi; Li Sun; Lili Liu; Xueyan Guo; Yuanyuan Lu; Jun Wang; Jie Liang; Daiming Fan

    2007-01-01

    Background: Hypoxia-inducible factor 1? (HIF-1?) has been reported to be expressed aberrantly in gastric cancer cells. Stability and transactivation of HIF-1 were associated with the change of intracellular calcium. We hypothesized that KCl depolarization may modulate HIF-1 activity in gastric cancer cells through calcium involvement. Methods: HIF-1? expression and its transcriptional activity were determined in SGC7901 gastric cancer cells treated

  3. Novel Roles of Local Insulin-Like Growth Factor-1 Activation in Gastric Ulcer Healing

    PubMed Central

    Nguyen, Tom; Chai, Jianyuan; Li, Aihua; Akahoshi, Tomohiko; Tanigawa, Tetsuya; Tarnawski, Andrzej S.

    2007-01-01

    The precise role of insulin-like growth factor (IGF)-1 in gastric ulcer healing is unknown. In experimental rat gastric ulcers, we examined expression of IGF-1 mRNA and protein by reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent assay and immunostaining, respectively. In cultured rat gastric epithelial RGM1 cells, we examined effects of exogenous IGF-1 on cell migration, re-epithelialization, and proliferation—essential components of ulcer healing. We also examined whether IGF-1 induces cyclooxygenase (COX)-2 expression and determined the role of phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways in mediating IGF-1 actions. Gastric ulceration triggered an approximately threefold increase in IGF-1 expression in epithelial cells of the ulcer margins (P < 0.001 versus control), especially in cells re-epithelizing granulation tissue and in mucosa in proximity to the ulcer margin. Treatment of RGM1 cells with IGF-1 caused a dramatic increase in actin polymerization, an eightfold increase in cell migration (P < 0.001), a 195% increase in cell proliferation (P < 0.05), and a sixfold increase in COX-2 expression (P < 0.01). Inhibitor of phosphatidylinositol 3-kinase abolished IGF-1-induced RGM1 cell migration and proliferation, actin polymerization, and COX-2 expression. The up-regulation of IGF-1 in gastric ulcer margin accelerates gastric ulcer healing by promoting cell re-epithelization, proliferation, and COX-2 expression via the phosphatidylinositol 3-kinase pathway. PMID:17392162

  4. Loperamide has antisecretory activity in the human jejunum in vivo

    Microsoft Academic Search

    S Hughes; N B Higgs; L A Turnberg

    1984-01-01

    We investigated the possibility that loperamide might influence absorption and secretion in the human jejunum in vivo. Using a triple lumen tube perfusion technique in healthy normal volunteers we showed that loperamide did not affect net absorption of water or electrolytes under basal condition. When secretion was induced by prostaglandin E2, however, loperamide significantly reduced that secretion and in three

  5. Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing.

    PubMed

    Opoka, W; Adamek, D; Plonka, M; Reczynski, W; Bas, B; Drozdowicz, D; Jagielski, P; Sliwowski, Z; Adamski, P; Brzozowski, T

    2010-10-01

    Zinc has been reported to exert a gastroprotective action against various experimental gastric lesions suggesting that this trace element is involved in the integrity of the gastric mucosa. Compounds containing zinc, such as polaprezinc, were developed in Japan and used as an antiulcer drugs in the treatment of human peptic ulcer disease. However, the precise mechanism of Zn(2+) containing compounds and their effects on mucosal integrity, gastroprotection and ulcer healing remain unclear. We have determined the efficacy of zinc hydroaspartate, a compound containing Zn(2+), in the mechanism of gastric secretion and ulcer healing in rats with chronic gastric ulcers induced by acetic acid (initial ulcer area = 28 mm(2)). Rats with gastric ulcers were randomized into two groups: A) with gastric fistulas (GF) and B) without gastric fistulas and received a daily treatment with zinc hydroaspartate (32-130 mg/kg-d i.g.) for 3, 7 and 14 days. At the termination of each treatment, the area of gastric ulcers were examined by planimetry, the gastric blood flow (GBF) at ulcer margin was assessed by laser Doppler flowmetry and H(2)-gas clearance methods. The venous blood was withdrawn for a measurement of plasma gastrin levels by radioimmunoassay (RIA). The concentration of Zn(2+) in the gastric juice and mucosa at the ulcer margin were determined by differential pulse anodic stripping voltammetry (DPASV) and flame atomic absorption spectrometry (FAAS) methods and the gastric biopsy samples were taken for histopathological assessment of the quality of ulcer healing. The ulcers healed gradually, with the ulcer area in the vehicle control rats being diminished by 15%, 48% and 78% upon ulcer induction at 3, 7 and 14 days, respectively. Zinc hydroaspartate dose-dependently inhibited the area of gastric ulcer, the dose reducing this area by 50% (ID(50)) being about 60 mg/kg-d. The mucosal concentration of Zn(2+) significantly was unchanged from the baseline immediately after ulcer induction (day 0) and at day 3 but then it rose significantly at day 7 after ulcer induction. Treatment with zinc hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric luminal and mucosal levels of Zn(2+), significantly accelerated ulcer healing at day 7 upon ulcer induction. The GBF, which reached a significantly higher value at the ulcer margin than the ulcer bed, was significantly increased in rats treated with zinc hydroaspartate compared with vehicle-controls. The gastric acid output was significantly inhibited in GF rats with gastric ulcer at day 3 then restored at day 14 followed by a significant rise in the plasma gastrin levels. Treatment with zinc hydroaspartate significantly inhibited gastric secretion and also significantly raised the plasma gastrin level when compared to vehicle-control rats. We concluded that 1) trace micronutrients such as Zn(2+) could be successfully measured in the gastric juice and gastric mucosa during ulcer healing; 2) compounds chelating of Zn(2+) can exert a beneficial influence on the ulcer healing via Zn(2+) mediated increase in gastric microcirculation, antisecretory activity and gastrin release, which may enhance the cell proliferation and differentiation during ulcer healing, ultimately exerting a trophic action on the ulcerated gastric mucosa. PMID:21081802

  6. The Sum of Its Parts—Effects of Gastric Distention, Nutrient Content and Sensory Stimulation on Brain Activation

    PubMed Central

    Spetter, Maartje S.; de Graaf, Cees; Mars, Monica; Viergever, Max A.; Smeets, Paul A. M.

    2014-01-01

    During food consumption the brain integrates multiple interrelated neural and hormonal signals involved in the regulation of food intake. Factors influencing the decision to stop eating include the foods' sensory properties, macronutrient content, and volume, which in turn affect gastric distention and appetite hormone responses. So far, the contributions of gastric distention and oral stimulation by food on brain activation have not been studied. The primary objective of this study was to assess the effect of gastric distention with an intra-gastric load and the additional effect of oral stimulation on brain activity after food administration. Our secondary objective was to study the correlations between hormone responses and appetite-related ratings and brain activation. Fourteen men completed three functional magnetic resonance imaging sessions during which they either received a naso-gastric infusion of water (stomach distention), naso-gastric infusion of chocolate milk (stomach distention + nutrients), or ingested chocolate-milk (stomach distention + nutrients + oral exposure). Appetite ratings and blood parameters were measured at several time points. During gastric infusion, brain activation was observed in the midbrain, amygdala, hypothalamus, and hippocampus for both chocolate milk and water, i.e., irrespective of nutrient content. The thalamus, amygdala, putamen and precuneus were activated more after ingestion than after gastric infusion of chocolate milk, whereas infusion evoked greater activation in the hippocampus and anterior cingulate. Moreover, areas involved in gustation and reward were activated more after oral stimulation. Only insulin responses following naso-gastric infusion of chocolate milk correlated with brain activation, namely in the putamen and insula. In conclusion, we show that normal (oral) food ingestion evokes greater activation than gastric infusion in stomach distention and food intake-related brain areas. This provides neural evidence for the importance of sensory stimulation in the process of satiation. Trial Registration ClinicalTrials.gov NCT01644539. PMID:24614074

  7. Thrombin conducts epithelial?mesenchymal transition via protease?activated receptor?1 in human gastric cancer.

    PubMed

    Otsuki, Tadayoshi; Fujimoto, Daisuke; Hirono, Yasuo; Goi, Takanori; Yamaguchi, Akio

    2014-12-01

    Epithelial-mesenchymal transition (EMT) is thought to be a key step for cancer metastasis. Using an immunohistochemical approach with gastric carcinoma tissue, we found the expression of protease-activated receptor-1 (PAR1), along with a metalloproteinase known to activate PAR1, were associated with poorer prognosis, compared with expression-negative tumors, and activated PAR1 promotes gastric cancer cell invasion and proliferation in vivo. In this study we observed EMT induction by the PAR1 agonist ?-thrombin, in human gastric cell lines stably expressing PAR1. We investigated ?-thrombin-induced changes in the cell forms of pcDNA3.1-MKN45 (MKN45/Mock), pcDNA3.1?PAR1 transfected MKN45 (MKN45/PAR1), and MKN74. Expression levels of epithelial and mesenchymal markers as well as the distribution of transcriptional factors of E-cadherin in the cytoplasm and nucleus were also noted in these cell lines. We observed ?-thrombin-induced morphological changes in MKN45/PAR1 and MKN74 cells. Western blotting and immunohistochemistry of these cells indicated a fall in the expression level of E-cadherin and an increase in fibronectin expression after 48 h. PAR1 activation also induced significant increases in nuclear levels of the Snail which is a repressor of E-cadherin gene expression. We found EMT in gastric cancer cell lines that underwent ?-thrombin-induced PAR1 activation. PMID:25231630

  8. Trefoil factor 2 requires Na/H exchanger 2 activity to enhance mouse gastric epithelial repair.

    PubMed

    Xue, Lin; Aihara, Eitaro; Wang, Timothy C; Montrose, Marshall H

    2011-11-01

    Trefoil factor (TFF) peptides are pivotal for gastric restitution after surface epithelial damage, but TFF cellular targets that promote cell migration are poorly understood. Conversely, Na/H exchangers (NHE) are often implicated in cellular migration but have a controversial role in gastric restitution. Using intravital microscopy to create microscopic lesions in the mouse gastric surface epithelium and directly measure epithelial restitution, we evaluated whether TFFs and NHE isoforms share a common pathway to promote epithelial repair. Blocking Na/H exchange (luminal 10 ?m 5-(N-ethyl-N-isopropyl) amiloride or 25 ?m HOE694) slows restitution 72-83% in wild-type or NHE1(-/-) mice. In contrast, HOE694 has no effect on the intrinsically defective gastric restitution in NHE2(-/-) mice or TFF2(-/-) mice. In TFF2(-/-) mice, NHE2 protein is reduced 23%, NHE2 remains localized to apical membranes of surface epithelium, and NHE1 protein amount or localization is unchanged. The action of topical rat TFF3 to accelerate restitution in TFF2(-/-) mice was inhibited by AMD3100 (CXCR4 receptor antagonist). Furthermore, rat TFF3 did not rescue restitution when NHE2 was inhibited [TFF2(-/-) mice +HOE694, or NHE2(-/-) mice]. HOE694 had no effect on pH at the juxtamucosal surface before or after damage. We conclude that functional NHE2, but not NHE1, is essential for mouse gastric epithelial restitution and that TFFs activate epithelial repair via NHE2. PMID:21900251

  9. Gastric saline infusion reduces ultrasonic vocalizations and brown fat activity in suckling rat pups.

    PubMed

    Nelson, Eric E; Alberts, Jeffrey R

    2002-03-01

    Under standard conditions involving isolation and cooling, it has been documented that intraoral infusion of milk and injection of the intestinal peptide cholecystokinin (CCK) result in an attenuation in ultrasonic vocalizations (USV) emitted by infant rat pups. One of the most effective stimuli in inhibiting ingestion in suckling rat pups is gastric distension, but the effect of gastric distension on USV production has not been reported. In this experiment, we subjected infant rats to intragastric infusion of isotonic saline (2% body weight) to produce a natural level of gastric distension and hydration. We found that this stimulus resulted in a powerful reduction in USV emissions in isolated 10-day-old rats. In a subsequent experiment, we found that gastric saline infusion also diminished brown adipose tissue (BAT) thermogenesis. There were different time courses of the gastric saline infusion effects on BAT thermogenesis and on USV emissions, however, suggesting that these processes may be independently regulated. We hypothesize that this stimulus induces a transient activation of the parasympathetic nervous system, which overrides the sympathetic control of BAT and USV production. PMID:11857330

  10. Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models

    Microsoft Academic Search

    Kaori Fujimoto-Ouchi; Fumiko Sekiguchi; Hideyuki Yasuno; Yoichiro Moriya; Kazushige Mori; Yutaka Tanaka

    2007-01-01

    Purpose  To clarify the antitumor activity of trastuzumab and its potential as an effective treatment for gastric cancer patients.\\u000a \\u000a \\u000a \\u000a Methods  Levels of HER2 expression in tumor tissues of gastric cancer cell lines were examined using immunohistochemistry (IHC), fluorescence\\u000a in situ hybridization (FISH), and mRNA quantification. Efficacy of trastuzumab was examined as a single agent or in combination\\u000a with chemotherapeutic agents widely used

  11. Effects of 2-deoxy-D-glucose, glucose and insulin on efferent activity in gastric vagus nerve

    Microsoft Academic Search

    T. Hirano; A. Niijima

    1980-01-01

    Summary Intracarotid injection of 2-deoxy-D-glucose and insulin increased the efferent activity in the gastric vagus nerve of anesthetized rats, while glucose injection transiently decreased vagus activity.

  12. Synchronized Dual Pulse Gastric Electrical Stimulation Induces Activation of Enteric Glial Cells in Rats with Diabetic Gastroparesis

    PubMed Central

    Yang, Wei; Wang, Nian; Shi, Xue; Chen, Jie

    2014-01-01

    Objective. The aims of this study were to investigate the effects of synchronized dual pulse gastric electrical stimulation (SGES) on gastric motility in different periods for diabetic rats and try to explore the possible mechanisms of the effects. Methods. Forty-six rats were used in the study. Gastric slow waves were recorded at baseline, 7–14-day diabetes and 56–63-day diabetes before and after stimulation and the age-matched control groups. SGES-60?mins and SGES-7 days (60?mins/day) were performed to test the effects on gastric motility and to evaluate glial marker S100B expression in stomach. Results. (1) Gastric emptying was accelerated in 7–14-day diabetes and delayed in 56–63-day diabetes. (2) The S100B expression in 56–63-day diabetes decreased and the ultrastructure changed. (3) The age-associated loss of EGC was observed in 56–63-day control group. (4) SGES was able to not only accelerate gastric emptying but also normalize gastric slow waves. (5) The S100B expression increased after SGES and the ultrastructure of EGC was partially restored. The effect of SGES-7 days was superior to SGES-60?mins. Conclusions. Delayed gastric emptying due to the growth of age may be related to the EGC inactivation. The effects of the SGES on gastric motility may be associated with EGC activation. PMID:24860604

  13. Phase coupling analysis of gastric pressure activity via wavelet packet based diagonal slice spectra.

    PubMed

    Yan, Rongguo; Yan, Guozheng; Zhang, Wenqiang; Zhang, Genfu

    2006-09-01

    We propose a new analysis method to detect quadratic phase coupling (QPC) behavior of human gastric interdigestive pressure activity that has been acquired by a telemetric capsule-like mini-robot. The method is referred to as diagonal slice spectra. They are the Fourier transforms of the diagonal slices of the triple correlations, and can actually detect the phase coupling and coupled components respectively by expanding the real process into the complex counterpart through Hilbert transform. In order to learn more about the QPC structure in a certain frequency band that we are mostly interested in and obtain a higher frequency resolution, the method, named the wavelet packet based diagonal slice spectrum, is introduced. It shows that the nonlinear QPC behavior occurs during gastric contractions (phase II), whereas no distinct phase coupling occurs during gastric motor quiescence (phase I). It is the nonlinear cell-to-cell coupling mechanisms, existence of fast and slow waves and their interactions that nonlinear QPC structure of the gastric pressure activity occurs. PMID:16930765

  14. Anticancer activity of CopA3 dimer peptide in human gastric cancer cells.

    PubMed

    Lee, Joon Ha; Kim, In-Woo; Kim, Sang-Hee; Yun, Eun-Young; Nam, Sung-Hee; Ahn, Mi-Young; Kang, Dong-Chul; Hwang, Jae Sam

    2014-07-22

    CopA3 is a homodimeric ?-helical peptide derived from coprisin which is a defensin-like antimicrobial peptide that was identified from the dung beetle, Copris tripartitus. CopA3 has been reported to have anticancer activity against leukemia cancer cells. In the present study, we investigated the anticancer activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and it was cytotoxic to gastric cancer cells in the MTS and LDH release assay, respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer cells by flow cytometric analysis and acridine orange/ethidium bromide staining. CopA3-induced cell death was mediated by specific interactions with phosphatidylserine, a membrane component of cancer cells. Taken together, these data indicated that CopA3 mainly caused necrosis of gastric cancer cells, probably through interactions with phosphatidylserine, which suggests the potential utility of CopA3 as a cancer therapeutic. PMID:25047444

  15. Anti-inflammatory\\/anti-pyretic salicylic acid esters with low gastric ulcerogenic activity

    Microsoft Academic Search

    K. D. Rainsford; M. W. Whitehouse

    1980-01-01

    The methyl and some other esters of acetylsalicylic and salicylic acids and their derivatives were found to have much lower gastric ulcerogenic activity (when assayed in the stress-sensitized rat) compared with their corresponding acids. There was little or no loss in therapeutic potencies of these salicylate esters as determined by assessment of anti-inflammatory activity (against the carrageenan-induced oedema) and antipyretic

  16. Activation of FOXO3a suggests good prognosis of patients with radically resected gastric cancer

    PubMed Central

    Yu, Shan; Yu, Yiyi; Sun, Yihong; Wang, Xuefei; Luo, Rongkui; Zhao, Naiqing; Zhang, Wen; Li, Qian; Cui, Yuehong; Wang, Yan; Li, Wei; Liu, Tianshu

    2015-01-01

    Objective: This study sought to investigate the role of the forkhead transcription factor FOXO3a in the prognosis of stage II/III gastric cancer patients. Materials and methods: A single-institution cohort of 289 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor and adjacent normal specimens were used for tissue microarray construction. Tissue sections were immunostained with FOXO3a. Microscopic evaluation to assess the presence and localization of FOXO3a in tumor and adjacent normal tissues was performed. Results were analyzed for association with clinicopathological characters and overall survival (OS). Results: FOXO3a expression was significantly higher in tumor tissues compared with adjacent normal tissues, and nuclear FOXO3a staining was observed to be more common in tumor samples than adjacent normal tissues. Poorer prognosis was seen in patients with tumors harboring lower expression of FOXO3a and also patients with adjacent normal tissues harboring higher expression of FOXO3a. High expression of FOXO3a in tumor tissues served as a good prognostic marker with multivariate hazard ratio (HR) of 0.737 (95% CI, 0.574 to 0.947; P = 0.017) for OS. Conclusion: The expression of FOXO3a was upregulated and activated in gastric cancer tissues, and was significantly associated with a favorable prognosis in stage II/III gastric cancer patients.

  17. Organ-specific activation of the gastric branch of the efferent vagus nerve by ghrelin in urethane-anesthetized rats.

    PubMed

    Habara, Hiromi; Hayashi, Yujiro; Inomata, Norio; Niijima, Akira; Kangawa, Kenji

    2014-01-01

    Ghrelin plays multiple physiological roles such as growth hormone secretion and exerting orexigenic actions; however, its physiological roles in the electrical activity of autonomic nerves remain unclear. Here, we investigated the effects of human ghrelin on several autonomic nerve activities in urethane-anesthetized rats using an electrophysiological method. Intravenous injection of ghrelin at 3 ?g/kg significantly and transiently potentiated the efferent activity of the gastric vagus nerve; however, it did not affect the efferent activity of the hepatic vagus nerve. The activated response to ghrelin in the gastric efferent vagus nerve was not affected by the gastric afferent vagotomy, suggesting that this effect was not induced via the gastric afferent vagus nerve. Ghrelin did not affect the efferent activity of the brown adipose tissue, adrenal gland sympathetic nerve, and the renal sympathetic nerve. In addition, rectal temperature and the plasma concentrations of norepinephrine, corticosterone, and renin were also not changed by ghrelin. These findings demonstrate that ghrelin stimulates the gastric efferent vagus nerve in an organ-specific manner without affecting the gastric afferent vagus nerve and that ghrelin does not acutely affect the efferent basal activity of the sympathetic nerve in rats. PMID:24366191

  18. Proteinase activated-receptors-associated signaling in the control of gastric cancer.

    PubMed

    Sedda, Silvia; Marafini, Irene; Caruso, Roberta; Pallone, Francesco; Monteleone, Giovanni

    2014-09-14

    Gastric cancer (GC) is the fourth most common cancer in the world and the second cause of cancer-related death. Gastric carcinogenesis is a multifactorial process, in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC cells. One such a pathway is regulated by proteinase activated-receptors (PARs), seven transmembrane-spanning domain G protein-coupled receptors, which comprise four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4) activated by various proteases. Both PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways, which sustain gastric carcinogenesis. There is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of patients. Consistently, data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC patients. In contrast, PAR-4 levels are down-regulated in GC and correlate inversely with the aggressiveness of GC, thus suggesting a negative role of this receptor in the control of GC. In this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior. PMID:25232234

  19. Weight, Dietary and Physical Activity Behaviors Two Years after Gastric Bypass

    Microsoft Academic Search

    Heidi J. Silver; Alfonso Torquati; Gordon L. Jensen; William O. Richards

    2006-01-01

    Background: This cross-sectional survey was designed to determine the self-reported weight management, dietary and physical\\u000a activity behaviors of Roux-en-Y gastric bypass (RYGBP) patients who were 1 to 4 years after the RYGBP operation, and to identify\\u000a gaps in follow-up nutrition-related chronic disease prevention. Methods: Questionnaires including behavioral items from the\\u000a 2003 and 2004 Behavioral Risk Factor Surveillance System (BRFSS) were

  20. Role of c-Src activity in the regulation of gastric cancer cell migration

    PubMed Central

    YANG, YUN; BAI, ZHI-GANG; YIN, JIE; WU, GUO-CONG; ZHANG, ZHONG-TAO

    2014-01-01

    Gastric cancer is associated with increased migration and invasion. In the present study, we explored the role of c-Src in gastric cancer cell migration and invasion. BGC-823 gastric cancer cells were used to investigate migration following treatment of these cells with the c-Src inhibitors, PP2 and SU6656. Migration and invasion were analyzed by wound healing and Transwell assays. Western blot analysis was used to detect the expression of MT1-MMP and VEGF-C, while the activity of MMP2 and MMP9 was monitored with gelatin zymography assay. Immunoprecipitation was used to detect interactions among furin, pro-MT1-MMP and pro-VEGF-C. MT1-MMP and VEGF-C expression levels were inhibited by PP2 and SU6656 treatment, in accordance with decreased c-Src activity. Similarly, the zymography assay demonstrated that the activity of MMP2 and MMP9 was decreased following PP2 or SU6656 treatment. Blockade of c-Src also inhibited the invasive and migratory capacity of BGC-823 cells. Notably, c-Src interacted with furin in vivo, while interactions between furin and its substrates, pro-MT1-MMP and pro-VEGF-C, were decreased by c-Src inhibitors. In conclusion, the interaction among furin and pro-MT1-MMP or pro-VEGF-C or other tumor-associated precursor enzymes can be regulated by c-Src activity, thus reducing or changing the expression of these enzymes in order to reduce the development of gastric cancer, invasion and metastasis. PMID:24841138

  1. Gastric Banding

    MedlinePLUS

    ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco ... of Gastric Banding Lifestyle Changes after Gastric Banding Surgery Gastric banding is a weight loss option for ...

  2. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    PubMed Central

    Alvarez-Suarez, José M.; Dekanski, Dragana; Risti?, Slavica; Radonji?, Nevena V.; Petronijevi?, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species. PMID:22016781

  3. Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men

    Microsoft Academic Search

    Caroline G. MacIntosh; Michael Horowitz; Marc A. M. T. Verhagen; Andre J. P. M. Smout; Judith Wishart; Howard Morris; Elizabeth Goble; John E. Morley; Ian M. Chapman

    2001-01-01

    OBJECTIVE:The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity.METHODS:Thirteen older (65–84 yr) and 13 young (18–32 yr) healthy men received isovolumetric, intraduodenal (ID) infusions of

  4. Cyclooxygenase2 Inhibitor Nimesulide Suppresses Telomerase Activity by Blocking Akt\\/PKB Activation in Gastric Cancer Cell Line

    Microsoft Academic Search

    Yu Baoping; Hu Guoyong; Yu Jieping; Ran Zongxue; Luo Hesheng

    2004-01-01

    Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to have antiproliferative effectsin neoplastic cells of different origin during the past few decades. We aimed to study the effects of theselective COX-2 inhibitor, nimesulide, on cell viability and telomerase and Akt\\/PKB activity in thehuman gastric cancer cell line MKN-45 and to explore the molecular mechanism for the antitumoractivity of the selective COX-2

  5. Effect of 13-hydroperoxyoctadecadienoic acid on the glucosamine synthetase activity in rabbit gastric mucosa.

    PubMed

    Fujita, T; Sakuma, S; Fudemoto, M; Watanabe, K; Nishida, H; Fujimoto, Y

    1997-05-01

    The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, in rabbit gastric corporal mucosa was examined. 13-HPODE inhibited the glucosamine synthetase activity at concentrations ranging from 10 to 100 microM. The effect was concentration-dependent, and the concentration required for 50% inhibition was approximately 20 microM. Experiments utilizing Fe2+ and 13-hydroxyoctadecadienoic acid revealed that the inhibitory effect of 13-HPODE on the glucosamine synthetase activity is not due to the alcohol adduct and hydroxyl radical which are expected to be formed from 13-HPODE, and that the hydroperoxyl functional group is a prerequisite. The fact that tert-butyl hydroperoxide exhibited about 50 times weaker inhibition than 13-HPODE indicates the relative specificity of fatty acyl hydroperoxides in the modulation of the glucosamine synthetase activity. These results suggest that 13-HPODE has the potential to modulate the synthesis of gastric mucus by affecting the glucosamine synthetase activity. PMID:9226755

  6. Effects of aqueous extract from Silybum marianum on adenosine deaminase activity in cancerous and noncancerous human gastric and colon tissues

    PubMed Central

    Öztürk, Bahad?r; Kocao?lu, Ender Hilmi; Durak, Zahide Esra

    2015-01-01

    Objective: Investigation of possible effects of Silybum marianum extract (SME) on adenosine deaminase (ADA) activity in cancerous and noncancerous human gastric and colon tissues to obtain information about possible mechanism of anticancer action of S. marianum. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues removed from patients by surgical operations were used in the studies. The extract was prepared in distilled water. Before and after treatment with the extract, ADA activities in the samples were measured. Results: ADA activity was found to be lowered significantly in cancerous gastric tissues but not in noncancerous gastric tissues after treatment with the SME. In the colon tissues, ADA activities were however found to increase after the treatment of SME. Conclusion: Our results suggest that the aqueous extract from S. marianum inhibits ADA activity in cancerous gastric tissues significantly. It is suggested that in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of ADA might also play a part in the anticancer properties of the S. marianum. PMID:25709224

  7. Role of gastric antioxidant and anti-Helicobactor pylori activities in antiulcerogenic activity of plantain banana (Musa sapientum var. paradisiaca).

    PubMed

    Goel, R K; Sairam, K; Rao, C V

    2001-07-01

    Studies with plantain banana (Musa sapientum var. paradisiaca) have indicated its ulcer protective and healing activities through its predominant effect on various mucosal defensive factors [Sanyal et.al, Arch Int Pharmacodyn, 149 (1964) 393; 155 (1965) 244]. Oxidative stress and Helicobactorpylori colonization are considered to be important factors in the pathogenesis of gastric ulcers. In the present study methanolic extract of plantain banana pulp (BE) was evaluated for its (i) antiulcer and antioxidant activities in 2 hr cold restraint stress and (ii) anti-H.pylori activity in vitro. The extract (BE, 50 mg/kg, twice daily for 5 days) showed significant antiulcer effect and antioxidant activity in gastric mucosal homogenates, where it reversed the increase in ulcer index, lipid peroxidation and super oxide dismutase values induced by stress. However it did not produce any change in catalase values, which was significantly decreased by stress. Further, in the in vitro study. BE (0.32-1,000 microg/ml) did not show any anti-H.pylori activity. The results suggest absence of anti-H. pyloric activity of methanolic extract of banana in vitro and its antioxidant activity may be involved in its ulcerprotective activity. PMID:12019769

  8. Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer

    PubMed Central

    Shen, Xiao-Jun; Zhang, Hao; Tang, Gu-Sheng; Wang, Xu-Dong; Zheng, Rui; Wang, Yang; Zhu, Yan; Xue, Xu-Chao; Bi, Jian-Wei

    2015-01-01

    Stromal fibroblasts play an important role in chronic cancer-related inflammation and the development as well as progression of malignant diseases. However, the difference and relationship between inflammation-associated fibroblasts (IAFs) and cancer-associated fibroblasts (CAFs) are poorly understood. In this study, gastric cancer-associated fibroblasts (GCAFs) and their corresponding inflammation-associated fibroblasts (GIAFs) were isolated from gastric cancer (GC) with chronic gastritis and cultured in vitro. These activated fibroblasts exhibited distinct secretion and tumor-promoting behaviors in vitro. Using proteomics and bioinformatics techniques, caveolin-1 (Cav-1) was identified as a major network-centric protein of a sub-network consisting of 121 differentially expressed proteins between GIAFs and GCAFs. Furthermore, immunohistochemistry in a GC cohort showed significant difference in Cav-1 expression score between GIAFs and GCAFs and among patients with different grades of chronic gastritis. Moreover, silencing of Cav-1 in GIAFs and GCAFs using small interfering RNA increased the production of pro-inflammatory and tumor-enhancing cytokines and chemokines in conditioned mediums that elevated cell proliferation and migration when added to GC cell lines AGS and MKN45 in vitro. In addition, Cav-1 status in GIAFs and GCAFs independently predicted the prognosis of GC. Our findings indicate that Cav-1 loss contributes to the distinct activation statuses of fibroblasts in GC microenvironment and gastritis mucosa, and Cav-1 expression in both GCAFs and GIAFs may serve as a potential biomarker for GC progression. PMID:25798057

  9. Convective washout reduces the antidiarrheal efficacy of enterocyte surface–targeted antisecretory drugs

    PubMed Central

    Jin, Byung-Ju; Thiagarajah, Jay R.

    2013-01-01

    Secretory diarrheas such as cholera are a major cause of morbidity and mortality in developing countries. We previously introduced the concept of antisecretory therapy for diarrhea using chloride channel inhibitors targeting the cystic fibrosis transmembrane conductance regulator channel pore on the extracellular surface of enterocytes. However, a concern with this strategy is that rapid fluid secretion could cause convective drug washout that would limit the efficacy of extracellularly targeted inhibitors. Here, we developed a convection–diffusion model of washout in an anatomically accurate three-dimensional model of human intestine comprising cylindrical crypts and villi secreting fluid into a central lumen. Input parameters included initial lumen flow and inhibitor concentration, inhibitor dissociation constant (Kd), crypt/villus secretion, and inhibitor diffusion. We modeled both membrane-impermeant and permeable inhibitors. The model predicted greatly reduced inhibitor efficacy for high crypt fluid secretion as occurs in cholera. We conclude that the antisecretory efficacy of an orally administered membrane-impermeant, surface-targeted inhibitor requires both (a) high inhibitor affinity (low nanomolar Kd) to obtain sufficiently high luminal inhibitor concentration (>100-fold Kd), and (b) sustained high luminal inhibitor concentration or slow inhibitor dissociation compared with oral administration frequency. Efficacy of a surface-targeted permeable inhibitor delivered from the blood requires high inhibitor permeability and blood concentration (relative to Kd). PMID:23359285

  10. Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis.

    PubMed

    Chen, Ping; Zhao, Deshou; Sun, Yunwei; Huang, Liya; Zhang, Shuxian; Yuan, Yaozong

    2012-12-01

    Protein inhibitor of activated STAT-1 (PIAS1) is a novel modulator of the JAK/STAT signaling pathway that negatively regulates the inflammatory response. It has been also reported to be downregulated in a variety of human cancer cell lines. However, the role of PIAS1 in gastric cancer remains unclear. In this study, we investigated the prognostic value of PIAS1 expression and its regulated mechanisms in gastric cancer cell metastasis. Therefore, the expression of PIASI was explored in gastric cancer tissues and adjacent tissues of gastric cancer with 31 cases of patients, and the prognostic value was analyzed. In addition, the growth and invasion in SGC7901 cells were investigated in the restoration of PIAS1 expression with Ad5/F35-PIAS1 or Ad5/F35-vector or PBS treatment, and the activity of P38MAPK, P-P38MAPK, JNK/SAPK, P-JNK/SAPK, ERK and P-ERK, were detected by western blotting. The tumor migratory factors MMP-9, MMP-2 and ICAM-1 were analyzed by western blotting. The results demonstrated that 22 of 31 (70.9%) gastric cancer specimens showed low levels of PIAS1 expression from immunohistochemistry staining using tissue microarrays. Statistical analysis suggested that the downregulation of PIAS1 was significantly correlated with tumor staging. Furthermore, we found that the restoration of PIAS1 expression mediated by Ad5/F35 virus suppressed cell proliferation and invasion accompanied by the inhibition of P38MAPK and ERK protein expression and activity, but not JNK/SAPK protein. Notably, PIAS1 restoration with the transfection of Ad5/F35-PIAS1 robustly decreased the expression of tumor migratory factors including MMP-9, MMP-2 and ICAM-1 compared to Ad5/F35-vector. These data suggest that PIAS1 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting the MAPK signaling pathway. PMID:22972521

  11. GESTATIONAL AGE AT BIRTH AND RISK OF GASTRIC ACID-RELATED DISORDERS IN YOUNG ADULTHOOD

    PubMed Central

    Crump, Casey; Winkleby, Marilyn A.; Sundquist, Jan; Sundquist, Kristina

    2012-01-01

    Purpose Preterm birth is associated with gastric acid-related disorders in infancy, but no studies have examined this association beyond early childhood. We used antisecretory medication data to explore whether preterm birth is associated with gastric acid-related disorders in young adulthood. Methods National cohort study of 626,811 individuals born in Sweden in 1973–1979, followed up for antisecretory (proton pump inhibitor and H2-receptor antagonist) medication prescriptions from all outpatient and inpatient pharmacies nationwide in 2005–2009 (ages 25.5–37.0 years). We excluded individuals with congenital anomalies, and examined potential confounding by other comorbidities identified on the basis of oral anti-inflammatory or corticosteroid medication prescription. Results Gestational age at birth was inversely associated with antisecretory medication prescription in young adulthood. Adjusted odds ratios for ?1 antisecretory medication prescription/year were 3.38 (95% CI, 1.73–6.62) for individuals born at 22–27 weeks, 1.38 (95% CI, 1.19–1.60) for those born at 28–34 weeks, and 1.19 (95% CI, 1.06–1.32) for those born at 35–36 weeks, relative to those born full-term (37–42 weeks). Exclusion of individuals who were prescribed oral anti-inflammatory or corticosteroid medications (?1/year) had little effect on these results. Conclusion These findings suggest that low gestational age at birth may be independently associated with an increased risk of gastric acid-related disorders in young adulthood. PMID:22382080

  12. Expression of the EGF Family in Gastric Cancer: Downregulation of HER4 and Its Activating Ligand NRG4

    PubMed Central

    Nielsen, Trine Ostergaard; Friis-Hansen, Lennart; Poulsen, Steen Seier; Federspiel, Birgitte; Sorensen, Boe Sandahl

    2014-01-01

    Gastric cancer is a major cause of cancer-related deaths in both men and women. The epidermal growth factor receptors are EGFR, HER2, HER3 and HER4. Of the four epidermal growth factor receptors, EGFR and HER2 are well-known oncogenes involved in gastric cancer. Little, however, is known about the role played by HER3 and HER4 in this disease. We obtained paired samples from the tumor and the adjacent normal tissue from the same patient undergoing surgery for gastric cancer. Using RT-qPCR, we quantified the mRNA expression of the four receptors including the HER4 splicing isoforms and all the ligands activating these receptors. Using immunohistochemistry, the protein expression of HER4 was also quantified. We found that HER2 mRNA expression was upregulated in the tumor tissue compared to the matched normal tissue (p?=?0.0520). All ligands with affinity for EGFR were upregulated, whereas the expression of EGFR was unchanged. Interestingly, we found the mRNA expression of HER4 (p?=?0.0002) and its ligand NRG4 (p?=?0.0009) to be downregulated in the tumor tissue compared to the matched normal tissue. HER4 downregulation was demonstrated for all the alternatively spliced isoforms of this receptor. These results support the involvement of EGFR and HER2 in gastric cancer and suggest an interesting association of reduced HER4 expression with development of gastric cancer. PMID:24728052

  13. Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling.

    PubMed

    Wu, Fang; Lv, Tianmin; Chen, Gang; Ye, Huajun; Wu, Wei; Li, Gang; Zhi, Fa-Chao

    2015-07-01

    Dual-specificity phosphatase 9 (DUSP9) is a strong negative regulator of transcription factor activating kinases (ERK, JNK and p38) in the mitogen-activated protein kinase (MAPK) pathways. The aim of this study was to examine the CpG island methylation status of DUSP9 using bisulfite sequencing PCR (BSP) in gastric cancer (GC). The investigation was conducted on 30 clinical GC samples and selected corresponding tumor-free normal gastric mucosa tissues, using BSP for the determination of the promoter methylation status. The methylation status of the tumor samples was compared to the corresponding tumor-free samples. DUSP9 was silenced by promoter region hypermethylation and G2/M phase arrest was induced by DUSP9 in the MKN-1 GC cell line. MKN-1 proliferation was suppressed by DUSP9 by inhibiting c-Jun, which was induced by JNK signaling. The expression levels of CCND1, c-Jun, CDK4 and CDK6 were upregulated while p21 was downregulated by DUSP9 in MKN-1 cells. However, DUSP9-induced resulted in the regulation of the levels of cycle-related molecules, whivh were inhibited when the JNK inhibitor SP600125 was added. In conclusion, DUSP9 was frequently methylated in human GC and the expression of DUSP9 is silenced by promoter region hypermethylation. The results of this study, combined with previous studies, suggested that therapeutic intervention to increase the expression or activity of DUSP9 may enable the activation of anti-proliferation signals in malignant cells. PMID:25998184

  14. Effects of Saffron and its Active Constituents, Crocin and Safranal, on Prevention of Indomethacin Induced Gastric Ulcers in Diabetic and Nondiabetic Rats

    Microsoft Academic Search

    Mozaffari K; Kavosh Boulevard; Supa Boulevard

    Background: Saffron is the dried stigmata of the flowers of saffron (Crocus sativus L., Iridaceae). Saffron is well known for the treatment of gastric disorders in traditional medicine. Objectives: In the search for new potential antiulcer agents, the effects of the ethanol extract of saffron and its active constituents crocin and safranal as compared with omeprazole against gastric ulcer induced

  15. Quinidine blockade of the carbachol-activated nonselective cationic current in guinea-pig gastric myocytes.

    PubMed Central

    Kim, S. J.; Ahn, S. C.; So, I.; Kim, K. W.

    1995-01-01

    1. In guinea-pig gastric myocytes isolated from the antral circular layer, stimulation of muscarinic receptors by carbachol (CCh) induces a cationic current (ICCh) which is known as the main mechanism of depolarization induced by muscarinic stimulation. 2. We tested the effects of a number of ion channel blockers on ICCh and focused upon quinidine which was a highly potent blocker. Externally applied quinidine suppressed ICCh (IC50 = 0.25 microM) in a reversible and voltage-dependent manner. Applied internally, quinidine was about 100 times less potent than when applied externally. Persistent activation of G-protein by GTP gamma S also induced a cationic current similar to ICCh and this current was also blocked by quinidine. 4-Aminopyridine and tetraethylammonium also suppressed ICCh in a dose-dependent manner (IC50 = 3.3 mM and 4.1 mM, respectively). 3. Pretreatment with quinidine (2 microM) selectively blocked the acetylcholine (ACh)-induced depolarization which was recorded in the multicellular tissues by a conventional intracellular microelectrode technique. 4. Voltage-dependent K-currents were also suppressed by quinidine but in a higher concentration range (IC50 = 3 microM). Quinidine, 10 microM, decreased the amplitude of the voltage-dependent Ca current to only a small extent (15% decrease at 0 mV). Quinidine, 2 microM, also suppressed only a minute proportion of the Ca-activated K current (11.1% decrease at 45 mV). 5. From these experiments, it is concluded that some organic agents known as K channel blockers are able to block the CCh-activated cation channel in a non-specific manner and among them, quinidine can be used as an effective blocker for ICCh in guinea-pig gastric myocytes. PMID:8564199

  16. Alphastatin downregulates vascular endothelial cells sphingosine kinase activity and suppresses tumor growth in nude mice bearing human gastric cancer xenografts

    PubMed Central

    Chen, Lin; Li, Tao; Li, Rong; Wei, Bo; Peng, Zheng

    2006-01-01

    AIM: To investigate whether alphastatin could inhibit human gastric cancer growth and furthermore whether sphingosine kinase (SPK) activity is involved in this process. METHODS: Using migration assay, MTT assay and Matrigel assay, the effect of alphastatin on vascular endothelial cells (ECs) was evaluated in vitro. SPK and endothelial differentiation gene (EDG)-1, -3, -5 mRNAs were detected by reverse transcription-polymerase chain reaction (RT-PCR). SPK activity assay was used to evaluate the effect of alphastatin on ECs. Matrigel plug assay in nude mice was used to investigate the effect of alphastatin on angiogenesis in vivo. Female nude mice were subcutaneously implanted with human gastric cancer cells (BGC823) for the tumor xenografts studies. Micro vessel density was analyzed in Factor VIII-stained tumor sections by the immunohistochemical SP method. RESULTS: In vitro, alphastatin inhibited the migration and tube formation of ECs, but had no effect on proliferation of ECs. RT-PCR analysis demonstrated that ECs expressed SPK and EDG-1, -3, -5 mRNAs. In vivo, alphastatin sufficiently suppressed neovascularization of the tumor in the nude mice. Daily administration of alphastatin produced significant tumor growth suppression. Immunohistochemical studies of tumor tissues revealed decreased micro vessel density in alphastatin-treated animals as compared with controls. CONCLUSION: Downregulating ECs SPK activity may be one of the mechanisms that alphastatin inhibits gastric cancer angiogenesis. Alphastatin might be a useful and relatively nontoxic adjuvant therapy in the treatment of gastric cancer. PMID:16830360

  17. Electrogastrography in Adults and Children: The Strength, Pitfalls, and Clinical Significance of the Cutaneous Recording of the Gastric Electrical Activity

    PubMed Central

    Indrio, Flavia

    2013-01-01

    Cutaneous electrogastrography (EGG) is a non-invasive technique to record gastric myoelectrical activity from the abdominal surface. Although the recent rapid increase in the development of electrocardiography, EGG still suffers from several limitations. Currently, computer analysis of EGG provides few reliable parameters, such as frequency and the percentage of normal and altered slow wave activity (bradygastria and tachygastria). New EGG hardware and software, along with an appropriate arrangement of abdominal electrodes, could detect the coupling of the gastric slow wave from the EGG. At present, EGG does not diagnose a specific disease, but it puts in evidence stomach motor dysfunctions in different pathological conditions as gastroparesis and functional dyspepsia. Despite the current pitfalls of EGG, a multitasking diagnostic protocol could involve the EGG and the 13C-breath testing for the evaluation of the gastric emptying time—along with validated gastrointestinal questionnaires and biochemical evaluations of the main gastrointestinal peptides—to identify dyspeptic subgroups. The present review tries to report the state of the art about the pathophysiological background of the gastric electrical activity, the recording and processing methodology of the EGG with particular attention to multichannel recording, and the possible clinical application of the EGG in adult and children. PMID:23762836

  18. Epidermal growth factor is digested to smaller, less active forms in acidic gastric juice

    Microsoft Academic Search

    Raymond J. Playford; Tania Marchbank; Denis P. Calnan; John Calam; Patrick Royston; Jeremy J. Batten; Hans F. Hansen

    1995-01-01

    Background\\/Aims: Epidermal growth factor (EGF) is present in gastric juice and has potent mitogenic properties. The stability of EGF in gastric juice under various physiological and pathophysiological conditions was examined. Methods: Recombinant human EGF1–53 was incubated with HCl containing pepsin. We also determined the forms of EGF present in the gastric juice of patients under basal conditions, patients taking the

  19. Gastroprotective activity of Eriobotrya japonica seed extract on experimentally induced gastric lesions in rats.

    PubMed

    Yokota, Junko; Takuma, Daisuke; Hamada, Atsuhide; Onogawa, Masahide; Yoshioka, Saburo; Kusunose, Masahiko; Miyamura, Mitsuhiko; Kyotani, Shojiro; Nishioka, Yutaka

    2008-01-01

    The effect of Eriobotrya japonica seed extract (ESE) prepared with 70% ethanol on gastric mucosal injury was investigated. Six experimental models with different action mechanisms were used for the evaluation. Three concentrations of ESE were prepared for each model. ESE administration was initiated 14 days before induction of gastric mucosal injury, and its effect was investigated. ESE inhibited formation of gastric mucosal injury. PMID:18404352

  20. Nardilysin and ADAM proteases promote gastric cancer cell growth by activating intrinsic cytokine signalling via enhanced ectodomain shedding of TNF-?

    PubMed Central

    Kanda, Keitaro; Komekado, Hideyuki; Sawabu, Tateo; Ishizu, Shoko; Nakanishi, Yuki; Nakatsuji, Masato; Akitake-Kawano, Reiko; Ohno, Mikiko; Hiraoka, Yoshinori; Kawada, Mayumi; Kawada, Kenji; Sakai, Yoshiharu; Matsumoto, Kyoichi; Kunichika, Makoto; Kimura, Takeshi; Seno, Hiroshi; Nishi, Eiichiro; Chiba, Tsutomu

    2012-01-01

    Nardilysin (NRDc), a metalloendopeptidase of the M16 family, promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of ADAM proteins. Here, we show the growth-promoting role of NRDc in gastric cancer cells. Analyses of clinical samples demonstrated that NRDc protein expression was frequently elevated both in the serum and cancer epithelium of gastric cancer patients. After NRDc knockdown, tumour cell growth was suppressed both in vitro and in xenograft experiments. In gastric cancer cells, NRDc promotes shedding of pro-tumour necrosis factor-alpha (pro-TNF-?), which stimulates expression of NF-?B-regulated multiple cytokines such as interleukin (IL)-6. In turn, IL-6 activates STAT3, leading to transcriptional upregulation of downstream growth-related genes. Gene silencing of ADAM17 or ADAM10, representative ADAM proteases, phenocopied the changes in cytokine expression and cell growth induced by NRDc knockdown. Our results demonstrate that gastric cancer cell growth is maintained by autonomous TNF-?–NF-?B and IL-6–STAT3 signalling, and that NRDc and ADAM proteases turn on these signalling cascades by stimulating ectodomain shedding of TNF-?. PMID:22351606

  1. Helicobacter pylori Infection Stimulates Plasminogen Activator Inhibitor 1 Production by Gastric Epithelial Cells

    Microsoft Academic Search

    A. C. Keates; S. Tummala; R. M. Peek Jr; E. Csizmadia; B. Kunzli; K. Becker; P. Correa; J. Romero-Gallo; M. B. Piazuelo; S. Sheth; C. P. Kelly; S. C. Robson; S. Keates

    2008-01-01

    Chronic infection with the gastric pathogen Helicobacter pylori significantly increases the risk of developing atrophic gastritis, peptic ulcer disease, and gastric adenocarcinoma. H. pylori strains that possess the cag patho- genicity island, which translocates CagA into the host cells, augment these risks. The aim of this study was to determine the molecular mechanisms through which H. pylori upregulates the expression

  2. Activation of the calcium sensing receptor stimulates gastrin and gastric acid secretion in healthy participants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastric acid secretion is a complex process regulated by neuronal and hormonal pathways. Ex vivo studies in human gastric tissues indicate that the calcium sensing receptor (CaR), expressed on the surface of G and parietal cells, may be involved in this regulation. We sought to determine whether cin...

  3. Abamectin attenuates gastric mucosal damage induced by ethanol through activation of vagus nerve in rats

    Microsoft Academic Search

    Ming-Yie Liu; James Po-Jung Chiang; Dur-Zong Hsu; Jou-Fang Deng

    2003-01-01

    Some type A gamma-aminobutyric acid (GABAA) receptor agonists are effective in protecting against the formation of stomach lesions induced by ethanol. Natural product abamectin, one of the existing GABAA receptor agonists, might protect against the development of gastric ulcers induced by ethanol. We investigated the protective effect of abamectin against the formation of gastric mucosal lesions induced by ethanol in

  4. A synergistic interaction between transcription factors nuclear factor-?B and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion

    PubMed Central

    2013-01-01

    Background The transcription factor nuclear factor-?B (NF-?B) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-?B and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells. Methods Immunohistochemistry for NF-?B p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-?B inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-?B repressor mutant of I?B?, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. Results NF-?B and STAT3 were constitutively activated and were positively correlated (P?=?0.038) in gastric cancer tissue specimens. In cell culture experiments, NF-?B inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-?B activation. Moreover, both NF-?B inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-?B activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P?=?0.001 and P?=?0.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. Conclusion NF-?B and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-?B and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer. PMID:23402362

  5. Acidified bile acids increase hTERT expression via c-myc activation in human gastric cancer cells.

    PubMed

    Wang, Xiaolong; Zhou, Peihua; Sun, Xuejun; Zheng, Jianbao; Wei, Guangbing; Zhang, Li; Wang, Hui; Yao, Jianfeng; Lu, Shaoying; Jia, Pengbo

    2015-06-01

    Human telomerase reverse transcriptase (hTERT) is upregulated in most cancer cell types as well in immortalized cells. The underlying mechanism for such upregulation, however, remains largely unknown. We report here that bile acids under acidified media increase hTERT expression via c-myc activation in primary human gastric cancer cell lines. Human gastric cancer MKN28, MGC803 and SGC7901 cells were treated with 100 µM deoxycholic acid (DCA) or chenodeoxycholic acid (CDCA) with or without acidified media in the presence or absence of the c-myc inhibitor 10058-F4 for 24 h. hTERT and c-myc protein levels were determined by western blot analysis. hTERT and c-myc mRNA levels were determined by RT-PCR. The promoter activities of hTERT and c-myc transcription were determined using promoter reporter luciferase assays for both. Telomerase enzyme activity was analyzed by stretch PCR. hTERT mRNA and protein levels were significantly increased by bile acids in acidified media and were accompanied with enhanced telomerase activity. No changes were found at a pH of 7.0 or with acidified media alone. Similarly, the mRNA and protein levels of c-myc were also increased by bile acids in acidified media but not at a pH of 7.0 or with acidified media alone. Importantly, pharmacologic inhibition of c-myc using 10058-F4 prevented hTERT induction by DCA or CDCA in gastric cancer cells under acidic conditions. Bile acids (DCA and CDCA) under acidic conditions increased hTERT expression in human gastric cancer cells by activation of c-myc transcription. This suggests that acidified bile acids may promote tumorigenesis and affect cell ageing via telomerase activation. PMID:25873431

  6. A system and method for online high-resolution mapping of gastric slow-wave activity.

    PubMed

    Bull, Simon H; O'Grady, Gregory; Du, Peng; Cheng, Leo K

    2014-11-01

    High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed "off-line" (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for "online" HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application. PMID:24860024

  7. Detecting Phase Coupling of Gastric Interdigestive Pressure Activity via Diagonal Slice Spectra.

    PubMed

    Yan, Rongguo; Yan, Guozheng; Zhang, Wenqiang; Wang, Long

    2005-01-01

    We propose a new analysis method to detect phase coupling behaviour of the human gastric interdigestive pressure wave that has been acquired by a telemetric capsule-like mini-robot. The method is referred to as diagonal slice spectra, which are the Fourier transforms of the diagonal slices of the triple correlation and can detect the phase coupling and coupled components respectively. It is shown that nonlinear quadratic phase coupling occurs during gastric contraction (phase II), whereas no distinct phase coupling occurs during gastric motor quiescence (phase I). PMID:17282176

  8. Gastric lavage.

    PubMed

    Lanphear, W F

    1986-01-01

    Gastric lavage has been used to manage toxic ingestions since the early 1800s. The entire realm of gastrointestinal decontamination has been extensively studied for the past 30 years. Recommendations are still evolving and remain controversial. The current indications for lavage are obtundation, unprotected airway, seizures, the need for urgent removal, and the tendency to form concretions. Hydrocarbon management depends on specific toxicity and viscosity. Contraindications for this procedure are insignificant ingestions, prolonged time since ingestion, and caustic poisoning. Proper technique minimizes complications and maximizes toxin removal. Activated charcoal and a cathartic are given after lavage. Complications include nasal trauma, esophageal perforation, tracheal intubation, aspiration, electrolyte imbalance, and hypothermia. PMID:3734388

  9. MicroRNA-500 sustains nuclear factor-?B activation and induces gastric cancer cell proliferation and resistance to apoptosis

    PubMed Central

    Yuan, Zhongyu; Liu, Junling; Sun, Jian; Lei, Fangyong; Wu, Shu; Li, Su; Zhang, Dongsheng

    2015-01-01

    Ubiquitin deconjugation of key signalling molecules by deubiquitinases (DUBs) such as cylindromatosis (CYLD), A20, and OTU deubiquitinase 7B (OTUD7B) has emerged as an important regulatory mechanism in the downregulation of NF-?B signalling and homeostasis. However, how these serial negative regulations are simultaneously disrupted to result in constitutive activation of NF-?B signalling in cancers remains puzzling. Here, we report that the miR-500 directly repressed the expression of CYLD, OTUD7B, and the A20 complex component Tax1-binding protein 1 (TAX1BP1), leading to ubiquitin conjugation of receptor-interacting protein 1 (RIP1) and sustained NF-?B activation. Furthermore, we found that miR-500 promoted gastric cancer cell proliferation, survival, and tumorigenicity. Importantly, miR-500 was upregulated in gastric cancer and was highly correlated with malignant progression and poor survival. Hence, we report the uncovering of a novel mechanism for constitutive NF-?B activation, indicating the potentially pivotal role of miR-500 in the progression of gastric cancer. PMID:25595906

  10. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement

    PubMed Central

    Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

    2014-01-01

    The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

  11. Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells

    PubMed Central

    Ding, Song-Ze; Olekhnovich, Igor N.; Cover, Timothy L.; Peek, Richard M.; Smith, Michael F.; Goldberg, Joanna B.

    2008-01-01

    Emerging evidence has suggested a critical role for activator protein (AP)-1 in regulating various cellular functions. The goal of this study was to investigate the effects of H. pylori and mitogen-activated protein kinases (MAPKs) on AP-1 subcomponents expression and AP-1 DNA binding activity in gastric epithelial cells. We found that H. pylori infection resulted in a time- and dose-dependent increase in the expression of the proteins c-Jun, JunB, JunD, Fra-1, and c-Fos, which make up the major AP-1 DNA binding proteins in AGS and MKN45 cells, while the expression levels of Fra-2 and FosB remained unchanged. H. pylori infection and MAPK inhibition altered AP-1 subcomponent protein expression and AP-1 DNA-binding activity, but did not change the overall subcomponent composition. Different clinical isolates of H. pylori showed various abilities to induce AP-1 DNA binding. Mutation of cagA, cagPAI, or vacA, and the nonphosphorylateable CagA mutant (cagAEPISA) showed less H. pylori-induced AP-1 DNA binding activity, while mutation of the H. pylori flagella had no effect. ERK, p38, and JNK each selectively regulated AP-1 subcomponent expression and DNA binding activity. These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions. PMID:18625013

  12. TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells.

    PubMed

    Sayi, Ayca; Kohler, Esther; Toller, Isabella M; Flavell, Richard A; Müller, Werner; Roers, Axel; Müller, Anne

    2011-01-15

    B cells regulate autoimmune pathologies and chronic inflammatory conditions such as autoimmune encephalomyelitis and inflammatory bowel disease. The potential counterregulatory role of B cells in balancing pathogen-specific immune responses and the associated immunopathology is less well understood owing to the lack of appropriate persistent infection models. In this paper, we show that B cells have the ability to negatively regulate adaptive immune responses to bacterial pathogens. Using mouse models of infection with Helicobacter felis, a close relative of the human gastrointestinal pathogen H. pylori, we found that B cells activated by Helicobacter TLR-2 ligands induce IL-10-producing CD4(+)CD25(+) T regulatory-1 (Tr-1)-like cells in vitro and in vivo. Tr-1 conversion depends on TCR signaling and a direct T-/B-interaction through CD40/CD40L and CD80/CD28. B cell-induced Tr-1 cells acquire suppressive activity in vitro and suppress excessive gastric Helicobacter-associated immunopathology in vivo. Adoptive cotransfer of MyD88-proficient B cells and Tr-1 cells restores a normal gastric mucosal architecture in MyD88(-/-) and IL-10(-/-) mice in a manner that depends on T cellular, but not B cellular, IL-10 production. Our findings describe a novel mechanism of B cell-dependent Tr-1 cell generation and function in a clinically relevant disease model. In conclusion, we demonstrate that the B cell/Tr-1 cell axis is essential for balancing the control of Helicobacter infection with the prevention of excessive Th1-driven gastric immunopathology, promoting gastric mucosal homeostasis on the one hand and facilitating Helicobacter persistence on the other. PMID:21149607

  13. Antacid talcid activates in gastric mucosa genes encoding for EGF and its receptor. The molecular basis for its ulcer healing action.

    PubMed

    Tarnawski, A S; Tomikawa, M; Ohta, M; Sarfeh, I J

    2000-01-01

    In previous studies [Gut 35 (1994) 896-904], we demonstrated that antacid talcid (TAL) accelerates gastric ulcer healing and provides better quality of mucosal restoration within the scar than the omeprazole (OME). However, the mechanisms of TAL-induced ulcer healing are not clear. Since growth factors promote cell proliferation, re-epithelization, angiogenesis and ulcer healing, we studied whether TAL and/or OME affect expression of epidermal growth factor (EGF) and its receptors (EGF-R) in both normal and ulcerated gastric mucosae. Rats with or without acetic acid-induced gastric ulcers (n = 64) received i.g. twice daily 1 mL of either: A) placebo (PLA); B) TAL 100 mg; or C) OME 50 mg x kg(-1) for 14 d. Studies of gastric specimens: 1) ulcer size; 2) quantitative histology; 3) expression of EGF mRNAs was determined by RT/PCR; 4) gastric sections were immunostained with antibodies against EGF and its receptors. In non-ulcerated gastric mucosa of placebo or omeprazole treated group, EGF expression was minimal, while EGF-R was localized to few cells in the mucosal proliferative zone. Gastric ulceration triggered overexpression of EGF and its receptor in epithelial cells of the ulcer margin and scar. In ulcerated gastric mucosa TAL treatment significantly enhanced (versus PLA and omeprazole) expression of EGF and EGF-R. OME treatment reduced expression of EGF in ulcerated mucosa by 55 +/- 2% (P < 0.01). It is concluded that: 1) treatment with TAL activates genes for EGF and its receptor in normal and ulcerated gastric mucosae; 2) since EGF promotes growth of epithelial cells and their proliferation and migration, the above actions of TAL provide the mechanism for its ulcer healing action and improved (versus OME) quality of mucosal restoration. PMID:10791688

  14. Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

    PubMed Central

    LUO, GENGQIU; ZHOU, YANHONG; YI, WEI; YI, HONG

    2015-01-01

    Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. In advanced and metastatic GC, conventional chemotherapy results in limited efficacy and the average survival rate is currently approximately 10 months. Dysregulated activation of numerous genes, including zinc finger, DHHC-type containing 14; caspase-associated recruitment domain-containing protein; and Ras association domain family member 10, have been implicated in GC. The tumor suppressor function of lactotransferrin (LTF) has been reported in a variety of tumors, including GC, nasopharyngeal carcinoma (NPC) and prostate cancer. However, the mechanism of the tumor suppressor function of LTF in GC remains unclear. In the present study, the expression levels of LTF in patient GC tissue samples were investigated using reverse transcription-quantitative polymerase chain reaction, and it was demonstrated that the LTF mRNA expression level in GC tissue samples was reduced by ~20-fold compared with the adjacent non-cancerous tissues (t=4.56, P<0.01). A similar trend in LTF protein expression was observed by western blot analysis. Furthermore, the present study demonstrated that the mitogen-activated protein kinase (MAPK) signaling pathway intermediates p38, c-Jun N-terminal kinase (JNK) and c-Jun were highly expressed in GC tissue samples, and indicated that LTF downregulation may be associated with the dysregulation of the MAPK signaling pathway in GC tissues. In addition, the present study indicated that LTF overexpression reduced the expression of p38, JNK2 and c-Jun in the GC cell line, SGC7901. The present study demonstrates that LTF expression is downregulated in GC tissues and that LTF may serve an important role in the dysregulation of the MAPK signaling pathway.

  15. Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2.

    PubMed

    Zhang, Qiu-Yu; Wu, Lin-Qing; Zhang, Tao; Han, Yan-Fei; Lin, Xu

    2015-04-01

    High mobility group box-B1 (HMGB1), an autophagy activator, is crucial in tumorigenesis. However, its extracellular role and signaling in gastric cancer remain unclear. Samples were collected from gastric cancer patients and healthy controls. Immunohistochemistry and immunocytochemistry were used to determine the localization of HMGB1 in gastric cancer tissues, four gastric carcinoma cell lines (BGC-823, SGC-7901, MKN-28 and MKN-45) and a gastric epithelial cell line GES-1. Western blot analysis and ELISA were used to assess the effects of gefitinib, an epidermal growth factor receptor inhibitor, on autophagy and HMGB1 release in BGC-823 cells. MTT assay and western blot analysis assessed the effects of extracellular HMGB1 on cell proliferation and signaling transduction. Released HMGB1 promoted proliferation through activation of ERK1/2 MAPK. HMGB1 expression in gastric cancer tissues and serum was significantly increased compared to the controls and healthy serum. Gastric carcinoma cells showed an increased HMGB1 in the nuclei and cytoplasm, whereas GES-1 cells exhibited a lower HMGB1 with nuclear localization. Gefitinib increased autophagy and cytoplasmic HMGB1 release from the BGC-823 cells. Extracellular HMGB1 in autophagic cell supernatant promoted proliferation that was abolished by glycyrrhizic acid, an HMGB1 inhibitor. BGC-823 cells incubated with HMGB1 had increased ERK1/2 phosphorylation, while levels of JNK, p38 or AKT were not affected. Blocking RAGE?HMGB1 interaction with antibody or siRNA suppressed the ERK1/2 activation and gastric cancer cell growth, indicating that RAGE-mediated ERK1/2 signaling was necessary for tumor progression. PMID:25652880

  16. Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2

    PubMed Central

    ZHANG, QIU-YU; WU, LIN-QING; ZHANG, TAO; HAN, YAN-FEI; LIN, XU

    2015-01-01

    High mobility group box-B1 (HMGB1), an autophagy activator, is crucial in tumorigenesis. However, its extracellular role and signaling in gastric cancer remain unclear. Samples were collected from gastric cancer patients and healthy controls. Immunohistochemistry and immunocytochemistry were used to determine the localization of HMGB1 in gastric cancer tissues, four gastric carcinoma cell lines (BGC-823, SGC-7901, MKN-28 and MKN-45) and a gastric epithelial cell line GES-1. Western blot analysis and ELISA were used to assess the effects of gefitinib, an epidermal growth factor receptor inhibitor, on autophagy and HMGB1 release in BGC-823 cells. MTT assay and western blot analysis assessed the effects of extracellular HMGB1 on cell proliferation and signaling transduction. Released HMGB1 promoted proliferation through activation of ERK1/2 MAPK. HMGB1 expression in gastric cancer tissues and serum was significantly increased compared to the controls and healthy serum. Gastric carcinoma cells showed an increased HMGB1 in the nuclei and cytoplasm, whereas GES-1 cells exhibited a lower HMGB1 with nuclear localization. Gefitinib increased autophagy and cytoplasmic HMGB1 release from the BGC-823 cells. Extracellular HMGB1 in autophagic cell supernatant promoted proliferation that was abolished by glycyrrhizic acid, an HMGB1 inhibitor. BGC-823 cells incubated with HMGB1 had increased ERK1/2 phosphorylation, while levels of JNK, p38 or AKT were not affected. Blocking RAGE-HMGB1 interaction with antibody or siRNA suppressed the ERK1/2 activation and gastric cancer cell growth, indicating that RAGE-mediated ERK1/2 signaling was necessary for tumor progression. PMID:25652880

  17. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer

    PubMed Central

    Zou, Peng; Zhang, Junru; Xia, Yiqun; Kanchana, Karvannan; Guo, Guilong; Chen, Wenbo; Huang, Yi; Wang, Zhe; Yang, Shulin; Liang, Guang

    2015-01-01

    Gastric cancer is one of the leading causes of cancer mortality in the world, and finding novel agents and strategies for the treatment of advanced gastric cancer is of urgent need. Curcumin is a well-known natural product with anti-cancer ability, but is limited by its poor chemical stability. In this study, an analog of curcumin with high chemical stability, WZ35, was designed and evaluated for its anti-cancer effects and underlying mechanisms against human gastric cancer. WZ35 showed much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, our data showed that WZ35 induced reactive oxygen species (ROS) production, resulting in the activation of both JNK-mitochondrial and ER stress apoptotic pathways and eventually cell apoptosis in SGC-7901 cells. Blockage of ROS production totally reversed WZ35-induced JNK and ER stress activation as well as cancer cell apoptosis. In vivo, WZ35 showed a significant reduction in SGC-7901 xenograft tumor size in a dose-dependent manner. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human gastric cancer treatment. PMID:25714022

  18. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer.

    PubMed

    Zou, Peng; Zhang, Junru; Xia, Yiqun; Kanchana, Karvannan; Guo, Guilong; Chen, Wenbo; Huang, Yi; Wang, Zhe; Yang, Shulin; Liang, Guang

    2015-03-20

    Gastric cancer is one of the leading causes of cancer mortality in the world, and finding novel agents and strategies for the treatment of advanced gastric cancer is of urgent need. Curcumin is a well-known natural product with anti-cancer ability, but is limited by its poor chemical stability. In this study, an analog of curcumin with high chemical stability, WZ35, was designed and evaluated for its anti-cancer effects and underlying mechanisms against human gastric cancer. WZ35 showed much stronger anti-proliferative effects than curcumin, accompanied by dose-dependent induction of cell cycle arrest and apoptosis in gastric cancer cells. Mechanistically, our data showed that WZ35 induced reactive oxygen species (ROS) production, resulting in the activation of both JNK-mitochondrial and ER stress apoptotic pathways and eventually cell apoptosis in SGC-7901 cells. Blockage of ROS production totally reversed WZ35-induced JNK and ER stress activation as well as cancer cell apoptosis. In vivo, WZ35 showed a significant reduction in SGC-7901 xenograft tumor size in a dose-dependent manner. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human gastric cancer treatment. PMID:25714022

  19. Gastric dysrhythmias and nausea of pregnancy

    Microsoft Academic Search

    K. L. Koch; R. M. Stern; M. Vasey; J. J. Botti; G. W. Creasy; A. Dwyer

    1990-01-01

    Gastric dysrhythmias have been recorded from patients with a variety of nausea syndromes. The aim of this study was to measure gastric myoelectric activity in women with and without nausea during the first trimester of pregnancy. In 32 pregnant women gastric myoelectric activity was recorded for 30–45 min with cutaneous electrodes that yielded electrogastrograms (EGGs). Frequencies of the EGG waves

  20. Dermatoglyphs and gastric cancer.

    PubMed

    Zivanovi?-Posilovi?, Gordana; Milici?, Jasna; Bozicevi?, Dubravko

    2003-06-01

    Gastric cancer is very common malignant disease, etiology of which is still unknown. Some studies consider that it is caused by a joint activity of both genetic and environmental factors. Digito-palmar dermatoglyphs were already used to determine hereditary base of some malignant diseases (breast, lung and colorectal cancer) and it was the reason for investigations of the correlation of their quantity features at patients with gastric cancer (36 males and 32 females) and the control groups of phenotypically healthy persons (50 males and 50 females). By performing statistical data processing of the multivariate and univariate analysis, as well as of discriminant ones, it was possible to prove the existence of heterogeneity between the investigated groups. Higher incidence of gastric cancer and the blood group A could be confirmed, as well. From the obtained findings can be concluded, that the results of quantitative analysis of digitopalmar dermatoglyphs affirm the existence of genetic predisposition for development of gastric cancer. PMID:12974149

  1. Capacity for Physical Activity Predicts Weight Loss After Roux-en-Y Gastric Bypass

    Microsoft Academic Search

    Ida J. Hatoum; Heather K. Stein; Benjamin F. Merrifield; Lee M. Kaplan

    2009-01-01

    Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for

  2. Helicobacter pylori-induced loss of survivin and gastric cell viability is attributable to secreted bacterial gamma-glutamyl transpeptidase activity.

    PubMed

    Valenzuela, Manuel; Bravo, Denisse; Canales, Jimena; Sanhueza, Carlos; Díaz, Natalia; Almarza, Oscar; Toledo, Héctor; Quest, Andrew F G

    2013-10-01

    Helicobacter pylori is the etiologic agent of a series of gastric pathologies that may culminate in the development of gastric adenocarcinoma. An initial step in this process is the loss of glandular structures in the gastric mucosa, presumably as the consequence of increased apoptosis and reduced cellular regeneration, which may be attributed to the combination of several bacterial and host factors and to an unfavorable proinflammatory environment. In a previous study, we showed that survivin, a member of the inhibitor of apoptosis protein family, is expressed in the normal human gastric mucosa and that its levels decrease in the mucosa of infected patients and in gastric cells exposed in culture to the bacteria, coincident with increased cell death in the latter case. We investigated the bacterial factors responsible for loss of survivin in gastric cells exposed to H. pylori. The results of this study indicated that the loss of survivin due to H. pylori infection involves proteasome-mediated degradation of the protein. Studies with isogenic mutants deficient in either CagA, VacA, lipopolysaccharide, or gamma-glutamyl transpeptidase (GGT) implicated the latter in H. pylori-induced loss of survivin and cell viability. Moreover, experiments with the GGT inhibitor 6-diazo-5-oxo-l-norleucine and purified recombinant GGT protein indicated that secreted bacterial GGT activity was required and sufficient to induce these effects. PMID:23847060

  3. Effects of intragastric infusion of inosine monophosphate and l-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes

    PubMed Central

    Kitamura, Akihiko; Sato, Wataru; Uneyama, Hisayuki; Torii, Kunio

    2010-01-01

    In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and l-glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions. PMID:21132420

  4. Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes.

    PubMed

    Kitamura, Akihiko; Sato, Wataru; Uneyama, Hisayuki; Torii, Kunio; Niijima, Akira

    2011-01-01

    In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and L: -glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions. PMID:21132420

  5. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

    PubMed Central

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-01-01

    AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. METHODS: We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. RESULTS: Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 ?g/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation. CONCLUSION: GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves. PMID:16425415

  6. A gastric acid secretion model.

    PubMed Central

    de Beus, A M; Fabry, T L; Lacker, H M

    1993-01-01

    A theory of gastric acid production and self-protection is formulated mathematically and examined for clinical and experimental correlations, implications, and predictions using analytic and numerical techniques. In our model, gastric acid secretion in the stomach, as represented by an archetypal gastron, consists of two chambers, circulatory and luminal, connected by two different regions of ion exchange. The capillary circulation of the gastric mucosa is arranged in arterial-venous arcades which pass from the gastric glands up to the surface epithelial lining of the lumen; therefore the upstream region of the capillary chamber communicates with oxyntic cells, while the downstream region communicates with epithelial cells. Both cell types abut the gastric lumen. Ion currents across the upstream region are calculated from a steady-state oxyntic cell model with active ion transport, while the downstream ion fluxes are (facilitated) diffusion driven or secondarily active. Water transport is considered iso-osmotic. The steady-state model is solved in closed form for low gastric lumen pH. A wide variety of previously performed static and dynamic experiments on ion and CO2 transport in the gastric lumen and gastric blood supply are for the first time correlated with each other for an (at least) semiquantitative test of current concepts of gastric acid secretion and for the purpose of model verification. Agreement with the data is reported with a few outstanding and instructive exceptions. Model predictions and implications are also discussed. Images FIGURE 1 PMID:8396457

  7. Gastroprotective Activity of Ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylidene) Amino]benzoate against Ethanol-Induced Gastric Mucosal Ulcer in Rats

    PubMed Central

    Halabi, Mohammed Farouq; Shakir, Raied Mustafa; Bardi, Daleya Abdulaziz; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Hassandarvish, Pouya; Hajrezaie, Maryam; Norazit, Anwar; Abdulla, Mahmood Ameen

    2014-01-01

    Background The study was carried out to determine the cytotoxic, antioxidant and gastro-protective effect of ethyl-4-[(3,5-di-tert-butyl-2-hydroxybenzylid ene)amino] benzoate (ETHAB) in rats. Methodology/Principal Findings The cytotoxic effect of ETHAB was assessed using a MTT cleavage assay on a WRL68 cell line, while its antioxidant activity was evaluated in vitro. In the anti-ulcer study, rats were divided into six groups. Group 1 and group 2 received 10% Tween 20 (vehicle). Group 3 received 20 mg/kg Omeprazole. Groups 4, 5 and 6 received ETHAB at doses of 5, 10, and 20 mg/kg, respectively. After an hour, group 1 received the vehicle. Groups 2–6 received absolute ethanol to induce gastric mucosal lesions. In the WRL68 cell line, an IC50 of more than 100 µg/mL was observed. ETHAB results showed antioxidant activity in the DPPH, FRAP, nitric oxide and metal chelating assays. There was no acute toxicity even at the highest dosage (1000 mg/kg). Microscopy showed that rats pretreated with ETHAB revealed protection of gastric mucosa as ascertained by significant increases in superoxide dismutase (SOD), pH level, mucus secretion, reduced gastric lesions, malondialdehyde (MDA) level and remarkable flattened gastric mucosa. Histologically, pretreatment with ETHAB resulted in comparatively better gastric protection, due to reduction of submucosal edema with leucocyte infiltration. PAS staining showed increased intensity in uptake of Alcian blue. In terms of immunohistochemistry, ETHAB showed down-expression of Bax proteins and over-expression of Hsp70 proteins. Conclusion/Significance The gastroprotective effect of ETHAB may be attributed to antioxidant activity, increased gastric wall mucus, pH level of gastric contents, SOD activity, decrease in MDA level, ulcer area, flattening of gastric mucosa, reduction of edema and leucocyte infiltration of the submucosal layer, increased PAS staining, up-regulation of Hsp70 protein and suppressed expression of Bax. Key words: ethyl 4-(3, 5-di-ter-butyl-2-hydroxybenzylamino) benzoate; toxicity; antioxidant; gastric-ulcer; anti-ulcer; histology; immunohistochemistry. PMID:24800807

  8. Gastroprotective activity of ent-beyerene derivatives in mice: Effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

    PubMed

    Parra, Teresa; Benites, Julio; Ruiz, Lina M; Sepulveda, Beatriz; Simirgiotis, Mario; Areche, Carlos

    2015-07-15

    Seventeen compounds (2-18) synthetized from the diterpenoid ent-beyer-15-en-18-ol (1) isolated from aerial part of Baccharis tola were tested for their gastroprotective activity on the model of HCl/EtOH-induced gastric lesions in mice. Furthermore cytotoxicity test toward fibroblasts and AGS cells were performed. The results showed that compound 1 (ED50=50mg/kg), 2, 6 and 13 were the most active regarding gastroprotective activity. Compounds 8-10 and 17-18 showed the lowest cytotoxicity toward fibroblasts and AGS cells. Regarding to mode of gastroprotective action, the effect elicited by 6 (50mg/kg) was reversed by Indomethacin but not by N-ethylmaleimide, N(G)-nitro-l-arginine methyl ester or ruthenium red, which suggests that prostaglandins are involved in the mode of gastroprotective action of 6. PMID:26009162

  9. Omeprazole, a specific inhibitor of gastric (H/sup +/-K/sup +/)-ATPase, is a H/sup +/-activated oxidizing agent of sulfhydryl groups

    SciTech Connect

    Im, W.B.; Sih, J.C.; Blakeman, D.P.; McGrath, J.P.

    1985-04-25

    Omeprazole (5-methoxy-2-(((4-methoxy-3,5- dimethylpyridinyl)methyl)sulfinyl)-1H-benzimidazole) appeared to inhibit gastric (H/sup +/-K/sup +/)-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological reducing agents like cysteine or glutathione, however, were unable to reverse the inhibitory effect of omeprazole. Moreover, acidic environments enhanced the potency of omeprazole. The chemical reactivity of omeprazole with mercaptans is also consistent with the biological action of omeprazole. The N-sulfenylated compound reacted at neutral pH with another stoichiometric amount of ethyl mercaptan to produce omeprazole sulfide quantitatively. The gastric polypeptides of 100 kilodaltons representing (H/sup +/-K/sup +/)-ATPase in the rat gastric mucosa or isolated hog gastric membranes were covalently labeled with (/sup 14/C)omeprazole. The radioactive label bound to the ATPase, however, could not be displaced by mercaptoethanol under the identical conditions where the ATPase activity was fully restored. These observations suggest that the essential sulfhydryl groups which reacted with omeprazole did not form a stable covalent bond with the drug, but rather that they further reacted with adjacent sulfhydryl groups to form disulfides which could be reduced by mercaptoethanol.

  10. Physical Activity and Sedentary Behavior in Relation to Esophageal and Gastric Cancers in the NIH-AARP Cohort

    PubMed Central

    Cook, Michael B.; Matthews, Charles E.; Gunja, Munira Z.; Abid, Zaynah; Freedman, Neal D.; Abnet, Christian C.

    2013-01-01

    Introduction Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). Methods Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI) Results During 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR>5 times/week vs. never=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15–18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR5–6 hrs/day vs. <1 hr=0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. Conclusions We find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior. PMID:24367697

  11. Evaluation of the gastroprotective activity of the extracts, fractions, and pure compounds obtained from aerial parts of Rubus imperialis in different experimental models.

    PubMed

    Berté, Priscila Elisabeth; da Silva Lopes, Jhonny; Comandulli, Nicole Garbin; Rangel, Daniele Wolff; Monache, Franco Delle; Filho, Valdir Cechinel; Niero, Rivaldo; de Andrade, Sergio Faloni

    2014-04-01

    Previous phytochemical studies carried out with Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated the presence of triterpenes (niga-ichigoside F1 and 2?,3?,19?-trihydroxyursolic acid) in this species. The literature indicates that triterpenes are closely related to some pharmacological activities, including antiulcer activity. Therefore, in view of the previous promising results with this species, this work extends the phytochemical studies, as well as investigates its gastroprotective action in different models using rodents. The hydroalcoholic extract was tested using the following protocols in mice: ethanol/HCl and nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer, acetic acid-induced chronic ulcer, ligature pylorus model, and free mucus quantification in mucosa. Isolated triterpenes were investigated in the ethanol/HCl-induced ulcer model. The results of this study show that R. imperialis extract (100, 250, or 500 mg) displays gastroprotective activity in the ethanol-induced ulcer model with a percentage of inhibition of gastric lesions of 70, 71, and 86 %, respectively. The extract also significantly reduced the ulcerative lesions in the indomethacin-induced ulcer. In this model, the percentage of inhibition of ulcer was 41, 44, and 70 %, respectively. Regarding the model of gastric secretion, a reduction of gastric juice volume and total acidity was observed, as well as an increase in gastric pH; however, gastric mucus production was not altered by treatment with the extract. It was also observed that the ethyl acetate fraction presented higher activity, leading to the isolation of niga-ichigoside F1 and 2?,3?-19-?-trihydroxyursolic acid, which presented antiulcer activity comparable to that of omeprazole, with an inhibition percentage of 98 and 99 %, respectively. These results demonstrate that R. imperialis extract and isolated compounds (niga-ichigoside F1 and 2?,3?-19-?-trihydroxyursolic acid) produce gastroprotective effects, and this activity seems, at least in part, to be related to antisecretory effects. PMID:24402081

  12. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

    SciTech Connect

    Ma, Gui-Fen [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China)] [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: shiyao_chen@163.com [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China) [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Sun, Zhi-Rong [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China)] [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China); Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China)] [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Li-Li; Lian, Jing-Jing [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China)] [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Song, Dong-Li [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)] [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer The article revealed FoxP3 gene function in gastric cancer firstly. Black-Right-Pointing-Pointer Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. Black-Right-Pointing-Pointer Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. Black-Right-Pointing-Pointer Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Black-Right-Pointing-Pointer FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

  13. 13-Acetoxysarcocrassolide Induces Apoptosis on Human Gastric Carcinoma Cells Through Mitochondria-Related Apoptotic Pathways: p38/JNK Activation and PI3K/AKT Suppression

    PubMed Central

    Su, Ching-Chyuan; Chen, Jeff Yi-Fu; Din, Zhong-Hao; Su, Jui-Hsin; Yang, Zih-Yan; Chen, Yi-Jen; Wang, Robert Y.L.; Wu, Yu-Jen

    2014-01-01

    13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ??m, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways. PMID:25342459

  14. TRAIL-activated EGFR by Cbl-b-regulated EGFR redistribution in lipid rafts antagonises TRAIL-induced apoptosis in gastric cancer cells.

    PubMed

    Xu, Ling; Zhang, Ye; Liu, Jing; Qu, Jinglei; Hu, Xuejun; Zhang, Fan; Zheng, Huachuan; Qu, Xiujuan; Liu, Yunpeng

    2012-11-01

    Most gastric cancer cells are resistant to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Since TRAIL resistance is associated with lipid rafts, in which both death receptors and epidermal growth factor receptors (EGFR) are enriched, our aim is to identify how lipid raft-regulated receptor redistribution influences the sensitivity of TRAIL in gastric cancer cells. In TRAIL-resistant gastric cancer cells, TRAIL did not induce effective death-inducing signalling complex (DISC) formation in lipid rafts, accompanied with EGFR translocation into lipid rafts, and activation of EGFR pathway. Knockdown of casitas B-lineage lymphoma-b (Cbl-b) enhanced TRAIL-induced apoptosis by promoting DISC formation in lipid rafts. However, knockdown of Cbl-b also enhanced EGFR translocation into lipid rafts and EGFR pathway activation induced by TRAIL. Either using inhibitors of EGFR or depletion of EGFR with small interfering RNA (siRNA) prevented EGFR pathway activation, and thus increased TRAIL-induced apoptosis, especially in Cbl-b knockdown clones. Taken together, TRAIL-induced EGFR activation through Cbl-b-regulated EGFR redistribution in lipid rafts antagonised TRAIL-induced apoptosis. The contribution of DISC formation and the inhibition of EGFR signal triggered in lipid rafts are both essential for increasing the sensitivity of gastric cancer cells to TRAIL. PMID:22456178

  15. Activation of p38 MAPK by Reactive Oxygen Species Is Essential in a Rat Model of Stress-Induced Gastric Mucosal Injury1

    Microsoft Academic Search

    Yi-Tao Jia; Wei Wei; Bing Ma; Yu Xu; Wen-Jun Liu; Yu Wang; Kai-Yang Lv; Hong-Tai Tang; Duo Wei; Zhao-Fan Xia

    Stress ulceration is a common complication in critically ill patients and can result in significant upper gastrointestinal bleeding associated with a high morbidity and mortality. At present, little is known of the molecular mechanisms underlying the incidence of this type of gastric damage. In the present study, we investigated the temporal activation of the redox-sensitive p38 signaling transduction cascade and

  16. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    PubMed

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing. PMID:22914261

  17. Anticancer effect of retinoic acid via AP1 activity repression is mediated by retinoic acid receptor ? and ? in gastric cancer cells

    Microsoft Academic Search

    Qiao Wu; Zheng-ming Chen; Wen-jin Su

    2002-01-01

    To uncover the mechanisms relating to the anticancer effect of retinoic acids in gastric cancer cells, the mediation of activator protein-1 (AP-1) activity repression by retinoic acid receptors (RARs) was investigated. All-trans retinoic acid (ATRA) inhibited AP-1 activity in BGC-823 cells (RAR?+, RAR?+), but not in MKN-45 cells (RAR?lo, RAR??). Transient transfection of RAR? expression vector into MKN-45 cells significantly

  18. Compound 13, an ?1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis.

    PubMed

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-08-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel ?1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPK?1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPK?1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK-HO-1 signaling. PMID:26022128

  19. Anti-invasive activity of ethanol extracts of Ganoderma lucidum through tightening of tight junctions and inhibition of matrix metalloproteinase activities in human gastric carcinoma cells.

    PubMed

    Jang, Kyung-Jun; Son, In-Seok; Shin, Dong Yeok; Yoon, Hyun-Min; Choi, Yung Hyun

    2011-12-01

    This study investigated the effect of ethanol extracts of Ganoderma lucidum (EGL) on the correlation between tightening of the tight junctions (TJs) and the anti-invasive activity in human gastric adenocarcinoma AGS cells to elucidate further the possible anticancer mechanisms that G lucidum exerts. Within the concentrations of EGL that were not cytotoxic, EGL markedly inhibited the cell motility and invasiveness in a concentration-dependent manner. The activities of matrix metalloproteinases (MMP)-2 and MMP-9 in AGS cells were dose-dependently inhibited by treatment with EGL, and this was correlated with a decrease in expression of their mRNA and proteins and the upregulation of the expression of the tissue inhibitors of metalloproteinases. The anti-invasive activity of EGL was also found to be associated with the increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, EGL repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Furthermore, the levels of E-cadherin, a type I transmembrane glycoprotein, were inhibited by EGL treatment, however, those of snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were concentration-dependently increased in response to EGL treatment. Although further studies are needed, the present study indicates that TJs and MMPs are crucial targets of EGL-induced anti-invasiveness in human gastric cancer AGS cells. PMID:22196505

  20. Supra-additive antitumor activity of 5FU with tumor necrosis factor-related apoptosis-inducing ligand on gastric and colon cancers in vitro.

    PubMed

    Shimoyama, Shouji; Mochizuki, Yoshino; Kusada, Osamu; Kaminishi, Michio

    2002-09-01

    We investigated supra-additive cytotoxic effects of 5-fluorouracil (5FU) on gastric and colon cancer cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in vitro. p53 wild- and mutant-type gastric and colon cancer cell lines were treated by 5FU alone, TRAIL alone, and a combination of 5FU and TRAIL, and cell viability after each treatment was determined by MTT assay. The p53 wild-type cells were more sensitive to 5FU alone or to TRAIL alone than p53 mutant-type cells. The cell growth inhibitory effects of the combined treatment were supra-additive and more significant in proportion to the increasing concentrations of TRAIL as compared with 5FU alone both in p53 wild- and mutant-type cells. Furthermore, TRAIL could cause a decrease in 5FU IC(50) to within the range of clinically relevant doses, particularly in p53 wild-type cells. This is the first demonstration of the supra-additive antitumor activity of 5FU with TRAIL on gastric cancer cells, giving evidence that TRAIL can reduce the requirement for 5FU that ultimately results in minimizing risks for systemic side effects while increasing the antitumor activity of 5FU, suggesting the clinical applicability of this combination for gastric and colon cancers. PMID:12168112

  1. Effects of ursolic acid on contractile activity of gastric smooth muscles.

    PubMed

    Prissadova, Natalia; Bozov, Petko; Marinkov, Kiril; Badakov, Hristo; Kristev, Atanas

    2015-04-01

    Ursolic acid (UA) in concentrations of l x 10(7) mol/L - 5 x 10(5) mol/L induced relaxation in gastric smooth muscle (SM) tissues, in a concentration-dependent manner. The relaxation did not change membrane potential and slow wave contraction patterns. A significant decrease in amplitude and frequency of spike- potentials was observed. UA-induced reactivity was removed when SM preparations were treated with nifedipine (1 x 10(6) mol/L). Ca2+-induced contractions of the depolarized SM preparations (42 mmol/L K+; Ca2+-free Krebs solution) were substantially reduced in the presence of UA. It was determined that, in certain concentrations, UA influenced L - type Ca2+ channels, and reduced the Ca2+ influx. PMID:25973477

  2. H. pylori CagL Activates ADAM17 to Induce Repression of the Gastric H, K-ATPase ? Subunit

    PubMed Central

    Saha, Arindam; Backert, Steffen; Hammond, Charles E.; Gooz, Monika; Smolka, Adam J.

    2010-01-01

    Background & Aims Infection with H. pylori represses expression of the gastric H, K-ATPase ? subunit (HK?), which could contribute to transient hypochlorhydria. CagL, a pilus protein component of the H. pylori type IV secretion system, binds to the integrin ?5?1 to mediate translocation of virulence factors into the host cell and initiate signaling. ?5?1 binds ADAM17, a metalloenzyme that catalyzes ectodomain shedding of receptor tyrosine kinase ligands. We investigated whether H. pylori-induced repression of HK? is mediated by CagL activation of ADAM17 and release of heparin-binding epidermal growth factor (HB-EGF). Methods HK? promoter and ADAM17 activity were measured in AGS gastric epithelial cells transfected with HK? promoter-reporter constructs or ADAM17-specific small interfering (si)RNAs and infected with H. pylori. HB-EGF secretion was measured by ELISA analysis and ADAM17 interaction with integrins were investigated by co-immunoprecipitation analyses. Results Infection of AGS cells with wild-type H. pylori or an H. pylori cagL-deficient isogenic mutant that also contained a wild-type version of cagL (P12?cagL/cagL) repressed HK? promoter-Luc reporter activity and stimulated ADAM17 activity. Both responses were inhibited by point mutations in the NF-?B binding site of HK? or by infection with P12?cagL. siRNA-mediated silencing of ADAM17 in AGS cells inhibited the repression of wild-type HK? promoter and reduced ADAM17 activity and HB-EGF production, compared to controls. Coimmunoprecipitation studies of AGS lysates showed that wild-type H. pylori disrupted ADAM17–?5?1 complexes. Conclusions During acute H. pylori infection, CagL dissociates ADAM17 from the integrin ?5?1 and activates ADAM17-dependent, NF-?B–mediated repression of HK?. This might contribute to transient hypochlorhydria in patients with H. pylori infection. PMID:20303353

  3. FV-429 Induced Apoptosis Through ROS-Mediated ERK2 Nuclear Translocation and p53 Activation in Gastric Cancer Cells.

    PubMed

    Zhou, Yuxin; Wei, Libin; Zhang, Haiwei; Dai, Qinsheng; Li, Zhiyu; Yu, Boyang; Guo, Qinglong; Lu, Na

    2015-08-01

    Following our previous finding which revealed that FV-429 induces apoptosis in human hepatocellular carcinoma HepG2 cells, in this study, we found that FV-429 could also induce apoptosis in human gastric cancer cells. Firstly, FV-429 inhibited the viability of BGC-823 and MGC-803 cells with IC50 values in the range of 38.10?±?6.28 and 31.53?±?6.84?µM for 24?h treatment by MTT-assay. Secondly, FV-429 induced apoptosis in BGC-823 and MGC-803 cells through the mitochondrial-mediated pathway, showing an increase in Bax/Bcl-2 ratios, and caspase-9 activation, without change in caspase-8. Further research revealed that the mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular regulated kinase, and p38 mitogen-activated protein kinase, could be activated by FV-429-induced high level ROS. Moreover, FV-429 also promoted the ERK2 nuclear translocation, resulting in the co-translocation of p53 to the nucleus and increased transcription of p53-regulated proapoptotic genes. FV-429 significantly inhibited the nude mice xenograft tumors growth of BGC-823 or MGC-803 cells in vivo. J. Cell. Biochem. 116: 1624-1637, 2015. © 2015 Wiley Periodicals, Inc. PMID:25650185

  4. Immunotherapy in gastric cancer.

    PubMed

    Matsueda, Satoko; Graham, David Y

    2014-02-21

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright. PMID:24587645

  5. Immunotherapy in gastric cancer

    PubMed Central

    Matsueda, Satoko; Graham, David Y

    2014-01-01

    Gastric cancer is the second most common of cancer-related deaths worldwide. In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved, survival rates remain poor. Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer, prostate cancer and melanoma. Here, we provide an overview of concepts of modern cancer immunotherapy including the theory, current approaches, remaining hurdles to be overcome, and the future prospect of cancer immunotherapy in the treatment of gastric cancer. Adaptive cell therapies, cancer vaccines, gene therapies, monoclonal antibody therapies have all been used with some initial successes in gastric cancer. However, to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response. Here, we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy. We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment. We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells. Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being. Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright. PMID:24587645

  6. Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.

    PubMed

    Bimczok, D; Kao, J Y; Zhang, M; Cochrun, S; Mannon, P; Peter, S; Wilcox, C M; Mönkemüller, K E; Harris, P R; Grams, J M; Stahl, R D; Smith, P D; Smythies, L E

    2015-05-01

    Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation. PMID:25249167

  7. Anti-emetic and emetic effects of erythromycin in Suncus murinus: role of vagal nerve activation, gastric motility stimulation and motilin receptors.

    PubMed

    Javid, Farideh A; Bulmer, David C; Broad, John; Aziz, Qasim; Dukes, George E; Sanger, Gareth J

    2013-01-15

    Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 ?M or atropine 1 ?M, facilitated by l-NAME 300 ?M) were facilitated by motilin (1-100 nM) and erythromycin (10-30 ?M). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin. PMID:23201066

  8. SIRT1 counteracted the activation of STAT3 and NF-?B to repress the gastric cancer growth.

    PubMed

    Lu, Juanjuan; Zhang, Liping; Chen, Xiang; Lu, Qiming; Yang, Yuxia; Liu, Jingping; Ma, Xin

    2014-01-01

    Sirtuin-1 (SIRT1) possesses apparently dual roles in regulation of tumor. Previous reports have documented the crosstalk between SIRT1 with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-?B) signaling in leukemia, lymphoma and myeloma. In this study, the purpose was to survey the regulatory effects of SIRT1 on gastric cancer (GC) cells (AGS and MKN-45) and the relationships between SIRT1 and activation of STAT3 and NF-?B in GC cells. We found the SIRT1 activator (resveratrol RSV) contributed to the repression of viability and increase of senescence, which were rescued by SIRT1 inhibitor (nicotinamide NA) and SIRT1 depletion by CCK-8 assay and SA-?-gal assay respectively. Further study found SIRT1 activation (RSV supplement) not only inhibited the activation of STAT3 including STAT3 mRNA level, c-myc mRNA level phosphorylated STAT3 (pSTAT3) proteins and acetylizad STAT3 (acSTAT3) proteins, but also repression of pNF-?B p65 and acNF-?B p65. NA reversed the effects of RSV. In addition, either RSV or NA application could not change the cellular viability and senescence in MKN-45 cells with STAT3 knockdown or NF-?B knockdown. Overall, our findings suggested SIRT1 activation could induced the loss of viability and increases of senescence in GC in vitro. Moreover, our observations revealed SIRT1 displayed growth inhibitory activity in GC cells highly associated with causing repression of activation of STAT3 and NF-?B proteins via deacetylation. PMID:25664004

  9. SIRT1 counteracted the activation of STAT3 and NF-?B to repress the gastric cancer growth

    PubMed Central

    Lu, Juanjuan; Zhang, Liping; Chen, Xiang; Lu, Qiming; Yang, Yuxia; Liu, Jingping; Ma, Xin

    2014-01-01

    Sirtuin-1 (SIRT1) possesses apparently dual roles in regulation of tumor. Previous reports have documented the crosstalk between SIRT1 with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-?B) signaling in leukemia, lymphoma and myeloma. In this study, the purpose was to survey the regulatory effects of SIRT1 on gastric cancer (GC) cells (AGS and MKN-45) and the relationships between SIRT1 and activation of STAT3 and NF-?B in GC cells. We found the SIRT1 activator (resveratrol RSV) contributed to the repression of viability and increase of senescence, which were rescued by SIRT1 inhibitor (nicotinamide NA) and SIRT1 depletion by CCK-8 assay and SA-?-gal assay respectively. Further study found SIRT1 activation (RSV supplement) not only inhibited the activation of STAT3 including STAT3 mRNA level, c-myc mRNA level phosphorylated STAT3 (pSTAT3) proteins and acetylizad STAT3 (acSTAT3) proteins, but also repression of pNF-?B p65 and acNF-?B p65. NA reversed the effects of RSV. In addition, either RSV or NA application could not change the cellular viability and senescence in MKN-45 cells with STAT3 knockdown or NF-?B knockdown. Overall, our findings suggested SIRT1 activation could induced the loss of viability and increases of senescence in GC in vitro. Moreover, our observations revealed SIRT1 displayed growth inhibitory activity in GC cells highly associated with causing repression of activation of STAT3 and NF-?B proteins via deacetylation. PMID:25664004

  10. Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals.

    PubMed

    Qu, Xiujuan; Zhang, Ye; Li, Yingchun; Hu, Xuejun; Xu, Yingying; Xu, Ling; Hou, Kezou; Sada, Kiyonao; Liu, Yunpeng

    2009-07-01

    The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further investigation revealed that mitochondrial depolarization was enhanced by Cbl-b and decreased by Cbl-b (DN) in RBL-2H3 cells. Moreover, overexpression of Cbl-b significantly suppressed ERK activation, and Cbl-b (DN) strongly enhanced both ERK and Akt activation. Altogether, these results indicate that Cbl-b sensitized both leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial apoptotic pathway and modulating the ERK and Akt survival pathways. PMID:19508871

  11. Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.

    PubMed

    Ko, Bong-Kook; Lee, Sook-Yeon; Lee, Young-Ha; Hwang, In-Sik; Persson, Helena; Rockberg, Johan; Borrebaeck, Carl; Park, Dongeun; Kim, Kyu-Tae; Uhlen, Mathias; Lee, Jong-Seo

    2015-02-01

    The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers. PMID:25306393

  12. Helicobacter pylori FKBP-type PPIase promotes gastric epithelial cell proliferation and anchorage-independent growth through activation of ERK-mediated mitogenic signaling pathway.

    PubMed

    Zhu, Yanmei; Chen, Moye; Gong, Yuehua; Liu, Ziyang; Li, Aodi; Kang, Dan; Han, Fang; Liu, Jingwei; Liu, Jun; Yuan, Yuan

    2015-04-01

    Though Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factor(s) generated by H. pylori that causes gastric cancer remains to be fully determined. Here, we show that deletion of peptidyl-prolyl cis-trans isomerase (PPIase) prevented H. pylori from stimulating human gastric epithelial cell (AGS) proliferation. Consistent with this observation, ectopic expression of H. pylori PPIase promoted AGS cell proliferation and anchorage-independent growth. To gain insight into the biochemical mechanism of PPIase-induced effect, early signal events involved in mitogenic signaling pathways were evaluated. Expression of H. pylori PPIase caused an increase in basal as well as EGF-stimulated phosphorylation of ERK and EGF receptor at Tyr1086. Treatment with MEK inhibitor completely blocked PPIase-induced cell proliferation. Our results suggest that H. pylori PPIase has the potential to activate mitogenic signaling pathway and to promote transformation of gastric epithelial cells. H. pylori PPIase may represent a novel target for therapeutic management of gastric cancer patients. PMID:25687921

  13. Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production.

    PubMed

    Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

    2014-10-01

    Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200 mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200 mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production. PMID:25041839

  14. Mechanism of Rac1-induced amplification in gastric mucosal phospholipase C?2 activation in response to Helicobacter pylori: modulatory effect of ghrelin.

    PubMed

    Slomiany, B L; Slomiany, A

    2015-06-01

    Membrane recruitment followed by targeted phosphorylation of specific Tyr and Ser residues and the interaction with Rac GTPases are the crucial parts of an elaborate mechanism of PLC?2 activation essential for its role in linking the specific receptor responses to a variety of hormones and bacterial endotoxins with the intended intracellular targets. Here, we explored the involvement of Rac in mediation of PLC?2 activation associated with gastric mucosal inflammatory responses to H. pylori LPS and the hormone, ghrelin. We show that stimulation of gastric mucosal cells with the LPS leads to the membrane translocation of Rac1 as well as PLC?2, while the effect of ghrelin is manifested by elevation in the membrane PLC?2 activation and suppression in Rac1 translocation. However, blocking the LPS-induced Rac1 translocation, while detrimental to the PLC?2 activation, has no effect on its membrane translocation. We reveal further that PLC?2, localized in the membrane in association with Rac1 following the LPS stimulation, exhibits a marked increase in phosphorylation on Ser, while the modulatory effect of ghrelin, manifested by a drop in Rac1 translocation, is associated with a distinct decrease in PLC?2 phosphorylation on Ser. Thus, the results suggest that H. pylori-elicited increase in gastric mucosal PLC?2 phosphorylation on Ser serves as an essential platform for Rac1 colocalization and amplification in PLC?2 activation. PMID:25796615

  15. Periostin mediates the increased pro-angiogenic activity of gastric cancer cells under hypoxic conditions.

    PubMed

    Qiu, Feng; Shi, Chun-hua; Zheng, Jun; Liu, Yu-bin

    2013-07-01

    This study was conducted to investigate the biological role of periostin in gastric cancer (GC) under hypoxia. Western blot analysis revealed that along with an upregulation of hypoxia-inducible factor-1alpha, there was a time-dependent induction of periostin in MKN-45 cells under hypoxia (2% O2 ), increasing by eightfold as compared to normoxic cells. Pretreatment with 30 µM PD98059, an inhibitor of ERK1/2, significantly reduced hypoxia-stimulated periostin expression (P < 0.01). Periostin knockdown in MKN-45 cells was achieved by specific small interfering RNA (siRNA). The conditioned medium from periostin siRNA-transfected MKN-45 cells induced significantly less (P < 0.01) endothelial tube formation than control siRNA-transfected cells. Additionally, periostin silencing markedly decreased the mRNA expression and secretion of vascular endothelial growth factor (VEGF) in hypoxic MKN-45 cells. Thus, our data suggest that periostin is a hypoxia-response gene and mediates a cross talk between GC and endothelial cells under hypoxia, partially through regulation of the VEGF expression. PMID:23728938

  16. Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception

    PubMed Central

    Thanos, Panayotis K.; Michaelides, Mike; Subrize, Mike; Miller, Mike L.; Bellezza, Robert; Cooney, Robert N.; Leggio, Lorenzo; Wang, Gene-Jack; Rogers, Ann M.; Volkow, Nora D.; Hajnal, Andras

    2015-01-01

    Background Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure’s impact on the brain. This study examined the effects of RYGB on the brain’s response to the anticipation of highly palatable versus regular food. Methods High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (?PET). Results Bacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats. Conclusions RYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity. PMID:26039080

  17. Inhibiting enhancer of zeste homolog 2 promotes cellular senescence in gastric cancer cells SGC-7901 by activation of p21 and p16.

    PubMed

    Bai, Jie; Chen, Junhua; Ma, Muyuan; Cai, Ming; Xu, Fei; Wang, Guobin; Tao, Kaixiong; Shuai, Xiaoming

    2014-06-01

    Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Enhancer of zeste homolog 2 (EZH2) as a member of polycomb group proteins and its targets include cell cycle regulatory proteins, which govern cell cycle progression and cellular senescence. In this study, we report that EZH2 depletion promotes the senescent state in human gastric cancer cells SGC-7901. We found that EZH2 functionally suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2 depletion inhibited cell proliferation, arrested cellular cycle, restored features of a cellular senescence phenotype, and promoted doxorubicin-induced senescence. To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent manner. Taken together, our data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16, and could serve as a potential epigenetic target for gastric cancer therapy. PMID:24588771

  18. Effect of Antisecretory Drugs and Nitrates on the Risk of Ulcer Bleeding Associated With Nonsteroidal Anti-Inflammatory Drugs, Antiplatelet Agents, and Anticoagulants

    Microsoft Academic Search

    Anticoagulants Angel Lanas; Luis A. García-Rodríguez; Maria T. Arroyo; Luis Bujanda; Fernando Gomollón; Montserrat Forné; Sof ´ ia Aleman; David Nicolas; Faust Feu; Antonio González-Pérez; Ana Borda; Manuel Castro; Maria Jose Poveda; Juan Arenas; Angel Lanas

    2007-01-01

    OBJECTIVES:After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants.METHODS:This case–control

  19. Descending influences from the infralimbic cortex on vago–vagal reflex control of gastric motor activity in the rat

    Microsoft Academic Search

    S Panteleev; D Grundy

    2000-01-01

    In experiments on urethane anaesthetised rats the influence of electrical stimulation of ventral areas of the medial prefrontal cortex (mPFC) on spontaneous and vagally-mediated gastric motility were studied. Stimulation of the mPFC resulted in gastric relaxation manifested as a fall in intragastric pressure from a baseline value of 5.0±0.5 cm H2O. These were most prominent following a short latency when

  20. Experimental gastric dysrhythmias and its correlation with in vivo gastric muscle contractions

    PubMed Central

    Xing, Jinhong; Qian, Liwei; Chen, Jiande

    2006-01-01

    AIM: To study the direct correlation between gastric dysrhythmias and in vivo gastric muscle tone. METHODS: Five healthy dogs were implanted with 4 pairs of electrodes along the greater curvature, with a strain gauge (SG) being sutured parallel to the distal electrodes (2 cm above the pylorus). Intravenous vasopressin was given to induce gastric dysrhythmia. The percentage of regular slow waves and SG energy were calculated. RESULTS: (1) the regularity of gastric myoelectric activity (GMA) was reduced during and after infusion of vasopressin; (2) SG energy was significantly decreased during the infusion of vasopressin; (3) the decrease in SG energy was well correlated with the reduction in GMA regularity; (4) SG energy was negatively correlated with bradygastria and tachygastria. CONCLUSION: Vasopressin inhibits gastric contractions and impairs gastric slow waves; gastric dysrhythmias are associated with the reduced antral muscle contractions, and are indicative of antral hypomotility. PMID:16810746

  1. Component analysis and structure identification of active substances for anti-gastric ulcer effects in Radix Astragali by liquid chromatography and tandem mass spectrometry.

    PubMed

    Liu, Xiao-Hua; Zhao, Liang-Gong; Liang, Jing; Guo, Long; Yang, Ying-Lai; Hu, Fang; Zhu, Rui-Juan; Feng, Shi-Lan

    2014-06-01

    This study provided a comprehensive component analysis and structure identification of active substances for the anti-gastric ulcer effects of Radix Astragali. The data were generated by organically combining the results from in vivo pharmacodynamic experiments, a cell growth-promoting assay, structure identification, content determination, fingerprinting, and correlation analyses. The fingerprints from high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) and from HPLC coupled with evaporative light scattering detectors (ELSD) from 95% ethanol extracts of Radix Astragali (ERA) were determined using HPLC-DAD-ELSD. The structures of 16 compounds were identified using ultra-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS). The contents of these 16 compounds were simultaneously determined in a single run using HPLC-DAD-ELSD. The strength of the anti-ulceration effect of each of the 16 compounds was correlated to its content in the HPLC spectrum using gray relation statistics. The sequence of the contribution from each of the 16 compounds to the anti-gastric ulcer effect was determined. The results showed that ononin, astragalosideIII, and astragalosideIV contributed most to the observed anti-gastric ulcer effects and that these three compounds also exhibited strong growth-promoting effects in cultured GES-1 cells. The results of this study can be used to evaluate the quality of Radix Astragali and to provide a theoretical foundation for its further study. PMID:24780704

  2. Epigenetic regulation of Delta-Like1 controls Notch1 activation in gastric cancer

    E-print Network

    Piazzi, Giulia

    The Notch signaling pathway drives proliferation, differentiation, apoptosis, cell fate, and maintenance of stem cells in several tissues. Aberrant activation of Notch signaling has been described in several tumours and ...

  3. Helicobacter pylori pore-forming cytolysin orthologue TlyA possesses in vitro hemolytic activity and has a role in colonization of the gastric mucosa.

    PubMed

    Martino, M C; Stabler, R A; Zhang, Z W; Farthing, M J; Wren, B W; Dorrell, N

    2001-03-01

    Hemolysins have been found to possess a variety of functions in bacteria, including a role in virulence. Helicobacter pylori demonstrates hemolytic activity when cultured on unlysed blood agar plates which is increased under iron-limiting conditions. However, the role of an H. pylori hemolysin in virulence is unclear. Scrutiny of the H. pylori 26695 genome sequence suggests the presence of at least two distinct hemolysins, HP1086 and HP1490, in this strain. Previous studies have shown that the in vitro hemolytic activity of H. pylori is reduced when it is coincubated with dextran 5000, suggesting the presence of a pore-forming cytolysin. HP1086 has homology to pore-forming cytolysins (TlyA) from other bacterial species, and the introduction of the cloned H. pylori tlyA gene into a nonhemolytic Escherichia coli strain conferred hemolytic activity. An H. pylori tlyA defined mutant showed reduced in vitro hemolytic activity, which appears to be due to pore formation, as the hemolytic activity of the wild-type strain is reduced to the same level as the tlyA mutant by the addition of dextran 5000. The mutant also showed reduced adhesion to human gastric adenocarcinoma cells and failed to colonize the gastric mucosa of mice. These data clearly suggest a role in virulence for H. pylori TlyA, contrary to the suggestion that hemolytic activity is an in vitro phenomenon for this pathogen. PMID:11179345

  4. Prognostic role of urokinase plasminogen activator receptor in gastric and colorectal cancer: A systematic review and meta-analysis

    PubMed Central

    Guo, Hong; Ling, Chun; Ma, Yun-yun; Zhou, Lan-xia; Zhao, Li

    2015-01-01

    Purpose Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker remains controversial. In this study, we performed a literature review and meta-analysis to evaluate the association of uPAR expression with the prognosis of patients with GC and CRC. Method The PubMed database was searched for material published in English, and data were then extracted and assessed by two reviewers independently. Correlations between uPAR expression and clinicopathological features and overall survival (OS) of patients with GC or CRC were analyzed. Results A total of 2,082 patients with GC and CRC from ten studies were included. The results of the meta-analysis showed that the uPAR expression rate in GC and CRC tissues was higher than that in normal tissues (odds ratio [OR] =3.385; 95% confidence interval [CI] 2.605–4.400; P=0.000). Our meta-analysis also revealed a significant association between uPAR expression and lymph node metastasis (OR =1.366; 95% CI =1.086–1.718; P=0.008) and tumor stage (OR =3.076; 95% CI =2.330–4.061; P=0.000). Furthermore, we found that high uPAR expression correlated with poor OS (OR =1.937; 95% CI =1.570–2.930; P=0.000). Conclusion The uPAR expression may serve as a novel disease marker in GC and CRC, as well as a therapeutic target. PMID:26150727

  5. Nonsteroidal anti-inflammatory drug-activated gene-1 plays a role in the impairing effects of cyclooxygenase inhibitors on gastric ulcer healing.

    PubMed

    Colucci, Rocchina; Antonioli, Luca; Bernardini, Nunzia; Ippolito, Chiara; Segnani, Cristina; Awwad, Oriana; Tuccori, Marco; Blandizzi, Corrado; Scarpignato, Carmelo; Fornai, Matteo

    2012-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can impair gastric ulcer healing. This study investigates the involvement of NSAID-activated gene-1 (NAG-1) in ulcer repair impairment by cyclooxygenase (COX) inhibitors. Gastric ulcers were induced in rats by acetic acid. Four days later, animals received daily intragastric indomethacin (nonselective COX-1/COX-2 inhibitor; 1 mg/kg), 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560) (selective COX-1 inhibitor; 2.5 mg/kg), (5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) (selective COX-2 inhibitor; 5 mg/kg), celecoxib (selective COX-2 inhibitor; 1 mg/kg), and valdecoxib (selective COX-2 inhibitor; 1 mg/kg), for 1, 3, or 7 days. Ulcerated tissues were processed to assess: 1) COX-1, COX-2, NAG-1, proliferating cell nuclear antigen (PCNA), and activated caspase-3 expression; 2) ulcer area; and 3) prostaglandin E(2) (PGE(2)) levels. COX-1 expression in ulcerated tissues was decreased, whereas COX-2 expression was enhanced. Ulcer healing was delayed by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. Ulcer PGE(2) levels were decreased by SC-560, DFU, celecoxib, valdecoxib, and indomethacin. NAG-1 was overexpressed in ulcerated tissues and further enhanced by indomethacin, DFU, and SC-560, but not by celecoxib or valdecoxib. PCNA expression in ulcerated areas was reduced by indomethacin, but not by the other test drugs. The expression of activated caspase-3 in ulcers was increased and enhanced further by indomethacin, DFU, and SC-560, but not by celecoxib and valdecoxib. These findings indicate that: 1) COX inhibitors exert differential impairing effects on gastric ulcer healing, through mechanisms unrelated to the inhibition of COX isoforms and prostaglandin production; and 2) NAG-1 induction, followed by activation of proapoptotic pathways, can contribute to the impairing effects of COX inhibitors on ulcer healing. PMID:22495067

  6. Anticancer Effect of Lycopene in Gastric Carcinogenesis

    PubMed Central

    Kim, Mi Jung; Kim, Hyeyoung

    2015-01-01

    Gastric cancer ranks as the most common cancer and the second leading cause of cancer-related death in the world. Risk factors of gastric carcinogenesis include oxidative stress, DNA damage, Helicobacter pylori infection, bad eating habits, and smoking. Since oxidative stress is related to DNA damage, smoking, and H. pylori infection, scavenging of reactive oxygen species may be beneficial for prevention of gastric carcinogenesis. Lycopene, one of the naturally occurring carotenoids, has unique structural and chemical features that contributes to a potent antioxidant activity. It shows a potential anticancer activity and reduces gastric cancer incidence. This review will summarize anticancer effect and mechanism of lycopene on gastric carcinogenesis based on the recent experimental and clinical studies.

  7. Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop

    PubMed Central

    Liu, Dan; Sun, Limin; Chen, Hongyu; Deng, Que; Liu, Yanjun; Yu, Ming; Ma, Yuanfang; Guo, Ning; Shi, Ming

    2015-01-01

    In the present study, we demonstrate that prolonged treatment by trastuzumab induced resistance of NCI-N87 gastric cancer cells to trastuzumab. The resistant cells possessed typical characteristics of epithelial to mesenchymal transition (EMT)/cancer stem cells and acquired more invasive and metastatic potentials both in vitro and in vivo. Long term treatment with trastuzumab dramatically inhibited the phosphorylation of Akt, but triggered the activation of STAT3. The level of IL-6 was remarkably increased, implicating that the release of IL-6 that drives the STAT3 activation initiates the survival signaling transition. Furthermore, the Notch activities were significantly enhanced in the resistant cells, companied by upregulation of the Notch ligand Jagged-1 and the Notch responsive genes Hey1 and Hey2. Inhibiting the endogenous Notch pathway reduced the IL-6 expression and restored the sensitivities of the resistant cells to trastuzumab. Blocking of the STAT3 signaling abrogated IL-6-induced Jagged-1 expression, effectively inhibited the growth of the trastuzumab resistant cells, and enhanced the anti-tumor activities of trastuzumab in the resistant cells. These findings implicate that the IL-6/STAT3/Jagged-1/Notch axis may be a useful target and that combination of the Notch or STAT3 inhibitors with trastuzumab may prevent or delay clinical resistance and improve the efficacy of trastuzumab in gastric cancer. PMID:25669984

  8. EFFECT OF NIMBIDIN ON GASTRIC ACID SECRETION

    PubMed Central

    Pillai, N. R.; Santhakumari, G.

    1985-01-01

    Nimbidin, the crude bitter compound from neem has been investigated for its gastric anti secretory activity in rats and cats. It exhibited significant anti – secretory activity in pylorus ligated rats and cats. In lumen – perfused rats it suppressed the basal as well as histamine and carbachol stimulated gastric acid output at 40 mg/kg (i.v). However it had no effect on ASA – induced back – diffusion of H+ ions. This anti secretory activity of nimbidin was found to be similar to that of H2 – receptor antagonists, which are reported to suppress the histamine induced gastric secretion in animals and man. PMID:22557506

  9. A double-blind placebo-controlled comparison of the efficacy and safety of 50, 100, and 200 micrograms of misoprostol QID in the prevention of ibuprofen-induced gastric and duodenal mucosal lesions and symptoms.

    PubMed

    Lanza, F L; Fakouhi, D; Rubin, A; Davis, R E; Rack, M F; Nissen, C; Geis, S

    1989-06-01

    Ibuprofen, a commonly proscribed nonsteroidal anti-inflammatory drug that is also available in many countries, including the United States, without a prescription, is known to cause hemorrhage and erosion of the gastroduodenal mucosa. This study was conducted to compare the efficacy of 200, 100, and 50 micrograms of misoprostol and placebo administered qid for 6 days, with a final dose on the morning of the 7th day, in the prevention of gastric and duodenal lesions induced by the concurrent administration of 800 mg of ibuprofen qid. A total of 120 healthy subjects with endoscopically normal gastric and duodenal mucosae were enrolled in the study. The endoscopic examination was repeated 2 h after the final dose on day 7, and the mucosae were graded on a 0 to 4+ scale. In the stomach, all three misoprostol groups were significantly more protective than placebo and did not differ significantly from each other. In the duodenum, the endoscopic scores of the 200- and 100-micrograms misoprostol groups, but not the 50-micrograms group differed significantly from placebo. The 200- and 100-microgram groups did not differ significantly from each other, but both differed from the 50-micrograms group for duodenal mucosal injury. Subjective symptoms thought to be primarily attributable to the NSAID (e.g., pain, indigestion/heartburn and nausea) were recorded by each subject in a diary. Subjects in the 200-micrograms misoprostol group attained the greatest degree of mucosal protection and had a significantly higher incidence of indigestion/heartburn and abdominal pain than the placebo group. One can conclude that misoprostol in both antisecretory (200- and 100-micrograms) and non-antisecretory (50-micrograms) doses protects the gastric mucosa from injury from high anti-inflammatory doses of ibuprofen (3200 mg/day). Only the antisecretory doses (100 and 200 micrograms qid) were effective in the duodenum, suggesting that acid suppression is necessary for mucosal protection to occur in the duodenum. PMID:2499187

  10. The relationship between gastric motility and nausea: gastric prokinetic agents as treatments.

    PubMed

    Sanger, Gareth J; Broad, John; Andrews, Paul L R

    2013-09-01

    Nausea is one of a cluster of symptoms described subjectively by patients with delayed gastric emptying. The mechanisms and treatments are unclear (anti-emetic drugs are not fully effective against nausea). Can nausea be relieved by stimulating gastric emptying? Physostigmine (together with atropine) has been shown experimentally to stimulate gastric motility, relieve nausea and restore normal gastric motility. Is this mimicked by gastric prokinetic drugs? The answer is complicated by mixed pharmacology. Metoclopramide increases gastric motility by activating myenteric 5-HT4 receptors but also directly inhibits vomiting via D2 and 5-HT3 receptor antagonism; relationships between increased gastric motility and relief from nausea are therefore unclear. Similarly, the D2 receptor antagonist domperidone has direct anti-emetic activity. Nevertheless, more selective 5-HT4 and motilin receptor agonists (erythromycin, directly stimulating gastric motility) inhibit vomiting in animals; low doses of erythromycin can also relieve symptoms in patients with gastroparesis. Ghrelin stimulates gastric motility and appetite mostly via vagus-dependent pathways, and inhibits vomiting in animals. To date, ghrelin receptor activation has failed to consistently improve gastric emptying or symptoms in patients with gastroparesis. We conclude that nausea can be relieved by gastric prokinetic drugs, but more clinical studies are needed using drugs with selective activity. Other mechanisms (e.g. ghrelin, vagal and central pathways, influencing a mechanistic continuum between appetite and nausea) also require exploration. These and other issues will be further explored in a forthcoming special issue of the European Journal of Pharmacology, which focusses on mechanisms of nausea and vomiting. PMID:23831391

  11. Helicobacter pylori-Induced Signaling Pathways Contribute to Intestinal Metaplasia and Gastric Carcinogenesis

    PubMed Central

    Sue, Soichiro; Shibata, Wataru; Maeda, Shin

    2015-01-01

    Helicobacter pylori (H. pylori) induces chronic gastric inflammation, atrophic gastritis, intestinal metaplasia, and cancer. Although the risk of gastric cancer increases exponentially with the extent of atrophic gastritis, the precise mechanisms of gastric carcinogenesis have not been fully elucidated. H. pylori induces genetic and epigenetic changes in gastric epithelial cells through activating intracellular signaling pathways in a cagPAI-dependent manner. H. pylori eventually induces gastric cancer with chromosomal instability (CIN) or microsatellite instability (MSI), which are classified as two major subtypes of gastric cancer. Elucidation of the precise mechanisms of gastric carcinogenesis will also be important for cancer therapy.

  12. Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats

    Microsoft Academic Search

    Soojin Park; Ki-Baik Hahm; Tae-Young Oh; Joo-Hyun Jin; Ryowon Choue

    2004-01-01

    Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly

  13. Gastric dysmotility in major depression

    Microsoft Academic Search

    Carmen Quick; Anna Kliem; Sandy Berger; Michael Hocke; Manuel Tancer; Georg Juckel; Vikram K. Yeragani; Karl-Jürgen Bär

    2010-01-01

    BackgroundSomatic symptoms of the gastrointestinal tract occur frequently in major depressive disorder (MDD) and might be associated with the known autonomic imbalance in the disease. Hence, we have investigated gastric electrical activity in patients suffering from major depression before and after treatment by means of electrogastrography (EGG) to investigate a putative association with either the disease state and its symptoms

  14. Pectic polysaccharides of the fresh plum Prunus domestica L. isolated with a simulated gastric fluid and their anti-inflammatory and antioxidant activities.

    PubMed

    Popov, Sergey V; Ovodova, Raisa G; Golovchenko, Victoria V; Khramova, Daria S; Markov, Pavel A; Smirnov, Vasily V; Shashkov, Alexandre S; Ovodov, Yury S

    2014-01-15

    A pectic polysaccharide, designated as PD, was extracted from fresh plums (Prunus domestica L.) with a simulated gastric fluid. Galacturonan, which was partially substituted with methyl and O-acetyl ester groups, and rhamnogalacturonan were the main constituents of the linear regions of the sugar chains of PD. The ramified region contained mainly 1,4-linked ?-d-galactopyranose residues and, to a lesser extent, 1,5-linked ?-l-arabinofuranose residues. The separation of PD, by DEAE-cellulose column chromatography, yielded two pectic fractions: PD-1 and PD-2, eluted with 0.1 and 0.2 M NaCl, respectively. Enzymatic digestion of PD with 1,4-?-d-polygalacturonase yielded the fraction PD-E. The parent pectin PD and the PD-1 fraction were found to diminish the adhesion of peritoneal leukocytes at the concentrations of 0.05-1.0mg/ml. However, the PD-E fraction failed to have an effect on cell adhesion at the concentrations of 0.05-0.1mg/ml. PD, PD-1 and PD-E were found to inhibit the production of superoxide anion radicals by reducing xanthine oxidase activity by 38%, 97% and 47%, respectively. Therefore, the PD-1 fraction appeared to be an active fragment of pectic macromolecule isolated from fresh plum with a simulated gastric fluid. PMID:24054219

  15. Gastric dysmotility in patients with major depression

    Microsoft Academic Search

    Carmen Ruhland; Mandy Koschke; Wolf Greiner; Jeannine Peupelmann; Uta Pietsch; Michael Hocke; Vikram K. Yeragani; Karl-Jürgen Bär

    2008-01-01

    BackgroundDepressed patients frequently complain about vegetative symptoms. The aim of the present study was to evaluate gastric electrical activity in patients suffering from major depression in relation to their symptoms.

  16. Adjustable gastric banding (image)

    MedlinePLUS

    Restrictive gastric operations, such as an adjustable gastric banding procedure, serve only to restrict and decrease food intake and do not interfere with the normal digestive process. In this procedure, a hollow ...

  17. Stages of Gastric Cancer

    MedlinePLUS

    ... cancer) cells form in the lining of the stomach. The stomach is a J-shaped organ in ... Prevention Stomach (Gastric) Cancer Screening Age, diet, and stomach disease can affect the risk of developing gastric ...

  18. Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity

    PubMed Central

    2013-01-01

    Background Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect. PMID:23866830

  19. RAPTOR GASTRIC JUICE

    Microsoft Academic Search

    J. H. Cummings; G. E. Duke; A. A. Jegers

    1976-01-01

    To determine whether falconiforms digest the bones of their prey more thor- oughly than strigiforms because of greater gastric acidity in falconiforms, mouse bones were incubated in solutions simulating gastric juice from the two orders. Solutions simulating the gastric juice of falconiforms with a pH of 1.66 corroded bones more extensively than solutions simulating strigiform gastric juice with a pH

  20. Gastric cancer.

    PubMed Central

    McCulloch, P.

    1996-01-01

    We are gaining a clearer insight into the causes and mechanisms of gastric carcinogenesis, and may be able to reduce the incidence in the future by Helicobacter pylori eradication, perhaps in conjunction with nutritional supplements. The work required to establish this kind of prevention programme still has a long way to go. Surveillance and early detection are a key area, and current hopes rest with an increasingly low threshold for gastroscopy together with improved awareness in both patients and general practitioners. Identification of a high-risk group for surveillance would be a major advance, and may become possible due to advances in molecular biology. In terms of treatment, surgery remains the mainstay, but for useful analysis of its' efficacy, uniform and detailed pathological staging is vital. Pre-operative assessment has improved greatly in recent years, resulting in fewer nontherapeutic laparotomies, thanks to a combination of improved imaging techniques and laparoscopy. Limited endoscopic surgery is now feasible for very early disease. The extent of radical surgery remains controversial: a strong argument can be made for concentrating this kind of surgery in the hands of a limited number of specialist units who will have the numbers and the expertise to answer the outstanding questions. Chemotherapy has yet to prove its value, but there are hopes that the newest regimes may do this. Treatment results in the West remain unsatisfactory, but they have improved in the last two decades, and should be capable of considerable further improvement. Images Figure PMID:8796206

  1. Animal models of gastric bleeding induced by dual antiplatelet therapy using aspirin and clopidogrel--prophylactic effect of antiulcer drugs.

    PubMed

    Takeuchi, Koji; Izuhara, Chitose; Takayama, Shinichi; Momode, Takumi; Kojo, Masahiro; Hara, Daisuke; Amagase, Kikuko

    2014-01-01

    We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y?? receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into the rat stomach, one from the esophagus and another through the pylorus via an incision in the duodenum. In the first model, the stomach was perfused with 25 mM ASA dissolved in 50 mM HCl using an infusion pump, and gastric bleeding was measured as the hemoglobin concentration in perfusate collected every 15 min. In the second model, the stomach was perfused with ASA under stimulation of acid secretion by a continuous i.v. infusion of histamine (8 mg/kg/hr). Clopidogrel (30 mg/kg) was given p.o. 24 h before the ASA perfusion, while antiulcer drugs were given i.d. or i.v. 30 min before. Perfusion of the stomach with acidified ASA or ASA under histamine-stimulated acid secretion caused minimal bleeding in the stomach with few lesions. The ulcerogenic and bleeding responses to ASA under these conditions were markedly aggravated by pretreatment with clopidogrel, which by itself provoked neither bleeding nor damage. Antiulcer drugs, such as prostaglandin E?, irsogladine, rebamipide and teprenone, reduced the severity of gastric bleeding and damage in response to ASA plus clopidogrel in the presence of both exogenous and endogenous acid. In contrast, antisecretory drugs such as a proton pump inhibitor and histamine H? receptor antagonists markedly suppressed the gastric bleeding and lesion responses to ASA plus clopidogrel under histamine-stimulated acid secretion, but had no effect on the responses to acidified ASA plus clopidogrel. These results suggest that clopidogrel increases gastric bleeding induced by ASA and that antiulcer drugs are useful for preventing gastric bleeding caused by the dual antiplatelet therapy. PMID:23782140

  2. ?-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity

    PubMed Central

    Herman, Melissa A.; Alayan, Alisa; Sahibzada, Niaz; Bayer, Barbara; Verbalis, Joseph; Dretchen, Kenneth L.

    2010-01-01

    We examined the effects of altering ?-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 1–10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABAA receptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons. PMID:20489046

  3. Antitumor activity of polysaccharide extracted from Pleurotus ostreatus mycelia against gastric cancer in vitro and in vivo.

    PubMed

    Cao, Xiang-Yu; Liu, Jian-Li; Yang, Wei; Hou, Xiao; Li, Qi-Jiu

    2015-08-01

    The present study aimed to determine the antitumor effects of polysaccharides extracted from Pleurotus ostreatus mycelium on gastric cancer in vitro and in vivo. Polysaccharides were extracted from Pleurotus ostreatus mycelium and an antitumor component, known as Pleurotus ostreatus mycelium polysaccharides 2 (POMP2), with a relative molecular weight of 29 kDa, was then sequentially purified using Sephadex G200 size?exclusion chromatography and diethylaminoethyl?52 cellulose ion?exchange chromatography. The MTT method was used to determine the proliferation of BGC?823 cells treated with POMP2; cell migration assay, colony formation assay and in vivo antitumor tests were used to assess the effect of POMP2 on migration, cell survival and the in vivo tumor formation of BGH-823 cells. Results of the MTT assay indicated that POMP2 had a marked inhibitory effect on the BGC?823 human gastric cancer cell line; when administered at a concentration of 400 mg/l for 72 h, the rate of inhibition was 35.6%. In addition, the colony forming capacity of the BGC?823 cells was significantly reduced following treatment with POMP2. A migration assay indicated that the invasive capabilities of the BGC?823 cells were also significantly inhibited by POMP2. Furthermore, in vivo tests of mice engrafted with BGC?823 cancer cells demonstrated that both tumor weight and volume were markedly reduced following two weeks of treatment with POMP2. The results of the present study suggested that the polysaccharide POMP2 may have a potential application as a natural antitumor treatment for gastric cancer. PMID:25892617

  4. Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

    PubMed Central

    Dürr, Katharina L.; Tavraz, Neslihan N.; Friedrich, Thomas

    2012-01-01

    Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50?50, by ?100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P?E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ?90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P?E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P?E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ?0.5 and ?0.2, respectively. PMID:22448261

  5. Activation of intercellular adhesion molecule 1 expression by Helicobacter pylori is regulated by NF-kappaB in gastric epithelial cancer cells.

    PubMed

    Mori, N; Wada, A; Hirayama, T; Parks, T P; Stratowa, C; Yamamoto, N

    2000-04-01

    Interactions between leukocytes and epithelial cells may play a key role in Helicobacter pylori-associated gastric mucosal inflammation. This process is mediated by various cell adhesion molecules. The present study examined the molecular mechanisms leading to H. pylori-induced epithelial cell intercellular adhesion molecule-1 (ICAM-1; also called CD54) expression. Coculture of epithelial cells with cytotoxin-associated gene pathogenicity island-positive (cag PAI(+)) H. pylori strains, but not with a cag PAI(-) strain or H. pylori culture supernatants, resulted in upregulation of steady-state mRNA levels and cell surface expression of ICAM-1. Coculture with H. pylori induced an increase in luciferase activity in cells which were transfected with a luciferase reporter gene linked to the 5'-flanking region of the ICAM-1 gene. H. pylori activated the ICAM-1 promoter via the NF-kappaB binding site. An inducible nuclear protein complex bound to the ICAM-1 NF-kappaB site and was identified as the NF-kappaB p50-p65 heterodimer. H. pylori induced the degradation of IkappaB-alpha, a major cytoplasmic inhibitor of NF-kappaB, and stimulated the expression of IkappaB-alpha mRNA. Pretreatment of epithelial cells with pyrrolidine dithiocarbamate, which blocks NF-kappaB activation, inhibited H. pylori-induced ICAM-1 expression. THP-1 macrophagic cells, peripheral blood mononuclear cells, and purified neutrophils adhered to H. pylori-infected epithelial cells to a greater extent than to uninfected cells. These results show that H. pylori directly induces expression of ICAM-1 on gastric epithelial cells in an NF-kappaB-dependent manner that may support leukocyte attachment during inflammation. PMID:10722567

  6. Structure-activity relationships of ?-, ?(1)-, ?-, and ?-tomatine and tomatidine against human breast (MDA-MB-231), gastric (KATO-III), and prostate (PC3) cancer cells.

    PubMed

    Choi, Suk Hyun; Ahn, Jun-Bae; Kozukue, Nobuyuki; Kim, Hyun-Jeong; Nishitani, Yosuke; Zhang, Ling; Mizuno, Masashi; Levin, Carol E; Friedman, Mendel

    2012-04-18

    Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid ?-tomatine resulted in the formation of four products with three, two, one, and zero carbohydrate side chains, which were separated by high-performance liquid chromatography (HPLC) and identified by thin-layer chromatography (TLC) and liquid chromatography ion-trap time-of-flight mass spectrometry (LCMS-IT-TOF). The inhibitory activities in terms of IC(50) values (concentration that inhibits 50% of the cells under the test conditions) of the parent compound and the hydrolysates, isolated by preparative HPLC, against normal human liver and lung cells and human breast, gastric, and prostate cancer cells indicate that (a) the removal of sugars significantly reduced the concentration-dependent cell-inhibiting effects of the test compounds, (b) PC3 prostate cancer cells were about 10 times more susceptible to inhibition by ?-tomatine than the breast and gastric cancer cells or the normal cells, (c) the activity of ?-tomatine against the prostate cancer cells was 200 times greater than that of the aglycone tomatidine, and (d) the activity increased as the number of sugars on the aglycone increased, but this was only statistically significant at p < 0.05 for the normal lung Hel299 cell line. The effect of the alkaloids on tumor necrosis factor ? (TNF-?) was measured in RAW264.7 macrophage cells. There was a statistically significant negative correlation between the dosage of ?- and ?-tomatine and the level of TNF-?. ?-Tomatine was the most effective compound at reducing TNF-?. The dietary significance of the results and future research needs are discussed. PMID:22482398

  7. Gastric sensitivity and reflexes: basic mechanisms underlying clinical problems.

    PubMed

    Azpiroz, Fernando; Feinle-Bisset, Christine; Grundy, David; Tack, Jan

    2014-02-01

    Both reflex and sensory mechanisms control the function of the stomach, and disturbances in these mechanisms may explain the pathophysiology of disorders of gastric function. The objective of this report is to perform a literature-based critical analysis of new, relevant or conflicting information on gastric sensitivity and reflexes, with particular emphasis on the comprehensive integration of basic and clinical research data. The stomach exerts both phasic and tonic muscular (contractile and relaxatory) activity. Gastric tone determines the capacity of the stomach and mediates both gastric accommodation to a meal as well as gastric emptying, by partial relaxation or progressive recontraction, respectively. Perception and reflex afferent pathways from the stomach are activated independently by specific stimuli, suggesting that the terminal nerve endings operate as specialized receptors. Particularly, perception appears to be related to stimulation of tension receptors, while the existence of volume receptors in the stomach is uncertain. Reliable techniques have been developed to measure gastric perception and reflexes both in experimental and clinical conditions, and have facilitated the identification of abnormal responses in patients with gastric disorders. Gastroparesis is characterised by impaired gastric tone and contractility, whereas patients with functional dyspepsia have impaired accommodation, associated with antral distention and increased gastric sensitivity. An integrated view of fragmented knowledge allows the design of pathophysiological models in an attempt to explain disorders of gastric function, and may facilitate the development of mechanistically orientated treatments. PMID:24306100

  8. Gastric emptying in infants with gastroesophageal reflux

    Microsoft Academic Search

    Joel M. Andres; John R. Mathias; Mary H. Clench; Richard H. Davis

    1988-01-01

    It is well established that liquid emptying occurs in the absence of motor activity of the stomach. In contrast, solid-phase emptying is controlled in part by antral peristalsis and is, therefore, a more precise indicator of gastric motility. We developed a semisolid, radionuclide gastric emptying test using rice cereal and technetium-99m-sulfur colloid to assess antral physiology in infants with vomiting.

  9. Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN?45 gastric carcinoma cells.

    PubMed

    Tsuchiya, Mitsumasa; Yamaguchi, Fuminori; Shimamoto, Seiko; Fujimoto, Tomohito; Tokumitsu, Hiroshi; Tokuda, Masaaki; Kobayashi, Ryoji

    2014-12-01

    S100 proteins bind to numerous target proteins, as well as other S100 proteins and activate signaling cascades. S100 proteins can be modified by various post-translational modifications, such as phosphorylation, methylation and acetylation. In addition, oxidation is important for modulating their activities. Previous studies have shown that S100A1 interacts with S100A4 in vitro and in vivo. Due to this potential cross?talk among the S100 proteins, the aim of the present study was to examine whether S100A4 modulates the activity of S100A1. S100A4 was readily oxidized and formed disulfide-linked dimers and oligomers. Although non-oxidized S100A4 bound to protein phosphatase 5 (PP5), the Cu-oxidized S100A4 failed to bind PP5. Instead, the Cu-oxidized S100A4 directly interacted with S100A1 and prevented PP5 activation. Hydrogen peroxide induced S100A4 oxidation in MKN-45 gastric adenocarcinoma cells and decreased S100A1?PP5 interaction, resulted in the inhibition of PP5 activation by S100A1. These data indicate that oxidized S100A4 regulates PP5 activity in a unique manner under oxidative stress conditions. PMID:25269953

  10. Gastric dysmotility in healthy first-degree relatives of patients with schizophrenia

    Microsoft Academic Search

    Sandy Berger; Michael Hocke; Karl-Jürgen Bär

    2010-01-01

    Gastric dysmotility has been reported in patients suffering from major depression or schizophrenia. An increased sympathetic activity modulating the gastric pacemaker located in the antrum of the stomach has been suggested as the underlying pathology. Similar to patients suffering from schizophrenia, their first-degree relatives showed alterations in cardiac autonomic modulation. Here we aimed to investigate gastric myoelectrical activity in healthy

  11. Influence of experimental hypokinesia on gastric secretory function

    NASA Technical Reports Server (NTRS)

    Markova, O. O.; Vavryshchuk, V. I.; Rozvodovskyy, V. I.; Proshcheruk, V. A.

    1980-01-01

    The gastric secretory function of rats was studied in 4, 8, 16 and 30 day hypokinesia. Inhibition of both the gastric juice secretory and acid producing functions was found. The greatest inhibition was observed on day 8 of limited mobility. By days 16 and 30 of the experiment, a tendency of the gastric secretory activity to return to normal was observed, although it remained reduced.

  12. Gastric physiology and function: effects of fruit juices.

    PubMed

    Moukarzel, A A; Sabri, M T

    1996-10-01

    The stomach stores food and starts digesting protein and fat. Lipids, sugars, certain amino acids, and nutrients of high osmolality trigger sensory mechanisms from the intestine which inhibit gastric emptying. Food rich in carbohydrates leaves the stomach slower than protein-rich food, and emptying is slowest after a meal containing lipid. For carbohydrate beverages, the gastric emptying rate is primarily determined by the volume, caloric content, and osmolality of fluid ingested. Gastric emptying rates vary among isocaloric beverages of different type (e.g., sucrose, fructose, galactose) or forms (e.g., maltodextrins, starches) of carbohydrate. For instance, gastric emptying is faster for a fructose solution compared with isocaloric glucose and galactose solutions. A maltodextrin or a sucrose solution empties faster than a glucose solution. This is possibly due to the greater inhibitory feedback associated with the introduction of glucose in the duodenum. In addition, fruit juices contain soluble fibers which further modulate the gastric emptying. Noninvasive methods to study gastric emptying have recently been developed. The pattern of the myoelectric activity of the gastric contraction and the effect of meals on this pattern can now be recorded by cutaneous electrodes. In healthy children ingesting different juices, the myoelectric pattern of the stomach (indicator of the gastric emptying) correlates with the carbohydrate absorption (measured by breath hydrogen excretion). Fast gastric emptying was associated with greater production of breath hydrogen. The malabsorption of juice carbohydrates may in part be related to their effect on gastric motility. PMID:8892179

  13. Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells.

    PubMed

    Chan, Chien-Pin; Tsai, Yao-Ting; Chen, Yao-Li; Hsu, Yu-Wen; Tseng, Joseph T; Chuang, Hung-Yi; Shiurba, Robert; Lee, Mei-Hsien; Wang, Jaw-Yuan; Chang, Wei-Chiao

    2015-02-01

    Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 ?M lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture. PMID:23765435

  14. Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model

    PubMed Central

    2014-01-01

    Background A decoction of Crassocephallum vitellinum (Benth.) S. Moore (Asteraceae) is used in Kagera Region to treat peptic ulcers. This study seeks to evaluate an aqueous ethanol extract of aerial parts of the plant for safety and efficacy. Methods An 80% ethanolic extract of C. vitellinum at doses of 100, 200, 400 and 800 mg/kg body wt was evaluated for ability to protect Sprague Dawley rats from acidified ethanol gastric ulceration in comparison with 40 mg/kg body wt pantoprazole. The extract and its dichloromethane, ethyl acetate, and aqueous fractions were also evaluated for acute toxicity in mice, brine shrimp toxicity, and antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholera (clinical isolate), and Streptococcus faecalis (clinical isolate). The groups of phytochemicals present in the extract were also determined. Results The ethanolic extract of C. vitellinum dose-dependently protected rat gastric mucosa against ethanol/HCl insult to a maximum of 88.3% at 800 mg/kg body wt, affording the same level of protection as by 40 mg/kg body wt pantoprazole. The extract also exhibited weak antibacterial activity against S. typhi and E. coli, while its ethyl acetate, dichloromethane and aqueous fractions showed weak activity against K. pneumonia, S.typhi, E. coli and V. cholera. The extract was non-toxic to mice up to 5000 mg/kg body wt, and the total extract (LC50?=?37.49 ?g/ml) and the aqueous (LC50?=?87.92 ?g/ml), ethyl acetate (LC50?=?119.45 ?g/ml) and dichloromethane fractions (88.79 ?g/ml) showed low toxicity against brine shrimps. Phytochemical screening showed that the extract contains tannins, saponins, flavonoids, and terpenoids. Conclusion The results support the claims by traditional healers that a decoction of C.vitellinum has antiulcer activity. The mechanism of cytoprotection is yet to be determined but the phenolic compounds present in the extract may contribute to its protective actions. However, the dose conferring gastro-protection in the rat is too big to be translated to clinical application; thus bioassay guided fractionation to identify active compound/s or fractions is needed, and use of more peptic ulcer models to determine the mechanism for the protective action. PMID:24552147

  15. Regulatory role of guanine nucleotide exchange factor (GEF) Dock180 phosphorylation on Tyr/Ser in mediation of gastric mucosal Rac1 activation in response to Helicobacter pylori and ghrelin.

    PubMed

    Slomiany, B L; Slomiany, A

    2015-06-01

    A small GTPase, Rac1, is recognized as an important modulator of the inflammatory responses to bacterial lipopolysaccharide (LPS) by affecting the processes of phospholipase C activation. The activation of Rac1 involves the exchange of GDP for GTP and is catalyzed by the guanine nucleotide exchange factors (GEFs). Here, we report on the gastric mucosal GEF, Dock180, activation in response to H. pylori PS, and the hormone, ghrelin. We show that stimulation of gastric mucosal cells with the LPS leads to up-regulation in Dock180 phosphorylation on Tyr and Ser that is accompanied by a massive rise in Rac1-GTP level, while the effect of ghrelin, manifested by a drop in Dock180 phosphorylation on Ser, is associated with a decrease in Rac1-GTP formation. Furthermore, we demonstrate that phosphorylation on Tyr remains under the control of the Src family protein tyrosine kinases (SFK-PTKs), and is accompanied by Dock180 membrane translocation, while phosphorylation of the membrane-localized Dock180 on Ser represents the stimulatory contribution of protein kinase C? (PKC?) to Dock180 activation. Moreover, we reveal that the interaction between Dock180 and PKC? is dependent on Dock180 Tyr phosphorylation as well as the activity of PKC?. Thus, our findings point to the involvement of PKC? in the LPS-induced up-regulation of Dock180 activation, and suggest the modulatory mechanism of ghrelin influence on the gastric mucosal inflammatory responses to H. pylori. PMID:25957600

  16. Vection-induced gastric dysrhythmias and motion sickness

    NASA Technical Reports Server (NTRS)

    Koch, K. L.; Stern, R. M.

    1986-01-01

    Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects.

  17. KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis.

    PubMed

    Wang, Zhenran; Tang, Fang; Qi, Guangying; Yuan, Shengguang; Zhang, Guangyu; Tang, Bo; He, Songqing

    2015-01-01

    Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. KDM5B (also known as JARID1B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 4 on histone H3. Recent observations have shown oncogenic activity of KDM5B. However, the role of KDM5B in gastric cancer carcinogenesis remains unclear. In this study, we aimed to investigate the role of KDM5B in gastric cancer. Immunohistochemical analysis, western blotting, and qRT-PCR were used to measure the levels of KDM5B in gastric cancer cell lines, 45 pairs of gastric cancer tissues and the adjacent nonneoplastic tissues. KDM5B and shKDM5B were transfected into gastric cancer cells to investigate its role on regulating cell proliferation which was measured by MTT and colony formation assay. Cell's migration and invasion were measured by Transwell and Matrigel analysis in vitro. PCNA expression was measured by immunofluorescence staining and immunohistochemical analysis. The in vivo tumorigenesis and metastasis assays were performed in SCID mice. In clinical gastric cancer samples, we found that KDM5B expression was significantly up-regulated in cancer lesions compared with paired normal gastric tissues. By silencing or overexpressing KDM5B in gastric cancer cells, we found that KDM5B could promote cell growth and metastasis in vitro. An in vivo assay showed that KDM5B not only dramatically promoted gastric cancer cell xenograft formation and growth but also promoted gastric cancer cell metastasis in a liver metastasis model. Moreover, we demonstrated that KDM5B promoted gastric cancer metastasis via regulation of the Akt pathway. Our study provided evidence that KDM5B functions as a novel tumor oncogene in gastric cancer and may be a potential therapeutic target for gastric cancer management. PMID:25628922

  18. Multiple receptor tyrosine kinase activation attenuates therapeutic efficacy of the fibroblast growth factor receptor 2 inhibitor AZD4547 in FGFR2 amplified gastric cancer.

    PubMed

    Chang, Jinjia; Wang, Shanshan; Zhang, Zhe; Liu, Xinyang; Wu, Zheng; Geng, Ruixuan; Ge, Xiaoxiao; Dai, Congqi; Liu, Rujiao; Zhang, Qunling; Li, Wenhua; Li, Jin

    2015-02-10

    Fibroblast growth factor receptor 2 (FGFR2)-targeted therapy has attracted considerable attention as novel anticancer agents in gastric cancer (GC). However, intrinsic or acquired drug resistance has emerged as a major challenge to their clinical use. In this study, we demonstrated that several receptor tyrosine kinase (RTK), including EGFR, HER3 and MET, activations contributed to AZD4547 (a selective FGFR2 inhibitor) hyposensitivity in FGFR2 amplified GC cells. The rescue effect was abrogated by inhibiting these RTKs with their targeted tyrosine kinase inhibitors (TKIs). In addition, synergy in growth inhibition was observed when the GC cells were treated with a combination of AZD4547 and cetuximab (an EGFR monoclonal antibody) both in vitro and in vivo. More importantly, tissue microarray analysis revealed that these resistance-conferring RTKs were highly expressed in FGFR2 positive GC patients. Taken together, these observations demonstrated RTKs including EGFR, HER3 and MET activations as novel mechanisms of hyposensitivity to AZD4547. It will be clinically valuable to investigate the involvement of RTK-mediated signaling in intrinsicor acquired resistance to FGFR2 TKIs in GC. A combination targeted therapeutic strategy may be recommended for treating FGFR2 amplified GC patients with these RTK activations. PMID:25576915

  19. Multiple receptor tyrosine kinase activation attenuates therapeutic efficacy of the fibroblast growth factor receptor 2 inhibitor AZD4547 in FGFR2 amplified gastric cancer

    PubMed Central

    Zhang, Zhe; Liu, Xinyang; Wu, Zheng; Geng, Ruixuan; Ge, Xiaoxiao; Dai, Congqi; Liu, Rujiao; Zhang, Qunling; Li, Wenhua; Li, Jin

    2015-01-01

    Fibroblast growth factor receptor 2 (FGFR2)-targeted therapy has attracted considerable attention as novel anticancer agents in gastric cancer (GC). However, intrinsic or acquired drug resistance has emerged as a major challenge to their clinical use. In this study, we demonstrated that several receptor tyrosine kinase (RTK), including EGFR, HER3 and MET, activations contributed to AZD4547 (a selective FGFR2 inhibitor) hyposensitivity in FGFR2 amplified GC cells. The rescue effect was abrogated by inhibiting these RTKs with their targeted tyrosine kinase inhibitors (TKIs). In addition, synergy in growth inhibition was observed when the GC cells were treated with a combination of AZD4547 and cetuximab (an EGFR monoclonal antibody) both in vitro and in vivo. More importantly, tissue microarray analysis revealed that these resistance-conferring RTKs were highly expressed in FGFR2 positive GC patients. Taken together, these observations demonstrated RTKs including EGFR, HER3 and MET activations as novel mechanisms of hyposensitivity to AZD4547. It will be clinically valuable to investigate the involvement of RTK-mediated signaling in intrinsicor acquired resistance to FGFR2 TKIs in GC. A combination targeted therapeutic strategy may be recommended for treating FGFR2 amplified GC patients with these RTK activations. PMID:25576915

  20. Effect of Electrical Stimulation on Acupuncture Points in Diabetic Patients with Gastric Dysrhythmia: A Pilot Study

    Microsoft Academic Search

    Chi-Sen Chang; Chung-Wang Ko; Chun-Ying Wu; Gran-Hum Chen

    2001-01-01

    Background\\/Aims: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. Methods: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months

  1. Evaluation of antitumour effects of docetaxel (Taxotere®) on human gastric cancers In vitro and In vivo

    Microsoft Academic Search

    M. Tanaka; T. Obata; T. Sasaki

    1996-01-01

    In vitro antitumour effects of docetaxel (Taxotere®) were examined in nine cultured human gastric cancer cell lines and 18 clinical gastric cancer specimens. In vivo antitumour effects were examined in human gastric cancer xenografts in nude mice. The activity was compared with paclitaxel (Taxol®). Docetaxel was more effective than paclitaxel in six of the nine cell lines and the effectiveness

  2. Expression of the ?-phosphorylated histone H2AX in gastric carcinoma and gastric precancerous lesions

    PubMed Central

    GUO, ZHONG; PEI, SHUYAN; SI, TIANBIN; LI, JING; JIANG, CHAO; LI, SHANGBIAO; ZHAO, JIN

    2015-01-01

    The histone ?H2AX is a marker of activated DNA damage that is overexpressed in various cancers and corresponding precursor lesions, indicating that ?H2AX is a component in oncogenic transformation. The present study aimed to determine whether the immunohistochemical expression of ?H2AX is involved in the progression between superficial gastritis (n=20), atrophic gastritis (n=24) and gastric carcinoma (n=79). There was no increase in ?H2AX expression between superficial and atrophic gastritis, but there was a significant increase in ?H2AX expression between these two conditions and gastric carcinoma (?2=68.712; P<0.001). The expression of ?H2AX in moderately-differentiated gastric adenocarcinoma (n=49) was evidently higher compared with poorly-differentiated gastric adenocarcinoma (n=26; ?2=14.241; P<0.01). Staining for ?H2AX did not reveal a significant association between the expression of the histone and patient age, depth of invasion, lymph node metastasis or the tumor-node-metastasis stage of the gastric carcinoma. Overall, the present study demonstrated that enhanced ?H2AX expression may be closely associated with gastric carcinoma, but is less likely to be involved in the genesis of gastric carcinoma. PMID:25789044

  3. Gastric Infection by Helicobacter pylori

    PubMed Central

    Sachs, George; Wen, Yi; Scott, David R.

    2015-01-01

    Helicobacter pylori infection causes chronic active gastritis, ulcer disease, and gastric cancer. Current eradication regimens use a proton pump inhibitor (PPI) and two antibiotics. Triple therapy now has a success rate less than 80%, below the cutoff for efficacious eradication. Antibiotic resistance, inconsistent acid control by PPIs, and poor patient compliance contribute to the failure rate. H. pylori is a neutralophile that has developed special acid acclimation mechanisms to colonize its acidic gastric niche. Identifying the components of these mechanisms will provide novel bactericidal drug targets. Alternatively, better 24-hour acid control would increase the efficacy of antibiotics, leading to dual therapy with improved PPIs and amoxicillin. Studies of acid acclimation by H. pylori have identified several potential eradication targets including UreI, ?-carbonic anhydrase, and a two-component system. Continuing improvement of PPIs has led to the development of at least three candidate drugs with improved 24-hour acid control. PMID:19903421

  4. Long noncoding RNA linc-UBC1 is negative prognostic factor and exhibits tumor pro-oncogenic activity in gastric cancer

    PubMed Central

    Hu, Yiren; Pan, Jianghua; Wang, Yi; Li, Linjing; Huang, Yi

    2015-01-01

    Despite the advances in the management of gastric cancer, the prognosis of advanced gastric cancer remains relatively poor. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of gastric cancer. A growing volume of literature has indicated that lncRNAs are differentially expressed in a diverse array of cancer and play an important role in the development of cancer. Linc-UBC1, a recently identified long noncoding RNA, was initially found to be upregulated in bladder cancer. However, the role of linc-UBC1 in gastric cancer remains to be elusive. In this study, we found that linc-UBC1 was significantly upregulated in gastric cancer tissues compared to adjacent normal tissues. Furthermore, high linc-UBC1 expression was associated with lymph-node metastasis, tumor size, TNM stage and poorer prognosis. Inhibition of linc-UBC1 suppressed the proliferation, motility and invasion of gastric cancer cells. Our study suggests that linc-UBC1 may represent a novel diagnostic, prognostic biomarker and a potential therapeutic target of gastric cancer. PMID:25755750

  5. Malignant gastric ghrelinoma with hyperghrelinemia.

    PubMed

    Tsolakis, Apostolos V; Portela-Gomes, Guida M; Stridsberg, Mats; Grimelius, Lars; Sundin, Anders; Eriksson, Barbro K; Oberg, Kjell E; Janson, Eva T

    2004-08-01

    A characteristic feature of neuroendocrine tumors is production and release of peptide hormone. Ghrelin is a 28-amino acid hormone that stimulates GH release. In this paper, we describe a patient with a metastasizing gastric neuroendocrine tumor displaying intense immunoreactivity for ghrelin and extremely high circulating levels of ghrelin. Tumor tissue biopsies from the primary tumor and one liver metastasis were examined by immunohistochemistry. Ghrelin and several other hormones and tumor markers were measured in blood. The clinical course of the patient was followed. Tumor tissue biopsies showed immunoreactivity for cytokeratin, chromogranin A, human synaptic vesicle protein 2, synaptophysin, and ghrelin. Grossly elevated circulating levels of total ghrelin, 2100 microg/liter (reference interval < 5 microg/liter) and active ghrelin, 28 microg/liter (reference interval < 0.1 microg/liter) were found at presentation. Chromogranin A, chromogranin B, and calcitonin levels were also increased. Both total and active ghrelin increased, despite treatment, during follow-up of the patient. We have identified and characterized a patient with a malignant gastric neuroendocrine tumor secreting ghrelin as the main hormone. This might be a new tumor entity of the stomach, and it is suggested that patients with malignant gastric neuroendocrine tumors should be investigated for ghrelin production. PMID:15292299

  6. Clot lysis by gastric juice: an in vitro study

    Microsoft Academic Search

    S E Patchett; H Enright; N Afdhal; W OConnell; D P ODonoghue

    1989-01-01

    Gastric juice from patients with peptic ulcer disease and from patients with no upper gastrointestinal abnormality was studied in order to assess its effect on a formed fibrin clot. In both groups of patients gastric juice caused a marked increase in fibrinolysis as evidenced by a shortening of the euglobulin clot lysis time. This plasmin mediated fibrinolytic activity was found

  7. Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations

    Microsoft Academic Search

    W D Neithercut; A Milne; R S Chittajallu; A M el Nujumi; K E McColl

    1991-01-01

    Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection

  8. Alkylating activity in food products--especially sauerkraut and sour fermented dairy products--after incubation with nitrite under quasi-gastric conditions.

    PubMed

    Groenen, P J; Busink, E

    1988-03-01

    N-Nitroso compounds may well rank high among the genotoxic carcinogens present in our environment. Small amounts of such compounds may be formed in the human stomach after consumption of high-nitrate vegetables. Volatile nitrosamines can be conveniently determined but reliable methods of analysis for non-volatile N-nitroso compounds are still lacking. In this study we have used the 4-(4-nitrobenzyl)pyridine test to look for the formation of alkylating compounds such as N-nitroso-N-methylurea in a wide range of food products after incubation with nitrite under simulated gastric conditions. Our results indicate that many food products do not form alkylating compounds in appreciable amounts, even though the nitrite concentration used was five to ten times that found in saliva after a high-nitrate meal. Comparatively strong alkylating activity, however, was detected after incubation of samples of sauerkraut, certain dairy products (yoghurt, biogarde, quark, buttermilk and milk), wine and smoked mackerel. Samples of sauerkraut incubated with simulated gastric fluid, but without (added) nitrite, also displayed appreciable alkylating activity. The formation of alkylating substances in non-fat yoghurt was markedly inhibited by addition of ascorbic acid. The identity of the alkylating agents remains unknown. The isolation procedure was optimized for N-nitroso-N-methylurea, but will certainly result in the isolation of other compounds, such as C-nitroso-, C-nitro- or perhaps even C-nitroso-C'-nitro-compounds as well. Biogenic amines, glucosinolates, indole derivatives or other compounds may be involved as precursors. If alkylating agents are formed in vivo after ingestion of high-nitrate vegetables or drinking water, this is likely to occur only when the food products mentioned above are ingested simultaneously with or shortly after the nitrate load and not appreciably (except perhaps in the case of sauerkraut) when they are ingested alone, without a nitrate source. The health implications of these findings cannot yet be established. Many alkylating agents, however, have strong carcinogenic properties and continued investigation of food products (and their interaction products with nitrite) is indicated. PMID:3366423

  9. Additive effects of EGF and IL-1? regulate tumor cell migration and invasion in gastric adenocarcinoma via activation of ERK1/2.

    PubMed

    Han, Junyong; Xie, Yanchuan; Lan, Fenghua; Yu, Yinghao; Liu, Wei; Chen, Jinhua; Zheng, Feng; Ouyang, Xuenong; Lin, Xiangquan; Lin, Yanhong; Huang, Qiaojia; Wang, Lie; Tan, Jianming

    2014-07-01

    Growth and inflammatory factors are associated with poor prognosis in gastric adenocarcinoma (GA); however, the additive effects of growth and inflammatory factors in GA remain unclear. In this study, we investigated the ability of epidermal growth factor (EGF) and interleukin (IL-1?) to activate extracellular signal-regulated kinase (ERK)1/2 in GA cells, and correlated the relationships between their roles with the metastatic potential both in GA cells and GA tissues. The effects of EGF, IL-1? and EGF plus IL-1? in AGS and MKN-45 GA cells were examined using western blotting, Transwell migration and invasion assays, immunocytochemical staining and an activator protein (AP)-1 luciferase reporter gene assay, and was further characterized in GA tissues by immunohistochemistry. The results exhibited that EGF and IL-1? additively activated ERK1/2, increased migration and invasion than either EGF or IL-1? alone in AGS and MKN-45 cells. The mechanisms were involved in upregulating MMP-9 expression through increasing AP-1 transcriptional activity via ERK1/2 pathway; these effects were dose-dependently inhibited by silencing ERK1/2 or using U0126. In vivo data also confirmed that the overexpression of p-ERK1/2 in GA tissues correlated well with the EGF, IL-1?, EGF plus IL-1?, and was associated with metastasis, which was well correlation with the expression of MMP-9 and c-fos (AP-1). The results demonstrate that growth and inflammatory factors play an important role in metastasis of GA by additively activating ERK-1/2 and AP-1, and upregulating MMP-9. As both cytokines contribute to the migration and invasion of GA cells, EGF/IL-1?/ERK1/2 pathways may be key pathways closely associated with GA progression. PMID:24789460

  10. Gastric Bypass Operation for Obesity

    Microsoft Academic Search

    Mathias A. L. Fobi; Hoil Lee; Ronald Holness; DeGaulle Cabinda

    1998-01-01

    . Gastric bypass is considered by many to be the gold standard for surgical treatment of obesity. Gastric bypass was\\u000a a natural evolution from gastric operations that were used for the treatment of peptic ulcer disease. Gastric bypass, first\\u000a described in 1967, has undergone many modifications. It presently exists as a hybrid operation. Gastric bypass operation has\\u000a been extensively scrutinized

  11. Functional p53 is required for triptolide-induced apoptosis and AP1 and nuclear factor-?B activation in gastric cancer cells

    Microsoft Academic Search

    Xiao-Hua Jiang; Benjamin Chun-Yu Wong; Marie Chia-Mi Lin; Geng-Hui Zhu; Hsiang-Fu Kung; Shi-Hu Jiang; Dan Yang; Shiu-Kum Lam; B C-Y Wong

    2001-01-01

    Triptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In the present study we investigated the potential therapeutic effects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with different p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were

  12. Small Molecule R1498 as a Well-Tolerated and Orally Active Kinase Inhibitor for Hepatocellular Carcinoma and Gastric Cancer Treatment via Targeting Angiogenesis and Mitosis Pathways

    PubMed Central

    Zhang, Chao; Wu, Xihan; Zhang, Meifang; Zhu, Liangcheng; Zhao, Rong; Xu, Danqing; Lin, Zhaohu; Liang, Chungen; Chen, Taiping; Chen, Li; Ren, Yi; Zhang, Joe; Qin, Ning; Zhang, Xiongwen

    2013-01-01

    Protein kinases play important roles in tumor development and progression. Lots of kinase inhibitors have entered into market and show promising clinical benefits. Here we report the discovery of a novel small molecule, well-tolerated, orally active kinase inhibitor, R1498, majorly targeting both angiogenic and mitotic pathways for the treatment of hepatocellular carcinoma (HCC) and gastric cancer (GC). A series of biochemical and cell-based assays indicated that the target kinase cluster of R1498 included Aurora kinases and VEGFR2 et al. R1498 showed moderate in vitro growth inhibition on a panel of tumor cells with IC50 of micromole range. The in vivo anti-tumor efficacy of R1498 was evaluated on a panel of GC and HCC xenografts in a parallel comparison with another multikinase inhibitor sorafenib. R1498 demonstrated superior efficacy and toxicity profile over sorafenib in all test models with >80% tumor growth inhibition and tumor regression in some xenogratfts. The therapeutic potential of R1498 was also highlighted by its efficacy on three human GC primary tumor derived xenograft models with 10–30% tumor regression rate. R1498 was shown to actively inhibit the Aurora A activity in vivo, and decrease the vascularization in tumors. Furthermore, R1498 presented good in vivo exposure and therapeutic window in the pharmacokinetic and dose range finding studies. Theses evidences indicate that R1498 is a potent, well-tolerated, orally active multitarget kinase inhibitor with a unique antiangiogenic and antiproliferative profile, and provide strong confidence for further development for HCC and GC therapy. PMID:23755206

  13. Effects of removal of Na(+) and Cl(-) on spontaneous electrical activity, slow wave, in the circular muscle of the guinea-pig gastric antrum.

    PubMed

    Tomita, T; Hata, T

    2000-10-01

    In the circular muscle of the guinea-pig gastric antrum, a decrease in the external Na(+) to less than 20 mM produced depolarization of the membrane with transient prolongation of the slow wave. This was followed by a high rhythmic activity. The activity was inhibited by reapplication of Na(+) before recovery. The depolarization in Na(+)-deficient solution was prevented and rhythmic activity continued at about 5/min for at least 6 min by simultaneous removal of K(+), Ca(2+), or Cl(-). After exposure to a Na(+)- and Cl(-)-deficient solution for a few minutes, reapplication of the Na(+) in Cl(-)-deficient solution inhibited generation of the slow wave until Cl(-) reapplication. Similar results were obtained when Na(+) and Cl(-) were reapplied in the absence of K(+) after exposure to a Na(+)-, K(+)-free, and Cl(-)-deficient solution, although the inhibition was weaker than Na(+) reapplication in a Cl(-)-deficient solution. In the presence of furosemide or bumetanide, a strong inhibition of activity was produced by the reapplication of Na(+) and Cl(-) after exposure to an Na(+)- and Cl(-)-deficient solution. A hypothesis is presented that intracellular Ca(2+) concentration ([Ca(2+)](i)) is the most important factor determining the generation and frequency of the slow wave and that [Ca(2+)](i) is regulated by the Na(+) concentration gradient across the plasma membrane. The recovery of the Na(+) concentration gradient by Na(+) reapplication after removal of Na(+) and Cl(-) is mainly controlled by a Na(+)-K(+)-Cl(-) co-transport. PMID:11120913

  14. Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and {beta}-adrenergic receptor signaling pathways

    SciTech Connect

    Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.; Yu Jun; Leung, W.K. [Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong (Hong Kong); Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong (Hong Kong); Cho, C.H. [Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong (Hong Kong); Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong (Hong Kong); Sung, J.J.Y. [Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong (Hong Kong); Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong SAR (Hong Kong)], E-mail: joesung@cuhk.edu.hku

    2008-12-01

    Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor ({alpha}7 nAChR) and {beta}-adrenergic receptors. Treatment of cells with {alpha}-bungarotoxin ({alpha}-BTX, {alpha}7nAChR antagonist) or propranolol ({beta}-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE{sub 2} and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE{sub 2} induction can only be suppressed by propranolol, but not {alpha}-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis.

  15. Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori and Novel Targeted Therapy

    PubMed Central

    Nishizawa, Toshihiro

    2015-01-01

    The oxygen-derived free radicals that are released from activated neutrophils are one of the cytotoxic factors of Helicobacter pylori-induced gastric mucosal injury. Increased cytidine deaminase activity in H. pylori-infected gastric tissues promotes the accumulation of various mutations and might promote gastric carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric epithelial cells via bacterial type IV secretion system, and it causes inflammation and activation of oncogenic pathways. H. pylori infection induces epigenetic transformations, such as aberrant promoter methylation in tumor-suppressor genes. Aberrant expression of microRNAs is also reportedly linked to gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER-2) therapies. This updated review article highlights possible mechanisms of gastric carcinogenesis including H. pylori-associated factors. PMID:25945346

  16. Gallic acid inhibits gastric cancer cells metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity

    SciTech Connect

    Ho, Hsieh-Hsun [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Chi-Sen [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan (China); Ho, Wei-Chi [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China)] [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China); Liao, Sheng-You [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China)] [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Lin, Wea-Lung [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China) [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Wang, Chau-Jong, E-mail: wcj@csmu.edu.tw [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China) [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

    2013-01-01

    Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-?B activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-?B activity. Thus, GA might be a potential agent in treating gastric cancer. Highlights: ? GA could downregulate AKT signal via increased expression of RhoB. ? GA inhibits metastasis in vitro in gastric carcinoma. ? GA inhibits tumor growth in nude mice model.

  17. Hereditary Diffuse Gastric Cancer

    MedlinePLUS

    ... highest rate of gastric cancer is found in China, Japan, and other countries in Southeast Asia, as ... them to help patients and families make informed health care decisions. Find a Cancer Doctor ASCO Conquer ...

  18. Occupation and gastric cancer

    PubMed Central

    Raj, A; Mayberry, J; Podas, T

    2003-01-01

    Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration. PMID:12782770

  19. Gastroprotective potentials of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats.

    PubMed

    Gomathy, G; Venkatesan, D; Palani, S

    2014-12-01

    This study investigated the protective effects of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats. Gastric ulceration was induced by single intraperitoneal injection of indomethacin (30 mg/kg b.wt.). M. maderaspatana extract produced significant reduction in gastric mucosal lesions, malondialdehyde and serum tumour necrosis factor-? associated with a significant increase in gastric juice mucin content and gastric mucosal catalase, nitric oxide and prostaglandin E2 levels. The volume and acidity of the gastric juice decreased in pretreated rats. The plant extract was evaluated in the gastric juice of rats, untreated has showed near normal levels in pretreated rats. The M. maderaspatana was able to decrease acidity and increase the mucosal defence in the gastric area, therefore justifying its use as an antiulcerogenic agent. Ranitidine significantly increased pH value and decreased pepsin activity and gastric juice free and total acidity. The anti-ulcer effect was further confirmed histologically. PMID:25471339

  20. Capsaicin and Gastric Ulcers

    Microsoft Academic Search

    M. N. Satyanarayana

    2006-01-01

    In recent years, infection of the stomach with the organism Helicobacter Pylori has been found to be the main cause of gastric ulcers, one of the common ailments afflicting humans. Excessive acid secretion in the stomach, reduction in gastric mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer formation.The

  1. Gastroduodenal ulcers in rats induced by 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP): requirement for gastric acid secretion and the role of prostaglandins.

    PubMed

    Keshavarzian, A; Haydek, J M; Zepeda, D O; Stinneford, J G; Fields, J Z

    1990-10-01

    To better study the neuropathophysiology of duodenal and gastric ulcers (DU & GU) an appropriate animal model is needed. One such model was recently provided by 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), a neurotoxin, which reliably induces DU and GU in rats that are macroscopically similar to human ulcers. However, the underlying ulcerogenic mechanism is not known. Accordingly, we investigated the roles of prostaglandins (PG) (cytoprotective factors) and omeprazole and atropine (inhibitors of gastric acid secretion) in DU, with GU as the secondary outcome measure. Compounds known to effectively inhibit gastric acid secretion in rats, omeprazole or atropine, totally prevented DU and GU. Doses of misoprostol, a PGE1 analog, that are known to be cytoprotective but not anti-secretory in rats decreased the frequency of DU but not GU. Meclofenamate or BW755c, compounds known to inhibit both cyclo-oxygenase and lipo-oxygenase and thus eicosanoid formation, worsened DU & GU. In order to further evaluate the role of PGs, levels of PGE2-alpha in gastric and duodenal mucosa were measured using an RIA assay. Following 4 days of MPTP injections, PGE2-alpha levels were significantly lowered in duodenal but not gastric mucosa. Thus, as in human ulcer disease, 1) MPTP-induced ulcers in rats also appears to require at least some gastric acid; 2) prostaglandins have an anti-ulcer effect against MPTP-induced DU but not GU. In addition, the mechanisms of DU and GU appear to be different even though there is a single etiology namely, MPTP. PMID:2124715

  2. Accelerated gastric epithelial proliferation.

    PubMed Central

    Gray, M R; Darnton, S J; Hunt, J A; Irlam, R W; Nemeth, J; Wallace, H M

    1995-01-01

    Gastric body mucosal proliferation was quantified and localised under conditions of increased gastrin drive using a variety of techniques. Rats were given omeprazole 400 mumol/kg/day by gavage and after 30 days mean serum gastrin rose 11-fold (p < 0.001). Total mucosal polyamines rose 220% from 15.9 to 50.9 nmol/mg protein (p < 0.001). This was associated with a 238% increase in crypt cell production rate from 0.541 to 1.83 crypt cells/h by vincristine metaphase arrest (p < 0.02). Using computer aided counting of proliferating cell nuclear antigen (PCNA) immunostained nuclei to assess epithelial proliferation in hypergastrinaemia rat stomach: mucus neck cell PCNA labelling was increased by 41% (p < 0.001) and gland cell PCNA labelling was increased by 222% (p < 0.001). PCNA/AgNOR (argyrophilic nuclear organiser regions) co-stained sections were used to assess proliferative activity in cycling and non-cycling cell populations. Data from these experiments suggest that, in addition to increasing the number of mucosal cells in cycle, cell life and cell cycle duration may be reduced in hypergastrinaemia. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7737557

  3. Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer

    PubMed Central

    Mizrak, Dilsa; Alkan, Ali; Erdogdu, Batuhan; Utkan, Gungor

    2015-01-01

    Osteogenesis imperfecta (OI) is a rare, inherited skeletal disorder characterized by abnormalities of type 1 collagen. Malignancy is rarely reported in patients with OI and it was suggested that this disease can protect against cancer. Here, we report a 41-year-old woman with symptoms of achalasia where repeated treatment of pneumatic dilation and stent replacement was unsuccessful; therefore, surgery was performed. Pathology showed gastric adenocarcinoma unexpectedly. Chemotherapy was given after assessing dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can be deficient in OI patients. This is the first report of gastric cancer mimicking achalasia in a patient with OI. PMID:25874139

  4. Endoscopic treatment for early gastric cancer

    PubMed Central

    Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Kim, Jae J.

    2014-01-01

    Gastric cancer remains one of the most common causes of cancer death. However the proportion of early gastric cancer (EGC) at diagnosis is increasing. Endoscopic treatment for EGC is actively performed worldwide in cases meeting specific criteria. Endoscopic mucosal resection can treat EGC with comparable results to surgery for selected cases. Endoscopic submucosal dissection (ESD) increases the en bloc and complete resection rates and reduces the local recurrence rate. ESD has been performed with expanded indication and is expected to be more widely used in the treatment of EGC through the technological advances in the near future. This review will describe the techniques, indications and outcomes of endoscopic treatment for EGC. PMID:24782609

  5. Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.

    PubMed Central

    Nilsson, O.; Wängberg, B.; Johansson, L.; Modlin, I. M.; Ahlman, H.

    1992-01-01

    The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied. Images FIG. 1 FIG. 2 FIG. 3 PMID:1341076

  6. Role of cyclooxygenase-2 in gastric cancer development and progression

    PubMed Central

    Cheng, Jian; Fan, Xiao-Ming

    2013-01-01

    Although the incidence of gastric cancer has been declining in recent decades, it remains a major public health issue as the second leading cause of cancer death worldwide. In China, gastric cancer is still the main cause of death in patients with malignant tumors. Most patients are diagnosed at an advanced stage and mortality is high. Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostanoid synthesis and plays an important role in the development and progression of gastric cancer. The expression of COX-2 in gastric cancer is upregulated and its molecular mechanisms have been investigated. Helicobacter pylori infection, tumor suppressor gene mutation and the activation of nuclear factor-kappa B may be responsible for the elevated expression of COX-2 in gastric cancer. The mechanisms of COX-2 in the development and progression of gastric cancer are probably through promoting the proliferation of gastric cancer cells, while inhibiting apoptosis, assisting angiogenesis and lymphatic metastasis, and participating in cancer invasion and immunosuppression. This review is intended to discuss, comment and summarize recent research progress on the role of COX-2 in gastric cancer development and progression, and elucidate the molecular mechanisms which might be involved in the carcinogenesis. PMID:24259966

  7. [Mechanisms of H. pylori infection-induced gastric carcinogenesis].

    PubMed

    Marusawa, Hiroyuki

    2010-01-01

    Many epidemiological studies have demonstrated a strong association between H. pylori (Helicobacter pylori) infection and human gastric cancer development. The precise mechanisms accounting for gastric cancer development induced by H. pylori infection are still not completely understood. However, it should be reasonable to assume that there are two distinct molecular pathways for gastric carcinogenesis by H. pylori infection; the direct action of the bacteria itself on gastric epithelial cells, and the accumulation of genetic changes caused by prolonged bacterial infection and chronic inflammation. As a direct action of H. pylori, bacterial proteins such as CagA could be delivered into gastric epithelial cells via the type IV secretion apparatus and modify the host cell functions related to cell proliferation. In addition to the direct bacterial action, H. pylori infection and the resultant inflammatory response cause various genetic and epigenetic changes in tumor-related genes of the gastric epithelial cells. Notably, expression of AID (activation-induced cytidine deaminase), a DNA editing enzyme that undergoes somatic hypermutation on human genes, is induced in response to H. pylori infection and proinflammatory cytokine stimulation in human gastric epithelial cells. As a result, the accumulation of genetic alterations would persist until the clinical stage of atrophic gastritis and eventually trigger the malignant transformation of gastric cells. PMID:20087030

  8. Laparoscopic gastric bypass versus laparoscopic adjustable gastric banding

    Microsoft Academic Search

    Laurent Biertho; Rudolf Steffen; Thomas Ricklin; Fritz F Horber; Alfons Pomp; William B Inabnet; Daniel Herron; Michel Gagner

    2003-01-01

    BackgroundIndications for and results of laparoscopic adjustable gastric banding (LAGB) and laparoscopic gastric bypass (LGB) are still controversial, especially between Europe and the United States. The recent availability of gastric bandings in the United States made it necessary to compare the two techniques.

  9. Gastric emphysema secondary to laparoscopic gastric band erosion

    PubMed Central

    Su, Michael Z.; Munro, William S.

    2014-01-01

    INTRODUCTION Gastric band erosion is a known complication of adjustable gastric band surgery. There are no previous reports of gastric band erosion associated with gastric emphysema (GE) or emphysematous gastritis (EG), a rare condition with a mortality rate exceeding 50%. PRESENTATION OF CASE We report the first known case of GE found in a 58-year-old lady presenting with acute onset epigastric abdominal pain and haematemesis in the setting of a chronically eroded gastric band. GE was visualised in the anterior gastric wall of the stomach without evidence of EG. Endoscopic and surgical examination of the stomach was undertaken along with band removal followed by defect repair. DISCUSSION GE can result from obstructive, traumatic and pulmonary causes. EG is a rare and often lethal form of GE resulting from bacterial invasion of the gastric wall through a mucosal defect leading to sepsis and gastric necrosis. Early reports documented early definitive operative debridement of necrotic gastric wall of patients with EG while recent reports have demonstrated a feasible non-operative approach among highly selected patients with no evidence of gastric necrosis. There are no previous reports on the treatment of patients with gastric band erosion and suspected EG. CONCLUSION Patients presenting acutely with symptomatic gastric band erosion, radiological evidence of GE with evidence of leucocytosis, peritonism or sepsis may develop EG. A high index of suspicion, low threshold for operative exploration and optimal management with antimicrobial therapy and close supportive care are necessary to ensure the best survival outcomes for these patients. PMID:25216194

  10. A review on gastric diverticulum

    PubMed Central

    2012-01-01

    The gastric fundal diverticulae are rare. They can present with variable symptoms. We are enclosing a literature review on gastric fundal diverticulum. Lessons have emerged which may help in the management of this rare condition in future. PMID:22257431

  11. Gastric teratoma with intramural extension

    Microsoft Academic Search

    J. P. Dunlap; C. A. James; R. T. Maxson; J. M. Bell; C. W. Wagner

    1995-01-01

    Gastric teratoma is an extremely rare neoplasm which accounts for less than two percent of all teratomas. Unlike other teratomas, gastric teratomas are all benign and predominantly occur in males. As gastric teratomas generally present as a palpable abdominal mass, more aggressive solid masses of childhood must be excluded. In this case, CT imaging delineates both cystic and fatty components

  12. Do We Need Gastric Acid?

    Microsoft Academic Search

    D. Pohl; M. Fox; M. Fried; B. Göke; C. Prinz; H. Mönnikes; G. Rogler; M. Dauer; J. Keller; F. Lippl; I. Schiefke; U. Seidler; H. D. Allescher

    2008-01-01

    Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage;

  13. Fundoplication enhances gastric emptying.

    PubMed Central

    Maddern, G J; Jamieson, G G

    1985-01-01

    Fundoplication of the stomach is an established surgical treatment of gastroesophageal reflux. Its mechanism of action remains unclear. To assess its effect on gastric emptying, 21 patients (11 men, 10 women), median age 47 years (range 19-72), underwent a gastric emptying study before and 6 months after fundoplication. Gastric emptying studies were performed after an overnight fast using a dual isotope technic. Solid and liquid emptying rates were assessed over 120 minutes. The time taken for 50% of the liquid marker to leave the gastric region was a median of 22 minutes before surgery (range 9-35) and 13 minutes after surgery (range 9-27) (p less than 0.01). The percentage of solid remaining in the stomach 100 minutes after ingestion was 50% before surgery (range 19-90) and 44% after surgery (range 5-89) (p less than 0.01). We conclude that gastric emptying of both solids and liquids tends to be increased following fundoplication. This observation suggests a further mechanism for the efficacy of this operation in the treatment of gastroesophageal reflux. PMID:3977428

  14. Hyperplastic gastric polyp causing progressive gastric outlet obstruction.

    PubMed

    Dean, P G; Davis, P M; Nascimento, A G; Farley, D R

    1998-10-01

    Hyperplastic polyps represent 75 to 90% of gastric polypoid lesions. The manifestations of these unique gastric neoplasms vary, including abdominal pain, nausea, and vomiting or gastrointestinal bleeding. The vast majority of these lesions are small, asymptomatic, and found incidentally on radiologic evaluation or endoscopic examination of the upper gastrointestinal tract. Herein we describe a large, benign, pedunculated hyperplastic polyp that led to progressive gastric outlet obstruction. In addition, we provide an overview of gastric polyps and a review of the literature. Excision of gastric polyps by endoscopic or surgical means is recommended as prudent treatment to eliminate occurrence of malignant foci. PMID:9787747

  15. Macrophage Migration Inhibitory Factor and Interleukin8 Produced by Gastric Epithelial Cells during Helicobacter pylori Exposure Induce Expression and Activation of the Epidermal Growth Factor Receptor

    Microsoft Academic Search

    Ellen J. Beswick; Victor E. Reyes

    2008-01-01

    While a link between Helicobacter pylori exposure and gastric cancer has been established, the underlying mechanisms remain unclear. H. pylori induces a chronic inflammatory response in infected individuals. A link between chronic inflammation and carcinogenesis has long been suggested but never elucidated. Epidermal growth factor receptor (EGFR) signaling plays an important role in both proinflammatory and procarcino- genic mechanisms and

  16. Performance of microbial phytases for gastric inositol phosphate degradation.

    PubMed

    Nielsen, Anne Veller Friis; Nyffenegger, Christian; Meyer, Anne S

    2015-01-28

    Microbial phytases catalyze dephosphorylation of phytic acid, thereby potentially releasing chelated iron and improving human iron absorption from cereal-based diets. For this catalysis to take place in vivo, the phytase must be robust to low pH and proteolysis in the gastric ventricle. This study compares the robustness of five different microbial phytases, evaluating thermal stability, activity retention, and extent of dephosphorylation of phytic acid in a simulated low-pH/pepsin gastric environment and examines secondary protein structural changes at low pH via circular dichroism. The Peniophora lycii phytase was found to be the most thermostable, but the least robust enzyme in gastric conditions, whereas the Aspergillus niger and Escherichia coli phytases proved to be most resistant to gastric conditions. The phytase from Citrobacter braakii showed intermediate robustness. The extent of loss of secondary structure at low pH correlated positively with the extent of activity loss at low pH. PMID:25562369

  17. Prediction Model for Gastric Cancer Incidence in Korean Population

    PubMed Central

    Kim, Sohee; Shin, Aesun; Yang, Hye-Ryung; Park, Junghyun; Choi, Il Ju; Kim, Young-Woo; Kim, Jeongseon; Nam, Byung-Ho

    2015-01-01

    Background Predicting high risk groups for gastric cancer and motivating these groups to receive regular checkups is required for the early detection of gastric cancer. The aim of this study is was to develop a prediction model for gastric cancer incidence based on a large population-based cohort in Korea. Method Based on the National Health Insurance Corporation data, we analyzed 10 major risk factors for gastric cancer. The Cox proportional hazards model was used to develop gender specific prediction models for gastric cancer development, and the performance of the developed model in terms of discrimination and calibration was also validated using an independent cohort. Discrimination ability was evaluated using Harrell’s C-statistics, and the calibration was evaluated using a calibration plot and slope. Results During a median of 11.4 years of follow-up, 19,465 (1.4%) and 5,579 (0.7%) newly developed gastric cancer cases were observed among 1,372,424 men and 804,077 women, respectively. The prediction models included age, BMI, family history, meal regularity, salt preference, alcohol consumption, smoking and physical activity for men, and age, BMI, family history, salt preference, alcohol consumption, and smoking for women. This prediction model showed good accuracy and predictability in both the developing and validation cohorts (C-statistics: 0.764 for men, 0.706 for women). Conclusions In this study, a prediction model for gastric cancer incidence was developed that displayed a good performance. PMID:26186332

  18. Helicobacter pylori inhibits gastric cell cycle progression

    Microsoft Academic Search

    Amel Ahmed; Duane Smoot; George Littleton; Robert Tackey; Curla S. Walters; Fatah Kashanchi; Cornell R. Allen; Hassan Ashktorab

    2000-01-01

    Helicobacter pylori infection of the gastric mucosa is associated with changes in gastric epithelial cell proliferation. In vitro studies have shown that exposure to H. pylori inhibits proliferation of gastric cells. This study sought to investigate the cell cycle progression of gastric epithelial cell lines in the presence and absence of H. pylori. Unsynchronized and synchronized gastric epithelial cell lines

  19. Gastric ulceration in horses

    Microsoft Academic Search

    Richard Hepburn

    2011-01-01

    Equine gastric ulceration syndrome (EGUS) was first described in 1986 and is common in all types of horses. The clinical signs are variable and often vague but EGUS can be easily diagnosed following thorough history taking and physical examination, and confirmed using gastroscopy. Ulcers can be effectively treated and prevented by introducing changes in management practices and instituting drug therapy.

  20. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    SciTech Connect

    Becker, Jan C. [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)]. E-mail: beckeja@uni-muenster.de; Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

    2006-07-07

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

  1. The effectiveness of gastric bypass over gastric partition in morbid obesity: consequence of distal gastric and duodenal exclusion.

    PubMed Central

    Pories, W J; Flickinger, E G; Meelheim, D; Van Rij, A M; Thomas, F T

    1982-01-01

    Eighty-seven morbidly obese patients were prospectively randomized to two operations: gastric bypass was performed on 42 and gastric partition on 45. Gastric bypass proved to be more effective; gastric bypass patients lost 15% more of their original weight at 12 months and 21% more at 18 months. There were no failures in the gastric bypass group; 28 of the 45 operations failed in the gastric partition group. An additional 60 patients underwent gastric bypass since the completion of the study. In the total series of 147 patients who underwent gastric bypass or gastric partition, there was no mortality, and the surgical complication rate was 12%. Because the gastric pouches and the anastomoses were similar in the two operations, the superiority of the gastric bypass may well be due to a heretofore unexplained effect of distal gastric and duodenal exclusion. PMID:7125726

  2. Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells

    Microsoft Academic Search

    Koga Komatsu; Susumu Suzuki; Tooru Shimosegawa; Jun-ichi Miyazaki; Takayoshi Toyota

    2000-01-01

    Dysregulation of apoptosis may be closely related to the development of cancer and its chemoresistance. Overexpression of Bax, an inducer of apoptosis, has led to increased cell death in a variety of cancer cell lines. In this study, we investigated the effect of Bax overexpression in two gastric cancer cell lines, MKN-28 and MKN-45, using a Cre-loxP-mediated inducible expression system.

  3. Expression of HER2 in Human Gastric Cancer Cells Directly Correlates with Antitumor Activity of a Recombinant Disulfide-Stabilized Anti-HER2 Immunotoxin

    Microsoft Academic Search

    Hisashi Shinohara; Shinsho Morita; Masaru Kawai; Akiko Miyamoto; Toyooki Sonoda; Ira Pastan; Nobuhiko Tanigawa

    2002-01-01

    Background. Amplification of the human epidermal growth factor receptor 2 (HER2) gene and overexpression of the HER2 protein have been associated with an unfavorable prognosis. We determined the efficacy of an anti-HER2 immunotoxin, erb-38 [e23(dsFv)PE38], against human gastric cancer cells.Methods. Immunotoxin was made by fusing the disulfide-stabilized Fv fragments (dsFv) of a monoclonal antibody e23 to a truncated mutant of

  4. A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer

    Microsoft Academic Search

    Y H Park; B-Y Ryoo; S-J Choi; H-T Kim

    2004-01-01

    Capecitabine and docetaxel have considerable single-agent activity in gastric cancer with distinct mechanisms of action and no overlap of key toxicities. A synergistic interaction between these two drugs is mediated by taxane-induced upregulation of thymidine phosphorylase. We investigated the activity and the feasibility of capecitabine and docetaxel combination chemotherapy in patients with previously untreated advanced gastric cancer (AGC). From September

  5. Green tea extract (AR25®) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro

    Microsoft Academic Search

    Christine Juhel; Martine Armand; Yan Pafumi; Christelle Rosier; Jacques Vandermander; Denis Lairon

    2000-01-01

    In this study, we aimed to evaluate in vitro the inhibitory activity of a green tea extract (AR25® standardized at 25% catechins) on gastric and pancreatic lipase activities. We first used tributyrin as a substrate to evaluate the capability of AR25 to induce digestive lipase inhibition. Gastric lipase was totally inhibited by 40 mg AR25\\/g tributyrin whereas pancreatic lipase inhibition

  6. Gastric Migration and Strangulation After Adjustable Gastric Banding

    Microsoft Academic Search

    Gwenyth Fischer; Jonathan A. Myers; Wendy Huang; Vafa Shayani

    2008-01-01

    We present a case of gastric strangulation 6 months after laparoscopic adjustable gastric banding (LAGB). The 45-year-old\\u000a woman presented to our emergency department with acute left upper quadrant abdominal pain. Initial upper gastrointestinal\\u000a studies after emergency department presentation showed no flow through the gastric band and an unusual air\\/fluid level just\\u000a above the band, not communicating with the proximal pouch. The

  7. Drugs Approved for Stomach (Gastric) Cancer

    MedlinePLUS

    ... Questions to Ask Your Doctor about Treatment Research Drugs Approved for Stomach (Gastric) Cancer This page lists ... Gastric) Cancer Drugs Approved for Gastroenteropancreatic Neuroendocrine Tumors Drugs Approved for Stomach (Gastric) Cancer Adrucil (Fluorouracil) Cyramza ( ...

  8. Genetics Home Reference: Hereditary diffuse gastric cancer

    MedlinePLUS

    ... OMIM Genetic disorder catalog Conditions > Hereditary diffuse gastric cancer On this page: Description Genetic changes Inheritance Diagnosis ... Reviewed January 2014 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is an inherited ...

  9. Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer.

    PubMed

    Chen, Jing; Zhang, Chundong; Xu, Xiaoyang; Zhu, Xinjiang; Dai, Dongqiu

    2015-08-01

    A disintegrin and metallopeptidase with thrombospondin motif type 1 (ADAMTS1) is a metalloproteinase with antiangiogenic activity. It was previously observed that the mRNA and protein levels of ADAMTS1 are downregulated in primary gastric tumors. The aim of the present study was to examine whether the reduction in the expression of ADAMTS1 is due to aberrant methylation of the gene in primary gastric tumor tissues and gastric cancer cell lines. In addition, the association between ADAMTS1 methylation and clinicopathological features in were investigated in patients with primary gastric cancer. The results revealed that the frequency of ADAMTS1 methylation in primary gastric tumor tissues was significantly higher, compared with the corresponding normal gastric tissues. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated primary gastric tumor tissues, compared with the unmethylated primary gastric tumor tissuess. A significant association was observed between the ADAMTS1 methylation status and the depth of tumor invasion and tumor, node, metastasis stage in primary gastric cancer. The mRNA expression of ADAMTS1 was significantly lower in 60% (3 of 5) of the gastric cancer cell lines. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated gastric cancer cell lines, compared with the unmethylated gastric cancer cell lines. Furthermore, the expression of ADAMTS1 was significantly restored following treatment with the 5?Aza?2'?deoxycytidine demethylating agent in the MGC?803, HGC?27 and AGS gastric cancer cell lines, and the demethylation of the MGC?803 cell line inhibited cell invasion. Together, these results suggested for the first time, to the best of our knowledge, ADAMTS1 as a novel antitumor protease, and this function was lost following epigenetic silencing in the gastric cancer cells and gastric tumor tissues. Therefore, the aberrant methylation of ADAMTS1 may be involved in the development and progression of gastric cancer. PMID:25936341

  10. Downregulation of A disintegrin and metallopeptidase with thrombospondin motif type 1 by DNA hypermethylation in human gastric cancer

    PubMed Central

    CHEN, JING; ZHANG, CHUNDONG; XU, XIAOYANG; ZHU, XINJIANG; DAI, DONGQIU

    2015-01-01

    A disintegrin and metallopeptidase with thrombospondin motif type 1 (ADAMTS1) is a metalloproteinase with antiangiogenic activity. It was previously observed that the mRNA and protein levels of ADAMTS1 are downregulated in primary gastric tumors. The aim of the present study was to examine whether the reduction in the expression of ADAMTS1 is due to aberrant methylation of the gene in primary gastric tumor tissues and gastric cancer cell lines. In addition, the association between ADAMTS1 methylation and clinicopathological features in were investigated in patients with primary gastric cancer. The results revealed that the frequency of ADAMTS1 methylation in primary gastric tumor tissues was significantly higher, compared with the corresponding normal gastric tissues. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated primary gastric tumor tissues, compared with the unmethylated primary gastric tumor tissuess. A significant association was observed between the ADAMTS1 methylation status and the depth of tumor invasion and tumor, node, metastasis stage in primary gastric cancer. The mRNA expression of ADAMTS1 was significantly lower in 60% (3 of 5) of the gastric cancer cell lines. The relative mRNA expression levels of ADAMTS1 were significantly lower in the methylated gastric cancer cell lines, compared with the unmethylated gastric cancer cell lines. Furthermore, the expression of ADAMTS1 was significantly restored following treatment with the 5-Aza-2?-deoxycytidine demethylating agent in the MGC-803, HGC-27 and AGS gastric cancer cell lines, and the demethylation of the MGC-803 cell line inhibited cell invasion. Together, these results suggested for the first time, to the best of our knowledge, ADAMTS1 as a novel antitumor protease, and this function was lost following epigenetic silencing in the gastric cancer cells and gastric tumor tissues. Therefore, the aberrant methylation of ADAMTS1 may be involved in the development and progression of gastric cancer. PMID:25936341

  11. Clinical epidemiology of gastric cancer

    PubMed Central

    Ang, Tiing Leong; Fock, Kwong Ming

    2014-01-01

    Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. There are, however, distinct differences in incidence rates in different geographic regions. While the incidence rate of gastric cancer has been falling, that of gastric cardia cancers is reportedly on the rise in some regions. Helicobacter pylori (H. pylori) infection is a major risk factor of non-cardia gastric cancer, and data has emerged concerning the role of H. pylori eradication for primary prevention of gastric cancer. Dietary, lifestyle and metabolic factors have also been implicated. Although addressing these other factors may contribute to health, the actual impact in terms of cancer prevention is unclear. Once irreversible histological changes have occurred, endoscopic surveillance would be necessary. A molecular classification system offers hope for molecularly tailored, personalised therapies for gastric cancer, which may improve the prognosis for patients. PMID:25630323

  12. Gastric cancer review

    PubMed Central

    Carcas, Lauren Peirce

    2014-01-01

    Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Despite an overall decline in incidence over the last several decades, gastric cancer remains the fourth most common type of cancer and is the second leading cause of cancer-related death worldwide. This review aims to discuss the global distribution of the disease and the trend of decreasing incidence of disease, delineate the different pathologic subtypes and their immunohistochemical (IHC) staining patterns and molecular signatures and mutations, explore the role of the pathogen H. pylori in tumorgenesis, discuss the increasing incidence of the disease in the young, western populations and define the role of biologic agents in the treatment of the disease. PMID:25589897

  13. Gastric ulcer in Karachi.

    PubMed

    Ahmed, W; Qureshi, H; Alam, S E; Zuberi, S J

    1992-09-01

    Of 138 endoscopically or surgically confirmed cases of gastric ulcer, 102 (74%) were males and 36 (26%) females. Both sexes were affected most commonly in the 6th decade of life. Pain, vomiting and gastrointestinal bleeding were the major presenting symptoms, with a median duration of 6 months. Cigarette smoking was the most common (44%) addiction and 10% were on analgesics or nonsteroidal anti-inflammatory drugs (NSAID). Family history of ulcer was uncommon (2%) and no predilection for any blood group was noted. Among males 53% were skilled workers while 94% of females were housewives. Forty five percent patients were migrants from India and the rest belonged to different provinces of Pakistan. Presentation and behaviour of different sites of gastric ulcers though varied but the results were not significant. Healing rates with H2 receptor antagonists were 33% at 4 weeks and 78% at 8 weeks. PMID:1433804

  14. NME2 Reduces Proliferation, Migration and Invasion of Gastric Cancer Cells to Limit Metastasis

    PubMed Central

    Liu, Yan-fei; Yang, Aijun; Liu, Wei; Wang, Chenyu; Wang, Min; Zhang, Lihan; Wang, Dongcang; Dong, Jing-fei; Li, Min

    2015-01-01

    Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2), which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression. PMID:25700270

  15. Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a rat model.

    PubMed

    Somekawa, Shinji; Hayashi, Naoki; Niijima, Akira; Uneyama, Hisayuki; Torii, Kunio

    2012-01-01

    Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a stimulator of gastric vagal afferent nerves. The aim of the present study was to examine the possibility that l-Glu supplementation of a protein-rich liquid diet may prevent the incidence of diarrhoea during repetitive intra-gastric tube feeding. The gastric vagal afferent nerve recording of rats indicated that intra-gastric administration of a protein-rich liquid diet supplemented with 0·5 % monosodium glutamate enhanced the basal afferent activities seen with the protein-rich diet alone. The examination of the faeces showed that the addition of monosodium glutamate to the liquid diet significantly prevented the incidence of diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra-gastric tube feeding by sending visceral glutamate information from the stomach to the brain. PMID:21733333

  16. Efficacy and safety of herbal medicines in treating gastric ulcer: A review

    PubMed Central

    Bi, Wei-Ping; Man, Hui-Bin; Man, Mao-Qiang

    2014-01-01

    Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects. PMID:25493014

  17. HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

    PubMed Central

    2014-01-01

    The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-?-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of ?-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the ?-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future. PMID:24948895

  18. HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

    NASA Astrophysics Data System (ADS)

    Wang, Can; Bao, Chenchen; Liang, Shujing; Zhang, Lingxia; Fu, Hualin; Wang, Yutian; Wang, Kan; Li, Chao; Deng, Min; Liao, Qiande; Ni, Jian; Cui, Daxiang

    2014-05-01

    The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-?-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of ?-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the ?-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.

  19. Changes in gastric sodium-iodide symporter (NIS) activity are associated with differences in thyroid gland sensitivity to perchlorate during metamorphosis.

    PubMed

    Carr, James A; Murali, Sharanya; Hu, Fang; Goleman, Wanda L; Carr, Deborah L; Smith, Ernest E; Wages, Mike

    2015-08-01

    We investigated stage-dependent changes in sensitivity of the thyroid gland to perchlorate during development of African clawed frog tadpoles (Xenopus laevis) in relation to non-thyroidal iodide transporting tissues. Perchlorate-induced increases in thyroid follicle cell size and colloid depletion were blunted when exposures began at Nieuwkoop-Faber (NF) stage 55 compared to when exposures began at NF stages 49 or 1-10. To determine if the development of other iodide transporting tissues may contribute to this difference we first examined which tissues expressed transcripts for the sodium dependent iodide symporter (NIS). RT-PCR analysis revealed that NIS was expressed in stomach and small intestine in addition to the thyroid gland of X. laevis tadpoles. NIS mRNA was not detected in lung, kidney, skin, gill, muscle, heart or liver. Perchlorate sensitive (125)I uptake was found in stomach, lung, kidney, gill, and small intestine but not muscle, liver, or heart. Perchlorate-sensitive (125)I uptake by stomach was 6-10 times greater than in any other non-thyroidal tissue in tadpoles. While NF stage 49 tadpoles exhibited perchlorate-sensitive uptake in stomach it was roughly 4-fold less than that observed in NF stage 55 tadpoles. Although abundance of NIS gene transcripts was greater in stomachs from NF stage 55 compared to NF stage 49 tadpoles this difference was not statistically significant. We conclude that gastric iodide uptake increases between NF stages 49 and 55, possibly due to post-translational changes in NIS glycosylation or trafficking within gastric mucosal cells. These developmental changes in gastric NIS gene expression may affect iodide availability to the thyroid gland. PMID:25448256

  20. Controlling on-demand gastric acidity in obese subjects: a randomized, controlled trial comparing a single dose of 20 mg rabeprazole and 20 mg omeprazole

    PubMed Central

    2014-01-01

    Background Obesity is associated with a risk of gastroesophageal reflux disease. The pharmacodynamic efficacy of proton pump inhibitors has not been specifically evaluated in obese subjects. The aim of this study was to compare the antisecretory response to a single oral dose of 20 mg rabeprazole, 20 mg omeprazole and placebo in obese subjects. Methods Gastric pH was monitored for 24 hours on three separate occasions in eighteen H. pylori-negative, asymptomatic obese subjects. Subjects were given omeprazole, rabeprazole or placebo in a randomized order and in a double-blind fashion. The main analysis criterion was 24-h percent of time post dose with intragastric pH above 3; secondary criteria were percentage of time above pH 4, median pH, [H+] concentrations and nocturnal acid breakthrough (NAB). Results were analyzed using linear mixed models and Wilks test comparing variances. Results 24-h median [IQ] percentages of time with gastric pH above 3 and 4 were higher with rabeprazole than omeprazole (46 [37–55] vs. 30 [15–55] %, 9 [5-11] % for placebo) but the differences did not reach statistical significance (p?=?0.11 and 0.24, respectively). Median acid concentrations were significantly lower with rabeprazole than with omeprazole and placebo (22 [14–53] vs. 54 [19–130] and 95 [73–170] mmoles/l, p?gastric antisecretory response to a single dose of rabeprazole and omeprazole was strong and not significantly different between drugs despite a significantly more homogeneous response with rabeprazole. Trial registration ClinicalTrial.gov: NCT01136317 PMID:25027286

  1. Automated Classification of Spatiotemporal Characteristics of Gastric Slow Wave Propagation

    PubMed Central

    Paskaranandavadivel, Niranchan; Gao, Jerry; Du, Peng; O'Grady, Gregory; Cheng, Leo K.

    2014-01-01

    Gastric contractions are underpinned by an electrical event called slow wave activity. High-resolution electrical mapping has recently been adapted to study gastric slow waves at a high spatiotemporal detail. As more slow wave data becomes available, it is becoming evident that the spatial organization of slow wave plays a key role in the initiation and maintenance of gastric dsyrhythmias in major gastric motility disorders. All of the existing slow wave signal processing techniques deal with the identification and partitioning of recorded wave events, but not the analysis of the slow wave spatial organization, which is currently performed visually. This manual analysis is time consuming and is prone to observer bias and error. We present an automated approach to classify spatial slow wave propagation patterns via the use of Pearson cross correlations. Slow wave propagations were grouped into classes based on their similarity to each other. The method was applied to high-resolution gastric slow wave recordings from four pigs. There were significant changes in the velocity of the gastric slow wave wavefront and the amplitude of the slow wave event when there was a change in direction to the slow wave wavefront during dsyrhythmias, which could be detected with the automated approach. PMID:24111441

  2. Pregnancy after adjustable gastric banding

    Microsoft Academic Search

    Louis F. Martin; Kathleen M. Finigan; Thomas E. Nolan

    2000-01-01

    Objective: To determine outcomes of pregnancies of obese women who had surgical placement of an adjustable gastric band to treat obesity.Methods: We conducted two clinical trials to evaluate adjustable gastric banding that involved 359 obese women of reproductive potential (age 18–51 years), of whom 20 conceived resulting in 23 pregnancies. Specific information about pregnancies and fetal outcomes was collected from

  3. Mouse Models of Gastric Cancer

    PubMed Central

    Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

    2013-01-01

    Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

  4. Low-Dose Oxaliplatin Enhances the Antitumor Efficacy of Paclitaxel in Human Gastric Cancer Cell Lines

    Microsoft Academic Search

    Jinyu Gu; Hirofumi Yamamoto; Xueying Lu; Chew Yee Ngan; Tadashi Tsujino; Ken Konishi; Ichiro Takemasa; Masataka Ikeda; Hiroshi Nagata; Shusuke Hashimoto; Takeshi Matsuzaki; Mitsugu Sekimoto; Akimitsu Takagi; Morito Monden

    2006-01-01

    Background: The enhanced antitumor effect of paclitaxel when used with oxaliplatin in gastric cancer is reported, however the underlying biological mechanism is unknown. Methods: We tested the cytotoxic activity, apoptosis, and mitotic catastrophe of paclitaxel and oxaliplatin in MKN-28 and MKN-45 gastric cancer cell lines. The modulation of survivin expression was determined by Western blotting. Results: WST-1 assay indicated that

  5. Protective effects of escin against indomethacin-induced gastric ulcer in mice.

    PubMed

    Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

    2014-12-01

    Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18?mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8?mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6?h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-?, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-?, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect. PMID:25137224

  6. Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis

    Microsoft Academic Search

    J I Wyatt; B J Rathbone; M F Dixon; R V Heatley

    1987-01-01

    Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the

  7. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro

    Microsoft Academic Search

    R. A. Giannella; S. A. Broitman; N. Zamcheck

    1972-01-01

    Reassessment of the `gastric bactericidal barrier' to enteric bacteria in man included studies of the bactericidal activity of (1) the normal and achlorhydric stomach in vivo and (2) normal and achlorhydric gastric juice and other media in vitro. Within 30 minutes virtually all bacteria (Serratia marcescens) were eliminated in the normal stomach whereas no reduction occurred in the achlorhydric stomach

  8. Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.

    PubMed

    Kumar, J Dinesh; Steele, Islay; Moore, Andrew R; Murugesan, Senthil V; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea; Dockray, Graham J

    2015-07-15

    The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling. PMID:25977510

  9. Role of transient receptor potential ankyrin 1 in gastric accommodation in conscious guinea pigs.

    PubMed

    Koseki, Junichi; Oshima, Tadayuki; Kondo, Takashi; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Hattori, Tomohisa; Kase, Yoshio; Miwa, Hiroto

    2012-04-01

    We report the establishment of a new model for measuring gastric tone and liquid meal-induced accommodation in conscious guinea pigs and the role played by transient receptor potential ankyrin 1 (TRPA1). An indwelling polyethylene bag was placed in proximal stomachs of 5-week-old male Hartley guinea pigs. Gastric tone was measured by distending the bag and recording changes in intrabag pressure at various volumes. Gastric accommodation was measured by administering liquid meals and recording intrabag pressure over time. N(?)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a nitric-oxide synthase inhibitor), atropine sulfate (atropine) (a muscarinic receptor antagonist), allyl isothiocyanate (AITC) (a TRPA1 agonist), or theophylline-7-(N-4-isopropylphenyl) acetamide (HC-030031) (a selective TRPA1 antagonist) was administered 15 to 60 min before measurement. Gastric tone was increased by stepwise distension of the bag and was further significantly increased by L-NAME and significantly decreased by atropine. A liquid meal (15% w/v; 1.7 kcal) significantly decreased intrabag pressure 5 to 20 min after administration, indicating gastric accommodation; this was completely suppressed by L-NAME and further enhanced by atropine. AITC significantly increased gastric tone; this increase was decreased by HC-030031 and atropine. A combination of AITC and L-NAME significantly increased gastric tone compared with L-NAME alone. HC-030031 alone significantly decreased gastric tone. Liquid meal-induced gastric accommodation was significantly suppressed by pretreatment with AITC. We established a new model for measuring gastric tone and accommodation in conscious guinea pigs. TRPA1 activation suppresses gastric accommodation by increasing gastric tone through cholinergic neuronal pathways. PMID:22262922

  10. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

    PubMed

    Arab, Hany H; Salama, Samir A; Omar, Hany A; Arafa, El-Shaimaa A; Maghrabi, Ibrahim A

    2015-01-01

    Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-? (TNF-?) levels along with nuclear factor kappa B (NF-?B) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses. PMID:25821971

  11. Management of gastric varices.

    PubMed

    Sarin, S K; Lahoti, D

    1992-09-01

    Gastric varices (GV) are a common (20%) accompaniment of portal hypertension; they are more often seen in those patients who bleed than in those who do not (27% versus 4%, p < 0.01). They can develop in both segmental and generalized portal hypertension. Depending on their location and relation with oesophageal varices, GVs can be classified as gastrooesophageal varices (GOV) and isolated gastric varices (IGV); each of these can be further subdivided as follows: GOV1 (extension of oesophageal varices along lesser curve) and GOV2 (extension of oesophageal varices towards fundus); and IGV1 (varices in the fundus) and IGV2 (isolated varices anywhere in the stomach). The common presentation of GVs is variceal bleeding and encephalopathy. In comparison with oesophageal varices, GVs bleed significantly less often (64% versus 25%, p < 0.01) but more severely (2.9 +/- 0.3 versus 4.8 +/- 0.6 transfusion units, p < 0.01). Patients with GOV2 and IGV1 bleed more often than patients with other types of GVs. Sclerotherapy for oesophageal varices can significantly influence the natural history of GVs. GOV1, or lesser curve varices, disappear in the majority of cases (59%) after obliteration of oesophageal varices. In those with persisting GOV1, the incidence of bleeding and mortality is high and these patients require gastric variceal sclerotherapy (GVS). During oesophageal variceal sclerotherapy, bleeding can occasionally be induced from GVs. After obliteration of oesophageal varices, recurrence as GVs (secondary GVs) can occur in about 9% of patients. Emergency GVS is quite effective in controlling acute bleeding from GVs, more so than balloon tamponade. Potent sclerosants like tetradecyl sulphate and alcohol and a glue, bucrylate, have been quite effective. Elective GVS can achieve obliteration of GVs in nearly 70% of patients. Rebleeding and ulceration are common complications of GVS; probably related to incomplete obliteration and mucosal injury respectively. Splenectomy is quite effective in treating GVs due to segmental protal hypertension. For GV bleeding due to generalized portal hypertension, a shunt operation is often effective. TIPS procedure appear to be a very promising therapy for GV bleeding. Liver transplantation may be a superior alternative to sclerotherapy and shunt surgery for gastric varices. PMID:1421599

  12. Internal Hernias and Gastric Perforation After a Laparoscopic Gastric Bypass

    Microsoft Academic Search

    Carlos Serra; Aniceto Baltasar; Rafael Bou; Javier Miró; L. A. Cipagauta

    1999-01-01

    A 27-year-old woman underwent laparoscopic Roux-en-Y gastric bypass. A retrocolic-retrogastric herniation of most of the small\\u000a bowel and later a gastric perforation due to internal hernia at the mesenteric defect of the jejuno-jejunostomy occurred.\\u000a These unusual, but not rare, complications are directly related to the neoanatomy that follows gastric bypass and can lead\\u000a to rapidly progressing and life-threatening situations. Proper

  13. Cytostatic activity of the duplex drug linking 2?-deoxy-5-fluorouridine (5FdU) with 3?-C-ethynylcytidine (ECyd) against gastric adenocarcinoma cell lines

    Microsoft Academic Search

    Jürgen Weinreich; Sarah Schott; Ingmar Königsrainer; Derek Zieker; Alfred Königsrainer; Herbert Schott

    Summary  The cytostatic potential of the new duplex drug 2?-deoxy-5-fluorouridylyl-(5??5?)-3?-C-ethynylcytidine (5FdU(5?-5?)ECyd) was\\u000a evaluated in comparison to those of 5-fluorouracil (5FU), 2?-deoxy-5-fluorourindine (5FdU), 3?-C-ethynylycytidine (ECyd),\\u000a cisplatin, an equimolar mixture of 5FdU + ECyd and a three component-mixture of 0.75 ?M epirubicin\\/0.90 ?M cisplatin\\/3.0 ?M\\u000a 5FU (ECF) by incubation of the two human gastric adenocarcinoma cell lines 23132\\/87 and MKN-45. The molar composition of ECF\\u000a was

  14. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ?aŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spycha?a, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  15. Comprehensive molecular characterization of gastric adenocarcinoma.

    PubMed

    2014-09-11

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  16. Photodynamic therapy of gastric cancer

    NASA Astrophysics Data System (ADS)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  17. Sonic hedgehog pathway contributes to gastric cancer cell growth and proliferation.

    PubMed

    Wan, Jianhua; Zhou, Ji; Zhao, Hailong; Wang, Mei; Wei, Zhuanqin; Gao, Hongyan; Wang, Yongzhong; Cui, Hongjuan

    2014-04-01

    The Sonic Hedgehog (Shh) signaling pathway is commonly activated in gastrointestinal cancer. However, our understanding of the Shh pathway in gastric cancer remains limited. Here we examined the effects of cyclopamine, a specific inhibitor of the Shh signaling pathway, on cell growth and proliferation in gastric primary cancer cells GAM-016 and the MKN-45 cell line. The results showed that the Shh signaling molecules SHH, PTCH, SMO, GLI1, and GLI2 were intact and activated in both types of cells. Furthermore, we observed that cyclopamine inhibited gastric cancer cell proliferation through cell cycle arrest and apoptosis. An in vivo study using NOD/SCID mouse xenografts demonstrated that cyclopamine significantly prevented tumor growth and development. Our study indicated that Shh signaling pathway could promote gastric cancer cell proliferation and tumor development, and blocking this pathway may be a potential strategy in gastric cancer treatment. PMID:24804165

  18. Inhibition of the JAK2/STAT3 Pathway Reduces Gastric Cancer Growth In Vitro and In Vivo

    PubMed Central

    Ling, Hui; Jackson, Cameron B.; Howlett, Meegan; Kalantzis, Anastasia; Priebe, Waldemar; Giraud, Andrew S.

    2014-01-01

    Signal Transducer and Activator of Transcription-3 (STAT3) is constitutively activated in many cancers where it promotes growth, inflammation, angiogenesis and inhibits apoptosis. We have shown that STAT3 is constitutively activated in human gastric cancer, and that chronic IL-11-driven STAT3 transcriptional activity induces gastric tumourigenesis in the gp130757FF mouse model of gastric cancer development. Here we show that treatment of human AGS gastric cancer cells with the Janus Kinase (JAK) inhibitor WP1066 dose-, and time-dependently inhibits STAT3 phosphorylation, in conjunction with reduced JAK2 phosphorylation, reduced proliferation and increased apoptosis. In addition, application of intraperitoneal WP1066 for 2 weeks, reduced gastric tumour volume by 50% in the gp130757FF mouse coincident with reduced JAK2 and STAT3 activation compared with vehicle-treated, littermate controls. Gastric tumours from WP1066- treated mice had reduced polymorphonuclear inflammation, coincident with inhibition of numerous proinflammatory cytokines including IL-11, IL-6 and IL-1?, as well as the growth factors Reg1 and amphiregulin. These results show that WP1066 can block proliferation, reduce inflammation and induce apoptosis in gastric tumour cells by inhibiting STAT3 phosphorylation, and that many cytokines and growth factors that promote gastric tumour growth are regulated by STAT3-dependent mechanisms. WP1066 may form the basis for future therapeutics against gastric cancer. PMID:24804649

  19. RNA interference targeting raptor inhibits proliferation of gastric cancer cells

    SciTech Connect

    Wu, William Ka Kei; Lee, Chung Wa [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)] [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Cho, Chi Hin [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China) [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Chan, Francis Ka Leung [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)] [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Yu, Jun, E-mail: junyu@cuhk.edu.hk [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)] [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China); Sung, Joseph Jao Yiu, E-mail: joesung@cuhk.edu.hk [Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (China)

    2011-06-10

    Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G{sub 0}/G{sub 1}-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 1}-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

  20. Gastric Emptying in the Elderly.

    PubMed

    Soenen, Stijn; Rayner, Chris K; Horowitz, Michael; Jones, Karen L

    2015-08-01

    Aging is characterized by a diminished homeostatic regulation of physiologic functions, including slowing of gastric emptying. Gastric and small intestinal motor and humoral mechanisms in humans are complex and highly variable: ingested food is stored, mixed with digestive enzymes, ground into small particles, and delivered as a liquefied form into the duodenum at a rate allowing efficient digestion and absorption. In healthy aging, motor function is well preserved whereas deficits in sensory function are more apparent. The effects of aging on gastric emptying are relevant to the absorption of oral medications and the regulation of appetite, postprandial glycemia, and blood pressure. PMID:26195094

  1. Helicobacter pylori in the pathogenesis of gastric cancer and gastric lymphoma

    PubMed Central

    Kim, Sung Soo; Ruiz, Victoria E.; Carroll, Jaqueline D.; Moss, Steven F.

    2010-01-01

    Chronic gastric infection by the gram-negative bacterium H. pylori is strongly associated with the development of distal gastric carcinoma and gastric mucosal lymphoma in humans. Eradication of H. pylori with combination antibiotic therapy cures most cases of gastric lymphoma and slows progression to gastric adenocarcinoma. H. pylori promotes gastric neoplasia, principally via the induction of an intense gastric inflammatory response that lasts over decades. This persistent inflammatory state produces chronic oxidative stress and adaptive changes in gastric epithelial and immune cell pathobiology that in a minority of infected subjects eventually proceeds to frank neoplastic transformation. PMID:20692762

  2. Helicobacter pylori Releases a Factor(s) Inhibiting Cell Cycle Progression of Human Gastric Cell Lines by Affecting Cyclin E\\/cdk2 Kinase Activity and Rb Protein Phosphorylation through Enhanced p27 KIP1 Protein Expression

    Microsoft Academic Search

    Patrizia Sommi; Monica Savio; Lucia A. Stivala; Claudia Scotti; Paola Mignosi; Ennio Prosperi; Vanio Vannini; Enrico Solcia

    2002-01-01

    Helicobacter pylori, the main cause of chronic gastritis, plays a central role in the etiology of peptic ulcer disease and gastric cancer. In vitro studies have shown that H. pylori increases gastric epithelial cell turnover, thus increasing the risk for the development of neoplastic clones. The mechanisms by which H. pylori promotes perturbation of cell proliferation are not yet elucidated.

  3. Serological assessment of gastric mucosal atrophy in gastric cancer

    PubMed Central

    2012-01-01

    Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio. Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer. PMID:22289789

  4. SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells

    PubMed Central

    Cui, Yang; Qin, Lili; Wu, Jing; Qu, Xuan; Hou, Chen; Sun, Wenyan; Li, Shiyong; Vaughan, Andrew T. M.; Li, Jian Jian; Liu, Jiankang

    2015-01-01

    SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells. PMID:26121691

  5. Expression of TRAF6 and ubiquitin mRNA in skeletal muscle of gastric cancer patients

    PubMed Central

    2012-01-01

    Objective To investigate the prognostic significance of tumor necrosis factor receptor (TNFR),-associated factor 6 (TRAF6),-and ubiquitin in gastric cancer patients. Methods Biopsies of the rectus abdominis muscle were obtained intra operatively from 102 gastric cancer patients and 29 subjects undergoing surgery for benign abdominal diseases, and muscle TRAF6 and ubiquitin mRNA expression and proteasome proteolytic activities were assessed. Results TRAF6 was significantly upregulated in muscle of gastric cancer compared with the control muscles. TRAF6 was upregulated in 67.65% (69/102) muscle of gastric cancer. Over expression of TRAF6 in muscles of gastric cancer were associated with TNM stage, level of serum albumin and percent of weight loss. Ubiquitin was significantly upregulated in muscle of gastric cancer compared with the control muscles. Ubiquitin was upregulated in 58.82% (60/102) muscles of gastric cancer. Over expression of ubiquitin in muscles of gastric cancer were associated with TNM (Tumor-Node-Metastasis) stage and weight loss. There was significant relation between TRAF6 and ubiquitin expression. Conclusions We found a positive correlation between TRAF6 and ubiquitin expression, suggesting that TRAF6 may up regulates ubiquitin activity in cancer cachexia. While more investigations are required to understand its mechanisms of TRAF6 and ubiquitin in skeletal muscle. Correct the catabolic-anabolic imbalance is essential for the effective treatment of cancer cachexia. PMID:23013936

  6. Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric Injury.

    PubMed

    Sohn, Yoon Ah; Hwang, Seon A; Lee, Sun Yi; Hwang, In Young; Kim, Sun Whoe; Kim, So Yeon; Moon, Aree; Lee, Yong Soo; Kim, Young Ho; Kang, Keum Jee; Jeong, Choon Sik

    2015-01-01

    In this study, we investigated the inhibitory activities on gastritis and gastric ulcer using liriodendrin which is a constituent isolated from Kalopanax pictus. To elucidate its abilities to prevent gastric injury, we measured the quantity of prostaglandin E2 (PGE2) as the protective factor, and we assessed inhibition of activities related to excessive gastric acid be notorious for aggressive factor and inhibition of Helicobacter pylori (H. pylori) colonization known as a cause of chronic gastritis, gastric ulcer, and gastric cancer. Liriodendrin exhibited higher PGE2 level than rebamipide used as a positive control group at the dose of 500 ?M. It was also exhibited acid-neutralizing capacity (10.3%) and H(+)/K(+)-ATPase inhibition of 42.6% (500 ?M). In pylorus-ligated rats, liriodendrin showed lower volume of gastric juice (4.38 ± 2.14 ml), slightly higher pH (1.53 ± 0.41), and smaller total acid output (0.47 ± 0.3 mEq/4 hrs) than the control group. Furthermore liriodendrin inhibited colonization of H. pylori effectively. In vivo test, liriodendrin significantly inhibited both of HCl/EtOH-induced gastritis (46.9 %) and indomethacin-induced gastric ulcer (46.1%). From these results, we suggest that liriodendrin could be utilized for the treatment and/or protection of gastritis and gastric ulcer. PMID:25593644

  7. Helicobacter pylori infection and gastric cardia cancer in Chaoshan region.

    PubMed

    Wang, Yunsheng; Liu, Shuhui; Zhang, Ying; Bi, Chao; Xiao, Yinping; Lin, Runhua; Huang, Bo; Tian, Dongping; Ying, Songmin; Su, Min

    2014-10-01

    Helicobacter pylori (H. pylori) infection represents the most important risk factor for gastric cancer, while its association with gastric cardia cancer (GCC) has not been recognized yet. In this current study, we aim to investigate the status of H. pylori infection in the gastric cardia tissue samples from high-risk populations in Chaoshan littoral region, and the relationship between H. pylori infection and chronic inflammation as well as the proliferative activity of the gastric cardia epithelial cells. A total of 706 gastric cardia biopsy specimens were obtained from 372 GCC cases and 334 tumor-free controls in Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. Immunohistochemistry and Giemsa staining were employed for the verification of H. pylori infection. H. pylori infection rate was significantly higher in GCC (81.5%, P < 0.01) and gastric carditis (80.1%, P < 0.01) in comparison with that in the healthy group (34.8%). A significant higher prevalence of chronic inflammation was found in H. pylori+ samples (96.9%) than that in H. pylori- specimens (80.5%) (P < 0.01). To explore the possible role of H. pylori infection-related chronic inflammation in the GCC, we found that the expression of Ki-67 was progressively increased in tissues with chronic inflammation degrees from normal to severe inflammation (P < 0.01). Collectively, these results suggest that persistent H. pylori infection and the related chronic inflammation may contribute to the high incidence of GCC in Chaoshan littoral. PMID:25038396

  8. In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

    SciTech Connect

    Pandi, Narayanan Sathiya, E-mail: sathiyapandi@gmail.com; Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-10-04

    Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-? signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-? signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.

  9. Gastric vagal afferent modulation by leptin is influenced by food intake status.

    PubMed

    Kentish, Stephen J; O'Donnell, Tracey A; Isaacs, Nicole J; Young, Richard L; Li, Hui; Harrington, Andrea M; Brierley, Stuart M; Wittert, Gary A; Blackshaw, L Ashley; Page, Amanda J

    2013-04-01

    Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high-fat diet or were food restricted. The expression of leptin receptor (Lep-R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse-transcription polymerase chain reaction, and the relationship between leptin-immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet-induced obesity, potentiation of mucosal afferents by leptin was lost and Lep-R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet-induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet-induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3-kinase-dependent activation of large-conductance calcium-activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C-dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to gastric distension following food intake. PMID:23266933

  10. Gastric Lymphosarcoma and Pseudolymphoma

    PubMed Central

    Berry, G. R.; Mathews, W. H.

    1967-01-01

    Lymphoma localized to one organ is known to have a good prognosis. After a study of 131 cases of lymphosarcoma of the stomach Smith and Helwig3 reported that 42 were in reality a benign lymphoproliferative disorder which has been termed pseudolymphoma of the stomach. Of our series of 12 cases, six are now thought to be pseudolymphoma. Jacobs7 has enumerated the differentiating criteria. We have found a polymorphic cellular infiltrate, in nodular or diffuse pattern, associated with a fibrotic reaction located in the submucosa, muscularis or serosa, to be the most helpful criterion. The “good prognosis” associated with gastric lymphoma may be due partly to the difficulty in differentiating these two conditions and to the inclusion of cases of pseudolymphoma in any large series of these lymphomas. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:6071581

  11. Laparoscopic Gastric Banding: preliminary series

    Microsoft Academic Search

    Antonio Catona; Marcus Gossenberg; Antonella La Manna; Giovanni Mussini

    1993-01-01

    Gastric banding as a laparoscopic procedure was performed on 40 morbidly obese patients. This operation matches the advantages\\u000a of the gastric banding (efficacy, reversibility and low invasivity) with the advantages of the laparoscopic procedure (low\\u000a surgical risk, short hospital stay and less complications in the short and long term). The maximum follow-up is 6 months and\\u000a so far the weight

  12. Gastric emptying in marathon runners

    Microsoft Academic Search

    I. Carrio; M. Estorch; R. Serra-grima; M. Ginjaume; R. Notivol; R. Cal-abuig; F. Vilardell

    1989-01-01

    Radionuclide gastric emptying studies using 99m-Tc human serum albumin egg omelette have been carried out in 10 long distance runners at rest and during a 90 minute run at sustained speed. Resting values are compared with controls comprising 10 sedentary subjects. Runners show a significantly accelerated basal gastric emptying (runners t 1\\/2 = 67.7 (5.9) min; sedentaries t 1\\/2 =

  13. Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

    PubMed Central

    Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F.; Aguirre, Vincent; Gupta, Rana K.; Clegg, Deborah J.

    2015-01-01

    Objective Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These ‘BRITE/beige’ adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as “browning.” Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. ?3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions Upregulation of Nppb, Npr1, Npr2, and ?3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive effect of RYGB on metabolic parameters and may in part be mediated through upregulation of natriuretic peptides. PMID:25973390

  14. Targeted therapy in gastric cancer.

    PubMed

    Thiel, Alexandra; Ristimäki, Ari

    2015-05-01

    Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer. PMID:25706252

  15. Gene methylation in gastric cancer.

    PubMed

    Qu, Yiping; Dang, Siwen; Hou, Peng

    2013-09-23

    Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. PMID:23669186

  16. Malignant gastric lymphoma with spontaneous perforation

    PubMed Central

    Shimada, Satoko; Gen, Tokichi; Okamoto, Hiroyuki

    2013-01-01

    Malignant gastric lymphoma, accounting only for 1% of primary gastric carcinoma, is usually a diffuse large B-cell lymphoma. Toyota et al reported that 37% of gastric perforations involved malignancy, generally gastric carcinoma. Fukuda et al found that less than 5% of malignant gastric lymphomas perforate. While it is relatively well known that perforations often take place during chemotherapy, they are rare in patients not receiving chemotherapy. To our knowledge, spontaneous perforation is rare in gastric malignant lymphoma, having been reported in the Japanese literature only 26 times, including this case, in the last 25?years. PMID:23329705

  17. Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune responses.

    PubMed Central

    Hoft, D F; Farrar, P L; Kratz-Owens, K; Shaffer, D

    1996-01-01

    Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect vector to humans by exposure of mucosal surfaces to infected insect excreta. We have used an oral challenge murine model that mimics vector-borne transmission to study T. cruzi mucosal infection. Although gastric secretions have microbicidal activity against most infectious pathogens, we demonstrate that T. cruzi can invade and replicate in the gastric mucosal epithelium. In addition, gastric mucosal invasion appears to be the unique portal of entry for systemic T. cruzi infection after oral challenge. The mucosal immune responses stimulated by T. cruzi gastric infection are protective against a secondary mucosal parasite challenge. This protective mucosal immunity is associated with increased numbers of lymphocytes that secrete parasite-specific immunoglobulin A. Our results document the first example of systemic microbial invasion through gastric mucosa and suggest the feasibility of a mucosal vaccine designed to prevent infection with this important human pathogen. PMID:8751932

  18. MED30 Regulates the Proliferation and Motility of Gastric Cancer Cells

    PubMed Central

    Lee, Yong Joo; Han, Myoung-Eun; Baek, Su-Jin; Kim, Seon-Young; Oh, Sae-Ock

    2015-01-01

    MED30 is an essential member of the mediator complex that forms a hub between transcriptional activators and RNA polymerase II. However, the expressions and roles of MED30 have been poorly characterized in cancer. In this study, we examined the functional roles of MED30 during gastric cancer progression. It was found that MED30 was overexpressed in gastric cancer tissues and cell lines. Moreover, MED30 overexpression increased the proliferation, migration, and invasion of gastric cancer cells, whereas MED30 knockdown inhibited these effects. Furthermore the knockdown significantly inhibited tumorigenicity in SCID mice. MED30 also promoted the expressions of genes related to epithelial-mesenchymal transition and induced a fibroblast-like morphology. This study shows MED30 has pathophysiological roles in the proliferation, migration, and invasion of gastric cancer cells and suggests that MED30 should be viewed as a potent therapeutic target for malignant gastric carcinoma PMID:26110885

  19. Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats.

    PubMed

    Cheng, C L; Koo, M W

    2000-10-13

    Centella asiatica is a herbal medicine widely used in China and India for wound healing. The aim of this study was to examine its effects on the prevention of ethanol induced gastric lesions in rats. Gastric transmucosal potential difference (PD) was reduced by the application of 50% ethanol in the gastric ex-vivo chamber model and Centella extract (CE) accelerated its recovery. Oral administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol administration significantly inhibited gastric lesions formation (58% to 82% reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose dependent manner. These results suggested that CE prevented ethanol induced gastric mucosal lesions by strengthening the mucosal barrier and reducing the damaging effects of free radicals. PMID:11104366

  20. [Protective activity of S-PT84, a heat-killed preparation of Lactobacillus pentosus, against oral and gastric candidiasis in an experimental murine model].

    PubMed

    Hayama, Kazumi; Ishijima, Sanae; Ono, Yoshiko; Izumo, Takayuki; Ida, Masayuki; Shibata, Hiroshi; Abe, Shigeru

    2014-01-01

    The effect of S-PT84, a heat-killed preparation of Lactobacillus pentosus on growth of Candida albicans was examined in vitro and in vivo. The mycelial growth was effectively inhibited by S-PT84 and seemed to bind to the hyphae. We assessed the potential of S-PT84 for treatment of oral and gastric candidiasis using a murine model. When 2 mg of S-PT84 was administered three times into the oral cavity of orally Candida infected mice, the score of lesions on the tongue was improved on day 2. When 50 ?l and 200 ?l of S-PT84 (10 mg/ml) were administered three times into the oral cavity (0.5 mg × 3) and the stomach (2 mg × 3) of the same mouse model, the number of viable Candida cells in the stomach was reduced significantly on day 2. These findings suggest the possibility that S-PT84 has potential as a food ingredient supporting anti-Candida treatment, especially for Candida infection in the gastrointestinal tract. PMID:25231227

  1. Helicobacter pylori colonization critically depends on postprandial gastric conditions

    PubMed Central

    Bücker, Roland; Azevedo-Vethacke, Marina; Groll, Claudia; Garten, Désirée; Josenhans, Christine; Suerbaum, Sebastian; Schreiber, Sören

    2012-01-01

    The risk of Helicobacter pylori infection is highest in childhood, but the colonization process of the stomach mucosa is poorly understood. We used anesthetized Mongolian gerbils to study the initial stages of H. pylori colonization. Prandial and postprandial gastric conditions characteristic of humans of different ages were simulated. The fraction of bacteria that reached the deep mucus layer varied strongly with the modelled postprandial conditions. Colonization success was weak with fast gastric reacidification typical of adults. The efficiency of deep mucus entry was also low with a slow pH decrease as seen in pH profiles simulating the situation in babies. Initial colonization was most efficient under conditions simulating the postprandial reacidification and pepsin activation profiles in young children. In conclusion, initial H. pylori colonization depends on age-related gastric physiology, providing evidence from an in vivo infection model that suggests an explanation why the bacterium is predominantly acquired in early childhood. PMID:23251780

  2. Gastric lipase: localization of the enzyme in the stomach

    SciTech Connect

    DeNigris, S.J.; Hamosh, M.; Hamosh, P.; Kasbekar, D.K.

    1986-03-05

    Isolated gastric glands prepared from human and rabbit stomach secrete lipase in response to secretagogues. They have investigated the localization of this enzyme in three species (rabbit, baboon, guinea pig). Gastric mucosa was sampled from the cardia (C), fundus-smooth (FS), fundus-ruggae (FR) and the antral area (A). Lipase activity was measured in mucosal homogenates using /sup 3/H-triolein as substrate and is expressed in units (U) = nmols free fatty acid released/min/mg wet weight. The localization of lipase is compared with that of pepsin (measured by hydrolysis of 2% hemoglobin at pH 1.8 and expressed in I.U.). Lipase is localized in a well defined area in the rabbit and is diffusely distributed in both guinea pig and baboon. The distribution of lipase and pepsin containing cells differs in all three species. The cellular origin of gastric lipase remains to be determined.

  3. Net1 and Myeov: computationally identified mediators of gastric cancer

    Microsoft Academic Search

    J Leyden; D Murray; A Moss; M Arumuguma; E Doyle; G McEntee; C O'Keane; P Doran; P MacMathuna

    2006-01-01

    Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated

  4. Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix

    Microsoft Academic Search

    Won Ae Lee

    2005-01-01

    BACKGROUND: Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium. CASE PRESENTATION: A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT) for routine medical examination. Gastric endoscopic examination revealed a

  5. Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients

    Microsoft Academic Search

    Chuan Zhang; Nobutaka Yamada; Yun-Lin Wu; Min Wen; Takeshi Matsuhisa; Norio Matsukura

    2005-01-01

    METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin- eosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation,

  6. Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

    PubMed Central

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-01-01

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-“aging gastropathy”-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-?-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications (e.g., NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically. PMID:24782600

  7. Nitric Oxide Releasing Aspirin Protects the Gastric Mucosa against Stress and Promotes Healing of Stress-Induced Gastric Mucosal Damage: Role of Heat Shock Protein 70

    Microsoft Academic Search

    Peter C. Konturek; Tomasz Brzozowski; Agata Ptak; Joanna Kania; Eckhart G. Hahn

    2002-01-01

    Background\\/Aim: Nitric oxide (NO) releasing nonsteroidal anti-inflammatory drugs do not cause gastric mucosal damage, despite inhibition of the cyclooxygenase activity to a similar extent as conventional nonsteroidal anti-inflammatory drugs that induce such damage. We compared the effects of native aspirin (ASA) with those of NO-releasing ASA (NO-ASA) on the development and healing of acute gastric lesions induced by water immersion

  8. Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption.

    PubMed

    Ye, Liang; Morse, Leslie R; Zhang, Li; Sasaki, Hajime; Mills, Jason C; Odgren, Paul R; Sibbel, Greg; Stanley, James R L; Wong, Gee; Zamarioli, Ariane; Battaglino, Ricardo A

    2015-03-01

    Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium-phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake. PMID:25811986

  9. Synthesis, spectroscopic and DFT structural characterization of two novel ruthenium(III) oxicam complexes. In vivo evaluation of anti-inflammatory and gastric damaging activities.

    PubMed

    Tamasi, Gabriella; Bernini, Caterina; Corbini, Gianfranco; Owens, Natalie F; Messori, Luigi; Scaletti, Federica; Massai, Lara; Giudice, Pietro Lo; Cini, Renzo

    2014-05-01

    The reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru(III)Cl2(H2PIR)(HPIR)],·1, and [Ru(III)Cl2(H2TEN)(HTEN)],·2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects. PMID:24518539

  10. Optimal management of resectable gastric adenocarcinoma.

    PubMed

    Buscariollo, Daniela L; Mamon, Harvey J

    2015-08-01

    The worldwide incidence of gastric adenocarcinoma has rapidly declined in the past century, but gastric cancer remains the fifth most common malignancy in the world. Approximately half of all cases of gastric cancer are diagnosed in Eastern Asia. In this review, we provide an overview of the landmark studies investigating neoadjuvant and adjuvant therapies in resectable gastric cancer and highlight ongoing efforts to define optimal population-adapted management strategies. PMID:26165449

  11. Helicobacter pylori infection and gastric MALT lymphoma.

    PubMed

    Lehours, P; Mégraud, F

    2005-01-01

    Helicobacter pylori infection is implicated in the development of two different gastric cancers: gastric adenocarcinoma and gastric MALT lymphoma. The association with the gastric MALT lymphoma is strong and causal. It is currently the only cancer which can be treated by a simple antibiotic treatment. However, the evolution of an H. pylori infection towards lymphoma is exceptional. Host susceptibility factors and environmental factors predisposing a patient to lymphoma have not yet been determined. The bacterial factors are currently being identified. PMID:16358940

  12. Immature gastric teratoma in an infant.

    PubMed

    Anilkumar, M G; Jagadishkumar, K; Girish, G N; Sunila

    2013-06-01

    Gastric teratomas are very rare tumors accounting for less than 1 % of all teratomas of infants and children. Little more than 100 cases of gastric teratomas are reported in the literature; out of which, very few of them are of immature variety. Complete excision of the gastric teratoma carries a good prognosis. We hereby report a case of immature gastric teratoma in a 3-month-old baby. PMID:24426646

  13. Chestnut extract induces apoptosis in AGS human gastric cancer cells

    PubMed Central

    Lee, Hyun Sook; Kim, Eun Ji

    2011-01-01

    In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with 200 µg/mL CPE for 24 hr. CPE at various concentrations (0-200 µg/mL) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPE exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer. PMID:21779520

  14. Subtotal gastrectomy for gastric cancer

    PubMed Central

    Santoro, Roberto; Ettorre, Giuseppe Maria; Santoro, Eugenio

    2014-01-01

    Although a steady decline in the incidence and mortality rates of gastric carcinoma has been observed in the last century worldwide, the absolute number of new cases/year is increasing because of the aging of the population. So far, surgical resection with curative intent has been the only treatment providing hope for cure; therefore, gastric cancer surgery has become a specialized field in digestive surgery. Gastrectomy with lymph node (LN) dissection for cancer patients remains a challenging procedure which requires skilled, well-trained surgeons who are very familiar with the fast-evolving oncological principles of gastric cancer surgery. As a matter of fact, the extent of gastric resection and LN dissection depends on the size of the disease and gastric cancer surgery has become a patient and “disease-tailored” surgery, ranging from endoscopic resection to laparoscopic assisted gastrectomy and conventional extended multivisceral resections. LN metastases are the most important prognostic factor in patients that undergo curative resection. LN dissection remains the most challenging part of the operation due to the location of LN stations around major retroperitoneal vessels and adjacent organs, which are not routinely included in the resected specimen and need to be preserved in order to avoid dangerous intra- and postoperative complications. Hence, the surgeon is the most important non-TMN prognostic factor in gastric cancer. Subtotal gastrectomy is the treatment of choice for middle and distal-third gastric cancer as it provides similar survival rates and better functional outcome compared to total gastrectomy, especially in early-stage disease with favorable prognosis. Nonetheless, the resection range for middle-third gastric cancer cases and the extent of LN dissection at early stages remains controversial. Due to the necessity of a more extended procedure at advanced stages and the trend for more conservative treatments in early gastric cancer, the indication for conventional subtotal gastrectomy depends on multiple variables. This review aims to clarify and define the actual landmarks of this procedure and the role it plays compared to the whole range of new and old treatment methods. PMID:25320505

  15. Gastric adenocarcinoma associated with isolated granulomatous gastritis

    Microsoft Academic Search

    Christopher Newton; Lucien Nochomovitz; Jonathan M. Sackier

    1998-01-01

    Background: Granulomatous gastritis is a rarely observed pathological diagnosis. This condition often mimics gastric adenocarcinoma clinically, resulting in gastric resection. However, granulomatous gastritis has long been viewed as a benign process not observed in association with adenocarcinoma of the stomach. This article describes a patient with granulomatous gastritis occurring in close proximity to an area of superficially invading gastric adenocarcinoma.

  16. Helicobacter pylori and early gastric cancer

    Microsoft Academic Search

    M E Craanen; P Blok; W Dekker; G N Tytgat

    1994-01-01

    The relation between Helicobacter pylori, intestinal metaplasia, and early gastric cancer was studied by examining gastrectomy specimens from 31 intestinal type and 22 diffuse type carcinomas. A total of 298 patients with antral gastritis were used as controls. Atrophic changes and intestinal metaplasia were significantly more common in intestinal type early gastric cancer compared with diffuse type early gastric cancer

  17. Conventional dose of omeprazole alters gastric flora

    Microsoft Academic Search

    Y. Karmeli; R. Stalnikowitz; R. Eliakim; G. Rahav

    1995-01-01

    Quantitative cultures were carried out on samples from gastric juice obtained from 12 ambulatory patients with esophagitis before and one month after omeprazole therapy. An increase in the number of patients in whom gastric juice was culture-positive, as well as an increment in the bacterial counts were noted. The spectrum of microorganisms isolated from gastric juice was identical to the

  18. Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer.

    PubMed

    Bathaie, S Zahra; Hoshyar, Reyhane; Miri, Hamidreza; Sadeghizadeh, Majid

    2013-12-01

    This study investigated the therapeutic effect of crocetin, a carotenoid derived from saffron, on gastric adenocarcinoma (AGS) cells and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced gastric cancer in rats. An MTT assay showed a significant dose- and time-dependent inhibition of AGS cell proliferation as a result of crocetin administration. Flow cytometry and caspases activity assays revealed apoptosis had been induced in these cells; RT-PCR and Western blot analyses revealed the suppression of Bcl-2 and up-regulation of Bax expression in AGS cells treated with crocetin. These changes were not observed in normal human fibroblast (HFSF-PI3) cells. Pathological study of the tumor tissue in MNNG-induced gastric cancer in rats indicated the dose-dependent inhibition of tumor progression. In addition, crocetin reversed some changed biochemical parameters, including serum antioxidant activity and lactate dehydrogenase in rat serum. The present study demonstrates the antioxidant, anti-proliferative, and apoptotic activities of crocetin against gastric cancer that may benefit human stomach cancer treatment. PMID:24219281

  19. MMP-9 is increased in the pathogenesis of gastric cancer by the mediation of HER2.

    PubMed

    Shan, Y-Q; Ying, R-C; Zhou, C-H; Zhu, A-K; Ye, J; Zhu, W; Ju, T-F; Jin, H-C

    2015-04-01

    Human epidermal growth factor receptor 2 (HER2) overexpression is not only closely associated with the tumor growth, but is also related to tumor invasion. We here aimed to investigate the mechanism of HER2 mediation in the pathogenesis of gastric cancer. The human gastric cancer cell lines SGC-7901, MKN-45, AGS, the immortalized cell line GES-1 derived from normal gastric mucosa. Cell transfection and selection of stable cell lines and the gene and protein levels of HER2 and Matrix metalloproteinase-9 (MMP-9) were examined to determine the molecular relationship between them in the pathogenesis of gastric cancer. The human gastric cancer cell lines SGC-7901, MKN-45, AGS, the immortalized cell line GES-1 derived from normal gastric mucosa. Cell transfection and selection of stable cell lines and the gene and protein levels of HER2 and MMP-9 were examined to determine the molecular relationship between them in the pathogenesis of gastric cancer. We demonstrated that vector-based shRNA significantly knocked down the expression of HER2 and considerably inhibited both the migration and invasion of gastric cancer cells. HER2 knockdown resulted in the downregulation of the expression of MMP-9, whereas HER2 overexpression improved the transcription of MMP-9 through the activation of an MMP-9 promoter. The promoter region of MMP-9 between -2500 and -2000?bp was found to be crucial for the upregulation of HER2-mediated transcription. Furthermore, a truncated promoter (-70 to +63) did not display any transcriptional activity. Cell invasion activity was almost completely inhibited when MMP-9 was knocked down. Conversely, the overexpression of MMP-9 partly rescued the invasion ability of cell strains with knockdown HER2. These findings help further understanding of the molecular mechanisms through which HER2 promotes malignancy, and suggest that targeting both HER2 and MMP-9 may be required to effectively block HER2 signaling in gastric cancer therapy. PMID:25633484

  20. p75 Neurotrophin Receptor Suppresses the Proliferation of Human Gastric Cancer Cells

    PubMed Central

    Jin, Haifeng; Pan, Yanglin; Zhao, Lina; Zhai, Huihong; Li, Xiaohua; Sun, Li; He, Lijie; Chen, Yu; Hong, Liu; Du, Yulei; Fan, Daiming

    2007-01-01

    Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (?p75NTR) showed that the death domain transduced antiproliferative activity in a ligand-independent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer. PMID:17603629

  1. Roles of Wnt/?-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment

    PubMed Central

    Mao, J; Fan, S; Ma, W; Fan, P; Wang, B; Zhang, J; Wang, H; Tang, B; Zhang, Q; Yu, X; Wang, L; Song, B; Li, L

    2014-01-01

    The Wnt1 protein, a secreted ligand that activates Wnt signaling pathways, contributes to the self-renewal of cancer stem cells (CSCs) and thus may be a major determinant of tumor progression and chemoresistance. In a series of gastric cancer specimens, we found strong correlations among Wnt1 expression, CD44 expression, and the grade of gastric cancer. Stable overexpression of Wnt1 increased AGS gastric cancer cells' proliferation rate and spheroids formation, which expressed CSC surface markers Oct4 and CD44. Subcutaneous injection of nude mice with Wnt1-overexpressing AGS cells resulted in larger tumors than injection of control AGS cells. Salinomycin, an antitumor agent, significantly reduced the volume of tumor caused by Wnt1-overexpressing AGS cells in vivo. This is achieved by inhibiting the proliferation of CD44+Oct4+ CSC subpopulation, at least partly through the suppression of Wnt1 and ?-catenin expression. Taken together, activation of Wnt1 signaling accelerates the proliferation of gastric CSCs, whereas salinomycin acts to inhibit gastric tumor growth by suppressing Wnt signaling in CSCs. These results suggest that Wnt signaling might have a critical role in the self-renewal of gastric CSCs, and salinomycin targeting Wnt signaling may have important clinical applications in gastric cancer therapy. PMID:24481453

  2. Novel therapeutic approaches to gastric and duodenal ulcers: an update.

    PubMed

    Dajani, E Z; Klamut, M J

    2000-07-01

    Over the last 25 years, a remarkable revolution in the pathophysiology and treatment of gastric and duodenal ulcers has occurred. Effective therapies were developed not only to heal ulcers, but also to cure most patients. The two principal causes for gastric and duodenal ulcers are either infection with Helicobacter pylori or the use of non-steroidal anti-inflammatory drugs (NSAIDs). With H. pylori eradication, gastric and duodenal ulcers are rapidly becoming historical diseases. This communication reviews the salient pharmacology of the novel anti-ulcer drugs currently in development, with particular emphasis on the treatment of gastric and duodenal ulcers. Intense research is currently focused on the development of proton pump inhibitors primarily for the treatment and prevention of gastroesophageal reflux disease. The older proton pump inhibitors, omeprazole and lansoprazole, are effective in healing gastric and duodenal ulcers. Furthermore, both drugs are effective in eradicating H. pylori when given with various antibiotics. Pantoprazole, rabeprazole and esomeprazole are new proton pump inhibitors, which appear to have comparable therapeutic profiles with omeprazole and lansoprazole. Rebamipide is a new mucosal protective drug, which is effective in healing gastric ulcers. Polaprezinc and nocloprost are also mucosal protective drugs, which are in clinical development. However, none of these three cytoprotective drugs have been evaluated for their efficacy in eradicating H. pylori when given in combination with antibiotics. Likewise, no published literature exists on the use of these drugs for preventing NSAID-induced ulcers. With the rapid eradication of H. pylori currently happening in the developed world, the therapeutic challenge is now directed toward preventing NSAID-associated ulcer. Significant reduction of NSAID-induced ulcers is achieved by using continuous prophylactic anti-ulcer therapy (misoprostol or omeprazole) or by using NSAIDs possessing selective COX-2 inhibitory activity. However, outcome clinical studies are needed to compare the adjuvant anti-ulcer therapies given with COX-1 inhibitors versus the selective COX-2 inhibitors given alone. PMID:11060758

  3. Induction of hRAD9 Is Required for G2\\/M Checkpoint Signal Transduction in Gastric Cancer Cells

    Microsoft Academic Search

    Ken Hayashi; Hiroki Kuniyasu; Naohide Oue; Hideo Shigeishi; Kazuya Kuraoka; Hirofumi Nakayama; Wataru Yasui

    2002-01-01

    DNA damage triggers the activation of checkpoints that delay cell cycle progression to allow for DNA repair. Loss of G2 checkpoints provides a growth advantage for tumor cells undergoing aberrant mitosis. However, the precise mechanisms of G2 checkpoints acting in gastric cancer are unknown. Here, we analyzed the G2 checkpoint function in two gastric cancer cells, MKN-28 cells containing a

  4. Megaduodenum associated with gastric strongyloidiasis

    PubMed Central

    da Silva, Amanda Pinter Carvalheiro; Boteon, Yuri Longatto; Tercioti, Valdir; Lopes, Luiz Roberto; de Souza Coelho Neto, João; Andreollo, Nelson Adami

    2014-01-01

    Gastric strongyloidiasis and megaduodenum are rare diseases. Gastrointestinal (GI) strongyloidiasis has many clinical features. One of them is megaduodenum. We describe a case of a 32-years-old man who has come to us from an endemic area for Strongyloides stercoralis. He had had megaduodenum diagnosed in his childhood. We submitted him to two surgeries. He has recovered just after the second surgery, a Roux-en-Y partial gastrectomy. After that, his follow-up was uneventful and the patient has gained 10 kg in weight. Histopathology confirmed gastric strongyloidiasis. In conclusion, if patients arrive from an endemic area of S. stercoralis and if they present GI symptoms or a previous diagnosis of megaduodenum, they must be considered for a histological evaluation for gastric strongyloidiasis. PMID:25951613

  5. Angiogenic factor thymidine phosphorylase associates with angiogenesis and lymphangiogenesis in the intestinal-type gastric cancer.

    PubMed

    Zhang, Xianglan; Zheng, Zhenlong; Shin, You Keun; Kim, Ki-Yeol; Rha, Sun Young; Noh, Sung Hoon; Chung, Hyun Cheol; Jeung, Hei-Cheul

    2014-06-01

    As an angiogenic factor, thymidine phosphorylase (TP) expression in primary tumours has been thought to be a risk factor for lymph node (LN) and hepatic metastasis in patients with gastric adenocarcinoma. However, the molecular basis for the induction of metastasis by TP is largely unknown. We aim to elucidate the role of TP expression in gastric cancer neovascularisation and LN metastasis.The angiogenic and lymphangiogenic activity (CD31, D2-40, Ki-67, VEGFC, VEGFR3) and expression status of TP were detected in 103 resected human gastric carcinoma samples by immunohistochemistry. The influence of TP expression on neovascularisation and cancer cell invasion was further comparatively investigated in two groups of nude mice intraperitoneally injected with TP overexpressing MKN-45 cells (MKN-45/TP) and control cells (MKN-45/CV). In gastric cancer tissues, we found that high TP expression and various angiogenic and lymphangiogenic activities were significantly associated with poor prognostic outcomes. In addition, TP expression was also found to be associated with neovascularisation activity of gastric cancer tissues. In vivo, the MKN-45/TP group exhibited significantly increased infiltrating tumour nodules and neovascularisation activity compared to the MKN-45/CV group. TP could strongly influence gastric cancer progression via the dual activities of angiogenesis and lymphangiogenesis. PMID:24798152

  6. Calcitonin suppresses gastric emptying of a radiolabelled solid meal in humans.

    PubMed Central

    Jonderko, G; Golab, T; Jonderko, K

    1987-01-01

    The effects on gastric emptying of calcitonin/i.v. 1.5 i.u. kg-1 body mass bolus or 10 i.u. followed by infusion to overall 1.5 i.u. kg-1 body mass dose vs placebo were studied in four healthy volunteers and in four patients with an active peptic ulcer. Gastric emptying of a radiolabelled solid meal was surveyed. Pronounced delay in gastric emptying was observed in all studied subjects, mean transit time MTT90 calcitonin 39.2 +/- 0.85 min vs placebo 32.8 +/- 1.31 min, P less than 0.001. PMID:3304382

  7. Role of neutrophils in acrylonitrile-induced gastric mucosal damage.

    PubMed

    Hamdy, Nadia M; Al-Abbasi, Fahad A; Alghamdi, Hassan A; Tolba, Mai F; Esmat, Ahmed; Abdel-Naim, Ashraf B

    2012-01-25

    Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic ?bers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important target of its toxicity. ACN has been previously reported to require metabolic activation to reactive intermediates and finally to cyanide (CN?). The current study aimed at exploring the potential role of neutrophils in ACN-induced gastric damage in rats. Experimental neutropenia was attained by injecting rats with methotrexate. This significantly ameliorated gastric mucosal injury induced by ACN. This is evidenced by protection against the increase in gastric ulcer index, myeloperoxidase (MPO) activity and CN? level. Also, neutropenia guarded against the decrease in prostaglandin E2 (PGE2), induction of oxidative stress and reduction of total nitrites and alleviated histopathological alterations in rat stomachs. These data indicate that neutrophil infiltration is, at least partly, involved in ACN-induced gastric damage in rats. PMID:22062130

  8. Endoscopic ultrasonography for gastric cancer

    Microsoft Academic Search

    I. S. Ganpathi; J. B.-Y. So; K.-Y. Ho

    2006-01-01

    Background  This study aimed to evaluate the utility and shortcomings of endoscopic ultrasound (EUS) in tumor node metastasis (TNM) staging\\u000a of gastric cancer and its influence on treatment.\\u000a \\u000a \\u000a \\u000a Methods  The series included 126 patients (65 men and 44 women) with gastric cancer who underwent EUS from July 1997 to June 2003 at\\u000a the National University Hospital, Singapore. The final analysis included 109 patients

  9. The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide.

    PubMed

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2015-01-01

    Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue. PMID:25478868

  10. Helicobacter pylori Protein JHP0290 Exhibits Proliferative and Anti-Apoptotic Effects in Gastric Epithelial Cells

    PubMed Central

    Tavares, Raquel; Pathak, Sushil Kumar

    2015-01-01

    The influence of Helicobacter pylori infection on gastric epithelial cell proliferation, apoptosis and signaling pathways contributes to the development of infection-associated diseases. Here we report that JHP0290, which is a poorly functionally characterized protein from H. pylori, regulates multiple responses in human gastric epithelial cells. The differential expression and release of JHP0290 homologues was observed among H. pylori strains. JHP0290 existed in monomeric and dimeric forms in H. pylori cell extracts and culture broth. Recombinant purified JHP0290 (rJHP0290) also showed monomeric and dimeric forms, whereas the rJHP0290 C162A mutant exhibited only a monomeric form. The dimeric form of the protein was found to bind more efficiently to gastric epithelial cells than the monomeric form. The exposure of gastric epithelial cells to rJHP0290 induced proliferation in a dose-dependent manner. Faster progression into the cell cycle was observed in rJHP0290-challenged gastric epithelial cells. Furthermore, we detected an anti-apoptotic effect of rJHP0290 in gastric epithelial cells when the cells were treated with rJHP0290 in combination with Camptothecin (CPT), which is an inducer of apoptosis. CPT-induced caspase 3 activation was significantly reduced in the presence of rJHP0290. In addition, the activation of ERK MAPK and the transcription factor NF?B was observed in rJHP0290-challenged gastric epithelial cells lines. Our results suggest that JHP0290 may affect H. pylori-induced gastric diseases via the regulation of gastric epithelial cell proliferation and anti-apoptotic pathways. PMID:25879227

  11. Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

    PubMed Central

    Lu, Xinping; Zhao, Xilin; Feng, Jianying; Liou, Alice P.; Anthony, Shari; Pechhold, Susanne; Sun, Yuxiang; Lu, Huiyan

    2012-01-01

    Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-?. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-? in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion. PMID:22678998

  12. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells

    PubMed Central

    Wei, Jinxiong; Nagy, Toni A.; Vilgelm, Anna; Zaika, Elena; Ogden, Seth R.; Romero-Gallo, Judith; Piazuelo, Maria B.; Correa, Pelayo; Washington, Mary K.; El-Rifai, Wael; Peek, Richard M.; Zaika, Alexander

    2010-01-01

    Background & Aims Infection with the gastric mucosal pathogen H. pylori is the strongest identified risk factor for distal gastric cancer. These bacteria colonize a significant part of the world’s population. We investigated the molecular mechanisms of p53 regulation in H. pylori-infected cells. Methods Mongolian gerbils were challenged with H. pylori and their gastric tissues were analyzed by immunohistochemistry and immunoblotting with p53 antibodies. Gastric epithelial cells were co-cultured with H. pylori and the regulation of p53 was assessed by real-time PCR, immunoblotting, immunofluorescence, and cell survival assays. shRNA and dominant-negative mutants were used to inhibit activities of HDM2 and AKT. Results We found that in addition to previously reported up-regulation of p53, H. pylori can also negatively regulate p53 by increasing ubiquitination and proteasomal degradation via activation of the serine/threonine kinase AKT, which phosphorylates and activates the ubiquitin ligase HDM2. These effects were mediated by the bacterial virulence factor, CagA; ectopic expression of CagA in gastric epithelial cells increased phosphorylation of HDM2 along with the ubiquitination and proteasomal degradation of p53. The decrease in p53 levels increased survival of gastric epithelial cells that had sustained DNA damage. Conclusion H. pylori is able to inhibit the tumor suppressor p53. H. pylori activates AKT, resulting in phosphorylation and activation of HDM2 and subsequent degradation of p53 in gastric epithelial cells. H. pylori-induced dysregulation of p53 is a potential mechanism by which the microorganism increases the risk of gastric cancer in infected individuals. PMID:20547161

  13. Role of Transient Receptor Potential A1 in Gastric Nociception

    Microsoft Academic Search

    Takashi Kondo; Tadayuki Oshima; Koichi Obata; Jun Sakurai; Charles H. Knowles; Takayuki Matsumoto; Koichi Noguchi; Hiroto Miwa

    2010-01-01

    Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. However, little is known about the molecules involved in mechanonociception from the upper gastrointestinal tract. We recently reported that activation of extracellular signal-regulated kinase 1\\/2 (ERK1\\/2), a member of the mitogen-activated protein kinase cascade in primary afferent neurons, was induced by noxious gastric distention in

  14. Gastric dysrhythmias and the current status of electrogastrography

    NASA Technical Reports Server (NTRS)

    Koch, K. L.

    1989-01-01

    Myoelectrical activity recorded simultaneously from mucosal, serosal, and cutaneous electrodes has confirmed that the 3-cpm signal from such electrodes reflects gastric slow-wave activity. Now, the observation that patients with unexplained nausea and vomiting may have very rapid slow-wave frequencies (tachygastrias) and very slow, slow-wave frequencies (bradygastrias) suggests that electrogastrography, a reliable and noninvasive technique, may be useful in the diagnosis and management of patients with upper abdominal symptoms and gastroparesis.

  15. Regulation of CRADD-caspase 2 cascade by histone deacetylase 1 in gastric cancer

    PubMed Central

    Shen, Qi; Tang, Wanfen; Sun, Jie; Feng, Lifeng; Jin, Hongchuan; Wang, Xian

    2014-01-01

    CRADD, also referred as RAIDD, is an adaptor protein that could interact with both caspase 2 and RIP that can promote apoptosis once activated. HDAC inhibitors are promising anti-cancer agents by inducing apoptosis of various cancer cells. In this study, we found that CRADD was induced by TSA (trichostatin A) to activate caspase 2-dependent apoptosis. CRADD was downregulated in gastric cancer and the restoration of its expression suppressed the viability of gastric cancer cells. HDAC1 was responsible for its downregulation in gastric cancer since HDAC1 siRNA upregulated CRADD expression and HDAC1 directly bound to the promoter of CRADD. Therefore, the high expression of HDAC1 can downregulate CRADD to confer gastric cancer cells the resistance to caspase 2-dependent apoptosis. HDAC inhibitors, potential anti-cancer drugs under investigation, can promote caspase 2-dependent apoptosis by inducing the expression of CRADD. PMID:25360218

  16. Loss of parietal cell superoxide dismutase leads to gastric oxidative stress and increased injury susceptibility in mice.

    PubMed

    Jones, Michael K; Zhu, Ercheng; Sarino, Edna V; Padilla, Oscar R; Takahashi, Takamune; Shimizu, Takahiko; Shirasawa, Takuji

    2011-09-01

    Mitochondrial superoxide dismutase (SOD2) prevents accumulation of the superoxide that arises as a consequence of oxidative phosphorylation. However, SOD2 is a target of oxidative/nitrosative inactivation, and reduced SOD2 activity has been demonstrated to contribute to portal hypertensive gastropathy. We investigated the consequences of gastric parietal cell-specific SOD2 deficiency on mitochondrial function and gastric injury susceptibility. Mice expressing Cre recombinase under control of the parietal cell Atpase4b gene promoter were crossed with mice harboring loxP sequences flanking the sod2 gene (SOD2 floxed mice). Cre-positive mice and Cre-negative littermates (controls) were used in studies of SOD2 expression, parietal cell function (ATP synthesis, acid secretion, and mitochondrial enzymatic activity), increased oxidative/nitrosative stress, and gastric susceptibility to acute injury. Parietal cell SOD2 deficiency was accompanied by a 20% (P < 0.05) reduction in total gastric SOD activity and a 93% (P < 0.001) reduction in gastric SOD2 activity. In SOD2-deficient mice, mitochondrial aconitase and ATP synthase activities were impaired by 36% (P < 0.0001) and 44% (P < 0.005), respectively. Gastric tissue ATP content was reduced by 34% (P < 0.002). Basal acid secretion and peak secretagogue (histamine)-induced acid secretion were reduced by 43% (P < 0.0001) and 40% (P < 0.0005), respectively. There was a fourfold (P < 0.02) increase in gastric mucosal apoptosis and 41% (P < 0.001) greater alcohol-induced gastric damage in the parietal cell SOD2-deficient mice. Our findings indicate that loss of parietal cell SOD2 leads to mitochondrial dysfunction, resulting in perturbed energy metabolism, impaired parietal cell function, and increased gastric mucosal oxidative stress. These alterations render the gastric mucosa significantly more susceptible to acute injury. PMID:21719741

  17. Sulphydryl blocker induced gastric damage is ameliorated by scavenging of free radicals.

    PubMed Central

    Karmeli, F; Okon, E; Rachmilewitz, D

    1996-01-01

    BACKGROUND: Sulphydryl compounds and nitric oxide are essential in maintaining gastric mucosal integrity. AIMS: To characterise the gastric damage induced by a sulphydryl blocker, to evaluate the role of nitric oxide in its pathogenesis, and to reveal its possible prevention by scavenging of free radicals. METHODS: Gastritis was induced in rats by addition of iodoacetamide (0.1%) to the drinking water, with and without daily intragastric administration of TEMPOL. After death, the stomach was resected, washed, lesion area assessed, and mucosal inflammatory mediators, myeloperoxidase and nitric oxide synthase activities were determined. RESULTS: Administration of iodoacetamide induced gastric mucosal erosions present for up to two weeks. Myeloperoxidase activity was increased for up to seven days and nitric oxide synthase activity was significantly decreased for up to 14 days. Treatment for seven days with the free radical scavenger, TEMPOL, decreased by 68% the damage induced by iodoacetamide. CONCLUSIONS: Gastric damage induced by iodoacetamide, a sulphydryl alkylator, accompanied by inhibition of nitric oxide synthase activity shows the important contribution of sulphydryl compounds and nitric oxide to the maintenance of gastric mucosal integrity. Nitric oxide donation and scavenging of free radicals may be a novel approach to prevent gastric damage. Images Figure 2 Figure 3 PMID:8984018

  18. Role of the Wnt/?-catenin pathway in gastric cancer: An in-depth literature review

    PubMed Central

    Chiurillo, Miguel Angel

    2015-01-01

    Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancer-related deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The aberrant activation of the Wnt/?-catenin signaling pathway is involved in the development and progression of a significant proportion of gastric cancer cases. This review focuses on the participation of the Wnt/?-catenin pathway in gastric cancer by offering an analysis of the relevant literature published in this field. Indeed, it is discussed the role of key factors in Wnt/?-catenin signaling and their downstream effectors regulating processes involved in tumor initiation, tumor growth, metastasis and resistance to therapy. Available data indicate that constitutive Wnt signalling resulting from Helicobacter pylori infection and inactivation of Wnt inhibitors (mainly by inactivating mutations and promoter hypermethylation) play an important role in gastric cancer. Moreover, a number of recent studies confirmed CTNNB1 and APC as driver genes in gastric cancer. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput “omics” approaches will help in the search for Wnt pathway antagonist in the near future. PMID:25992323

  19. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

    PubMed Central

    Lee, Sena; Kim, Myung-Gyou; Ko, Sung Kwon; Kim, Hye Kyung; Leem, Kang Hyun; Kim, Youn-Jung

    2013-01-01

    The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80). Ginsenoside Re (20 mg/kg or 100 mg/kg) was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration) and xanthine oxidase (XO) and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue. PMID:24748832

  20. [Hemolysis-inducing substances in gastric secretion, incidence-rate of lysolecithin].

    PubMed

    Clémençon, G; Bürgi, W

    1977-07-01

    Samples of gastric contents from 152 patients with pyloric reflex were taken during gastroscopy after an overnight fast and examined for hemolytic activity. Hemolysis was induced by 97 specimens (64%). The hemolysis test was positive in 45% of patients with a histologically normal gastric mucosa, in 76% of patients suffering from chronic atrophic gastritis with intestinal metaplasia, in 83% with gastric erosions and in 67% with gastric ulcer. No lysolecithin was found in 9 of the 97 positive specimens. The other aspirates contained widely differing values up to 320 mg/100 ml. The average quantities of lysolecithin in gastric contents varied in the different patient groups from 20 to 60 mg/100 ml. These values are much higher than the mean value of 0.9 mg/100 ml quantified in patients without pyloric reflex during an earlier investigation. It is now widely accepted that pyloric reflex promotes gastritis. Furthermore, it has been shown on several occasions that bile constituents exert a damaging effect on the gastric mucosa barrier. The same is true of lysolecithin, which promotes (for example) acute cholecystitis under experimental conditions. These findings, together with the results of our investigation, seem to afford evidence that lysolecithins may exert a pathogenic influence in the development of different gastric lesions. PMID:897630

  1. Complement Receptor 1 Genetic Variants Contribute to the Susceptibility to Gastric Cancer in Chinese Population

    PubMed Central

    Zhao, Lina; Zhang, Zhi; Lin, Jia; Cao, Lei; He, Bing; Han, Sugui; Zhang, Xuemei

    2015-01-01

    As the receptor for C3b/C4b, type 1 complement receptor (CR1/CD35) plays an important role in the regulation of complement activity and is further involved in carcinogenesis. This study aimed to elucidate the association of CR1 genetic variants with the susceptibility to gastric cancer in Chinese population. Based on the NCBI database, totally 13 tag single nucleotide polymorphisms (SNPs) were selected by Haploview program and genotyped using iPlex Gold Genotyping Assay and Sequenom MassArray among 500 gastric cancer cases and 500 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression to evaluate the association of each SNP with gastric cancer. Of all selected Tag SNPs , CR1 rs9429942 T > C was found to confer to the risk of developing gastric cancer. Compared with the carriers with rs9429942 TT genotype, those with CT genotype had 88% decreased risk of developing gastric cancer with OR (95%CI) of 0.12 (0.03-0.50). Generalized multifactor dimensionality reduction (GMDR) analysis revealed a significant three-way interaction among rs75422544 C > A, rs10494885 C > T and rs7525160 G > C in the development of gastric cancer with a maximum testing balance accuracy of 56.07% and a cross-validation consistency of 7/10 (P = 0.011). In conclusion, our findings demonstrated the genetic role of CR1 gene in the development of gastric cancer in Chinese population. PMID:26000043

  2. Serum Helicobacter pylori NapA antibody as a potential biomarker for gastric cancer.

    PubMed

    Liu, Jingjing; Liu, Huimin; Zhang, Tingting; Ren, Xiyun; Nadolny, Christina; Dong, Xiaoqun; Huang, Lina; Yuan, Kexin; Tian, Wenjing; Jia, Yunhe

    2014-01-01

    Helicobacter pylori (H. pylori) infection is strongly associated with gastric cancer. However, only a minority of infected individuals ever develop gastric cancer. This risk stratification may be in part due to differences among strains. The relationship between neutrophil-activating protein (NapA) and gastric cancer is unclear. The purpose of this study is to evaluate the significance of NapA as a biomarker in gastric cancer. We used enzyme linked immunosorbent assay (ELISA) to determine the status of H. pylori infection. Indirect ELISA method was used for detection of NapA antibody titer in the serum of H. pylori infected individuals. Unconditional logistic regressions were adopted to analyze the variables and determine the association of NapA and gastric cancer. The results of study indicated serum H. pylori NapA antibody level were associated with a reduced risk for development of gastric cancer. It may be used in conjugation with other indicators for gastric cancer detection. PMID:24553293

  3. Gastric stimulation for weight loss

    PubMed Central

    Mizrahi, Meir; Ben Ya'acov, Ami; Ilan, Yaron

    2012-01-01

    The prevalence of obesity is growing to epidemic proportions, and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss. Behavior and lifestyle therapy are safe treatments for obesity in the short term, but the durability of the weight loss is limited. Although promising obesity drugs are in development, the currently available drugs lack efficacy or have unacceptable side effects. Surgery leads to long-term weight loss, but it is associated with morbidity and mortality. Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders. GES is a promising, minimally invasive, safe, and effective method for treating obesity. External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time. In addition, data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES. This may involve alteration of secretion of hormones associated with hunger or satiety. Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment’s outcome. Here, we review the current status, potential mechanisms of action, and possible future applications of gastric stimulation for obesity. PMID:22654422

  4. Tyrosine kinases and gastric cancer

    Microsoft Academic Search

    Wen-chang Lin; Hsiao-Wei Kao; Daniel Robinson; Hsing-Jien Kung; Chew-Wun Wu; Hua-Chien Chen

    2000-01-01

    Carcinoma of the stomach is one of the most prevalent cancer types in the world today. Two major forms of gastric cancer are distinguished according to their morphological and clinicopathological classifications (well differentiated\\/intestinal type and poorly differentiated\\/diffuse type), characteristics that could also be attributed to the altered expression of different types of oncogenes or tumor suppressor genes. Significant differences exist

  5. Biphasic nature of gastric emptying

    Microsoft Academic Search

    J A Siegel; J L Urbain; L P Adler; N D Charkes; A H Maurer; B Krevsky; L C Knight; R S Fisher; L S Malmud

    1988-01-01

    The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the

  6. Insulin hypoglycemia and gastric secretion

    Microsoft Academic Search

    Frank P. Brooks

    1965-01-01

    HE EFI,'ECT of insulin-induced hypoglycemia on the secretion o[ hydrochloric acid by the stomach is a phenomenon valuable for research in gastrointestinal physiology) Babkin ~ used this phenomenon as a model of nervous as opposed to humoral stimulation of gastric secretion. Hollander ~ adapted it for a clinical test of the completeness of vagotomy in man. French and his associates

  7. [Risk of gastric cancer dependent on serological markers of atrophic gastritis: cohort study].

    PubMed

    Reshetnikov, O V; Openko, T G; Simonova, G I; Kurilovich, S A; Maliushina, S K; Ragino, Iu I; Voevoda, M I

    2012-01-01

    In a prospective study the risk of subsequent gastric cancer (GC) was assessed in persons aged 45-69 over 5 years after the initial testing with a set of serological tests (pepsinogen I, pepsinogen II, gastrin-17, antibodies to Helicobacter pylori). The presence of gastric atrophy markers was a significant predictor of GC in the forthcoming years. Non-invasive techniques may be used in the formation of high-risk groups, followed by GC active surveillance. PMID:23600281

  8. Growth inhibition and cell-cycle arrest of human gastric cancer cells by Lycium barbarum polysaccharide

    Microsoft Academic Search

    Ying Miao; Bingxiu Xiao; Zhen Jiang; Yanan Guo; Fang Mao; Junwei Zhao; Xia Huang; Junming Guo

    2010-01-01

    Lycium barbarum polysaccharide (LBP) is extracted from the traditional Chinese herb Lycium barbarum, and has potential anticancer activity. However, the detailed mechanisms are largely unknown. The purpose of this study was\\u000a to observe the anticancer effect of LBP on human gastric cancer, and its possible mechanisms. Human gastric cancer MGC-803\\u000a and SGC-7901 cells were treated with various concentrations of LBP

  9. Gene Structure of the Helicobacter pylori Cytotoxin and Evidence of Its Key Role in Gastric Disease

    Microsoft Academic Search

    John L. Telford; Paolo Ghiara; Mariangela Dell' Orco; Maurizio Comanducci; Daniela Burroni; Massimo Bugnoli; Mario F. Tecce; Stefano Censini; Antonello Covacci; Zhaoying Xiang; Emanuele Papini; Cesare Montecucco; Luca Parente; Rino Rappuoli

    S BITIITI ary The gram negative, microaerophilic bacterium Helicobacter I~Iori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration

  10. 64Cu DOTA-Trastuzumab PET in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2015-01-09

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer

  11. Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

    PubMed Central

    Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

    2012-01-01

    This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5?mL/kg. OSWE (100 and 200?mg/kg) was administered to rats 2?h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000?mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes. PMID:23118790

  12. Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis

    PubMed Central

    Ding, Song-Ze; Goldberg, Joanna B; Hatakeyama, Masanori

    2010-01-01

    Chronic colonization of the human stomach by Helicobacter pylori, a Gram-negative bacterium, is the major cause of chronic gastritis, peptic ulcers and gastric cancer. Recent progress has elucidated important bacterial and host factors that are responsible for H. pylori-induced gastric inflammation and gastric malignancy. H. pylori cytotoxin-associated antigen A is the major oncogenic factor injected into host cells from bacteria and it disrupts epithelial cell functions. Together with H. pylori cag pathogenicity island, it causes general inflammatory stress within gastric mucosa and activates multiple oncogenic pathways in epithelial cells. A growing list of these pathways includes NF-?B, activator protein-1, PI3K, signal transducers and activators of transcription 3, Wnt/?-catenin and cyclooxygenase 2. H. pylori induces epigenetic alterations, such as DNA methylation and histone modification, which play critical roles in oncogenic transformation. In addition, investigations into gastric stem cell or progenitor cell biology have shed light on the mechanisms through which gastric cancer may originate. Continued investigation in these areas will yield novel insights and help to elucidate the mechanisms of bacteria-induced carcinogenesis. PMID:20465395

  13. Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric carcinogenesis.

    PubMed

    Ding, Song-Ze; Goldberg, Joanna B; Hatakeyama, Masanori

    2010-05-01

    Chronic colonization of the human stomach by Helicobacter pylori, a Gram-negative bacterium, is the major cause of chronic gastritis, peptic ulcers and gastric cancer. Recent progress has elucidated important bacterial and host factors that are responsible for H. pylori-induced gastric inflammation and gastric malignancy. H. pylori cytotoxin-associated antigen A is the major oncogenic factor injected into host cells from bacteria and it disrupts epithelial cell functions. Together with H. pylori cag pathogenicity island, it causes general inflammatory stress within gastric mucosa and activates multiple oncogenic pathways in epithelial cells. A growing list of these pathways includes NF-kappaB, activator protein-1, PI3K, signal transducers and activators of transcription 3, Wnt/beta-catenin and cyclooxygenase 2. H. pylori induces epigenetic alterations, such as DNA methylation and histone modification, which play critical roles in oncogenic transformation. In addition, investigations into gastric stem cell or progenitor cell biology have shed light on the mechanisms through which gastric cancer may originate. Continued investigation in these areas will yield novel insights and help to elucidate the mechanisms of bacteria-induced carcinogenesis. PMID:20465395

  14. HSulf-1 suppresses cell growth and down-regulates Hedgehog signaling in human gastric cancer cells

    PubMed Central

    MA, HUI-YAN; ZHANG, FANG; LI, JIE; MO, MIN-LI; CHEN, ZHAO; LIU, LILI; ZHOU, HAI-MENG; SHENG, QING

    2011-01-01

    Gastric cancer is the second most lethal cancer worldwide. Despite the current surgical and adjuvant therapies, 5-year survival remains less than 20–25% in the US, Europe and China. Therefore, there is an urgent need to identify new therapeutic targets for treating this malignant disease. Accumulating evidence has supported that aberrant activation of the Hedgehog signaling pathway plays a crucial role in tumorigenesis and progression of gastric cancer. Human sulfatase-1 (HSulf-1) is a recently identified enzyme that desulfates cell surface heparan sulfate proteoglycans (HSPGs), which is critical for Hedgehog signal transduction under a highly sulfated state. HSulf-1 has recently emerged as a tumor suppressor gene in certain types of cancer, including ovarian, breast, myeloma and hepatocellular carcinoma; however, its role in gastric cancer remains to be elucidated. Therefore, we established HSulf-1-expressing monoclonal MKN28 gastric cancer cells to investigate its function in gastric cancer. Expression of HSulf-1 significantly suppressed cellular proliferation and growth in MKN28 gastric cancer cells. Notably, HSulf-1 inhibits Gli-mediated transcription and down-regulates the expression of Hedgehog target genes, including GLI1, PTCH1/2, HHIP, CCND1, C-MYC and BCL-2. Collectively, the study provides evidence that HSulf-1 may function as a tumor suppressor in gastric cancer. It suppresses gastric cancer cell proliferation, possibly through abrogating the Hedgehog signaling pathway. The study provides new mechanistic insight into HSulf-1- mediated tumor suppression, and supports the use of HSulf-1 as a potential new therapeutic target in treating gastric cancer. PMID:22848304

  15. Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

    ClinicalTrials.gov

    2015-04-15

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  16. Pteridium aquilinum and its ptaquiloside toxin induce DNA damage response in gastric epithelial cells, a link with gastric carcinogenesis.

    PubMed

    Gomes, Joana; Magalhães, Ana; Michel, Valérie; Amado, Inês F; Aranha, Paulo; Ovesen, Rikke G; Hansen, Hans C B; Gärtner, Fátima; Reis, Celso A; Touati, Eliette

    2012-03-01

    The multifactorial origin of gastric cancer encompasses environmental factors mainly associated with diet. Pteridium aquilinum-bracken fern-is the only higher plant known to cause cancer in animals. Its carcinogenic toxin, ptaquiloside, has been identified in milk of cows and groundwater. Humans can be directly exposed by consumption of the plant, contaminated water or milk, and spore inhalation. Epidemiological studies have shown an association between bracken exposure and gastric cancer. In the present work, the genotoxicity of P. aquilinum and ptaquiloside, including DNA damaging effects and DNA damage response, was characterized in human gastric epithelial cells and in a mouse model. In vitro, the highest doses of P. aquilinum extracts (40 mg/ml) and ptaquiloside (60 ?g/ml) decreased cell viability and induced apoptosis. ?H2AX and P53-binding protein 1 analysis indicated induction of DNA strand breaks in treated cells. P53 level also increased after exposure, associated with ATR-Chk1 signaling pathway activation. The involvement of ptaquiloside in the DNA damage activity of P. aquilinum was confirmed by deregulation of the expression of a panel of genes related to DNA damage signaling pathways and DNA repair, in response to purified ptaquiloside. Oral administration of P. aquilinum extracts to mice increased gastric cell proliferation and led to frameshift events in intron 2 of the P53 gene. Our data demonstrate the direct DNA damaging and mutagenic effects of P. aquilinum. These results are in agreement with the carcinogenic properties attributed to this fern and its ptaquiloside toxin and support their role in promoting gastric carcinogenesis. PMID:22143989

  17. [Melatonin as a therapeutic factor in gastric ulcer healing under experimental diabetes].

    PubMed

    Magierowski, Marcin; Jasnos, Katarzyna; Brzozowska, Iwona; Drozdowicz, Danuta; Sliwowski, Zbigniew; Nawrot, Elizbieta; Szczyrk, Urszula; Kwiecie?, S?awomir

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a hormon secreted mostly by the pineal gland in the brain which maintains the body's circadian rhythm. Interestingly, this indol derivative is produced by enterochromaffin-like cells (ECL) in the gastrointestinal tract (GIT) in amount about 400 fold greater than detected in the pinealocytes. Previous studies revealed that melatonin exerts beneficial action against acute gastric damage induced by stress ethanol, aspirin and ischemia-reperfusion. Hyperglycemia, which is the main symptom of diabetes mellitus, is known to induce mitochondrial dysfunction and endoplasmic reticulum stress, both promoting the generation of reactive oxygen species (ROS). ROS were shown to exhibit higher activity than molecular oxygen under basal conditions due to unpaired electron in its outermost shell of electrons. ROS lead to damage of cellular proteins, nucleic acids and membrane polyunsaturated fatty lipids. In this study, we induced diabetes mellitus by the application of strep. tozocin in presence of gastric ulcers. Male Wistar rats were used in this model. 9 days after gastric ulcers and diabetes mellitus induction, groups of rats were treated with saline or melatonin (20 mg/kg i.g.). At the termination of the experiment, rats were anesthetized, abdomen was opened and gastric blood flow (GBF) was measured. Stomachs were removed for determination of gastric ulcers area by planimetry. Tissue samples were collected for biochemical assays. We demonstrated that melatonin significantly accelerates gastric ulcers healing with and without coexistence of diabetes mellitus. This effect was accompanied by increase of GBF level. Moreover, we observed an increase in superoxide dismutase (SOD) activity and an decrease in lipid peroxidation products concentration within gastric tissue homogenates of animals treated with melatonin, as compared with control group. Melatonin application accelerates gastric ulcers healing with and without presence of diabetes mellitus. We conclude that melatonin can physiologically regulate anti-oxidative enzymes activity and increase GBF level. PMID:24697035

  18. Gastric cancer after Roux-en-Y gastric bypass.

    PubMed

    Escalona, Alex; Guzmán, Sergio; Ibáñez, Luis; Meneses, Luis; Huete, Alvaro; Solar, Antonieta

    2005-03-01

    Roux-en-Y gastric bypass (RYGBP) is one of the most commonly performed surgical procedures for morbid obesity. Several complications that may develop in the short- and long-term have been reported. We present a patient who presented with cancer in the bypassed stomach 8 years after RYGBP. Although the development of this lesion is rare and only a few cases have been reported, there are aspects worthy of discussion. Several monitoring, diagnostic and therapeutic alternatives are analyzed. PMID:15826480

  19. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    PubMed

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. PMID:15551386

  20. Molecular targeting to treat gastric cancer

    PubMed Central

    Aoyagi, Keishiro; Kouhuji, Kikuo; Kizaki, Junya; Isobe, Taro; Hashimoto, Kousuke; Shirouzu, Kazuo

    2014-01-01

    Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed. PMID:25320512

  1. Molecular targeting to treat gastric cancer.

    PubMed

    Aoyagi, Keishiro; Kouhuji, Kikuo; Kizaki, Junya; Isobe, Taro; Hashimoto, Kousuke; Shirouzu, Kazuo

    2014-10-14

    Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed. PMID:25320512

  2. Gastric emptying of solids: When should we sample

    SciTech Connect

    Sfakianakis, G.; Spoliansky, G.; Cassady, J.; Barkin, J.; Serafini, A.

    1984-01-01

    Gastric emptying of solids has been studied for 20 normal volunteers using Tc-99m-sulfur-colloid labeled chicken liver or eggs. Residual gastric activity measured in 15 min intervals for 2 1/2 hrs was used to calculate gastric emptying. The procedure was proposed and is used to examine patients for suspected abnormal emptying. This approach however ties up one gamma camera and one technologist for a period of 2 1/2 - 3 hrs. Furthermore to classify any value more the 1SD below the mean as abnormal includes 16% of normals as abnormally low (false positives). In order to find the pattern of abnormalities and the best time to study patients we analyzed the results of 54 studies performed in patients with a variety of clinical problems. Gastric emptying was measured in 30 min intervals for 2 1/2 hrs after a standard meal of 2 scrambled eggs labeled with 1 mCi of Tc-99m-sulfur-colloid, 2 slices of bread and 300 ml of juice. To choose the point important to observe the authors studied the distribution of values at each time-point to determine when there is the greatest variability from the reported normal. When there is delayed emptying the 2 1/2 hr observation is the best discriminator and when there is accelerated emptying the 60 min observation is the best discriminator. In the group of patients the 150 min observation had no correlation with the age of the patients. It is possible that sampling at a later time could be more discriminatory. The authors propose sampling at 0, 60, and 150 min time as the most informative and cost effective approach to study the solid gastric emptying. The 2SD rather than 1SD below and above the mean should be used as the level to separate normal from abnormal results.

  3. Prostaglandin regulation of gastric slow waves and peristalsis.

    PubMed

    Forrest, Abigail S; Hennig, Grant W; Jokela-Willis, Sari; Park, Chong Doo; Sanders, Kenton M

    2009-06-01

    Gastric emptying depends on functional coupling of slow waves between the corpus and antrum, to allow slow waves initiated in the gastric corpus to propagate to the pyloric sphincter and generate gastric peristalsis. Functional coupling depends on a frequency gradient where slow waves are generated at higher frequency in the corpus and drive the activity of distal pacemakers. Simultaneous intracellular recording from corpus and antrum was used to characterize the effects of PGE(2) on slow waves in the murine stomach. PGE(2) increased slow-wave frequency, and this effect was mimicked by EP(3), but not by EP(2), receptor agonists. Chronotropic effects were due to EP(3) receptors expressed by intramuscular interstitial cells of Cajal because these effects were not observed in W/W(V) mice. Although the integrated chronotropic effects of EP(3) receptor agonists were deduced from electrophysiological experiments, no clear evidence of functional uncoupling was observed with two-point electrical recording. Gastric peristalsis was also monitored by video imaging and spatiotemporal maps to study the impact of chronotropic agonists on propagating contractions. EP(3) receptor agonists increased the frequency of peristaltic contractions and caused ectopic sites of origin and collisions of peristaltic waves. The impact of selective regional application of chronotropic agonists was investigated by use of a partitioned bath. Antral slow waves followed enhanced frequencies induced by stimulation of the corpus, and corpus slow waves followed when slow-wave frequency was elevated in the antrum. This demonstrated reversal of slow-wave propagation with selective antral chronotropic stimulation. These studies demonstrate the impact of chronotropic agonists on regional intrinsic pacemaker frequency and integrated gastric peristalsis. PMID:19359421

  4. Helicobacter pylori PoreForming Cytolysin Orthologue TlyA Possesses In Vitro Hemolytic Activity and Has a Role in Colonization of the Gastric Mucosa

    Microsoft Academic Search

    M. CELESTE MARTINO; RICHARD A. STABLER; ZUN W. ZHANG; MICHAEL J. G. FARTHING; BRENDAN W. WREN; NICK DORRELL

    2001-01-01

    Hemolysins have been found to possess a variety of functions in bacteria, including a role in virulence. Hel- icobacter pylori demonstrates hemolytic activity when cultured on unlysed blood agar plates which is increased under iron-limiting conditions. However, the role of an H. pylori hemolysin in virulence is unclear. Scrutiny of the H. pylori 26695 genome sequence suggests the presence of

  5. Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer

    Microsoft Academic Search

    Mark S McClain; Carrie L Shaffer; Dawn A Israel; Richard M Peek

    2009-01-01

    BACKGROUND: Persistent colonization of the human stomach by Helicobacter pylori is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of H. pylori strains from patients with gastritis or duodenal ulcer disease have been analyzed. In this study, we analyzed the genome sequences of

  6. Ndrg2 promoter hypermethylation triggered by helicobacter pylori infection correlates with poor patients survival in human gastric carcinoma

    PubMed Central

    Ling, Zhi-Qiang; Ge, Ming-Hua; Lu, Xiao-Xiao; Han, Jin; Wu, Yi-Chen; Liu, Xiang; Zhu, Xin; Hong, Lian-Lian

    2015-01-01

    N-myc downstream regulated gene 2 (Ndrg2) is a candidate suppressor of cancer metastasis. We found that Ndrg2 promoter was frequently hypermethylated in gastric cancer cell lines and in 292 gastric tumor tissues. This resulted in down-regulation of Ndrg2 mRNA and protein. Ndrg2 promoter methylation was associated with H. pylori infection and worse prognosis of gastric cancer patients, which is an independent prognostic factor for the disease-free survival (DFS). We found that H. pylori silenced Ndrg2 by activating the NF-?B pathway and up-regulating DNMT3b, promoting gastric cancer progression. These findings uncover a previously unrecognized role for H. pylori infection in gastric cancer. PMID:25823664

  7. Gastric cancer treatment guidelines in Japan

    Microsoft Academic Search

    Toshifusa Nakajima

    2002-01-01

    .  \\u000a Recent developments in treatment modalities for gastric cancer have allowed the selection of a variety of treatments, and\\u000a this has resulted in some confusion in daily practice. The Japan Gastric Cancer Association issued the first edition of Gastric cancer treatment guidlelines in March, 2001 to provide a common basis of understanding of the extent of disease and selection of

  8. Bisabolol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide, and KATP+ channels.

    PubMed

    Bezerra, S B; Leal, L K A M; Nogueira, N A P; Pinto, N A N; Campos, A R

    2009-12-01

    The effects of Matricaria recutita and alpha-bisabolol, a bioactive component from Chamomile species, were investigated against gastric damage induced by absolute ethanol (96%, 1 mL per animal) in rats. The effects of M. recutita extract and alpha-bisabolol on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area. Mechanistic studies were carried out at with 100 mg=kg alpha-bisabolol. We further examined the possible participation of prostaglandins, nitric oxide, and KATP+ channels in its mechanism. M. recutita reduced gastric damage in all doses tested. Alpha-bisabolol at oral doses of 50 and 100 mg=kg markedly attenuated the gastric lesions induced by ethanol to the extent of 87% and 96%, respectively. Pretreatments with the nitric oxide antagonist N-nitro-l-arginine methyl ester (10 mg=kg, i.p.) or with indomethacin, an inhibitor of cyclooxygenase, failed to block effectively the gastroprotective effect of alpha-bisabolol. Furthermore, the alpha-bisabolol effect was significantly reduced in rats pretreated with glibenclamide, an inhibitor of KATP+ channel activation. Thus we provide evidence that alpha-bisabolol reduces the gastric damage induced by ethanol, at least in part, by the mechanism of activation of KATP+ channels. PMID:20041801

  9. Intracellular Poly(I:C) Initiated Gastric Adenocarcinoma Cell Apoptosis and Subsequently Ameliorated NK Cell Functions

    PubMed Central

    Qu, Jing; Hou, Zhaohua; Han, Qiuju; Jiang, Wen; Zhang, Cai; Tian, Zhigang

    2014-01-01

    Natural killer (NK) cells are granular lymphocytic cells that exert essential functions in viral infection defense and tumor immune surveillance. However, the functions of NK cells were impaired in cancer patients. Polycytidylic acid [poly(I:C)] has been used as an immune adjuvant to improve innate and adaptive immune responses. In this study, intracellular poly(I:C) could trigger gastric adenocarcinoma cells apoptosis quickly. Meanwhile, the sensitivity of poly(I:C)-treated gastric adenocarcinoma cells to NK cell cytolysis was increased, concomitant with the elevated expression of MICA/B and Fas. Furthermore, the cytolytic activity of NK cells against tumor cells was augmented significantly by the supernatant from poly(I:C)-transfected tumor cells compared with NK cells treated by the supernatant from untreated tumor cells, as well as the proliferation and migration abilities of NK cells. In this process, the activating receptors and cytolysis-associated molecules of NK cells were up-regulated. Further investigation showed that type I interferon (IFN) produced by poly(I:C)-transfected gastric adenocarcinoma cells played an important role in this process. Our findings demonstrated that intracellular poly(I:C) not only triggered gastric adenocarcinoma cell apoptosis, but also enhanced NK responses via inducing type I IFN production by gastric adenocarcinoma cells. These functions make poly(I:C) a promising therapeutic medicine for gastric adenocarcinoma. PMID:24032591

  10. Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats.

    PubMed Central

    Esplugues, J.; Lloris, J. M.; Martí-Bonmatí, E.; Morcillo, E. J.

    1982-01-01

    1. Experiments were designed to evaluate the effect of the pharmacological activation of beta-adrenoceptors on various models of gastric ulcer in the rat. 2. Pretreatment with the beta-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that beta 2-adrenoceptors mediate this response. 3. In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol. 4. Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti-ulcer effect is not necessarily dependent on acid inhibition. 5. Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin). 6. Long-term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer. 7. In anaesthetized rats, salbutamol produced a dose-related increase in mucosal blood flow which may contribute to its mode of action. 8. It is concluded that beta-adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through beta-adrenoceptor activation. PMID:6125225

  11. Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids.

    PubMed

    Tarnawski, Andrzej; Ahluwalia, Amrita; Jones, Michael K

    2013-01-01

    This article updates current views on gastric mucosal defense, injury, protection and ulcer healing with a focus on mucosal protective and ulcer healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of ulcerogenic and necrotizing agents - even such strong inducers of injury as 100% ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate healing of erosions and gastric ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors. PMID:22950493

  12. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    SciTech Connect

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-? and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-?B (NF-?B) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-?B expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-?B expression and MPO accumulation in ethanol-induced gastric tissue.

  13. High expression of RELM-? correlates with poor prognosis and promotes angiogenesis in gastric cancer.

    PubMed

    Chen, Ping; Zhao, Deshou; Wang, Weiyi; Zhang, Yongping; Yuan, Yaozong; Wang, Lifu; Wu, Yunlin

    2015-07-01

    Accumulating evidence indicates that resistin?like molecule-? (RELM-?) is involved in angiogenesis, while the clinical significance and the exact role of RELM-? in gastric cancer remain obscure. The aim of the present study was to evaluate the clinical significance of RELM-? in gastric cancer, and to investigate its effective mechanisms in order to identify a potential therapeutic target. The expression levels of RELM-? in 92 gastric cancer and adjacent normal tissues were investigated and the relationship between RELM-? expression and the clinicopathological characteristics was explored. To investigate the potential role of RELM-? in gastric cancer cell biological behavior, the cell proliferation, migration and invasion assays were conducted using two gastric cancer cell lines (SGC7901 and MKN45). We also assessed whether RELM-? gene silencing modulates angiogenesis using small interference RNA in cancer cell lines, and investigated its effect on nuclear factor (NF)-?B activation and vascular endothelial growth factor (VEGF) and MMP-9 expression. Contrasting sharply with the strong RELM-?-positive tumors, adjacent normal tissues and cell lines exhibited negative or weakly positive expression (P<0.01). High expression level of RELM-? was associated with advanced stage and tumor size (P<0.01). The silencing of RELM-? expression by Ad5/F35-siRNA treatment significantly inhibited cell migratory and invasive ability in SGC7901 and MKN45 gastric cancer cells compared with the control and Ad5/F35 vector-transfected cell lines (P<0.01). However, the silencing of RELM-? expression also significantly blocked NF-?B activation and attenuated VEGF and MMP-9 expression. The data demonstrated that RELM-? is a promising novel biomarker of angiogenesis in patients with gastric cancer. The study identified that the silencing of RELM-? expression may regulate the proliferation, invasion and migration of gastric cancer cells by targeting VEGF/MMP-9, and the mechanism involved tissue angiogenesis via the NF-?B signaling pathway. PMID:25937206

  14. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review.

    PubMed

    Asano, Naoki; Iijima, Katsunori; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

    2015-07-14

    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-?B) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-?B activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status. PMID:26185372

  15. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review

    PubMed Central

    Asano, Naoki; Iijima, Katsunori; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

    2015-01-01

    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-?B) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-?B activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status. PMID:26185372

  16. Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2

    PubMed Central

    Zhang, Ping; Luo, He-Sheng; Li, Ming; Tan, Shi-yun

    2015-01-01

    Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V–fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic agent for gastric cancer. PMID:25945055

  17. Pathogenetic mechanisms in gastric cancer

    PubMed Central

    Shi, Jing; Qu, Yi-Ping; Hou, Peng

    2014-01-01

    Gastric cancer (GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis, as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways, such as gene mutations, copy number variants, aberrant gene methylation and histone modification, nucleosome positioning, and microRNAs. Some of these genetic/epigenetic alterations represent effective diagnostic and prognostic biomarkers and therapeutic targets for GC. This information has now opened unprecedented opportunities for better understanding of the molecular mechanisms of gastric carcinogenesis and the development of novel therapeutic strategies for this cancer. The pathogenetic mechanisms of GC are the focus of this review. PMID:25320518

  18. Gastric Syphilis and Membranous Glomerulonephritis.

    PubMed

    Roh, Min; Sohn, Joo Hyun; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-05-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  19. Gastric Syphilis and Membranous Glomerulonephritis

    PubMed Central

    Roh, Min; Kim, Tae Yeob; Kim, Sung Jong; Kim, Ji Soong; Chung, Sung Jun; Pyo, Ju Yeon; Oh, Young-Ha

    2015-01-01

    Syphilis is a chronic systemic infectious disease caused by the bacterium Treponema pallidum. Gastric involvement and nephrotic syndrome are uncommon but well documented complications of syphilis, but the co-occurrence of these two complications in the same patient is extremely rare. Thus, because of their nonspecific presentation, suspicion of gastric syphilis (GS) and nephrotic syndrome is essential for diagnosis. Patients should be investigated thoroughly and a diagnosis made based on clinical, endoscopic, and histological findings, in order to initiate appropriate therapy. We report of a 34-year-old male patient with a history of epigastric pain and a diagnosis of GS and syphilis-associated membranous glomerulonephritis confirmed by gastroscopy and kidney biopsy, who was treated successfully with penicillin G benzathine. This case report provides information on the typical features of GS that should help raise awareness of this rare disease entity among clinicians, resulting in earlier diagnosis and administration of appropriate therapy. PMID:26064828

  20. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    PubMed Central

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  1. Development and Verification of a Mouse Model for Roux-en-Y Gastric Bypass Surgery with a Small Gastric Pouch

    PubMed Central

    Hao, Zheng; Zhao, Zhiyun; Berthoud, Hans-Rudolf; Ye, Jianping

    2013-01-01

    Existing mouse models of Roux-en-Y gastric bypass (RYGB) surgery are not comparable to human RYGB in gastric pouch volume for a large or absent gastric volume. The aim of this study was to develop and characterize a mouse RYGB model that closely replicates gastric pouch size of human RYGB surgery of about 5% of total gastric volume. We established this model in diet-induced obese (DIO) mice of C57BL/6J. This surgery resulted in a sustained 30% weight loss, entirely accounted for by decreased fat mass but not lean mass, compared to sham-operated mice on the high fat diet. Compared to sham-operated mice, energy expenditure corrected for total body weight was significantly increased by about 25%, and substrate utilization was shifted toward higher carbohydrate utilization at 8 weeks after RYGB when body weight had stabilized at the lower level. The energy expenditure persisted and carbohydrate utilization was even more pronounced when the mice were fed chow diet. Although significantly increased during daytime, overall locomotor activity was not significantly different. In response to cold exposure, RYGB mice exhibited an improved capacity to maintain the body temperature. In insulin tolerance test, exogenous insulin-induced suppression of plasma glucose levels was significantly greater in RYGB mice at 4 weeks after surgery. Paradoxically, food intake measured at 5 weeks after surgery was significantly increased, possibly in compensation for increased fecal energy loss and energy expenditure. In conclusion, this new model is a viable alternative to existing murine RYGB models and the model matches human RYGB surgery in anatomy. This model will be useful for studying molecular mechanisms involved in the beneficial effects of RYGB on body weight and glucose homeostasis. PMID:23326365

  2. Helicobacter pylori Initiates a Mesenchymal Transition through ZEB1 in Gastric Epithelial Cells

    PubMed Central

    Baud, Jessica; Varon, Christine; Chabas, Sandrine; Chambonnier, Lucie; Darfeuille, Fabien; Staedel, Cathy

    2013-01-01

    Chronic Helicobacter pylori infection provokes an inflammation of the gastric mucosa, at high risk for ulcer and cancer development. The most virulent strains harbor the cag pathogenicity island (cagPAI) encoding a type 4 secretion system, which allows delivery of bacterial effectors into gastric epithelial cells, inducing pro-inflammatory responses and phenotypic alterations reminiscent of an epithelial-to-mesenchymal transition (EMT). This study characterizes EMT features in H. pylori-infected gastric epithelial cells, and investigates their relationship with NF-?B activation. Cultured human gastric epithelial cell lines were challenged with a cagPAI+ H. pylori strain or cag isogenic mutants. Morphological changes, epithelial and mesenchymal gene expression and EMT-related microRNAs were studied. H. pylori up-regulates mesenchymal markers, including ZEB1. This transcription factor is prominently involved in the mesenchymal transition of infected cells and its up-regulation depends on cagPAI and NF-?B activation. ZEB1 expression and NF-?B activation were confirmed by immunohistochemistry in gastric mucosa from cagPAI+ H. pylori-infected patients. Gastric epithelial cell lines express high miR-200 levels, which are linked to ZEB1 in a reciprocal negative feedback loop and maintain their epithelial phenotype in non-infected conditions. However, miR-200b/c were increased upon infection, despite ZEB1 up-regulation and mesenchymal morphology. In the miR-200b-200a-429 cluster promoter, we identified a functional NF-?B binding site, recruiting NF-?B upon infection and trans-activating the microRNA cluster transcription. In conclusion, in gastric epithelial cells, cagPAI+ H. pylori activates NF-?B, which transactivates ZEB1, subsequently promoting mesenchymal transition. The unexpected N-F?B-dependent increase of miR-200 levels likely thwarts the irreversible loss of epithelial identity in that critical situation. PMID:23565224

  3. MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box-binding homeobox 2.

    PubMed

    Du, Ying; Wang, Lingfei; Wu, Honghai; Zhang, Yiyin; Wang, Kan; Wu, Dingting

    2015-09-01

    Human microRNA (miR)-141 is a member of the miR?200 family, which has been reported to be downregulated in gastric cancer, and involved in the proliferation of gastric cancer cells. However, little is currently known regarding its role in the migration of gastric cancer. The present study investigated the function of miR?141 in gastric cancer cell migration, and evaluated the contribution of zinc finger E?box?binding homeobox 1 and 2 (ZEB1/2) in miR?141 mediated migration of gastric cancer cells. The expression levels of miR?141 and its potential ZEB1/2 targets were examined by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. The migration of SGC?7901 and HGC?27 gastric cancer cells, which had been transfected with an miRNA precursor, was examined by cell migration and wound healing assays. A luciferase activity assay was used to validate whether ZEB1/2 was a direct target of miR?141. The results demonstrated that overexpression of miR?141 markedly inhibited the migration of gastric cancer cells in vitro. Forced overexpression of miR?141 significantly reduced the luciferase activity of the 3'?untranslated region of ZEB2 in gastric cancer cells. Furthermore, the mRNA and protein expression levels of ZEB2 were reduced in cells overexpressing miR?141, whereas the protein expression levels of E?cadherin were increased. In gastric tumor samples the expression levels of ZEB2 were inversely correlated with the expression of miR?141. These results suggest that miR?141 may be involved in the inhibition of gastric cancer cell migration, and that ZEB2 is a target gene of miR-141. PMID:25975736

  4. Phase II study of pemetrexed disodium (Alimta(R)) administered with oral folic acid in patients with advanced gastric cancer

    Microsoft Academic Search

    E. Bajetta; L. Celio; R. Buzzoni; L. Ferrari; A. Marchianò; A. Martinetti; R. Longarini; C. Becerra; C. Ilardi; W. John

    2003-01-01

    Background: The aim of this study was to assess the activity of pemetrexed in patients with advanced gastric cancer. Patients and methods: Thirty-eight eligible patients (median age 60 years) received pemetrexed 500 mg\\/m 2

  5. A cephalic influence on gastric motility upon seeing food in domestic turkeys (Melagris gallopavo), great-horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis).

    PubMed

    Duke, G E; Evanson, O A; Redig, P T

    1976-11-01

    Strain gage transducers were permanently implanted on the muscular stomachs of 13 turkeys, 3 great-horned owls and 2 red-tailed hawks to monitor gastric motility before, during and after eating. Following fasting, the sight of food resulted in significant increases in gastric contractile activity in all three species. Gastric motility further increased when the birds were allowed to eat. In raptors, however, a brief interruption in gastric motility occurred immediately after eating. This is apparently analogous to receptive relaxation which occurs in the stomach of mammals. PMID:1019075

  6. Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

    PubMed Central

    Zhang, Lei; Gong, Ji T; Zhang, Hu Q; Song, Quan H; Xu, Guang H; Cai, Lei; Tang, Xiao D; Zhang, Hai F; Liu, Fang-E; Jia, Zhan S; Zhang, Hong W

    2015-01-01

    Background/Aims There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. Methods Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. Results The GRR and SPR were improved by noise stress compared with control (P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and malondialdehyde in gastric mucosa homogenate were increased by noise stress (P < 0.05). CGRP and superoxide dismutase activity in both of blood plasma and gastric mucosa homogenate were significantly decreased (P< 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde (P < 0.05). Conclusions Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones. PMID:25537679

  7. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    SciTech Connect

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China) [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)] [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China)] [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China)] [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)] [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-02-05

    Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

  8. Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration

    PubMed Central

    PARK, CHUL-HONG; SON, HYUNG-U; SON, MINSIK; LEE, SANG-HAN

    2011-01-01

    Acer mono Max. sap (AmMs) is called ‘Gol-Li-Su’ or ‘Go-Lo-Soe’ in Korean, which means ‘water beneficial to the bones’. It is reported that the sap contains several types of minerals and sugars. In particular, the calcium concentration of the sap is 36.5 times higher than that of commercial mineral water. Apart from its anti-osteoporosis effect, no reports have addressed the biological activities of AmMs against degenerative diseases. In the present study, we investigated whether AmMs alleviates gastric ulcer-related symptoms in a stress-induced mouse model. To assess the effect of AmMs on gastric ulcer-like symptoms, we carried out a water immersion restraint (WIRE) test and found that AmMs has potential in alleviating gastric ulcers in a concentration-dependent manner. These results indicate that the nutritional factors of the sap mitigate the gastric ulcer-related symptoms caused by stress-induced gastric lesions in mice. AmMs-treated mice exhibited a significant decrease in the ulcer index as compared to those treated with omeprazole or L-arginine. To examine one potential mechanism underlying this effect, we performed reverse transcription-polymerase chain reaction to ascertain whether molecular markers were associated with the mitigation of the gastric lesions. Epithelial and/or tissue nitric oxide synthase (NOS) was assessed to determine whether or not the genes were down-regulated dose-dependently by the sap. The levels of these enzymes were found to be lower in the tissue samples treated with AmMs compared with the levels in the control samples. These findings collectively suggest that AmMs significantly protects the gastric mucosa against WIRE stress-induced gastric lesions, at least in part, by alleviating inducible NOS and/or neuronal NOS expression. PMID:22977586

  9. Characterization and Functional Properties of Gastric Tissue-Resident Memory T Cells from Children, Adults, and the Elderly

    PubMed Central

    Booth, Jayaum S.; Toapanta, Franklin R.; Salerno-Goncalves, Rosangela; Patil, Seema; Kader, Howard A.; Safta, Anca M.; Czinn, Steven J.; Greenwald, Bruce D.; Sztein, Marcelo B.

    2014-01-01

    T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC) from gastric biopsies. Classic memory T subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC) obtained from children, adults, and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory T (TEM) phenotype was observed in gastric LPMC CD4+ and CD8+ T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM) cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8+ T cells either co-expressed CD103/CD69 (>70%) or expressed CD103 alone (~20%). Gastric LPMC CD4+ T cells also either co-expressed CD103/CD69 (>35%) or expressed at least one of these markers. Thus, gastric LPMC CD8+ and CD4+ T cells had the characteristics of TRM cells. Gastric CD8+ and CD4+ TRM cells produced multiple cytokines (IFN-?, IL-2, TNF-?, IL-17A, MIP-1?) and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC TEM counterparts. Furthermore, gastric CD8+ TRM and CD4+ TRM cells demonstrated differences in the frequency, susceptibility to activation, and cytokine/multi-cytokine production profiles among the age groups. Most notably, children’s gastric TRM cells responded differently to stimuli than gastric TRM cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric TRM, which exhibit diverse functional characteristics in children, adults, and the elderly. PMID:24995010

  10. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    PubMed

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid?Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post?explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13?52 h, as compared to normal cells, which had a doubling time of 20?53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin?secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer. PMID:25937205

  11. Downregulation of miR203 induces overexpression of PIK3CA and predicts poor prognosis of gastric cancer patients

    PubMed Central

    Liang, Min; Shi, Boyun; Liu, Jifang; He, Lu; Yi, Gao; Zhou, Lin; Yu, Guifang; Zhou, Xinke

    2015-01-01

    Background Despite advances in clinical therapies and technologies, the prognosis for patients with gastric cancer is still poor. The aim of this study is to investigate new predictive markers for prognosis of gastric cancer. Methods In this study, we evaluated the expression pattern of PIK3CA in 107 gastric cancer specimens and their adjacent nontumorous tissues. PIK3CA siRNA was synthesized and transfected into gastric cancer cell lines. Colony formation and MTT assays were employed to analyze the cell proliferation. PIK3CA expression was examined by using immunohistochemical analysis and Western blot assay. Transwell invasion assay was used to detect the invasion capability of the cells. Luciferase activity was examined by using 3?-untranslated region luciferase reporter assays. Results We observed that PIK3CA was significantly upregulated in gastric cancer tissues. High expression level of PIK3CA was detectable in 48 (44.86%) of the gastric cancer specimens, and correlated with poor prognosis. In addition, our study indicated that miR203 inhibits cell proliferation and invasion via directly targeting and suppressing the PIK3CA expression. MiR203 expression is downregulated in gastric cancer tissues. Moreover, low expression level of miR203 predicted poor prognosis of gastric patients and induced overexpression of PIK3CA. Our further study also reported that overexpression of miR203 inhibited phosphorylation of AKT, while cotransfection of PIK3CA reversed the effect of miR203. Conclusion Our study suggested a miR203-PIK3CA-AKT signaling pathway in gastric cancer cells. This signaling pathway might play an important role in gastric cancer genesis and development.

  12. Benign gastric ulceration in pernicious anemia

    Microsoft Academic Search

    J. Reid; T. V. Taylor; S. Holt; R. C. Heading

    1980-01-01

    Summary Benign gastric ulceration occurred in a patient with pernicious anemia in association with aspirin therapy. Previous reports of benign gastric ulceration in patients with achlorhydria are reviewed, and the potential role of aspirin in the pathogenesis of benign ulceration in the absence of acid is discussed.

  13. Palliative radiation therapy for primary gastric melanoma

    PubMed Central

    Slater, Jason M.; Ling, Ted C.; Slater, Jerry D.

    2014-01-01

    Introduction Primary gastric melanoma is an exceedingly rare cause of upper gastrointestinal bleeding (GI bleeding). Prior reports of primary gastric melanoma have mostly been treated with surgery with utilization of radiation therapy being unreported. Radiation therapy has been used to palliate bleeding of other cancers including lung, bladder, cervix, and more recently primary gastric cancers. Case presentation This case documents an 87-year-old male who presented with fatigue and melena, and was found to have severe anemia. Endoscopy with biopsy revealed an isolated focus of melanoma. After discharge, he presented two days later and was found to have continued bleeding. Because he was deemed a poor surgical candidate he elected to undergo palliative radiation therapy for bleeding control. Discussion The diagnosis of primary verses metastatic melanoma is a topic of debate. Case reports of patients with no known extra-gastric primary have undergone surgical treatment with varying outcomes. Patients with metastatic gastric melanoma have relied on chemotherapy and radiation in addition to surgery, with radiation being used in the palliative setting. The use of radiation to control bleeding in other cancers including primary gastric adenocarcinoma has been previously studied. This case documents the utilization of radiation therapy in bleeding due to primary gastric melanoma. Conclusions Radiation therapy can provide adequate bleeding palliation in patients with primary gastric melanoma. PMID:24490048

  14. Metformin potentiates rapamycin and cisplatin in gastric cancer in mice.

    PubMed

    Yu, Guanzhen; Fang, Wenzheng; Xia, Tian; Chen, Ying; Gao, Yunshu; Jiao, Xiaodong; Huang, Suyun; Wang, Jiejun; Li, Zhaosheng; Xie, Keping

    2015-05-20

    Here we showed that pAMPK? and PTEN were down-regulated and p-mTOR, p-S6, p-4EBP1, MMP7, and DCN1 were up-regulated in human gastric cancer tissue samples as compared to that in the noncancerous tissues. Metformin inhibited tumor growth in mice. Also it enhanced cisplatin- or rapamycin-induced reduction of tumor growth as compared with treatment of either drug alone. In addition to activation of AMPK and suppression of the mTOR pathway, a series of increased and decreased genes expression were induced by metformin, including PTEN, MMP7, and FN1. We suggest that metformin could potentially be used for the treatment of gastric cancer especially in combination with cisplatin or rapamycin. PMID:25909163

  15. Ticlopidine prevents the formation but delays the healing of ethanol-induced gastric lesions in the rat.

    PubMed

    Sibilia, V; Pagani, F; Lattuada, N; De Luca, V; Guidobono, F; Soglian, A; Netti, C

    2007-05-01

    The effects of acute or long-term oral ticlopidine administration in normal rat gastric mucosa or on gastric lesions induced by ethanol 50% (EtOH, 1 ml/rat, os) were examined and compared with those of acetylsalicylic acid (ASA). Ticlopidine does not affect gastric mucosal integrity either after acute (100 and 300 mg kg(-1)) or 1-week (100 mg kg(-1), die) oral administration. Ticlopidine (30-300 mg kg(-1), os) administered 1h before EtOH dose-dependently prevented the development of gastric haemorragic lesions. When ticlopidine was administered 1h after EtOH, it significantly (p<0.05) delays gastric lesions healing. Acute ASA (50 and 100 mg kg(-1), os) administration causes a mild irritant activity similar to that observed after 1 week of ASA (50 mg kg(-1), os/die) administration. In condition of mucosal damage, ASA does not modify either the induction or the healing of EtOH-induced gastric lesions. To assess the possible involvement of endogenous nitric oxide (NO) or prostaglandins (PG) in the gastric protective activity of ticlopidine, the rats were pretreated with an inhibitor of NO-synthesis, L-NAME (70 mg kg(-1), s.c.) or the inhibitor of PG synthesis, indomethacin (Indo, 10 mg kg(-1), s.c.). Indo, but not L-NAME, was able to significantly counteract the gastroprotective activity of ticlopidine against EtOH injury. Furthermore, ticlopidine increases (47%) gastric PGE(2) content in normal mucosa compared to the one detected in control rats, thus suggesting that endogenous PGs contribute to enhanced mucosal resistance by ticlopidine. These results indicate that ticlopidine exerts dual effects during the development and healing of gastric lesions induced by EtOH. PMID:17324584

  16. Phytohaemagglutinin inhibits gastric acid but not pepsin secretion in conscious rats.

    PubMed

    Kordás, K; Szalmay, G; Bardocz, S; Pusztai, A; Varga, G

    2001-01-01

    Phytohaemagglutinin (PHA), a kidney bean lectin, is known for its binding capability to the small intestinal surface. There has been no data available, however, on the biological activity of PHA in the stomach. Recent observations indicate that PHA is able to attach to gastric mucosal and parietal cells. Therefore, we examined whether PHA affects gastric acid and pepsin secretion in rats. Rats were surgically prepared with chronic stainless steel gastric cannula and with indwelling polyethylene jugular vein catheter. During experiments, animals were slightly restrained. Gastric acid secretion was collected in 30 min periods. Acid secretion was determined by titration of the collected gastric juice with 0.02 N NaOH to pH 7.0. Pepsin activity was estimated by measuring enzymatic activity. Saline, pentagastrin and histamine were infused intravenously. PHA or bovine serum albumin (BSA) were dissolved in saline and given intragastrically through the gastric cannula. PHA significantly inhibited basal acid secretion. Inhibition of acid output reached 72% during the first collection period following PHA administration when compared, then gradually disappeared. Pentagastrin-stimulated acid secretion was repressed dose-dependently by PHA as well. Maximal inhibition was observed during the first 30 min following application of PHA. Histamine-stimulated acid secretion was inhibited by PHA in a similar manner. Pepsin secretion was not affected by PHA under either basal or stimulated conditions. These results provide evidence that PHA is a potent inhibitor of gastric acid secretion in conscious rats, but it does not affect pepsin output from the stomach. PMID:11595455

  17. Gastric distention induced functional magnetic resonance signal changes in the rodent brain.

    PubMed

    Min, D K; Tuor, U I; Chelikani, P K

    2011-04-14

    Investigating the localization of gastric sensation within the brain is important for understanding the neural correlates of satiety. Previous rodent studies have identified the brain-stem and hypothalamus as key mediators of gastric distention-induced satiation. Although, recent blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) studies in humans have identified a role for higher cortico-limbic structures in mediating the satiation effects of gastric distention, the role of these regions in rodents remains to be characterized. We determined the effects of gastric distention on global spatio-temporal BOLD fMRI signal changes in the rodent brain. Brain images were acquired with a high resolution 9.4 T magnet during gastric distention with continuous monitoring of blood pressure in adult male Sprague Dawley rats (n=8-10). Distention of the stomach with an intragastric balloon, at rates which mimicked the rate of consumption and emptying of a mixed nutrient liquid meal, resulted in robust reduction in food intake and increase in blood pressure. Gastric distention increased BOLD fMRI activity within homeostatic regions such as the hypothalamus and nucleus tractus solitarius, as well as non homeostatic regions including the hippocampus, amygdala, thalamus, cerebellum and the cortex (cingulate, insular, motor and sensory cortices). Further, the increase in BOLD fMRI activity following distention was strongly correlated to an increase in blood pressure. These results indicate that gastric distention, mimicking the rate of intake and emptying of a liquid meal, increases BOLD fMRI activity in both homeostatic and non homeostatic brain circuits which regulate food intake, and that these BOLD fMRI signal changes may in part be attributable to transient increases in blood pressure. PMID:21284950

  18. Pathogenesis of gastric cancer in pernicious anaemia.

    PubMed

    Ruddell, W S; Bone, E S; Hill, M J; Walters, C L

    1978-03-11

    A pathogenetic mechanism to explain the increased incidence of gastric cancer in patients with pernicious anaemia (P.A.) is proposed. Mean nitrite concentration in gastric juice from thirteen fasting patients with P.A. was nearly fiftyfold greater than that of age-matched controls. The number of bacteria in the gastric juice of P.A. patients was also greatly increased. Small amounts of volatile nitrosamines were detected in simulated P.A. gastric juice in vitro, after addition of nitrite to achieve a concentration approximating to that found in vivo. If similar nitrosation occurs in vivo, the intragastric production of carcinogenic N-nitroso compounds could explain the high incidence of gastric cancer in patients with P.A. PMID:76069

  19. [Indications of laparoscopic surgery for gastric cancer].

    PubMed

    Li, Ziyu

    2014-08-01

    Consensus has been reached on the advantage and validity of laparoscopic surgery, but how to extend the usage of laparoscopic surgery in gastric cancer properly in China remains a problem as advanced gastric cancer occupies the majority of patients here. In the treatment of early gastric cancer, laparoscopic surgery nowadays is one of the standard treatments but surgeons still need to follow the indication of surgery strictly to avoid the excessive treatment in patients who are indicated for endoscopic therapy. There is still lack of evidence on the application of laparoscopic surgery in the treatment of advanced gastric cancer, therefore these procedures should be performed in the context of clinical trials. With the development of laparoscopic surgery in the treatment of advanced gastric cancer, training, certification and supervision systems are still not established. More attention should be paid to the choice of patients during the early period of learning curves and the indication of advanced stage. PMID:25164886

  20. Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer

    Microsoft Academic Search

    Y Y Cheng; H Jin; X Liu; J M T Siu; Y P Wong; E K O Ng; J Yu; W-k Leung; J J Y Sung; F K L Chan; FKL Chan

    2008-01-01

    Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was

  1. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils.

    PubMed

    Bae, Minkyung; Jang, Sungil; Lim, Joo Weon; Kang, Jieun; Bak, Eun Jung; Cha, Jeong-Heon; Kim, Hyeyoung

    2014-01-01

    Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-?B. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-1?, and iNOS; protein level of phospho-I?B? (which reflects the activation of NF-?B); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1?, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of I?B? and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1?, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa. PMID:24558304

  2. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

    PubMed Central

    Bae, Minkyung; Jang, Sungil; Lim, Joo Weon; Kang, Jieun; Bak, Eun Jung; Cha, Jeong-Heon; Kim, Hyeyoung

    2013-01-01

    Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-?B. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-1?, and iNOS; protein level of phospho-I?B? (which reflects the activation of NF-?B); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1?, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of I?B? and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1?, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa. PMID:24558304

  3. Back diffusion of hydrogen ions across gastric mucosa of patients with gastric ulcer and rheumatoid arthritis.

    PubMed

    Ivey, K J; Clifton, J A

    1974-01-01

    Ionic permeability of the gastric mucosa was measured in six patients with an acute exacerbation of severe generalized rheumatoid arthritis receiving either aspirin and prednisone or aspirin and indomethacin as therapy. The results were compared with those in four patients with benign gastric ulcer and nine normal subjects. Compared with controls H(+) concentration was decreased and Na(+) concentration increased while corrected H(+) flux out of the lumen and Na(+) flux into the lumen were significantly increased in the patient groups, indicating increased mucosal permeability. Abnormality of the gastric mucosal barrier persisted in two patients despite healing of their ulcers. Mucosal permeability of patients with rheumatoid arthritis and gastric ulcer did not differ significantly from one another. One rheumatoid patient with a gastric ulcer showed no difference in mucosal permeability to that of the other rheumatoid patients. These studies suggest that increased H(+) ion loss contributes to the apparent hyposecretion of acid in patients gastric ulcer; persistence of an abnormal gastric mucosal barrier to H(+) ions may explain the high recurrence rate of gastric ulcers; and an abnormal gastric mucosal barrier may be a precursor to gastric ulceration in rheumatoid arthritis. PMID:4808814

  4. Ameliorating Effect of Transcutaneous Electroacupuncture on Impaired Gastric Accommodation in Patients with Postprandial Distress Syndrome-Predominant Functional Dyspepsia: A Pilot Study

    PubMed Central

    Xu, Feng; Tan, Yan; Xu, Yuemei

    2015-01-01

    Patients with functional dyspepsia (FD) have both reduced gastric accommodation and impaired gastric motility that are difficult to treat. The aim of this study was to investigate the therapeutic potential of transcutaneous electroacupuncture (TEA) for both of these disorders in FD patients. Acute experiments were performed in FD patients to study the effect of TEA and sham-TEA on gastric accommodation assessed by a nutrient drink test and gastric motility assessed by the measurement of the electrogastrogram (EGG). TEA or sham-TEA was performed via cutaneous electrodes at acupoints ST36 and PC6 or sham-points nonacupoints. It was found that (1) gastric accommodation (maximum tolerable volume) was reduced in FD patients compared with the controls (P < 0.03). TEA improved gastric accommodation in FD patients (P < 0.02). (2) Acute TEA significantly increased the percentage and power of normal gastric slow waves in the fed state assessed in the FD patients by the EGG in comparison with sham-TEA. (3) TEA increased vagal activity assessed by the spectral analysis of the heart rate variability in the fed state in FD patients. It was concluded that needleless method of transcutaneous electroacupuncture may have a therapeutic potential for treating both impaired gastric accommodation and impaired gastric motility in patients with FD.

  5. ABH and Lewis antigen distributions in blood, saliva and gastric mucosa and H pylori infection in gastric ulcer patients

    Microsoft Academic Search

    Luisa Caricio Martins; Tereza Cristina de Oliveira Corvelo

    AIM: To investigate the ABH and Lewis antigen expres- sion in erythrocytes, saliva and gastric epithelium, as well as the association between H pylori and the pres- ence of gastric epithelial lesions. METHODS: The distribution of ABH and Lewis blood group antigens in erythrocytes, saliva and gastric mu- cosa of H pylori -infected gastric ulcer patients was ana- lyzed. Forty-two

  6. Targeting Notch signaling by ?-secretase inhibitor I enhances the cytotoxic effect of 5-FU in gastric cancer.

    PubMed

    Lee, Hyun-Woo; Kim, Seok-Jun; Choi, Il Ju; Song, Jaewhan; Chun, Kyung-Hee

    2015-08-01

    Current medication for gastric cancer patients has a low success rate and the patients develop rapid tolerance to these drugs. Therefore, the development of new regimens is desired. In this study, we determined that Notch-signaling-related genes were overexpressed and activated in gastric cancer patients and gastric cancer cell lines. According to recent studies, ?-secretase inhibitors (GSIs), which function as Notch signaling inhibitors, could be used as therapeutic drugs in cancer. We demonstrated that GSI I (cbz-IL-CHO) is the most effective GSI in gastric cancer cells. We also determined the cell survival signaling-related proteins that were affected by GSI I. The levels of phosphorylated AKT were significantly decreased upon GSI I treatment, and constitutively activated myristoylated AKT completely blocked GSI I-induced apoptosis and cell survival, suggesting that inhibition of AKT signaling is critical for GSI I-mediated effects in gastric cancer cells. In order to maximize the effects and safety of GSI I, a combination treatment with GSI I and 5-FU was performed. Inhibition of gastric cancer cell proliferation with the combination treatment was significantly better than that with the single treatment. All phosphorylated forms of AKT, p44/42, JNK, and p38 were drastically changed by the combination treatment. Orthotopically transplanted gastric tumor burdens in mice were reduced using the combined treatment. The outcomes of this study clearly demonstrated the therapeutic potential of GSI I in gastric cancer, as well as the greater efficacy of the combined treatment of GSI I with 5-FU. Therefore, we suggest that further clinical trials examining the potential of combined GSI I and 5-FU treatment in gastric cancer patients be undertaken. PMID:26134677

  7. Intestinalization of gastric signet ring cell carcinomas with progression

    Microsoft Academic Search

    T. Yamachika; Ken-ichi Inada; Yasunobu Fujimitsu; Shigeo Nakamura; Yoshitaka Yamamura; Tsuyoshi Kitou; Steven H. Itzkowitz; J. L. Werther; Kazumasa Miki; Masae Tatematsu

    1997-01-01

    Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and\\u000a intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type\\u000a to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation\\u000a in gastric signet ring cell carcinomas with progression in 203 surgically obtained

  8. Gastric tone determines the sensitivity of the stomach to distention

    Microsoft Academic Search

    Ricardo Notivol; Benoit Coffin; Fernando Azpiroz; Fermín Mearin; Jordi Serra; Juan-R. Malagelada

    1995-01-01

    Background\\/Aims: Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. Methods: Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure

  9. CARP Is a Potential Tumor Suppressor in Gastric Carcinoma and a Single-Nucleotide Polymorphism in CARP Gene Might Increase the Risk of Gastric Carcinoma

    PubMed Central

    Hu, Yu-chang; Gan, Lu; Shi, Yi; Yang, Han-shuo; Wei, Yu-quan

    2014-01-01

    Background The caspase-associated recruitment domain-containing protein (CARP) is expressed in almost all tissues. Recently, the tumor-suppressive function of CARP was discovered and attracted increasing attention. This study aimed to investigate the role of CARP in the carcinogenesis of human gastric carcinoma. Methodology/Principal Findings Compared with normal gastric tissue, the downregulation of CARP expression was observed in gastric carcinoma tissue by cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line (BGC-823) was stably transfected with pcDNA3.1B-CARP or plus CARP siRNA, and we used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion assay and western blot analysis to investigate the potential anti-tumor effects of CARP. The data showed that overexpressing CARP suppressed the malignancy of gastric carcinoma BGC-823 cell line, including significant increases in apoptosis, as well as obvious decreases in cell proliferation, migration, adhesion ability, and tumor growth. The tumor-suppressive effects of CARP were almost restored by siRNA-directed CARP silence. In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive effect of CARP was also verified. A single-nucleotide polymorphism (SNP) genotype of CARP (rs2297882) was located in the Kozak sequence of the CARP gene. The reporter gene assay showed that rs2297882 TT caused an obvious downregulation of activity of CARP gene promoter in BGC-823 cells. Furthermore, the association between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352 cases and 889 controls. It displayed that the TT genotype of rs2297882 in the CARP gene was associated with an increased risk of gastric carcinoma. Conclusions/Significance CARP is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of gastric carcinoma. PMID:24870804

  10. The Patient Journey to Gastric Band Surgery: A Qualitative Exploration

    PubMed Central

    Pulford, Amanda; Mahon, David; Ferguson, Yasmin; Lewis, Michael PN

    2013-01-01

    Aims This study explored the views and experiences of obese people preparing to undergo laparoscopic gastric banding (LAGB) leading up to the time of surgery. Background Weight loss surgery (WLS) is the most successful intervention available for the treatment of morbid obesity, and LAGB is among the most commonly used procedures in bariatric surgery. So far, the patient experience of deciding to undergo LAGB has been explored rarely and predominantly retrospectively. Design Semi-structured interviews took place with 23 patients about to undergo LAGB between June 2011 and March 2012. Data were analyzed using thematic analysis. Demographic and quality of life data situated the sample within the LAGB patient population. Results Three overarching themes were described. Participants were “living with obesity,” including the physical, social, and psychological challenges and consequences of being obese. These created in them a “desire to change,” expressed in multiple unsuccessful attempts to lose weight, and a quest for information, finally focusing on WLS. Eventually, “expectations toward LAGB” were formed, mainly to hand back a measure of control that enabled them to achieve, as well as ultimately to maintain, weight loss. This active process resulted in the patients' decision to undergo LAGB. When combined, these themes outline a distinct patient journey toward gastric banding. Conclusion Knowledge of the patient journey can inform both selection and care of patients awaiting gastric band surgery and is required by all health professionals working with this patient group. PMID:24761368

  11. Gastric emptying abnormal in duodenal ulcer

    SciTech Connect

    Holt, S.; Heading, R.C.; Taylor, T.V.; Forrest, J.A.; Tothill, P.

    1986-07-01

    To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.

  12. [Progress in chemotherapy for advanced gastric cancer].

    PubMed

    Xu, Rui-Hua; Teng, Kai-Yuan

    2009-10-01

    With the rapid development in cytotoxic agents and molecular targeting drugs, some progress in palliative chemotherapy for advanced gastric cancer has been achieved and the median survival of advanced gastric cancer patients is prolonged to about one year. In this review, we summarized the application of new agents, such as docetaxel, paclitaxel, oxaliplatin, irinotecan, capecitabine, S1 and targeting drugs in the treatment of patients with advanced gastric cancer. We focused on the results of phase III clinical trials and concluded that till now no standard regimens for the treatment of advanced gastric cancer are available. New combination regimens such as docetaxel-cisplatin-fluorouracil (DCF), epirubicin-oxaliplatin-capecitabine (EOX), fluorouracil-leucovorine-oxaliplatin (FLO), irinotecan, leucovorin and 5-FU (ILF), cispaltin plus xeloda, S1 plus cisplatin are considered as new options for the first-line chemotherapy of advanced gastric cancer. Due to uncertain efficacy and safety concerns, the role of molecular targeting agents in the treatment of advanced gastric cancer needs further investigation. It is suggested that neoadjuvant chemotherapy is a suitable choice for locally advanced gastric cancer. PMID:19799823

  13. Chemotherapy of advanced gastric cancer.

    PubMed

    Rivera, Fernando; Vega-Villegas, M Eugenia; López-Brea, Marta F

    2007-06-01

    Gastric cancer is the second most frequent cancer in the world. Approximately 84% of patients with gastric cancer will have advanced disease and median survival of these patients without chemotherapy is only 3-4 months. "Classical" chemotherapy regimens, mainly CF (cisplatin plus infusional 5FU) and ECF (cisplatin plus infusional 5FU plus Epirubicin) obtain responses in 20-40% of the patients and improve quality of life. Nevertheless, duration of these responses is short with very few complete responses. Median time to tumor progression (TTP) with these regimens is only about 4-5 months and median survival does not exceed 7-10 months. Moreover, benefit seems to be limited to patients with good performance status and treatment toxicity and discomfort are not negligible, specially that of regimens with cisplatin or infusional 5FU. Trying to improve these results, the incorporation of new drugs has been explored. Among the new combinations, the more developed ones are those with Docetaxel (DCF), oxaliplatin (EOX, FLO), Capecitabine (EOX, cisplatin-Xeloda) and irinotecan (ILF). We have final results from Phase III trials that suggest that all these regimens could have a role in the treatment of these patients but survival is still very poor and toxicity remains important. It would be interesting to investigate other new combinations and the incorporation of drugs directed against new therapeutic targets in this setting. It would be of utmost interest that these clinical trials would also explore clinical and molecular prognostic and predictive factors. PMID:17376598

  14. Gastric Metastasis of Ectopic Breast Cancer Mimicking Axillary Metastasis of Primary Gastric Cancer

    PubMed Central

    Kay?l?o?lu, Selami Ilgaz; Akyol, Cihangir; Esen, Ebru; Cans?z-Ersöz, Cevriye; Kocaay, Ak?n F?rat; Genç, Volkan; Kepenekçi, ?lknur; Demirer, Seher

    2014-01-01

    Ectopic breast tissue has the ability to undergo all the pathological changes of the normal breast, including breast cancer. Gastrointestinal metastasis of breast cancer is rarely observed and it is very difficult to differentiate gastric metastases from primary gastric cancer. We present a case of 52-year-old female, who suffered from abdominal pain. Physical examination showed a palpable mass in the left anterior axilla and computerized tomography revealed gastric wall thickening with linitis plastica. When gastroscopic biopsy showed no signs of malignancy, excisional biopsy was performed in the left axilla. Histological examination revealed invasive lobular carcinoma of the breast, consistent with ectopic breast cancer. Further gastroscopic submucosal biopsies and immunohistochemical studies revealed gastric metastases of invasive lobular carcinoma. Axillary ectopic breast tissue carcinomas can mimic axillary lymphadenopathies. Additionally, gastric metastasis of breast cancer is an uncommon but possible condition. To the best of our knowledge, this is the first report of ectopic breast cancer with gastric metastasis. PMID:25574403

  15. Late gastric prolapse with pouch necrosis after laparoscopic adjustable gastric banding.

    PubMed

    Lunca, Sorinel; Vix, Michel; Rikkers, Andrew; Rubino, Francesco; Marescaux, Jacques

    2005-04-01

    One of the most significant complications of the gastric banding procedure is gastric prolapse. However, pouch necrosis after gastric prolapse is an extremely rare complication. We present the case of a morbidly obese 41-year-old woman who had had a laparoscopic adjustable gastric banding procedure 3 years before. She developed a pouch necrosis after a late gastric prolapse. After failure of conservative treatment, a diagnostic laparoscopy was performed. This resulted in removal of the band and the diagnosis of pouch necrosis. A laparotomy was indicated and a sleeve gastrectomy was performed. A delay in the diagnosis of gastric prolapse can lead to major complications. Initial referral to a specialized center is necessary for proper care of this complication. Failure of conservative treatment mandates early operative intervention. PMID:15946441

  16. Effects of nimesulide, a preferential cyclooxygenase-2 inhibitor, on carrageenan-induced pleurisy and stress-induced gastric lesions in rats.

    PubMed

    Nakatsugi, S; Terada, N; Yoshimura, T; Horie, Y; Furukawa, M

    1996-12-01

    Intrapleural injection of carrageenan in rats increased prostaglandin E2 (PGE2) production and induced newly synthesized cyclooxygenase-2 (COX-2) in pleural exudate cells without affecting COX-1 levels. Nimesulide, a preferential inhibitor of COX-2, reduced pleural PGE2 production and was almost as active as indomethacin and 10 times more active than ibuprofen. Only COX-1, and nc COX-2, was detected in gastric mucosal cells, and PGE2 concentration of gastric mucosa was significantly decreased by indomethacin and ibuprofen. The decrease in gastric PGE2 production induced by indomethacin and ibuprofen was enhanced in stressed rats, resulting in aggravation of stress-induced gastric lesions at anti-inflammatory doses. However, nimesulide did not produce stress-induced gastric lesions even at 30 times the anti-inflammatory dose. This supports the hypothesis that inhibition of COX-1 causes unwanted side effects and inhibition of COX-2 produces anti-inflammatory effects. PMID:9014217

  17. Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection

    PubMed Central

    Kiga, Kotaro; Mimuro, Hitomi; Suzuki, Masato; Shinozaki-Ushiku, Aya; Kobayashi, Taira; Sanada, Takahito; Kim, Minsoo; Ogawa, Michinaga; Iwasaki, Yuka W.; Kayo, Hiroyuki; Fukuda-Yuzawa, Yoko; Yashiro, Masakazu; Fukayama, Masashi; Fukao, Taro; Sasakawa, Chihiro

    2014-01-01

    Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. Here we examine the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and find that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene is increased in Hp-positive human gastric biopsies as compared with Hp-negative controls. Moreover, silencing of miR-210 in gastric epithelial cells promotes proliferation. We identify STMN1 and DIMT1 as miR-210 target genes and demonstrate that inhibition of miR-210 expression augments cell proliferation by activating STMN1 and DIMT1 . Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection. PMID:25187177

  18. Surgical management of gastric cancer: Review and consideration for total care of the gastric cancer patient

    Microsoft Academic Search

    Samielle Brancato; Thomas J. Miner

    2008-01-01

    Opinion statement  Surgical therapy remains the most effective modality in the treatment of gastric cancer. Staging laparoscopy with laparoscopic\\u000a ultrasound may increase the accuracy of staging and prevent patients with unresectable gastric cancer from undergoing unnecessary\\u000a operations. Resection of proximal and distal gastric cancer is best accomplished with an appropriate gastrectomy that ensures\\u000a adequate resection margins. A D2 lymphadenectomy can be

  19. Severity of Helicobacter -induced gastric injury correlates with gastric juice ammonia

    Microsoft Academic Search

    Andrzej T. Triebling; Mark A. Korsten; Jan W. Dlugosz; Fiorenzo Paronetto; Charles S. Lieber

    1991-01-01

    We postulated that ammonia produced byHelicobacter pylori may contribute to gastric mucosal injury. This hypothesis was evaluated inHelicobacter-positive patients with chronic renal failure in whom a high urea concentration might amplify this phenomenon. Gastric urea and ammonia were measured, and the severity of gastritis was evaluated by counting mononuclear and polymorphonuclear, cells. High gastric ammonia and low urea inHelicobacter-positive patients,

  20. Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer

    Microsoft Academic Search

    Atsushi Sato; Minoru Kurihara; Masaaki Matsukawa; Ken Shimada; Takeshi Yamazaki; Masatoshi Nakamachi; Takahiko Koda

    2001-01-01

    Purpose: Irinotecan hydrochloride shows a strong activity against gastric cancer and colorectal cancer, while combined therapy with irinotecan and cisplatin is useful for gastric cancer. However, myelosuppression and diarrhea are still dose-limiting factors. To reduce such toxicities to enable therapy to be performed on an outpatient basis, we tested the effect of divided administration of cisplatin. Methods: Irinotecan (60 mg\\/m2)

  1. A simplified biophysical cell model for gastric slow wave entrainment simulation.

    PubMed

    Du, Peng; Gao, Jerry; O'Grady, Gregory; Cheng, Leo K

    2013-01-01

    Gastric electrical activity, also termed slow wave activity, is generated by a class of pacemaker cells called the interstitial cells of Cajal (ICC), which are organized with decreasing intrinsic frequencies along the stomach. In the healthy stomach, slow waves of different intrinsic frequencies converge to a single frequency with a constant phase-lag, in a process called entrainment. The main aim of this study was to develop a simplified biophysical ICC model that is capable of modeling the self-excitatory behavior and standard morphology of gastric slow waves. Entrainment of gastric slow waves was simulated in a one-dimensional (1D) model, with a linear gradient of intrinsic slow wave frequencies. In a coupled 1D model, the simulated slow waves were entrained to a single frequency; whereas in an uncoupled 1D model, the simulated slow waves occurred at different frequencies, resulting in loss of entrainment. The new cell model presents an option for future large multi-scale simulations of gastric slow waves in intact ICC network and diseased conditions where the loss of entrainment may lead to slow wave dysrhythmias and diminished gastric motility. PMID:24111242

  2. Innate Immunity Components and Cytokines in Gastric Mucosa in Children with Helicobacter pylori Infection

    PubMed Central

    Czerwionka-Szaflarska, Mieczyslawa; Szaflarska-Poplawska, Anna; Mierzwa, Grazyna; Marszalek, Andrzej; Nowak, Magdalena; Dzierzanowska-Fangrat, Katarzyna

    2015-01-01

    Purpose. To investigate the expression of innate immunity components and cytokines in the gastric mucosa among H. pylori infected and uninfected children. Materials and Methods. Biopsies of the antral gastric mucosa from children with dyspeptic symptoms were evaluated. Gene expressions of innate immunity receptors and cytokines were measured by quantitative real-time PCR. The protein expression of selected molecules was tested by immunohistochemistry. Results. H. pylori infection did not lead to a significant upregulation of MyD88, TLR2, TLR4, CD14, TREM1, and TREM2 mRNA expression but instead resulted in high mRNA expression of IL-6, IL-10, IFN-?, TNF-?, and CD163. H. pylori cagA(+) infection was associated with higher IL-6 and IL-10 mRNA expression, as compared to cagA(?) strains. H. pylori infected children showed increased IFN-? and TNF-? protein levels. IFN-? mRNA expression correlated with both H. pylori density of colonization and lymphocytic infiltration in the gastric mucosa, whereas TNF-? protein expression correlated with bacterial density. Conclusion. H. pylori infection in children was characterized by (a) Th1 expression profile, (b) lack of mRNA overexpression of natural immunity receptors, and (c) strong anti-inflammatory activities in the gastric mucosa, possibly resulting from increased activity of anti-inflammatory M2 macrophages. This may explain the mildly inflammatory gastric inflammation often observed among H. pylori infected children. PMID:25948881

  3. Laparoscopic resection for gastric carcinoma: Western experience.

    PubMed

    Strong, Vivian E

    2012-01-01

    There has been much speculation regarding differences in outcome for patients who have gastric cancer in the Eastern versus Western world. Among other factors, these differences have contributed to a unique cohort of patients and experience in the Western staging/evaluation of gastric cancer and in the application of minimally invasive approaches for treatment. This review summarizes the current state of laparoscopic approaches for the staging and treatment of gastric adenocarcinoma for patients presenting in Western countries, with their associated unique presentation, comorbidities, and outcomes. PMID:22098837

  4. Gastric outlet obstruction secondary to paraesophageal herniation of gastric antrum after laparoscopic fundoplication.

    PubMed

    Coskun, Selcuk; Soylu, Lutfi; Sahin, Mahir; Demiray, Taylan

    2015-04-01

    The most common causes of acute gastric outlet obstruction (GOO) are duodenal and type 3 gastric ulcers. However, mechanical or functional causes may also lead to this pathology. Acute GOO is characterized by delayed gastric emptying, anorexia, or nausea accompanied by vomiting. Herein we report a 56-year-old man diagnosed with GOO secondary to paraesophageal hiatal herniation of gastric antrum after laparoscopic fundoplication. Because of the rarity of this disease, common gastrointestinal complaints may mislead the emergency physician to diagnose a nonsurgical gastrointestinal disease if a detailed history and physical examinations are not obtained. PMID:25813602

  5. H(2)S-Releasing Aspirin Protects against Aspirin-Induced Gastric Injury via Reducing Oxidative Stress

    PubMed Central

    Liu, Lei; Cui, Jie; Song, Cheng-Jie; Bian, Jin-Song; Sparatore, Anna; Soldato, Piero Del; Wang, Xin-Yu; Yan, Chang-Dong

    2012-01-01

    The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H2S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H2S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1–10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE2 level. ACS14 reversed the decreased H2S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47phox and p67phox. In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue. PMID:23029468

  6. Protective effects of acetaminophen on ibuprofen-induced gastric mucosal damage in rats with associated suppression of matrix metalloproteinase.

    PubMed

    Fukushima, Eriko; Monoi, Noriyuki; Mikoshiba, Shigeo; Hirayama, Yutaka; Serizawa, Tetsushi; Adachi, Kiyo; Koide, Misao; Ohdera, Motoyasu; Murakoshi, Michiaki; Kato, Hisanori

    2014-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofen-induced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1? (IL-1?), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen. PMID:24496494

  7. H(2)S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress.

    PubMed

    Liu, Lei; Cui, Jie; Song, Cheng-Jie; Bian, Jin-Song; Sparatore, Anna; Soldato, Piero Del; Wang, Xin-Yu; Yan, Chang-Dong

    2012-01-01

    The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H(2)S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H(2)S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1-10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE(2) level. ACS14 reversed the decreased H(2)S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47(phox) and p67(phox). In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue. PMID:23029468

  8. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Luo, Yi-Pey; Chen, Yi-Ling

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin?embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/?-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

  9. Unusual Manifestation of Gastric Helicobacter pylori Infection

    PubMed Central

    Dutta, Amit K.; Chiba, Toshimi; Toya, Yosuke; Mizutani, Tomomi; Kasugai, Satoshi; Matsuda, Nozomi; Shibata, Sho; Abiko, Yukito; Akasaka, Risaburo; Yokoyama, Naoki; Oana, Shuhei; Hirota, Shigeru; Endo, Masaki; Uesugi, Noriyuki; Sugai, Tamotsu; Suzuki, Kazuyuki

    2012-01-01

    Infection with Helicobacter pylori (HP) is common in many parts of the world. While most patients are asymptomatic, it causes peptic ulcer disease and malignancy in some of them. Other rare conditions have occasionally been reported in association with this infection. We report a case of hypertrophic gastropathy caused by HP in a 52-year-old asymptomatic patient. He was found to have marked enlargement of the gastric mucosal folds on radiological imaging and endoscopy. A gastric mucosal biopsy showed HP colonization associated with neutrophilic inflammation. After exclusion of neoplasia, other infections and infiltrative disorders, HP was thought to be the cause of the gastric fold hypertrophy. The patient responded well to HP eradication therapy, with normalization of the gastric mucosal folds. HP infection should be considered in the differential diagnosis of hypertrophic gastropathy and treated accordingly. PMID:22855662

  10. Gastric involvement in Waldenstrom macroglobulinemia: CT findings

    Microsoft Academic Search

    H. M. Qutub; A. C. Wilbur; S. Dada

    1997-01-01

    .   Waldenstrom macroglobulinemia is a plasma cell dyscrasia that rarely presents with gastrointestinal involvement. We report\\u000a a case of gastric involvement of Waldenstrom macroglobulinemia detected by CT.

  11. Computed tomographic recognition of gastric varices

    SciTech Connect

    Balthazar, E.J.; Megibow, A.; Naidich, D.; LeFleur, R.S.

    1984-06-01

    The computed tomographic (CT) findings in 13 consecutive patients with proven gastric varices were analyzed and correlated with the radiographic, angiographic, and gastroscopic evaluations. In 11 patients, CT clearly identified large (five) or smaller (six) varices located mainly along the posteromedial wall of the gastric fundus and proximal body of the stomach. Well defined rounded or tubular densities that enhanced during intravenous administration of contrast material and could not be distinguished from the gastric wall were identified. Dense, enhancing, round or tubular, intraluminal filling defects were seen in the cases where the stomach was distended with water. In seven patients, the CT examination correctly diagnosed the pathogenesis of gastric varices by identifying hepatic cirrhosis, calcific pancreatis, and carcinoma of the pancreas.

  12. Medical and Endoscopic Management of Gastric Varices

    PubMed Central

    Al-Osaimi, Abdullah M. S.; Caldwell, Stephen H.

    2011-01-01

    In the past 20 years, our understanding of the pathophysiology and management options among patients with gastric varices (GV) has changed significantly. GV are the most common cause of upper gastrointestinal bleeding in patients with portal hypertension after esophageal varices (EV) and generally have more severe bleeding than EV. In the United States, the majority of GV patients have underlying portal hypertension rather than splenic vein thrombosis. The widely used classifications are the Sarin Endoscopic Classification and the Japanese Vascular Classifications. The former is based on the endoscopic appearance and location of the varices, while the Japanese classification is based on the underlying vascular anatomy. In this article, the authors address the current concepts of classification, epidemiology, pathophysiology, and emerging management options of gastric varices. They describe the stepwise approach to patients with gastric varices, including the different available modalities, and the pearls, pitfalls, and stop-gap measures useful in managing patients with gastric variceal bleed. PMID:22942544

  13. Drugs Approved for Stomach (Gastric) Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for stomach (gastric) cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  14. Malabsorptive gastric bypass in patients with superobesity

    Microsoft Academic Search

    Robert E. Brolin; Lisa B. LaMarca; Hallis A. Kenler; Ronald P. Cody; Ed. D

    2002-01-01

    Weight loss in superobese patients has been problematic after conventional gastric restrictive operations including conventional\\u000a Roux-en-Y gastric bypass (RYGB). The goal of the present study was to compare weight loss in patients with superobesity (body\\u000a mass index ?50 kg\\/m2) using a distal RYGB (D-RY) in which the Roux-en-Y anastomosis was performed 75 cm proximal to the ileocecal junction (N\\u000a =

  15. Definition for idiopathic gastric acid hypersecretion

    Microsoft Academic Search

    Martin J. Collen; Michael J. Sheridan

    1991-01-01

    Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq\\/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic

  16. Dysregulation of cellular signaling in gastric cancer

    Microsoft Academic Search

    William K. K. Wu; Chi H. Cho; Chung W. Lee; Daiming Fan; Kaichun Wu; Jun Yu; Joseph J. Y. Sung

    2010-01-01

    The pathogenesis of gastric cancer is complex and related to multiple factors. Dysregulation of intracellular signaling pathways represents a common pathogenic mechanism and may be amenable to drug targeting. Multiple well-established oncogenic pathways, such as those mediated by cell cycle regulators, nuclear factor-?B, cyclooxygenase-2 and epidermal growth factor receptor are implicated in gastric carcinogenesis. Emerging evidence also underscores the importance

  17. Maternal embryonic leucine zipper kinase enhances gastric cancer progression via the FAK/Paxillin pathway

    PubMed Central

    2014-01-01

    Background Elevated MELK expression is featured in multiple tumors and correlated with tumorigenesis and tumor development. This study is aimed to investigate the mechanisms of MELK-mediated development of gastric cancer. Methods MELK expression levels in human gastric cancer were determined by quantitative-PCR and immunohistochemistry. The effect of MELK on cell activity was explored by knockdown and overexpression experiments. Cell growth was measured using the CCK-8 assay. Apoptosis and cell cycle distributions were analyzed by flow cytometry. Migration and invasion were tested using a transwell migration assay. Cytoskeletal changes were analyzed by immunofluorescence. To explore the molecular mechanism and effect of MELK on migration and invasion, Western blotting was used to analyze the FAK/Paxillin pathway and pull down assays for the activity of small Rho GTPases. In vivo tumorigenicity and peritoneal metastasis experiments were performed by tumor cell engraftment into nude mice. Results MELK mRNA and protein expression were both elevated in human gastric cancer, and this was associated with chemoresistance to 5-fluorouracil (5-FU). Knockdown of MELK significantly suppressed cell proliferation, migration and invasion of gastric cancer both in vitro and in vivo, decreased the percentages of cells in the G1/G0 phase and increased those in the G2/M and S phases. Moreover, knockdown of MELK decreased the amount of actin stress fibers and inhibited RhoA activity. Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin-stimulated FAK/paxillin phosphorylation. By contrast, MELK overexpression had the opposite effect. Conclusions MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer. MELK may be a potential target for treatment against gastric cancer. PMID:24885567

  18. Epigenetic alterations in gastric cancer (Review).

    PubMed

    Fu, Du-Guan

    2015-09-01

    Gastric cancer is one of the most common types of cancer and the second most common cause of cancer-related mortality worldwide. An increasing number of recent studies have confirmed that gastric cancer is a multistage pathological state that arises from environmental factors; dietary factors in particulary are considered to play an important role in the etiology of gastric cancer. Improper dietary habits are one of the primary concerns as they influence key molecular events associated with the onset of gastric carcinogenesis. In the field of genetics, anticancer research has mainly focused on the various genetic markers and genetic molecular mechanisms responsible for the development of this of this disease. Some of this research has proven to be very fruitful, providing insight into the possible mechamisms repsonsible for this disease and into possible treatment modalities. However, the mortality rate associated with gastric cancer remains relatively high. Thus, epigenetics has become a hot topic for research, whereby genetic markers are bypassed and this research is directed towards reversible epigenetic events, such as methylation and histone modifications that play a crucial role in carcinogenesis. The present review focuses on the epigenetic events which play an important role in the development and progression of this deadly disease, gastric cancer. PMID:25997695

  19. [Carcinoma after gastric operations (author's transl)].

    PubMed

    Clémençon, G; Baumgartner, R; Leuthold, E; Miller, G; Neiger, A

    1976-07-01

    The incidence of carcinoma after gastric operations for benign lesions was analysed in the patient material of five gastroenterologists in private practice in Switzerland. Of 534 such patients 346 had had a gastric resection with gastrojejunostomy (Billroth II), 58 with gastroduodenostomy (Billroth I), and 130 other kinds of gastric operations. Among 326 patients who had a Billroth II procedure there were 21 with proven carcinoma in the residual stomach, but none after Billroth I and other operations. The incidence after Billroth II was 15.1% at or after ten years. Of 69 patients 10-19 years after gastric resection, six had developed carcinoma, compared with 15 of 70 who were 20 years or more after the resection. The incidence is unexpectedly high. On the other hand, among 29361 non-operated patients there were 279 with carcinoma of the stomach. The average interval between operation and the diagnosis of carcinoma in the residual stomach was 23.8 years. It is recommended that gastric resection should if possible be avoided for benign disease. All patients who have had a gastric resection should be endoscopically controlled annually from ten years after the resection onwards. PMID:942549

  20. Alkaloids from Mahonia bealei posses anti-H?/K?-ATPase and anti-gastrin effects on pyloric ligation-induced gastric ulcer in rats.

    PubMed

    Zhang, Su-Li; Li, Hui; He, Xin; Zhang, Run-Qi; Sun, Yu-He; Zhang, Chun-Feng; Wang, Chong-Zhi; Yuan, Chun-Su

    2014-09-25

    The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19 h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56 mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28 mm(2)) compared with model group (26.36 mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers. PMID:25172799

  1. Gastroprotective effects of L-lysine salification of ketoprofen in ethanol-injured gastric mucosa.

    PubMed

    Cimini, Annamaria; Brandolini, Laura; Gentile, Roberta; Cristiano, Loredana; Menghini, Paola; Fidoamore, Alessia; Antonosante, Andrea; Benedetti, Elisabetta; Giordano, Antonio; Allegretti, Marcello

    2015-04-01

    Ketoprofen L-lysine salt (KLS), a NSAID, is widely used for its analgesic efficacy and tolerability. L-lysine salification was reported to increase the solubility and the gastric absorption and tolerance of ketoprofen. Since the management of NSAIDs gastrotoxicity still represents a major limitation in prolonged therapies, mainly when gastric lesions are present, this study investigated the gastro-protective activity of L-lysine by using a well-established model of gastric mucosa injury, the ethanol-gastric injury model. Several evidences show that the damaging action of ethanol could be attributed to the increase of ROS, which plays a key role in the increase of lipid peroxidation products, including malonyldialdehyde and 4-hydroxy-2-nonenal. With the aim to unravel the mechanism of L-lysine gastroprotection, cellular MDA levels and 4-HNE protein adducts as markers of lipid peroxidation and a panel of key endogenous gastro-protective proteins were assayed. The data obtained indicate a gastroprotective effect of L-lysine on gastric mucosa integrity. PMID:25287669

  2. Modulation of gastric distension-induced sensations by small intestinal receptors.

    PubMed

    Feinle, C; Grundy, D; Fried, M

    2001-01-01

    Duodenal lipid exacerbates gastrointestinal sensations during gastric distension. Using luminal application of the local anesthetic benzocaine, we investigated the role of intestinal receptors in the induction of these sensations. Nine healthy subjects were studied on five occasions, during which isotonic saline or 20% lipid (2 kcal/min), combined with (duodenal or jejunal) 0.75% benzocaine or vehicle at 2.5 ml/min, was infused intraduodenally before and during gastric distension. Intragastric pressures and volumes, gastrointestinal sensations, and plasma CCK levels were determined. Duodenal lipid combined with vehicle increased gastric volume (in ml: saline, -10 +/- 18; lipid/vehicle, 237 +/- 30) and plasma CCK [mean levels (pmol/l): saline, 2.0 +/- 0. 2; lipid/vehicle, 8.0 +/- 1.6] and, during distensions, induced nausea (scores: saline, 3 +/- 2: lipid/vehicle, 58 +/- 19) and decreased pressures at which fullness and discomfort occurred. Duodenal but not jejunal benzocaine attenuated the effect of lipid on gastric volume, plasma CCK, and nausea during distension (135 +/- 38 and 216 +/- 40 ml, 4.6 +/- 0.6 pmol/l and not assessed, and 37 +/- 12 and 64 +/- 21 for lipid + duodenal benzocaine and lipid + jejunal benzocaine, respectively) and on pressures for sensations. In conclusion, intestinal receptors modulate gastrointestinal sensations associated with duodenal lipid and gastric distension. There is also the potential for local neural mechanisms to regulate CCK release and thereby reduce afferent activation indirectly. PMID:11123197

  3. The role of miR-100-mediated Notch pathway in apoptosis of gastric tumor cells.

    PubMed

    Yang, Geng; Gong, Yi; Wang, Qizhi; Wang, Yumeng; Zhang, Xiaobo

    2015-06-01

    MicroRNAs (miRNAs) are small non-coding regulatory molecules that influence many biological functions, including apoptosis, but their role in the regulation of apoptosis in gastric tumor cells has not been intensively investigated. Here, we showed that miR-100 was specifically upregulated in human epithelium-derived gastric cancer cells and that silencing miR-100 expression in human gastric epithelial cancer cells initiated a robust apoptotic response in vitro. Our in vivo assays indicated that the development of gastric cancer was inhibited by the miR-100 antagonism via initiating apoptosis of tumor. The results presented that antagonism of miR-100 increased the expression level of HS3ST2, the target gene of miR-100, and further resulted in the activation of the Notch-apoptosis pathway in tumor cells. The data also revealed that silencing of miR-100 expression sensitized gastric cancer cells to chemotherapy. Therefore our study presented a novel miR-100 mediated Notch pathway in apoptosis of tumor cells. PMID:25703026

  4. Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

    PubMed Central

    GU, HONGBING; LI, XU; ZHOU, CONGZHI; WEN, YUGANG; SHEN, YANG; ZHOU, LISHENG; LI, JIKUN

    2015-01-01

    Excessive activation of the hedgehog (Hh) signaling pathway is important in a variety of human cancer cell types, including gastric cancer. However, the underlying mechanisms of the Hh signaling pathway in inducing gastric tumorigenesis and its downstream target genes are largely unknown. In the present study, the inhibitory effect of cyclopamine on the Hh signaling pathway was investigated in the human gastric cancer AGS cell line. It was identified that cyclopamine treatment inhibited the proliferation, migration and invasion of the AGS cells in a dose- and time-dependent manner, and resulted in the downregulation of a number of key Hh signaling pathway-associated factors [glioma-associated oncogene homolog 1, C-X-C chemokine receptor type 4 and transforming growth factor (TGF)-?1] at the RNA and protein levels. Furthermore, the secretion of TGF-?1 was significantly reduced following the administration of cyclopamine to the AGS cells. The results of the present study provided insight into the mechanisms by which the Hh signaling pathway regulates gastric cancer formation and identified the Hh signaling pathway as a potential novel therapeutic target in human gastric cancer. PMID:26137001

  5. “Intensity-Response” Effects of Electroacupuncture on Gastric Motility and Its Underlying Peripheral Neural Mechanism

    PubMed Central

    Su, Yang-Shuai; He, Wei; Wang, Chi; Shi, Hong; Zhao, Yu-Feng; Xin, Juan-Juan; Wang, Xiao-Yu; Shang, Hong-Yan; Hu, Ling; Jing, Xiang-Hong; Zhu, Bing

    2013-01-01

    The aim of this study was to explore the “intensity-response” relationship between EAS and the effect of gastric motility of rats and its underlying peripheral neural mechanism by employing ASIC3 knockout (ASIC3?/?), TRPV1 knockout (TRPV1?/?), and C57BL/6 mice. For adult male Sprague-Dawley (n = 18) rats, the intensities of EAS were 0.5, 1, 3, 5, 7, and 9?mA, respectively. For mice (n = 8 in each group), only 1?mA was used, by which C fiber of the mice can be activated. Gastric antrum motility was measured by intrapyloric balloon. Gastric motility was facilitated by EAS at ST36 and inhibited by EAS at CV12. The half maximal facilitation intensity of EAS at ST36 was 2.1–2.3?mA, and the half maximal inhibitory intensity of EAS at CV12 was 2.8?mA. In comparison with C57BL/6 mice, the facilitatory effect of ST36 and inhibitive effect of CV12 in ASIC3?/? mice decreased, but the difference was not statistically significant (P > 0.05). However, these effects in TRPV1?/? mice decreased significantly (P < 0.001). The results indicated that there existed an “intensity-response” relationship between EAS and the effect of gastric motility. TRPV1 receptor was involved in the regulation of gastric motility of EAS. PMID:23935667

  6. An assessment of human gastric fluid composition as a function of PPI usage

    PubMed Central

    Foltz, Emily; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E.; Sanders, Nathan L.; Thompson, J. Will; Dubois, Laura G.; Parker, William; Keshavjee, Shaf; Palmer, Scott M.; Davis, R. Duane; Lin, Shu S.

    2015-01-01

    Abstract The standard of care for chronic gastro?esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000?fold range (gastricsin) and a maximum of a 1 × 106 –fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach. PMID:25626870

  7. Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer

    PubMed Central

    Liu, Jinfeng; McCleland, Mark; Stawiski, Eric W.; Gnad, Florian; Mayba, Oleg; Haverty, Peter M.; Durinck, Steffen; Chen, Ying-Jiun; Klijn, Christiaan; Jhunjhunwala, Suchit; Lawrence, Michael; Liu, Hanbin; Wan, Yinan; Chopra, Vivek; Yaylaoglu, Murat B.; Yuan, Wenlin; Ha, Connie; Gilbert, Houston N.; Reeder, Jens; Pau, Gregoire; Stinson, Jeremy; Stern, Howard M.; Manning, Gerard; Wu, Thomas D.; Neve, Richard M.; de Sauvage, Frederic J.; Modrusan, Zora; Seshagiri, Somasekar; Firestein, Ron; Zhang, Zemin

    2014-01-01

    Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we perform exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumours and 32 cell lines. Meta-analysis of exome data and previously published data sets reveals 24 significantly mutated genes in microsatellite stable (MSS) tumours and 16 in microsatellite instable (MSI) tumours. Over half the patients in our collection could potentially benefit from targeted therapies. We identify 55 splice site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumours. ZAK kinase isoform TV1 is preferentially upregulated in gastric tumours and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder and breast cancers. Overexpression of this particular isoform activates multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibits proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK. PMID:24807215

  8. Molecular targeted therapy for advanced gastric cancer

    PubMed Central

    2013-01-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies. PMID:23525404

  9. A phase II trial of weekly fractionated irinotecan and cisplatin for advanced gastric cancer

    Microsoft Academic Search

    Hei-Cheul Jeung; Sun Young Rha; Sung Hoon Noh; Jae Kyung Roh; Hyun Cheol Chung

    2007-01-01

    Purpose  This study was to evaluate the activity and the safety of a combination chemotherapy regimen of weekly fractionated irinotecan\\u000a and cisplatin in advanced gastric cancer patients.\\u000a \\u000a \\u000a \\u000a Methods  Patients with advanced gastric adenocarcinoma with either chemotherapy-naive or only one prior chemotherapy regimen received\\u000a irinotecan 50 mg\\/m2 followed by cisplatin 30 mg\\/m2. Both drugs were administered weekly for 3 consecutive weeks, followed by 1-week rest.

  10. Severe gastric impaction secondary to a gastric polyp in a horse

    PubMed Central

    Furness, Mary Catherine; Snyman, Heindrich Nicolaas; Abrahams, Miranda; Moore, Alison; Vince, Andrew; Anderson, Maureen E.C.

    2013-01-01

    A 13-year-old Percheron gelding was presented for refractory gastric impaction. At necropsy a pedunculated 10 cm × 11 cm × 14 cm mass, histologically identified as an inflammatory polyp, was suspected to have been partly obstructing the pylorus. This is the first report of a polyp resulting in gastric outflow obstruction in a horse. PMID:24155420

  11. An experimental study of gastric cancer in relation to gastric ulcer

    PubMed Central

    Stein-Werblowsky, R.

    1962-01-01

    This experimental study shows that carcinogens are relatively harmless on intact gastric mucosa but can induce lesions when the mucosa has been damaged, particularly when the injury is deep as in gastrostomy. Human gastric carcinogenesis is discussed in the light of these findings. ImagesFIG. 3FIG. 4FIG. 1FIG. 2 PMID:13916656

  12. Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress.

    PubMed

    Kwiecien, S; Konturek, P C; Sliwowski, Z; Mitis-Musiol, M; Pawlik, M W; Brzozowski, B; Jasnos, K; Magierowski, M; Konturek, S J; Brzozowski, T

    2012-04-01

    Gastric microcirculation plays an important role in the maintenance of the mucosal gastric integrity and the mechanism of injury as well as providing protection to the gastric mucosa. Disturbances in the blood perfusion, through the microcapillaries within the gastric mucosa may result in the formation of mucosal damage. Acute gastric mucosal lesions constitute an important clinical problem. Originally, one of the essential component of maintaining the gastric mucosal integrity was the biosynthesis of prostaglandins (PGs), an issue that has captured the attention of numerous investigations. PGs form due to the activity of cyclooxygenase (COX), an enzyme which is divided into 2 isoforms: constitutive (COX-1) and inducible (COX-2) ones. The inhibition of COX-1 by SC-560, or COX-2 by rofecoxib, reduces gastric blood flow (GBF) and impairs gastric mucosal integrity. Another detrimental effect on the gastric mucosal barrier results from the ablation of sensory afferent nerves by neurotoxic doses of capsaicin. Functional ablation of the sensory afferent nerves by capsaicin attenuates GBF and also renders the gastric mucosa more susceptible to gastric mucosal damage induced by ethanol, aspirin and stress. However, the role of reactive oxygen species (ROS) in the interaction between COX specific inhibitors and afferent sensory nerves has not been extensively studied. The aim of our present study was to determine the participation of ROS in pathogenesis of stress-induced gastric lesions in rats administered with SC-560 or rofecoxib, with or without ablation of the sensory afferent nerves. ROS were estimated by measuring the gastric mucosal tissue level of MDA and 4-HNE, the products of lipid peroxidation by ROS as well as the SOD activity and reduced glutathione (GSH) levels, both considered to be scavengers of ROS. It was demonstrated that exposure to 3.5 h of WRS resulted in gastric lesions, causing a significant increase of MDA and 4-HNE in the gastric mucosa, accompanied by a decrease of SOD activity and mucosal GSH level. Pretreatment with COX-1 and COX-2 inhibitors (SC-560 and rofecoxib, respectively) aggravated the number of gastric lesions, decreased GBF, attenuated GSH level without further significant changes in MDA and 4-HNE tissue levels and SOD activity. Furthermore, the capsaicin--nactivation of sensory nerves resulted in exaggeration of gastric mucosal damage induced by WRS and this was further augmented by rofecoxib. We conclude that oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity and the fall in GSH tissue level, may play an important role in the mechanism of interaction between the inhibition of COX activity and afferent sensory nerves releasing vasoactive neuropeptides. This is supported by the fact that the addition of specific COX-1 or COX-2 inhibitors to animals with capsaicin denervation led to exacerbation of gastric lesions, and further fall in the antioxidizing status of gastric mucosa exposed to stress. PMID:22653901

  13. The nitric oxide donor cis-[Ru(bpy)2(SO3)NO](PF6) increases gastric mucosa protection in mice--involvement of the soluble guanylate cyclase/K(ATP) pathway.

    PubMed

    Santana, Ana Paula M; Tavares, Bruno M; Lucetti, Larisse T; Gouveia, Florêncio S; Ribeiro, Ronaldo A; Soares, Pedro M G; Sousa, Eduardo H S; Lopes, Luiz G F; Medeiros, Jand-Venes R; Souza, Marcellus H L P

    2015-02-15

    Here, we have evaluated the protective effect of the NO donor cis-[Ru(bpy)2(SO3)NO](PF6) (FOR0810) in experimental models of gastric damage induced by naproxen or ethanol in mice, and the involvement of soluble guanylate cyclase (sGC) and ATP-sensitive K(+) channels (KATP) in these events. Swiss mice were pre-treated with saline, ODQ (a soluble guanylate cyclase inhibitor; 10 mg kg(-1)) or glibenclamide (a KATP channels blocker; 10 mg kg(-1)). After either 30 min or 1 h, FOR0810 (3 mg kg(-1)) was administered. At the end of 30 min, the animals received naproxen (300 mg kg(-1)) by gavage. After 6 h, the animals were sacrificed and gastric damage, myeloperoxidase (MPO) activity, and TNF-? and IL-1? gastric concentrations were evaluated. In addition, the effects of FOR0810 on naproxen-induced mesenteric leukocyte adherence were determined by intravital microscopy. Other groups, were pre-treated with saline, ODQ or glibenclamide. After either 30 min or 1 h, FOR0810 was administered. At the end of 30 min, the animals received 50% ethanol by gavage. After 1 h, the animals were sacrificed, and gastric damage, gastric reduced glutathione (GSH) concentration and malondialdehyde (MDA) levels were determined. In naproxen-induced gastric damage, FOR0810 prevented gastric injury, decreased gastric MPO activity and leukocyte adherence, associated with a decrease in TNF? and IL-1? gastric concentrations. FOR0810 also prevented ethanol-induced gastric damage by increase in GSH levels and decrease in MDA levels. ODQ and glibenclamide completely reversed FOR0810's ability to prevent gastric damage by either naproxen or ethanol. We infer that FOR0810 prevented gastric damage through the activation of both sGC and KATP channels, which triggered a decrease in both free radical and cytokine production via the blocking of neutrophil adhesion and infiltration. PMID:25681154

  14. Screening for gastric cancer: the usefulness of endoscopy.

    PubMed

    Choi, Kui Son; Suh, Mina

    2014-11-01

    Gastric cancer screening is common in countries with high prevalence rates of gastric cancer. However, data supporting the effectiveness of gastric cancer screening are lacking. Thus, the aim of this review was to examine the current evidence on gastric cancer screening. Herein, we reviewed radiographic and endoscopic tests as methods of gastric cancer screening. Previous cohort studies and case-control studies have demonstrated reduced gastric cancer mortality in study populations that had undergone gastric cancer screening with radiographic tests. Recently, a case-control study in Japan reported a 30% reduction in gastric cancer mortality when screening was undertaken via endoscopy. Also, endoscopic screening for gastric cancer exhibited higher sensitivity and specificity than radiographic screening. Moreover, most cost-effectiveness analyses on the best strategy for detecting early gastric cancer have generally concluded that endoscopy is more cost-effective than radiographic testing. Although data on the impact of endoscopy screening programs on gastric cancer mortality are limited, recent study results suggest that gastric cancer screening by endoscopy in average-risk populations performs better than radiography screening. Further evaluation of the impact of these screening methods should take into account cost and any associated reduction in gastric cancer mortality. PMID:25505713

  15. Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-?, NF-?B and Nrf2/HO-1 Signaling Pathways

    PubMed Central

    Mahmoud-Awny, Magdy; Attia, Ahmed S.; Abd-Ellah, Mohamed F.; El-Abhar, Hanan Salah

    2015-01-01

    Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have antisecretory and antioxidant gastroprotective effects against different gastric ulcer models; however, its molecular mechanism has not been previously elucidated. Therefore, the aim of this study was to test its modulatory effect on several signaling pathways using the ischemia/reperfusion model for the first time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The mechanistic studies revealed that MF mediated its gastroprotective effect partly via inducing the expression of Nrf2, HO-1 and PPAR-? along with downregulating that of NF-?B. Surprisingly, the effect of MF, especially the high dose, exceeded that mediated by OMP except for Nrf2. The molecular results were reflected on the biomarkers measured, where the antioxidant effect of MF was manifested by increasing total antioxidant capacity and glutathione, besides normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced nitric oxide elevation, an effect that was better than that of OMP. In the serum, MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced serum level of IL-1? and sE-selectin, effects that were mirrored on the tissue level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF possessed an antiapoptotic character evidenced by elevating Bcl-2 level and reducing that of caspase-3 in a dose related order. As a conclusion, the intimated gastroprotective mechanisms of MF are mediated, partially, by modulation of oxidative stress, inflammation and apoptosis possibly via the Nrf2/HO-1, PPAR-?/NF-?B signaling pathways. PMID:26196679

  16. Dual Roles of Gastric Gland Mucin-specific O-glycans in Prevention of Gastric Cancer

    PubMed Central

    Nakayama, Jun

    2014-01-01

    Gastric gland mucin is secreted from gland mucous cells, including pyloric gland cells and mucous neck cells located in the lower layer of the gastric mucosa. These mucins typically contain O-glycans carrying terminal ?1,4-linked N-acetylglucosamine residues (?GlcNAc) attached to the scaffold protein MUC6, and biosynthesis of the O-glycans is catalyzed by the glycosyltransferase, ?1,4-N-acetylglucosaminyltransferase (?4GnT). We previously used expression cloning to isolate cDNA encoding ?4GnT, and then demonstrated that ?GlcNAc functions as natural antibiotic against Helicobacter pylori, a microbe causing various gastric diseases including gastric cancer. More recently, it was shown that ?GlcNAc serves as a tumor suppressor for differentiated-type adenocarcinoma. This review summarizes these findings and identifies dual roles for ?GlcNAc in gastric cancer. PMID:24761044

  17. Efficacy of Sulforaphane in Eradicating Helicobacter pylori in Human Gastric Xenografts Implanted in Nude Mice

    Microsoft Academic Search

    Xavier Haristoy; K. Angioi-Duprez; A. Duprez; Alain Lozniewski

    2003-01-01

    Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be

  18. Evaluation of cultural techniques for isolating Campylobacter pyloridis from endoscopic biopsies of gastric mucosa

    Microsoft Academic Search

    C S Goodwin; E D Blincow; J R Warren; T E Waters; C R Sanderson; L Easton

    1985-01-01

    One hundred and three gastroscopic biopsies from 80 patients were cultured for Campylobacter pyloridis and studied histologically. Active chronic gastritis, as shown by the presence of polymorphonuclear leucocytes, was diagnosed in 51 biopsies and C pyloridis was found in 47. Sixteen gastric biopsies showed normal histology (no inflammation); C pyloridis was detected in only one of these, and a second

  19. Osteopontin depletion decreases inflammation and gastric epithelial proliferation during Helicobacter pylori infection in mice.

    PubMed

    Park, Jun Won; Lee, Su Hyung; Go, Du Min; Kim, Hark Kyun; Kwon, Hyo-Jung; Kim, Dae-Yong

    2015-06-01

    Osteopontin (OPN) is a multifunctional protein that plays a role in many physiological and pathological processes, including inflammation and tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD) cell lines. HP-infected OPN KO mice showed significantly reduced gastritis compared with wild-type (WT) mice with decreased infiltration of macrophages and a reduction in HP-induced upregulation of IL-1?, TNF-?, and IFN-?. HP-exposed OPN KD gastric cancer cells and macrophage-like cells showed an attenuated induction of these cytokines. We also demonstrated a reduction in the migration of monocytic and macrophage-like cells toward conditioned media harvested from HP-exposed OPN KD gastric cancer cells as well as reduced migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice showed decreased epithelial cell proliferation compared with HP-infected WT mice, in association with a reduction in MAPK pathway activation. OPN KD gastric cancer cell lines also showed lower proliferative activity and reduced MAPK activation than shRNA control cells after HP co-culture or after IL-1? and TNF-? treatment. Taken together, these results indicate that OPN exerts a considerable influence on HP-induced gastritis by modulating the production of cytokines and contributing to macrophage infiltration. Moreover, OPN-mediated activation of the MAPK pathway in gastric epithelial cells might contribute to epithelial changes following HP infection. PMID:25867766

  20. Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein

    Microsoft Academic Search

    Emilia Vassilopoulou; Neil Rigby; F. Javier Moreno; Laurian Zuidmeer; Jaap Akkerdaas; Ioannis Tassios; Nikos G. Papadopoulos; Photini Saxoni-Papageorgiou; Ronald van Ree; Clare Mills

    2006-01-01

    Background: Severe grape allergy has been linked to lipid transfer protein (LTP) sensitization. LTPs are known to be resistant to pepsin digestion, although the effect of gastroduodenal digestion on its allergenicity has not been reported. Objective: We sought to investigate the effect of gastric and gastroduodenal digestion on the allergenic activity of grape LTP. Methods: The proteolytic stability of grape

  1. A natural flavonoid and synthetic analogues protect the gastric mucosa from aspirin-induced erosions

    Microsoft Academic Search

    David A Lewis; Graham P Shaw

    2001-01-01

    The anti-ulcerogenic properties of plantain banana have been well established even though the active ingredient has only recently been identified as the flavonoid leucocyanidin. The aim of this study was to evaluate the ability of the natural flavonoid leucocyanidin and synthetic analogues to protect the gastric mucosa against aspirin challenge. Natural and synthetic flavonoids were added to the diet of

  2. Postprandial Response of Gastric Slow Waves: Correlation of Serosal Recordings with the Electrogastrogram

    Microsoft Academic Search

    Zhiyue Lin; J. D. Z. Chen; Bruce D. Schirmer; Richard W. McCallum

    2000-01-01

    Controversial interpretations have been given to the postprandial increase in the dominant power (amplitude) of the electrogastrogram (EGG). The aim of this study was to find an appropriate interpretation of the postprandial EGG power changes. Simultaneous serosal and cutaneous recordings of gastric myoelectrical activity were made in 11 patients with gastroparesis in the fasting state and after the ingestion of

  3. Effects of ALDH2 Genotype, PPI Treatment and L-Cysteine on Carcinogenic Acetaldehyde in Gastric Juice and Saliva after Intragastric Alcohol Administration

    PubMed Central

    Maejima, Ryuhei; Iijima, Katsunori; Kaihovaara, Pertti; Hatta, Waku; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru; Salaspuro, Mikko

    2015-01-01

    Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30–50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups. PMID:25831092

  4. Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration.

    PubMed

    Maejima, Ryuhei; Iijima, Katsunori; Kaihovaara, Pertti; Hatta, Waku; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru; Salaspuro, Mikko

    2015-01-01

    Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups. PMID:25831092

  5. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

    PubMed Central

    Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

    2014-01-01

    Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in animals and cancer patients. PMID:25525335

  6. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer.

    PubMed

    Graham, David Y

    2014-05-14

    Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases. PMID:24833849

  7. Gastroprotective effect of andrographolide sodium bisulfite against indomethacin-induced gastric ulceration in rats.

    PubMed

    Liu, Yu-Hong; Zhang, Zhen-Biao; Zheng, Yi-Feng; Chen, Hai-Ming; Yu, Xiu-Ting; Chen, Xiao-Ying; Zhang, Xie; Xie, Jian-Hui; Su, Zu-Qing; Feng, Xue-Xuan; Zeng, Hui-Fang; Su, Zi-Ren

    2015-06-01

    Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of andrographolide has been shown to possess anti-inflammatory, antipyretic and analgesic activities. However, there is no report on the gastroprotective effect of ASB against indomethacin-induced gastric ulcer. Here we investigated the possible anti-ulcerogenic potential of ASB and the underlying mechanism against indomethacin-induced gastric ulcer in rats. The ulcer area, histopathological assessment, contents of gastric mucosal glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malonaldehyde (MDA) and prostaglandin E2 (PGE2) were examined. In addition, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) mRNA expression and immunohistochemical evaluation of HSP70, Bcl-2 and Bax proteins were also investigated. Results indicated that ASB pre-treatment significantly reduced the ulcer areas induced by indomethacin compared with the vehicle group. The gastric levels of GSH, CAT and SOD were markedly increased by ASB while the level of MDA was decreased. In addition, ASB pretreatment significantly promoted the gastric PGE2 levels and up-regulated the COX-1 and COX-2 mRNA expression in comparison with the vehicle group. Immunohistochemistry analysis showed obvious up-regulation of HSP70 and Bcl-2 protein expression while suppression of Bax protein in the gastric tissue of ASB-pretreated group. Taken together, these findings indicated that the gastroprotective effect of ASB might be associated with the improvement of antioxidative status, activation of COX-mediated PGE2 synthesis, down-regulation of Bax proteins and up-regulation of Bcl-2 and HSP70 proteins. ASB might have the potential for further development as a promising alternative for antiulcer treatment. PMID:25916678

  8. Helicobacter heilmannii sp. nov., isolated from feline gastric mucosa.

    PubMed

    Smet, A; Flahou, B; D'Herde, K; Vandamme, P; Cleenwerck, I; Ducatelle, R; Pasmans, F; Haesebrouck, F

    2012-02-01

    Three gram-negative, microaerophilic bacteria, strains ASB1(T), ASB2 and ASB3, with a corkscrew-like morphology isolated from the gastric mucosa of cats were studied using a polyphasic taxonomic approach. The isolates grew on biphasic culture plates under microaerobic conditions at 37 °C and exhibited urease, oxidase and catalase activities. They were also able to grow in colonies on dry agar plates. Based on 16S rRNA gene sequence analysis, ASB1(T), ASB2 and ASB3 were identified as members of the genus Helicobacter and showed 98 to 99?% sequence similarity to strains of Helicobacter felis, Helicobacter bizzozeronii, 'Candidatus Helicobacter heilmannii', Helicobacter cynogastricus, Helicobacter baculiformis and Helicobacter salomonis, six related Helicobacter species previously detected in feline or canine gastric mucosa. Sequencing of the partial hsp60 gene demonstrated that ASB1(T), ASB2 and ASB3 constitute a separate taxon among the feline and canine Helicobacter species. The urease gene sequences of ASB1(T), ASB2 and ASB3 showed approximately 91?% similarity to those of 'Candidatus Helicobacter heilmannii'. Protein profiling, the absence of alkaline phosphatase activity and several other biochemical characteristics also allowed strains ASB1(T), ASB2 and ASB3 to be differentiated from other Helicobacter species of feline or canine gastric origin. The results of this polyphasic taxonomic study show that the cultured isolates constitute a new taxon corresponding to 'Candidatus Helicobacter heilmannii', which was previously demonstrated in the stomach of humans, wild felidae, cats and dogs. The name Helicobacter heilmannii sp. nov. is proposed for these isolates; the type strain is ASB1(T) (=DSM 24751 (T) =LMG 26292(T)) [corrected]. PMID:21421932

  9. Serum glycan signatures of gastric cancer.

    PubMed

    Ozcan, Sureyya; Barkauskas, Donald A; Renee Ruhaak, L; Torres, Javier; Cooke, Cara L; An, Hyun Joo; Hua, Serenus; Williams, Cynthia C; Dimapasoc, Lauren M; Han Kim, Jae; Camorlinga-Ponce, Margarita; Rocke, David; Lebrilla, Carlito B; Solnick, Jay V

    2014-02-01

    Glycomics, a comprehensive study of glycans expressed in biologic systems, is emerging as a simple yet highly sensitive diagnostic tool for disease onset and progression. This study aimed to use glycomics to investigate glycan markers that would differentiate patients with gastric cancer from those with nonatrophic gastritis. Patients with duodenal ulcer were also included because they are thought to represent a biologically different response to infection with Helicobacter pylori, a bacterial infection that can cause either gastric cancer or duodenal ulcer. We collected 72 serum samples from patients in Mexico City that presented with nonatrophic gastritis, duodenal ulcer, or gastric cancer. N-glycans were released from serum samples using the generic method with PNGase F and were analyzed by matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry. The corresponding glycan compositions were calculated based on accurate mass. ANOVA-based statistical analysis was performed to identify potential markers for each subgroup. Nineteen glycans were significantly different among the diagnostic groups. Generally, decreased levels of high-mannose-type glycans, glycans with one complex type antenna, bigalactosylated biantennary glycans, and increased levels of nongalactosylated biantennary glycans were observed in gastric cancer cases. Altered levels of serum glycans were also observed in duodenal ulcer, but differences were generally in the same direction as gastric cancer. Serum glycan profiles may provide biomarkers to differentiate gastric cancer cases from controls with nonatrophic gastritis. Further studies will be needed to validate these findings as biomarkers and identify the role of protein glycosylation in gastric cancer pathology. PMID:24327722

  10. Long lasting inhibitors of the gastric H,K-ATPase

    PubMed Central

    Shin, Jai Moo; Sachs, George

    2010-01-01

    Abstract/Summary Proton pump inhibitors (PPIs) are acid-activated prodrugs which covalently bind to the gastric H,K-ATPase on its luminal surface. Only active pumps can be inhibited. The short plasma residence time of current PPIs prevents inhibition of pumps synthesized or activated after the PPI has disappeared, limiting the degree of acid inhibition even with BID administration. PPIs with a longer residence time should improve acid control. Various K+ competitive inhibitors of the pump are being developed (APAs or PCABs), with the advantage of complete inhibition of acid secretion independent of pump activity. Early data on these suggest that twice a day administration would improve acid control compared to PPIs. PMID:21132072

  11. Modulation of protein tyrosine phosphorylation in gastric mucosa during re-epithelization processes

    PubMed Central

    Bogdanova, Olena V; Kot, Larysa I; Lavrova, Kateryna V; Bogdanov, Volodymyr B; Sloan, Erica K; Beregova, Tetyana V; Ostapchenko, Ludmyla I

    2010-01-01

    AIM: To investigate the role of protein tyrosine phosphorylation in gastric wound formation and repair following ulceration. METHODS: Gastric lesions were induced in rats using restraint cold stress. To investigate the effect of oxidative and nitrosative cell stress on tyrosine phosphorylation during wound repair, total activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), antioxidant enzymes, nitric oxide synthase (NOS), 2’,5’-oligoadenylate synthetase, hydroxyl radical and zinc levels were assayed in parallel. RESULTS: Ulcer provocation induced an immediate decrease in tyrosine kinase (40% in plasma membranes and 56% in cytosol, P < 0.05) and phosphatase activity (threefold in plasma membranes and 3.3-fold in cytosol), followed by 2.3-2.4-fold decrease (P < 0.05) in protein phosphotyrosine content in the gastric mucosa. Ulceration induced no immediate change in superoxide dismutase (SOD) activity, 30% increase (P < 0.05) in catalase activity, 2.3-fold inhibition (P < 0.05) of glutathione peroxidase, 3.3-fold increase (P < 0.05) in hydroxyl radical content, and 2.3-fold decrease (P < 0.05) in zinc level in gastric mucosa. NOS activity was three times higher in gastric mucosa cells after cold stress. Following ulceration, PTK activity increased in plasma membranes and reached a maximum on day 4 after stress (twofold increase, P < 0.05), but remained inhibited (1.6-3-fold decrease on days 3, 4 and 5, P < 0.05) in the cytosol. Tyrosine phosphatases remained inhibited both in membranes and cytosol (1.5-2.4-fold, P < 0.05). NOS activity remained increased on days 1, 2 and 3 (3.8-, 2.6-, 2.2-fold, respectively, P < 0.05). Activity of SOD increased 1.6 times (P < 0.05) days 4 and 5 after stress. Catalase activity normalized after day 2. Glutathione peroxidase activity and zinc level decreased (3.3- and 2-fold, respectively, P < 0.05) on the last day. Activity of 2’,5’-oligoadenylate synthethase increased 2.8-fold (P < 0.05) at the beginning, and 1.6-2.3-fold (P < 0.05) during ulcer recuperation, and normalized on day 5, consistent with slowing of inflammation processes. CONCLUSION: These studies show diverse changes in total tyrosine kinase activity in gastric mucosa during the recovery process. Oxidative and nitrosative stress during lesion formation might lead to the observed reduction in tyrosine phosphorylation during ulceration. PMID:21537468

  12. Cibenzoline, an ATP-sensitive K+ channel blocker, binds to the K+-binding site from the cytoplasmic side of gastric H+,K+-ATPase

    PubMed Central

    Tabuchi, Yoshiaki; Yashiro, Hiroaki; Hoshina, Satomi; Asano, Shinji; Takeguchi, Noriaki

    2001-01-01

    Cibenzoline, (±)-2-(2,2-diphenylcyclopropyl-2-imidazoline succinate, has been clinically used as one of the Class I type antiarrhythmic agents and also reported to block ATP-sensitive K+ channels in excised membranes from heart and pancreatic ? cells. In the present study, we investigated if this drug inhibited gastric H+,K+-ATPase activity in vitro. Cibenzoline inhibited H+,K+-ATPase activity of permeabilized leaky hog gastric vesicles in a concentration-dependent manner (IC50: 201??M), whereas no effect was shown on Na+,K+-ATPase activity of dog kidney (IC50: >1000??M). Similarly, cibenzoline inhibited H+,K+-ATPase activity of HEK-293 cells (human embryonic kidney cell line) co-transfected with rabbit gastric H+,K+-ATPase ?- and ?-subunit cDNAs (IC50: 183??M). In leaky gastric vesicles, inhibition of H+,K+-ATPase activity by cibenzoline was attenuated by the addition of K+ (0.5?–?5?mM) in a concentration-dependent manner. The Lineweaver-Burk plot of the H+,K+-ATPase activity shows that cibenzoline increases Km value for K+ without affecting Vmax, indicating that this drug inhibits H+,K+-ATPase activity competitively with respect to K+. The inhibitory effect of H+,K+-ATPase activity by cibenzoline with normal tight gastric vesicles did not significantly differ from that with permeabilized leaky gastric vesicles, indicating that this drug reacted to the ATPase from the cytoplasmic side of the membrane. These findings suggest that cibenzoline is an inhibitor of gastric H+,K+-ATPase with a novel inhibition mechanism, which inhibits gastric H+,K+-ATPase by binding its K+-recognition site from the cytoplasmic side. PMID:11739241

  13. T Cells in Gastric Cancer: Friends or Foes

    PubMed Central

    Amedei, Amedeo; Della Bella, Chiara; Silvestri, Elena; Prisco, Domenico; D'Elios, Mario M.

    2012-01-01

    Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer. PMID:22693525

  14. Down-regulated expressions of PPAR? and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren’s classification in gastric carcinoma

    PubMed Central

    Yu, Han

    2013-01-01

    Objective To explore the relationship between peroxisome proliferator activated receptor-gamma (PPAR?) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) expression in gastric carcinoma (GC), and analyze their correlations with clinicopathological features and clinical outcomes of patients. Methods The two-step immunohistochemical method was used to detect the expression of PPAR? and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting. Results The positive rates of PPAR? and PGC-1 expression were significantly lower in GC (54.75%, 49.16%) than in normal gastric mucosa (70.37%, 71.30%), respectively (P<0.05). The decreased expression of PGC-1 in GC was confirmed in our Western blot analysis (P=0.004). PPAR? and PGC-1 expressions were related to Lauren’s types of GC (P<0.05). Positive correlation was found between PPAR? and PGC-1 expression in GC (rk=0.422, P<0.001). The survival time of PPAR? negative and positive patients was 36.6±3.0 vs. 38.5±2.7 months, and no statistical difference was found between the 5-year survival rates of two groups (34.4% vs. 44.1%, P=0.522, log-rank test); the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups (32.0% vs. 48.2%, P=0.462, log-rank test) Conclusions Decreased expression of PPAR? and PGC-1 in GC was related to the Lauren’s classification. Their expressions in GC were positively correlated, indicating that their functions in gastric carcinogenesis may be closely related. PMID:24385698

  15. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo

    SciTech Connect

    Tan, Wei, E-mail: polo5352877@163.com [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China)] [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China); Zhou, Wei; Yu, Hong-gang; Luo, He-Sheng; Shen, Lei [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China)] [Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan (China)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Zebularine inhibited cell growth of gastric cancer in a time- and dose-dependent manner. Black-Right-Pointing-Pointer Chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Zebularine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by zebularine. -- Abstract: DNA methyltransferase (DNMT) inhibitor zebularine has been reported to potentiate the anti-tumor effect by reactivating the expression of tumor suppressor genes and apoptosis-related genes in various malignant cells. However, the apoptotic signaling pathway in gastric cancer cells induced by zebularine is not well understood. In the study, the effects of zebularine on the growth and apoptosis of gastric cancer cells were investigated by MTT assay, Hoechst assay, Western blot analysis, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL assay. Zebularine was an effective inhibitor of human gastric cancer cells proliferation in vitro and in vivo. The effects were dose dependent. A zebularine concentration of 50 {mu}M accounted for the inhibition of cell proliferation of 67% at 48 h. The treatment with zebularine upregulated Bax, and decreased Bcl-2 protein. Caspase-3 was activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, zebularine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay in xenograft tumor mouse model. These results demonstrated that zebularine induced apoptosis in gastric cancer cells via mitochondrial pathways, and zebularine might become a therapeutic approach for the treatment of gastric cancer.

  16. DC-LAMP+ Dendritic Cells Are Recruited to Gastric Lymphoid Follicles in Helicobacter pylori-Infected Individuals

    PubMed Central

    Hansson, Malin; Sundquist, Malin; Hering, Susanne; Lundin, B. Samuel; Hermansson, Michael

    2013-01-01

    Infection with Helicobacter pylori is associated with development of ulcer disease and gastrointestinal adenocarcinoma. The infection leads to a large infiltration of immune cells and the formation of organized lymphoid follicles in the human gastric mucosa. Still, the immune system fails to eradicate the bacteria, and the substantial regulatory T cell (Treg) response elicited is probably a major factor permitting bacterial persistence. Dendritic cells (DCs) are professional antigen-presenting cells that can activate naive T cells, and maturation of DCs is crucial for the initiation of primary immune responses. The aim of this study was to investigate the presence and localization of mature human DCs in H. pylori-infected gastric mucosa. Gastric antral biopsy specimens were collected from patients with H. pylori-associated gastritis and healthy volunteers, and antrum tissue was collected from patients undergoing gastric resection. Immunohistochemistry and flow cytometry showed that DCs expressing the maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC-LAMP; CD208) are enriched in the H. pylori-infected gastric mucosa and that these DCs are specifically localized within or close to lymphoid follicles. Gastric DC-LAMP-positive (DC-LAMP+) DCs express CD11c and high levels of HLA-DR but little CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that DC-LAMP+ DCs are in the same location as FoxP3-positive putative Tregs in the follicles. In conclusion, we show that DC-LAMP+ DCs with low costimulatory capacity accumulate in the lymphoid follicles in human H. pylori-infected gastric tissue, and our results suggest that Treg-DC interactions may promote chronic infection by rendering gastric DCs tolerogenic. PMID:23876802

  17. No Potassium, No Acid: K+ Channels and Gastric Acid Secretion

    NSDL National Science Digital Library

    2007-10-01

    The gastric H+-K+-ATPase pumps H+ into the lumen and takes up K+ in parallel. In the acid-producing parietal cells, luminal KCNE2/KCNQ1 K+ channels play a pivotal role in replenishing K+ in the luminal fluid. Inactivation of KCNE2/KCNQ1 channels abrogates gastric acid secretion and dramatically modifies the architecture of gastric mucosa.

  18. Helicobacter pylori infection induces gastric cancer in Mongolian gerbils

    Microsoft Academic Search

    Takeshi Watanabe; Mayumi Tada; Hirofumi Nagai; Satoshi Sasaki; Masafumi Nakao

    1998-01-01

    Background & Aims: Although epidemiological studies have indicated that Helicobacter pylori infection plays a crucial role in gastric carcinogenesis in humans, there is no direct proof that H. pylori is actually associated with gastric carcinogenesis. The purpose of this study was to elucidate the relationship between H. pylori infection and gastric carcinogenesis using an animal model of long-term H. pylori

  19. Survival benefit of metastasectomy for Krukenberg tumors from gastric cancer

    Microsoft Academic Search

    Jae Ho Cheong; Woo Jin Hyung; Jian Chen; Junuk Kim; Seung Ho Choi; Sung Hoon Noh

    2004-01-01

    Objective. An optimal treatment strategy for ovarian metastases of gastric cancer has not been clearly established. The aim of this study was to examine the role of a metastasectomy in the management of metachronous Krukenberg tumors after curative surgery for gastric cancer.Methods. Among 1235 female patients who had undergone a curative gastric resection for stomach cancer between 1987 and 1998,

  20. Helicobacter pylori infection and gastric juice vitamin C levels

    Microsoft Academic Search

    Theodoros Rokkas; Georgios Papatheodorou; Andreas Karameris; Anastasios Mavrogeorgis; Nikolaos Kalogeropoulos; Nikolaos Giannikos

    1995-01-01

    H. pylori has recently been recognized as a novel risk factor of gastric cancer, but its precise role in gastric carcinogenesis is as yet unknown. The aim of the present study was to assess the relationship betweenH. pylori infection and vitamin C levels in gastric juice and also to examine whether eradication ofH. pylori could have any impact on these

  1. Azithromycin levels in plasma and gastric tissue, juice and mucus

    Microsoft Academic Search

    J. D. Harrison; J. A. Jones; D. L. Morris

    1991-01-01

    Azithromycin is the first member of a new class called the azalides. Its distribution in gastric tissues was studied in 27 patients (mean age 66 years) with proven gastric cancer due to be resected. Five groups of patients received a single 500 mg oral dose of azithromycin 24, 48, 72, 96 or 120 h pre-operatively. Samples of blood, gastric juice,

  2. Promotion of cytoplasmic mislocalization of p27 by Helicobacter pylori in gastric cancer

    PubMed Central

    Wen, Sicheng; So, Yoshiya; Singh, Kamaljeet; Slingerland, Joyce M.; Resnick, Murray B.; Zhang, Songhua; Ruiz, Victoria; Moss, Steven F.

    2011-01-01

    The cyclin-dependent kinase inhibitor p27 plays an important role in cell cycle regulation. Reduced expression of p27 is commonly associated with poor prognosis in many malignancies, including gastric cancer. Cytoplasmic p27 mislocalization may be an additional indicator of high-grade tumors and poor prognosis in cancer. Since chronic infection by Helicobacter pylori is the most important risk factor for gastric cancer development, we evaluated the effects of H. pylori on p27 expression and localization in gastric cancer cells. Co-culture of gastric cells with H. pylori induced cytoplasmic p27 expression and reduced nuclear p27 expression in vitro. Cytoplasmic p27 expression was associated with and dependent upon phosphorylation of p27 at T157 and T198: wild type p27 accumulated in the cytoplasm, but non-phosphorylatable mutants affecting T157 or T198 were nuclear in H. pylori infected cells. These post-translational p27 changes were secondary to activation of cellular PI3K and AKT signaling pathways and dependent upon a functional H. pylori cag pathogenicity island. We investigated the clinical significance of cytoplasmic p27 mislocalization in 164 cases of resected gastric cancer in tissue microarrays. In 97 cases (59%) cytoplasmic p27 mislocalization was observed, and this was associated with increased mortality in multivariate analysis. These results show that H. pylori infection induces AKT/PI3K-mediated phosphorylation of p27 at T157 and T198 to cause cytoplasmic p27 mislocalization in gastric cancer, and that p27 mislocalization is an adverse prognostic feature in gastric cancer. This is the first demonstration of the translocation of a specific bacterial virulence factor that post-translationally regulates a host cell cyclin-dependent kinase inhibitor. This is of particular significance because p27 has both tumor-suppressive and oncogenic activities, depending upon its subcellular localization. Cytoplasmic mislocalization of p27 induced by H. pylori may be an important mechanistic link between H. pylori infection and gastric carcinogenesis. PMID:21841827

  3. Proximal Gastrectomy for Gastric Cancer

    PubMed Central

    Jung, Do Hyun; Ahn, Sang-Hoon; Kim, Hyung-Ho

    2015-01-01

    Laparoscopic proximal gastrectomy (LPG) is theoretically a superior choice of minimally-invasive surgery and function-preserving surgery for the treatment of proximal early gastric cancer (EGC) over procedures such as laparoscopic total gastrectomy (LTG), open total gastrectomy (OTG) and open proximal gastrectomy (OPG). However, LPG and OPG are not popular surgical options due to three main concerns: the first, oncological safety; the second, functional benefits; and the third, anastomosis-related late complications (reflux symptoms and anastomotic stricture). Numerous recent studies have concluded that OPG and LPG present similar oncological safety profiles and improved functional benefits when compared with OTG and LTG. While OPG with modified esophagogastrostomy does not provide satisfactory results, OPG with modified esophagojejunostomy showed similar rates of anastomosis-related late complications when compared to OTG. At this stage, no standard reconstruction method post-LPG exists in the clinical setting. We recently showed that LPG with double tract reconstruction (DTR) is a superior choice over LTG for proximal EGC in terms of maintaining body weight and preventing anemia. However, as there is no definitive evidence in favor of LPG with DTR, a randomized clinical trial comparing LPG with DTR to LTG was recommended. This trial, the Korean Laparoscopic Gastrointestinal Surgery Study-05 (NCT01433861), is expected to assist surgeons in choice of surgical approach and strategy for patients with proximal EGC.

  4. Gastric electrical stimulation for obesity.

    PubMed

    Chiu, Jenny D; Soffer, Edy

    2015-01-01

    Obesity is a growing health problem worldwide with a major impact on health and healthcare expenditures. Medical therapy in the form of diet and pharmacotherapy has limited effect on weight. Standard bariatric surgery is effective but is associated with morbidity and mortality, creating an unmet need for alternative therapies. One such therapy, the application of electrical stimulation to the stomach, has been studied extensively for the last two decades. Though pulse parameters differ between the various techniques used, the rationale behind this assumes that application of electrical current can interfere with gastric motor function or modulate afferent signaling to the brain or both. Initial studies led by industry failed to show an effect on body weight. However, more recently, there has been a renewed interest in this therapeutic modality with a number of concepts being evaluated in large human trials. If successful, this minimally invasive and low-risk intervention would be an important addition to the existing menu of therapies for obesity. PMID:25613177

  5. Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn’s disease

    PubMed Central

    2012-01-01

    Background Patients with Crohn’s disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores ? 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers. Results Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion Delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction. PMID:23216812

  6. Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water

    PubMed Central

    2014-01-01

    Background Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose–response relationship in the application of hydrogen is puzzling. We attempted to identify the dose–response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. Methods In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Results Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Conclusions Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose–response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress. PMID:24589018

  7. Essential elements for glucosensing by gastric vagal afferents: immunocytochemistry and electrophysiology studies in the rat.

    PubMed

    Grabauskas, Gintautas; Zhou, Shi-Yi; Lu, Yuanxu; Song, Il; Owyang, Chung

    2013-01-01

    Glucosensing nodose ganglia neurons mediate the effects of hyperglycemia on gastrointestinal motility. We hypothesized that the glucose-sensing mechanisms in the nodose ganglia are similar to those of hypothalamic glucose excited neurons, which sense glucose through glycolysis. Glucose metabolism leads to ATP-sensitive potassium channel (K(ATP)) channel closure and membrane depolarization. We identified glucosensing elements in the form of glucose transporters (GLUTs), glucokinase (GK), and K(ATP) channels in rat nodose ganglia and evaluated their physiological significance. In vitro stomach-vagus nerve preparations demonstrated the gastric vagal afferent response to elevated glucose. Western blots and RT-PCR revealed the presence of GLUT1, GLUT3, GLUT4, GK, and Kir6.2 in nodose ganglia neurons and gastric branches of the vagus nerve. Immunocytochemistry confirmed the expression of GLUT3, GK, and Kir6.2 in nodose ganglia neurons (46.3 ± 3%). Patch-clamp studies detected glucose excitation in 30% (25 of 83) of gastric-projecting nodose ganglia neurons, which was abolished by GLUT3 or GK short hairpin RNA transfections. Silencing GLUT1 or GLUT4 in nodose ganglia neurons did not prevent the excitatory response to glucose. Elevated glucose elicited a response from 43% of in vitro nerve preparations. A dose-dependent response was observed, reaching maximum at a glucose level of 250 mg/dl. The gastric vagal afferent responses to glucose were inhibited by diazoxide, a K(ATP) channel opener. In conclusion, a subset of neurons in the nodose ganglia and gastric vagal afferents are glucoresponsive. Glucosensing requires a GLUT, GK, and K(ATP) channels. These elements are transported axonally to the gastric vagal afferents, which can be activated by elevated glucose through modulation of K(ATP) channels. PMID:23211706

  8. A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer 1 Presented in part at the 21st Congress of the European Society for Medical Oncology, Vienna, November 1996. 1

    Microsoft Academic Search

    G. M Tierney; N. R Griffin; R. C Stuart; H Kasem; K. P Lynch; J. T Lury; P. D Brown; A. W Millar; R. J. C Steele; S. L Parsons

    1999-01-01

    The aim of this study was to evaluate the safety and tolerability of 4 weeks administration of marimastat, and to seek evidence of biological activity as observed by changes in the endoscopic appearance of the gastric tumours. 35 patients with advanced, inoperable gastric or gastro-oesophageal tumours were recruited. The dose of marimastat was reduced from the starting dose of 50mg

  9. Effect of Helicobacter pylori on gastric epithelial cells.

    PubMed

    Alzahrani, Shatha; Lina, Taslima T; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-09-28

    The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world's population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori's avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori. PMID:25278677

  10. Psychological Correlates of Laparoscopic Adjustable Gastric Band and Gastric Bypass Patients

    Microsoft Academic Search

    Steven Walfish

    2010-01-01

    Background  To compare psychological characteristics of patients seeking laparoscopic adjustable gastric band (LAGB) and gastric bypass\\u000a surgery.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In the present study, 898 women were assessed as part of a comprehensive presurgical evaluation. Of these 898 patients, 107\\u000a (12%) were seeking LAGB surgery and 791 (88%) were seeking gastric bypass surgery. Their scores on a battery of psychological\\u000a tests were compared with

  11. Clinical epidemiology of gastric cancer in Hehuang valley of China: A 10-year epidemiological study of gastric cancer

    PubMed Central

    Yan, Su; Li, Bin; Bai, Zhen-Zhong; Wu, Jun-Qi; Xie, Da-Wei; Ma, Ying-Cai; Ma, Xu-Xiang; Zhao, Jun-Hui; Guo, Xin-Jian

    2014-01-01

    AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient’s characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer. PMID:25132766

  12. Nutrient deficiencies after gastric bypass surgery.

    PubMed

    Saltzman, Edward; Karl, J Philip

    2013-01-01

    Bariatric surgery, and in particular, gastric bypass, is an increasingly utilized and successful approach for long-term treatment of obesity and amelioration of comorbidities. Nutrient deficiencies after surgery are common and have multiple causes. Preoperative factors include obesity, which appears to be associated with risk for several nutrient deficiencies, and preoperative weight loss. Postoperatively, reduced food intake, suboptimal dietary quality, altered digestion and absorption, and nonadherence with supplementation regimens contribute to risk of deficiency. The most common clinically relevant micronutrient deficiencies after gastric bypass include thiamine, vitamin B??, vitamin D, iron, and copper. Reports of deficiencies of many other nutrients, some with severe clinical manifestations, are relatively sporadic. Diet and multivitamin use are unlikely to consistently prevent deficiency, thus supplementation with additional specific nutrients is often needed. Though optimal supplement regimens are not yet defined, most micronutrient deficiencies after gastric bypass currently can be prevented or treated by appropriate supplementation. PMID:23642197

  13. Gastric emptying of enteric-coated tablets

    SciTech Connect

    Park, H.M.; Chernish, S.M.; Rosenek, B.D.; Brunelle, R.L.; Hargrove, B.; Wellman, H.N.

    1984-03-01

    To evaluate the gastric emptying time of pharmaceutical dosage forms in a clinical setting, a relatively simple dual-radionuclide technique was developed. Placebo tablets of six different combinations of shape and size were labeled with indium-111 DTPA and enteric coated. Six volunteers participated in a single-blind and crossover study. Tablets were given in the morning of a fasting stomach with 6 oz of water containing /sup 99m/Tc pertechnetate and continuously observed with a gamma camera. A scintigraph was obtained each minute. The results suggested that the size, shape, or volume of the tablet used in this study had no significant effect in the rate of gastric emptying. The tablets emptied erratically and unpredictably, depending upon their time of arrival in the stomach in relation to the occurrence of interdigestive myoelectric contractions. The method described is a relatively simple and accurate technique to allow one to follow the gastric emptying of tablets.

  14. The prognosis of gastric outlet obstruction.

    PubMed Central

    Jaffin, B W; Kaye, M D

    1985-01-01

    A retrospective study was undertaken to examine the prognosis of gastric outlet obstruction with specific reference to patients with obstruction due to peptic ulcer. During the 10-year period 1970-1979, 68 patients with gastric outlet obstruction were admitted to our hospital. Obstruction was caused by peptic ulceration in 55 of these patients, all of whom initially were managed conservatively. Thirty-four, however, required surgical decompression during their first admission for obstruction, and 11 needed surgery for a subsequent episode of obstruction. Of the ten patients who have not undergone surgery, six died within 3 years of their first episode of obstruction and three of the four survivors continue to have recurrent obstructive symptoms. Overall, 92% (45/49) of patients who have lived for more than 3 years after their presentation with gastric outlet obstruction due to peptic ulcer have required surgery for relief of obstruction. PMID:3970597

  15. Effect of gastrointestinal hormones on the pertechnetate imaging of ectopic gastric mucosa in experimental Meckel's diverticulum. [Dogs

    SciTech Connect

    Sfakianakis, G.N.; Anderson, G.F.; King, D.R.; Boles, E.T. Jr.

    1981-08-01

    Meckel's diverticula were simulated in 12 dogs by implanting vascularized patches of gastric wall onto Roux-en-Y loops of distal ileum. All animals had camera imaging studies every 10 min for 60 min, with computer acquisition following intravenous injection of 2 mCi of pertechnetate. The scintigrams were repeated following (a) subcutaneous injection of pentagastrin 15 min before injection of pertechnetate; (b) intravenous injection of glucagon 10 min after the tracer injection; (c) pretreatment with pentagastrin plus glucagon as above; and (d) pretreatment with pentagastrin plus secretin. Pentagastrin alone accelerated accumulation of the tracer but resulted in a decrease in the target-to-background ratio. Glucagon alone enhanced late gastric mucosal activity by preventing washout of the intraluminal activity. The combination of pentagastrin and glucagon enhanced visualization and kept background activity lowest. These findgings indicate a potential role for glucagon in the diagnosis of ectopic gastric mucosa in humans.

  16. RASSF10 is epigenetically silenced and functions as a tumor suppressor in gastric cancer

    SciTech Connect

    Wei, Ziran [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China)] [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China); Chen, Xia [Urology Department, Minhang District Central Hospital, Shanghai (China)] [Urology Department, Minhang District Central Hospital, Shanghai (China); Chen, Ji; Wang, Weimin [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China)] [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China); Xu, Xudong [Urology Department, Minhang District Central Hospital, Shanghai (China)] [Urology Department, Minhang District Central Hospital, Shanghai (China); Cai, Qingping, E-mail: qingping_caicz@163.com [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China)] [Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China)

    2013-03-22

    Highlights: ? Epigenetic silencing of RASSF10 gene expression in GC cells. ? RASSF10 overexpression inhibits cell growth in vitro and in vivo. ? RASSF10 induces apoptosis in GC cells. ? RASSF10 inhibits Wnt/?-catenin signaling pathway. -- Abstract: Ras association domain family (RASSF) proteins are encoded by several tumor suppressor genes that are frequently silenced in human cancers. In this study, we investigated RASSF10 as a target of epigenetic inactivation and examined its functions as a tumor suppressor in gastric cancer. RASSF10 was silenced in six out of eight gastric cancer cell lines. Loss or downregulation of RASSF10 expression was associated with promoter hypermethylation, and could be restored by a demethylating agent. Overexpression of RASSF10 in gastric cancer cell lines (JRST, BGC823) suppressed cell growth and colony formation, and induced apoptosis, whereas RASSF10 depletion promoted cell growth. In xenograft animal experiments, RASSF10 overexpression effectively repressed tumor growth. Mechanistic investigations revealed that RASSF10 inhibited tumor growth by blocking activation of ?-catenin and its downstream targets including c-Myc, cyclinD1, cyclinE1, peroxisome proliferator-activated receptor ?, transcription factor 4, transcription factor 1 and CD44. In conclusion, the results of this study provide insight into the role of RASSF10 as a novel functional tumor suppressor in gastric cancer through inhibition of the Wnt/?-catenin signaling pathway.

  17. Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer

    PubMed Central

    Huang, Jie; Zhang, Li; He, Changyu; Qu, Ying; Li, Jianfang; Zhang, Jianian; Du, Tao; Chen, Xuehua; Yu, Yingyan; Liu, Bingya; Zhu, Zhenggang

    2015-01-01

    Claudin-1 (CLDN1) is overexpressed in gastric cancer and correlated with tumor invasion, metastasis and poor outcome. Here, we both down and up regulated CLDN1 expression in gastric cancer cells to elucidate its role in gastric carcinogenesis and tumor progression. We found that deficiency of CLDN1 inhibited cells migration, invasion, and colony formation in vitro and tumorigenicity, metastasis in vivo. Also, CLDN1 promoted cell aggregation and increased anoikis resistance. Down or up regulation of CLDN1 was accompanied with changes of membrane ?-catenin expression as well as Akt and Src activities. When ?-catenin was up-regulated in CLDN1-KD cells, cell aggregation and anoikis resistance were restored, and Akt and Src signal pathways were re-activated. Taken together, these findings suggest that CLDN1 is oncogenic in gastric cancer and its malignant potential may be attributed in part to regulation of anoikis, by mediating membrane ?-catenin-regulated cell-cell adhesion and cell survival. PMID:25544763

  18. Intestinal metaplasia and anastomotic recurrence of gastric carcinoma

    PubMed Central

    Enow Orock, George; Ngowe, Marcelin Ngowe

    2014-01-01

    Intestinal metaplasia (IM) of the stomach has been shown to increase the relative risk of gastric cancer. Endoscopic surveillance has been proposed and advocated for populations at risk. Those patients who had undergone surgery for gastric malignancy exhibited precancerous lesions such as atrophic gastritis and IM, and the possibility of anastomotic recurrence is higher than for the patients who had undergone benign gastric surgery. At present, there are no other recognized good markers of gastric dysplasia or cancer. We reviewed the literature on IM of the stomach to ascertain whether residual premalignant (type III) IM may predispose to anastomotic recurrence of gastric cancer. PMID:25436128

  19. Laparoscopic gastric resection for gastrointestinal stromal tumors

    Microsoft Academic Search

    Jennifer A. Sexton; Richard A. Pierce; Valerie J. Halpin; J. Christopher Eagon; William G. Hawkins; David C. Linehan; L. Michael Brunt; Margaret M. Frisella; Brent D. Matthews

    2008-01-01

    Background  This study aimed to review clinical outcomes for patients selected to undergo laparoscopic resection for gastrointestinal\\u000a stromal tumor (GIST) of the stomach.\\u000a \\u000a \\u000a \\u000a Methods  All 112 laparoscopic gastric resections performed from February 1995 to March 2007 were reviewed. Pre- and postoperative variables\\u000a were analyzed, and data are given as mean ± standard deviation.\\u000a \\u000a \\u000a \\u000a Results  Laparoscopic gastric resection was attempted for 63 GIST in 61 patients

  20. Isomerization of lycopene in the gastric milieu.

    PubMed

    Re, R; Fraser, P D; Long, M; Bramley, P M; Rice-Evans, C

    2001-02-23

    There is considerable interest in the bioavailability of carotenoids from the diet and their bioactivity in vivo. Little is known, however, of the preabsorption events in the gastric lumen on the breakdown or isomerisation of dietary carotenoids. In this study the effects of the acidic environment found in the gastric milieu on lycopene have been investigated. The results show that under these conditions all-trans-lycopene is isomerised to cis-isomers, which may be implicated in enhanced absorption from the small intestine. Furthermore the pH, as well as the food matrix, seems to have an influence on the level of isomerisation of this carotenoid. PMID:11181086

  1. Video-laparoscopic staging of gastric cancer

    Microsoft Academic Search

    F. Asencio; J. Aguilo ´; J. L. Salvador; A. Villar; E. De la Morena; M. Ahamad; J. Escrig; J. Puche; V. Viciano; G. Sanmiguel; J. Ruiz

    1997-01-01

    Background: The high proportion of gastric carcinomas present in an unresectable stage, together with the emergence of multimodal treatments,\\u000a increases the usefulness of objective staging methods that avoid unnecessary laparotomies.\\u000a \\u000a \\u000a \\u000a \\u000a Methods: A prospective evaluation of the accuracy of laparoscopy in the staging of 71 patients with gastric adenocarcinoma is presented.\\u000a Serosal infiltration, retroperitoneal fixation, metastasis to lymph nodes, peritoneal and

  2. Muscarinic cholinergic receptors in human gastric mucosa

    Microsoft Academic Search

    Takao Tokunaga; Reiki Nishimura; Masanobu Akagi

    1984-01-01

    Muscarinic cholinergic receptor sites in human gastric mucosa were analyzed directly by using radioligand binding techniques\\u000a with the specific muscarinic antagonist3H-quinuclidinyl benzilate (QNB) as ligand. Specific binding of3H-QNB to membrane preparations from human gastric mucosa was saturable, of high affinity (Kd=4.17±1.94 nM, Bmax=0.37±0.04\\u000a pmol\\/mg protein) and selectively inhibited by muscarinic antagonists (atropine, scopolamine) and agonists (acetylcholine,\\u000a pilocarpine). These findings provide

  3. Protein profiling of Helicobacter pylori-associated gastric cancer.

    PubMed

    Lian, Guodong; Wei, Chengguo; Wang, Daguang; Cui, Miao; Wang, Zhiqing; Liu, Xiufen; Li, Wei; Wang, Lei; Wang, Qingfeng; Zhang, David Y; Suo, Jian; Ye, Fei

    2014-05-01

    Helicobacter pylori infection is an initiating factor in the development of gastric cancer. Gastric cancer can be divided into two groups on the basis of H. pylori serological status; seropositive H. pylori status predicts favorable prognosis in patients with gastric cancer. By using the protein pathway array, we identified 20 differentially expressed proteins in primary gastric cancer tissues between the H. pylori-seropositive and H. pylori-seronegative groups. Our results indicate that both brassinosteroid insensitive 1-associated kinase 1 and calpastatin are favorable prognostic factors in H. pylori-seropositive gastric cancer patients. In contrast, dachshund homolog 1 is a favorable prognostic factor in H. pylori-seronegative gastric cancer patients. Different signaling pathways were found to be altered between H. pylori-seropositive and H. pylori-seronegative gastric cancer, which may account for the different tumorigenesis and outcomes between these two subsets of patients. PMID:24589339

  4. Examination of visceral perception and gastric tone by gastric stimulation using air inflation during endoscopy.

    PubMed

    Suzuki, T; Hirano, M; Yamamoto, Y

    2005-01-01

    This study investigated the assessment of visceral perception and gastric tone using insufflation during endoscopy. The intragastric pressure was measured during insufflation in 16 patients with gastro-oesophageal reflux disease, 25 patients with functional dyspepsia and 24 normal controls, using a pressure transducer inserted through the forceps aperture until gastric symptoms appeared. The intragastric pressure at the visceral perception threshold, the time to threshold and the time-pressure curve gradient were measured. The visceral perception threshold was significantly reduced in the functional dyspepsia group compared with the normal controls. Balloons were also inserted into the duodenal bulbs of 10 normal controls to investigate the effect of efflux of air into the duodenum; the measured parameters were not influenced by inflation and deflation. These results suggest that it is possible to assess visceral perception and