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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. Antisecretory medication is associated with decreased Helicobacter pylori detection in gastric marginal zone lymphoma.

    PubMed

    Schaberg, Kurt B; Evans, Mark F; Wilcox, Rebecca; Lewis, Michael R

    2015-12-01

    Helicobacter pylori status influences the prognosis and management of gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), so accurate determination of H pylori status is of clinical importance. The low rate of histologic H pylori positivity among gastric MALT lymphoma cases at our institution prompted investigation for possible causes. A case series of 24 patients as having gastric MALT lymphoma (with no diffuse large B-cell component) in a tertiary care setting between 1997 and 2010 was identified, and clinical records were reviewed. Immunohistochemical staining for H pylori and BCL10 was performed. This study received institutional review board approval (protocol number M13-033). Thirty-nine percent of cases (9/23) were H pylori positive by histology, and 4 additional patients had positive serologic results; overall, 57% of cases (13/23) were positive for H pylori. Treatment with antisecretory medications was associated with a lower likelihood of histologic positivity (13% among treated patients vs 75% among untreated; P = .04). Nuclear localization of BCL10 was seen in 2 cases and was not associated with H pylori status. Antisecretory medications decrease the likelihood of histologic detection of H pylori in gastric MALT lymphoma cases. Incorporation of results of serologic or other testing is needed to ensure correct classification with respect to H pylori status. PMID:26615705

  3. Antisecretory, Gastroprotective, Antioxidant and Anti-Helicobcter Pylori Activity of Zerumbone from Zingiber Zerumbet (L.) Smith

    PubMed Central

    Sidahmed, Heyam Mohamed Ali; Hashim, Najihah Mohd; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Mohan, Syam; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Fai, Loke Mun; Vadivelu, Jamuna

    2015-01-01

    Background Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it’s locally known among the Malay people as “lempoyang” and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. Aim of the study The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. Materials and Methods Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. Results The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. Conclusion The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori. PMID:25798602

  4. Evaluation of Anti-Secretory and Anti-Ulcerogenic Activities of Avipattikar Churna on The Peptic Ulcers in Experimental Rats

    PubMed Central

    Gyawali, Sudesh; Khan, Gulam Muhammad; Lamichane, Shreekrishna; Gautam, Jaya; Ghimire, Saurav; Adhikari, Rashmi; Lamsal, Reshma

    2013-01-01

    Background: Avipattikar churna, a poly-herbal formulation, is one of the popular ayurvedic formulations which is used for peptic ulcer diseases but the scientific documentation with regards to its effect for the indication is lacking. Aims: This study was carried out to evaluate the anti-secretory and the anti-ulcerogenic activities of the churna and to compare its activity with that of ranitidine in a pyloric ligated model of rats. Material and methods: Four groups of rats with 6 animals in each served as the ulcer controls, churna low dose (500 mg/kg), churna high dose (750mg/kg) and ranitidine (25mg/kg). The control group rats received only vehicle (2% (v/v) gum acacia), while the rats of the other groups received the respective dose of the churna or ranitidine which was suspended in the vehicle. The treatments were given twice a day, orally, for two days. After 1 hour of the last dose, pyloric ligations were performed and the rats were sacrificed for evaluation after four hours of the ligations. The gastric contents were collected and its volume, pH and acidity were measured. The numbers of ulcers and their lengths were measured which were used to calculate the gastric irritancy index and the curative ratio. The histological examinations of the gastric tissues were also performed. Results: The churna, in both doses, significantly decreased the volumes of the gastric contents, the ulcer score, the length of the ulcer, the gastric irritancy index and pH increased as compared to those in the control group. The effects of the churna were comparable to that of ranitidine. The histopathological evaluation of the gastric tissue also supported the results. Conclusion: Avipattikar churna has anti-secretory and anti-ulcerogenic effects which are comparable to those of ranitidine in peptic ulcer diseases. PMID:23905120

  5. Drug interactions with antisecretory agents.

    PubMed

    Hansten, P D

    1991-01-01

    Antisecretory agents may affect the absorption, metabolism, and renal excretion of other drugs. Inhibition of gastric acid secretion may decrease the gastrointestinal absorption of drugs such as ketoconazole that dissolve poorly in the absence of adequate acid. With anti-secretory agents, the drug interaction mechanism most likely to result in adverse effects is the inhibition of hepatic oxidative drug metabolism, primarily a problem with cimetidine. Omeprazole also appears to inhibit the hepatic metabolism of some drugs, but available evidence indicates that it interacts with fewer drugs than cimetidine and the magnitude of the inhibition is lower. Cimetidine decreases the renal clearance of procainamide and its active metabolite, N-acetylprocainamide, probably through interference with active renal tubular secretion. In therapeutic doses, other H2-receptor antagonists probably have minimal effects on renal procainamide elimination. PMID:1679670

  6. Evaluation of antisecretory, gastroprotective and in-vitro antacid capacity of Fumaria indica in rats.

    PubMed

    Chandra, Phool; Kishore, Kamal; Ghosh, Ashoke Kumar

    2015-09-01

    Fumaria indica is used for its anthelmintic, antidyspeptic, cholagogue, diaphoretic, diuretic, laxative, stomachic, tonic properties and claimed to possess various properties for the ailments of blood, skin, gastrointestinal systems and central nervous system. The present study was undertaken to evaluate antisecretory, gastroprotective and in-vitro antacid capacity of ethanol extract from F. indica in rats. Evaluation of F. indica extract as antisecretory was carried out by pyloric ligation induced ulcer model. The gastroprotective effect was carried out by absolute ethanol induced ulcer model. Integrity of gastric mucosa was evaluated by estimation of GSH and gastric mucus level. The in-vitro antacid capacity was evaluated by titration method. Ethanol extract of F. indica at 200 mg kg(-1), orally showed inhibition of secretion in pyloric ligation model. GSH level (1.67 ?g mg(-1) protein), gastricwall mucus (240.76 ?g g(-1) wet glandular tissue) and percentage protection (77.59%) of ulcer were significantly (P < 0.05) increased in absolute ethanol induced ulcer model. The in-vitro antacid capacity of ethanol extract of F. indica was compared with the standard. Conclusively, it appears that F. indica possess antisecretory (inhibition of acid secretion), gastroprotective (potentiation of defensive factors) and in-vitro antacid activity. PMID:26521557

  7. Gastric Antiulcerogenic and Hypokinetic Activities of Terminalia fagifolia Mart. & Zucc. (Combretaceae)

    PubMed Central

    Nunes, Paulo Humberto M.; Martins, Maria do Carmo C.; Oliveira, Rita de Cássia M.; Chaves, Mariana H.; Sousa, Elcilene A.; Leite, José Roberto S. A.; Véras, Leiz Maria; Almeida, Fernanda Regina C.

    2014-01-01

    The acute toxicity, the antioxidant activity, and the pharmacological activity on the gastrointestinal tract of rodents of the ethanolic extract (TFEE) from the bark of Terminalia fagifolia Mart. & Zucc. (Combretaceae) and of its aqueous (TFAqF), hydroalcoholic (TFHAF), and hexanic (TFHEXF) partition fractions have been evaluated. TFEE presented low acute toxicity, antioxidant, and antiulcerogenic activity against ethanol-induced ulcers, which was partially blocked by pretreatment with L-NAME and indomethacin. It reduced the total acidity and raised the pH of gastric secretion. Additionally, TFEE delayed gastric emptying and slightly inhibited the small intestinal transit and also presented a weakly antidiarrheal activity. The antiulcerogenic and antioxidant activity were also detected in TFAqF and TFHAF but not in TFHEXF. The antisecretory and gastroprotective activity of TFEE partially involve the nitric oxide and prostaglandin participation. Nevertheless, TFEE, TFAqF, and TFHAF drastically reduced the mucus layer adhered to the gastric wall of rats treated with ethanol or indomethacin. Complementary studies are required in order to clarify the paradox of the presence of a gastroprotector activity in this plant that, at the same time, reduces the mucus layer adhered to the gastric wall. PMID:24900960

  8. Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences.

    PubMed

    Saha, Lekha

    2015-11-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPAR?, PPAR?/?, and PPAR?, have been identified so far. PPAR? is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPAR?/? is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPAR? or PPAR? target genes. PPAR?1 and ?2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPAR?1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPAR? agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPAR? agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPAR? activators. In all the studies, both the PPAR? activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPAR? and PPAR? may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs ? and ? in gastric ulcer. PMID:26558146

  9. Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences

    PubMed Central

    Saha, Lekha

    2015-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPAR?, PPAR?/?, and PPAR?, have been identified so far. PPAR? is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPAR?/? is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPAR? or PPAR? target genes. PPAR?1 and ?2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPAR?1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPAR? agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPAR? agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPAR? activators. In all the studies, both the PPAR? activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPAR? and PPAR? may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs ? and ? in gastric ulcer. PMID:26558146

  10. Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats.

    PubMed

    Alirezaei, Masoud; Dezfoulian, Omid; Neamati, Shima; Rashidipour, Marzyeh; Tanideh, Nader; Kheradmand, Arash

    2012-12-01

    Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague-Dawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50 mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12 mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages. PMID:22581435

  11. Telomerase activity in gastric cancer and its clinical implications

    PubMed Central

    Zhan, Wen-Hua; Ma, Jin-Ping; Peng, Jun-Sheng; Gao, Jing-Song; Cai, Shi-Rong; Wang, Jian-Ping; Zheng, Zhang-Qing; Wang, Lei

    1999-01-01

    AIM: To study the telomerase expression in gastric carcinoma and its clinical implications. METHODS: Telomerase activity was examined in gastric cancer an d corresponding normal tissues using a modified TRAP (telomeric repeat amplification protocol) assay (TRAP-eze) in tissue samples from 94 gastric carcinomas an d 58 normal tissues, 12 gastric adenomas and 9 gastric ulcer lesions. RESULTS: Telomerase activity was present in 81 of the 94 (86.2%) gastric cancer tissues, whereas no telomerase activity was detected in any normal tissues. The incidence of telomerase activity in gastric cancer tissues was unrelated to the tumor diameter, histological grade, tumor invasion in depth, lymph node metastasis and TNM stage. CONCLUSION: Telomerase plays an important role in carcinogenes is and progression of gastric cancer, and it is suggested to be a useful tumor marker. PMID:11819456

  12. 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.

  13. Reserpine, vagal adrenergic activity and stress-induced acute gastric mucosal injury in the rat.

    PubMed Central

    Salim, A S

    1987-01-01

    1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress-induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress-induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 +/- 2.7 mm2, mean +/- S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre-treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2-receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 +/- 3 mm2 and 27.5 +/- 2.3 mm2, respectively, mean +/- S.E., n = 10). Protection against the reserpine lesions by the alpha-adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P less than 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 +/- 3.4 mm2, mean +/- S.E., n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 +/- 4.5 mumol, mean +/- S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/- 2 mumol) or with atropine (19 +/- 1.8 mumol) or cimetidine (21 +/- 2 mumol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose-dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 +/- 4.1 mumol and 60.3 +/- 2.8 mumol vs. 61 +/- 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/- 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:2895809

  14. 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.

  15. Active Targeted Nanoparticles for Oral Administration of Gastric Cancer Therapy.

    PubMed

    Lin, Yu-Hsin; Chen, Zih-Rou; Lai, Chih-Ho; Hsieh, Chia-Hung; Feng, Chun-Lung

    2015-09-14

    Gastric carcinogenesis is a commonly diagnosed type of cancer and has a dismal prognosis because of the rate at which it aggressively spreads and because of the lack of effective therapies to stop its progression. This study evaluated a type of oral drug delivery system of a potential target-activated nanosizer comprising a fucose-conjugated chitosan and polyethylene glycol-conjugated chitosan complex with gelatin containing encapsulated green tea polyphenol extract epigallocatechin-3-gallate, allowing oral administration of the drug through a site-specific release in gastric cancer cells. The results demonstrated that the nanoparticles effectively reduced drug release within gastric acids and that a controlled epigallocatechin-3-gallate release inhibited gastric cancer cell growth, induced cell apoptosis, and reduced vascular endothelial growth factor protein expression. Furthermore, in vivo assay results indicated that the prepared epigallocatechin-3-gallate-loaded fucose-chitosan/polyethylene glycol-chitosan/gelatin nanoparticles significantly affected gastric tumor activity and reduced gastric and liver tissue inflammatory reaction in an orthotopic gastric tumor mouse model. PMID:26286711

  16. 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

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

    PubMed Central

    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

  18. Antisecretory factor suppresses intestinal inflammation and hypersecretion

    PubMed Central

    Johansson, E; Jennische, E; Lange, S; Lonnroth, I

    1997-01-01

    Background—Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin. ?Aims—To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa. ?Methods—Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 µg of toxin A or 3 µg of okadaic acid administered before or after injection of 0.1 µg of recombinant AF (rAF). ?Results—The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF. ?Conclusion—Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system. ?? Keywords: okadaic acid; Clostridium difficile toxin A; diarrhoea; neuropeptide; S5a; rat PMID:9414971

  19. Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Eliakim, R; Stalnikowicz, R; Ackerman, Z; Amir, G; Stamler, J S

    1994-01-01

    Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may have a role in tissue injury through its oxidative metabolism. Nitric oxide may have a role in the pathogenesis of duodenal ulcer and may be one of the mechanisms responsible for the association between gastric infection with Helicobacter pylori and peptic disease. In this study, calcium independent nitric oxide synthase activity was detected in human gastric mucosa suggesting expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral and fundic nitric oxide synthase activity was found to be two and 1.5-fold respectively higher than its activity in the antrum and fundus of 14 normal subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide synthase activity in H pylori positive duodenal ulcer patients was twofold higher than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients antral and fundic nitric oxide synthase activity resumed normal values after induction of ulcer healing with ranitidine. Eradication of H pylori did not further affect gastric nitric oxide synthase activity. These findings suggest that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase activity, though independent of the H pylori state, may contribute to the pathogenesis of the disease. PMID:7525417

  20. Inhibition of intestinal chloride secretion by piperine as a cellular basis for the anti-secretory effect of black peppers.

    PubMed

    Pongkorpsakol, Pawin; Wongkrasant, Preedajit; Kumpun, Saowanee; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2015-10-01

    Piperine is the principal alkaloid in black peppers (Piper nigrum L.), which is a commonly included spice in anti-diarrheal formulations. Piperine has antispasmodic activities, but its anti-secretory effect is not known. Therefore, this study investigated the anti-secretory effect of piperine and its underlying mechanism. Piperine inhibited cAMP-mediated Cl(-) secretion in human intestinal epithelial (T84) cells, similar to black pepper extract. Intraluminal administration of piperine (2?g/loop) suppressed cholera toxin-induced intestinal fluid accumulation by ?85% in mice. The anti-secretory mechanism of piperine was investigated by evaluating its effects on the activity of transport proteins involved in cAMP-mediated Cl(-) secretion. Notably, piperine inhibited CFTR Cl(-) channel activity (IC50#8'6#10?M) without affecting intracellular cAMP levels. The mechanisms of piperine-induced CFTR inhibition did not involve MRP4-mediated cAMP efflux, AMPK or TRPV1. Piperine also inhibited cAMP-activated basolateral K(+) channels, but it had no effect on Na(+)-K(+)-Cl(-) cotransporters or Na(+)-K(+) ATPases. Piperine suppressed Ca(2+)-activated Cl(-) channels (CaCC) without affecting intracellular Ca(2+) concentrations or Ca(2+)-activated basolateral K(+) channels. Collectively, this study indicates that the anti-secretory effect of piperine involves the inhibition of CFTR, CaCC and cAMP-activated basolateral K(+) channels. Piperine represents a novel class of drug candidates for the treatment of diarrheal diseases caused by the intestinal hypersecretion of Cl(-). PMID:26297981

  1. Apoptotic and proliferative activity of mouse gastric mucosa following oral administration of fumonisin B1

    PubMed Central

    Alizadeh, Ali Mohammad; Mohammadghasemi, Fahimeh; Zendehdel, Kazem; Kamyabi-moghaddam, Zahra; Tavassoli, Abbas; Amini-najafi, Fatemeh; Khosravi, Alireza

    2015-01-01

    Objective(s): Fumonisins are a group of toxic and carcinogenic mycotoxins, which contaminate the grains and their products. The aim of this study was to examine the apoptotic and proliferative activity of mouse gastric mucosa following administration of fumonisin B1 (FB1). Materials and Methods: Twenty-nine female mice divided into treatment (n=15) and control (n=14) groups. The treatment group received FB1 (150 mg/kg diet) for 16 weeks. The gastric atrophy was allocated using grading criteria modeled on the updated Sydney System. Immunohistochemistry studies were performed for evaluation of apoptosis and proliferative activity in gastric mucosa. Results: Mild to moderate gastric atrophy were observed in microscopic findings of the gastric mucosa in treated animals (P<0.05). Number of parietal cells significantly decreased in the treatment group in comparison with the control (P<0.05). Treatment with FB1 for 16 weeks significantly reduced both gastric mucosa height and mitotic index in the gastric glands (P<0.05). TUNEL- and Bax-labeled positive cell numbers significantly increased in the FB1-treated group compared to the control (P<0.05). In addition, proliferative activity of gastric glands in the treated group was significantly lower than the control (P<0.05). Conclusion: Oral administration of FB1 caused atrophy in gastric mucosa both via increasing of apoptosis and suppressing the mitotic activity of these cells. PMID:25810870

  2. Effects of gastrokine-2 expression on gastric cancer cell apoptosis by activation of extrinsic apoptotic pathways

    PubMed Central

    SHI, LIN-SEN; WANG, HAO; WANG, FENG; FENG, MIN; WANG, MENG; GUAN, WEN-XIAN

    2014-01-01

    Gastrokine-2 is a putative gastric cancer-specific tumor suppressor gene, the loss of which is known to be involved in the development and progression of gastric cancer, and restoration of gastrokine-2 expression inhibits growth of gastric cancer cells in vitro. However, the underlying mechanism of these effects requires elucidation. In the present study, expression patterns of gastrokine-2 protein were examined in gastric cancer tissues and cell lines. Expression of gastrokine-2 was restored in gastric cancer cells in order to assess its effect on cell viability, apoptosis and gene expression. A total of 76 gastric cancer tissues with corresponding normal mucosae samples, and two gastric cancer cell lines (SGC-7901 and AGS) were subjected to western blot analysis of gastrokine-2 expression. SGC-7901 cells were transiently transfected with gastrokine-2 cDNA and then treated with anti-CD95 and/or anti-Fas antibodies prior to analysis of cell viability, apoptosis and gene expression levels. Expression of gastrokine-2 protein was reduced or absent in gastric cancer tissues and gastric cancer cell lines. Following restoration of gastrokine-2 expression, the protein expression level of Fas was significantly increased, but no marked change was observed in the levels of bcl-2 and Bax proteins. Expression of gastrokine-2 protein reduced gastric cancer cell viability and induced apoptosis. Activity of caspase-3 and caspase-8 was increased, but caspase-9 activity remained unchanged in the SGC-7901 cells. Reduction or knockout of gastrokine-2 protein expression may contribute to gastric cancer development or progression, as the current study demonstrated that restoration of gastrokine-2 expression induces apoptosis of gastric cancer cells through the extrinsic apoptosis pathway. PMID:25270871

  3. Structure-activity relationships of eighteen somatostatin analogues on gastric secretion.

    PubMed Central

    Brown, M P; Coy, D H; Gomez-Pan, A; Hirst, B H; Hunter, M; Meyers, C; Reed, J D; Schally, A V; Shaw, B

    1978-01-01

    1. The effect of somatostatin and eighteen somatostatin analogues on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 microgram kg-1 hr-1 was found to be 1.29 +/- 0.13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp8 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-simatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity. PMID:349135

  4. [Gastric cancer].

    PubMed

    Uemura, Naomi

    2009-12-01

    From many findings, it has been established that persistent infection of Helicobacter pylori (H. pylori) causes chronic active gastritis and subsequently causes the gastric mucosa of the high risk for gastric cancer development. On the other hand, recent Japanese-study results have shown the possibility of gastric cancer prevention by H. pylor eradication. Moreover the development of gastric cancer in uninfected subjects is very rare; therefore, prevention of gastric cancer by H. pylori eradication becomes a topic in Japan. To get rid of gastric cancer from Japan, the risk of gastric cancer should be determined by presence of H. pylori infection in a young fellow, on the other hand, the risk by the examination that combined serum PG method with serum antibody method in subjects after middle aged. It is now expected that eradication treatment should be performed for these high-risk subjects. PMID:19999121

  5. Macrophage Infiltration Induces Gastric Cancer Invasiveness by Activating the ?-Catenin Pathway

    PubMed Central

    Wu, Ming-Hsun; Lee, Wei-Jiunn; Hua, Kuo-Tai; Kuo, Min-Liang; Lin, Ming-Tsan

    2015-01-01

    Background Despite evidence that activated macrophages act in an inflammatory microenvironment to promote gastric tumorigenesis via ?-catenin signaling, the effects of ?-catenin signaling on gastric cancer cell metastasis and the relationship of these cells with surrounding tumor associated macrophages have not been directly studied. Methods Immunohistochemical staining was employed to analyze 103 patients. An invasion assay was used to evaluate the relationship between macrophages and gastric cancer cells. ?-catenin gain-of-function and loss-of-function approaches were performed. To assess the ?-catenin regulation mechanism in gastric cancer cells, Western blotting and reverse-transcription polymerase chain reaction were used. Results Increased density of macrophages was associated with advanced stage and poor survival. Gastric cancer cell lines co-cultured with macrophages conditioned medium showed increased nuclear accumulation of ?-catenin and increased invading ability. AKT but not ERK regulated ?-catenin translocation. MMP7 and CD44, both ?-catenin downstream genes, were involved in macrophage-activated gastric cancer cell invasion. Conclusion(s) Collectively, the clinical data suggest that macrophage infiltration is correlated with increased grade and poor prognosis for gastric cancer patients who underwent radical resection. Macrophages may induce invasiveness by activating the ?-catenin pathway. PMID:26226629

  6. 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

  7. High antitumor activity of pladienolide B and its derivative in gastric cancer.

    PubMed

    Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji

    2014-01-01

    The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction. PMID:24635824

  8. High antitumor activity of pladienolide B and its derivative in gastric cancer

    PubMed Central

    Sato, Momoko; Muguruma, Naoki; Nakagawa, Tadahiko; Okamoto, Koichi; Kimura, Tetsuo; Kitamura, Shinji; Yano, Hiromi; Sannomiya, Katsutaka; Goji, Takahiro; Miyamoto, Hiroshi; Okahisa, Toshiya; Mikasa, Hiroaki; Wada, Satoshi; Iwata, Masao; Takayama, Tetsuji

    2014-01-01

    The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction. PMID:24635824

  9. 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

  10. Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

    PubMed

    Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

    2008-09-01

    The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine. PMID:18434110

  11. Refractory death rattle: deep aspiration facilitates the effects of antisecretory agents.

    PubMed

    Mercadante, Sebastiano; Villari, Patrizia; Ferrera, Patrizia

    2011-03-01

    Anticholinergic drugs, including atropine, hyoscine butylbromide, and scopolamine, have been shown to be equally effective in the treatment of death rattle. However, anticholinergic drugs may only be effective in reducing the production of further secretions, rather than eliminating the existing ones. A case is described in which a preventive procedure was undertaken to carefully eliminate secretions before starting anticholinergic drugs. Airway aspiration under light anesthesia removed secretions before starting anticholinergic drugs. Low doses of propofol were given intravenously to make a laryngoscopy feasible, allowing the complete aspiration of large amounts of tracheal secretions. No death rattle was perceived until death. Relatives were satisfied with the treatment and the peaceful death. Antisecretory agents may only prevent further accumulation of fluids along the airways and in the pharynx. The use of these drugs, supplemented by this aspiration procedure in carefully selected patients, may help eliminate death rattle in patients with advanced illness who are unable to cough or swallow. Explanation and reassurance to relieve fears and concerns regarding a procedure aimed to improve the quality of end-of-life care are of paramount importance, and active collaboration in decision making facilitates a timely intervention. This preliminary experience may help further research on the best treatment at the end of life. PMID:21131169

  12. Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

    PubMed Central

    Kim, Young-Woo; Eom, Bang Wool; Kook, Myeong-Cherl; Kim, Han-Seong; Kim, Mi-Kyung; Hwang, Hai-Li; Chandra, Vishal; Poojan, Shiv; Song, Yura; Koh, Jae-Soo; Bae, Chang-Dae; Ro, Jungsil; Hong, Kyeong-Man

    2015-01-01

    Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials. PMID:26542785

  13. Role of platelet activating factor on the fibrinolytic activation in the pathogenesis of gastric mucosal damage induced by endothelin-1.

    PubMed Central

    Kurose, I; Miura, S; Fukumura, D; Tashiro, H; Imaeda, H; Shiozaki, H; Suematsu, M; Nagata, H; Sekizuka, E; Tsuchiya, M

    1992-01-01

    We have examined the hypothesis that the release of tissue type plasminogen activator may play a prominent role in endothelin induced gastric mucosal injury. We determined tissue type plasminogen activator activity in the regional blood sample and the concentration of platelet activating factor in the gastric mucosa after the administration of endothelin-1 in a range of 50-500 pmol/kg into the left gastric artery of male Wistar rats. Endothelin-1 increased the tissue type plasminogen activator release and platelet activating factor formation, and induced subsequent gastric mucosal haemorrhagic change in a dose dependent manner. In addition CV-6209, a selective platelet activating factor blocker, attenuated the activation of regional tissue type plasminogen activator and the development of mucosal damage induced by endothelin-1. The results of this study showed that tissue type plasminogen activator activation may play an important role in the pathogenesis of endothelin induced mucosal injury of rat stomach, and suggest that the platelet activating factor may be involved in the process of regional fibrinolytic activation induced by endothelin-1. PMID:1644323

  14. Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility

    PubMed Central

    Takeuchi, Koji

    2012-01-01

    This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase in mucosal permeability, neutrophil infiltration and oxyradical production, and eventually producing gastric lesions. These lesions are prevented by pretreatment with PGE2 and antisecretory drugs, and also via an atropine-sensitive mechanism, not related to antisecretory action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach, the combined administration of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases prostaglandin E2 (PGE2) production and causes gastric hypermotility and an increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions, including adrenalectomy, arthritis, and Helicobacter pylori-infection. In summary, gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility, and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition. PMID:22611307

  15. 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

  16. Antiulcerogenic activity of Scutia buxifolia on gastric ulcers induced by ethanol in rats.

    PubMed

    Boligon, Aline Augusti; de Freitas, Robson Borba; de Brum, Thiele Faccim; Waczuk, Emily Pansera; Klimaczewski, Cláudia Vargas; de Ávila, Daiana Silva; Athayde, Margareth Linde; de Freitas Bauermann, Liliane

    2014-10-01

    Gastric ulcers affect many people around the world and their development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. Scutia buxifolia, commonly known as coronilha, has attracted the interest of the scientific community due to its pharmacological properties and its potential therapeutic applications. In this study, the preventive effects of the crude extract of Scutia buxifolia (ceSb) against gastric ulcer induced by 70% ethanol were evaluated in male Wistar rats. In addition, the composition of ceSb was clarified by high-performance liquid chromatography (HPLC). S. buxifolia extract (100, 200 and 400 mg/kg body weight) attenuated oxidative and histopathological features induced by ethanol. Moreover, all evaluated doses of ceSb caused significant (P<0.001 and P<0.0001) and dose-dependent increase in sulfhydryl groups (NPSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Furthermore, the administration of ceSb reversed the increase in lipid peroxidation produced by ethanol. The protective effect of the extract could be attributed to antioxidant compounds present in the ceSb, such as flavonoids and phenolic acids, which were quantified by HPLC. Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. These results indicate that S. buxifolia could have a beneficial role against ethanol toxicity by preventing oxidative stress and gastric tissue injury. PMID:26579405

  17. Antiulcerogenic activity of Scutia buxifolia on gastric ulcers induced by ethanol in rats

    PubMed Central

    Boligon, Aline Augusti; de Freitas, Robson Borba; de Brum, Thiele Faccim; Waczuk, Emily Pansera; Klimaczewski, Cláudia Vargas; de Ávila, Daiana Silva; Athayde, Margareth Linde; de Freitas Bauermann, Liliane

    2014-01-01

    Gastric ulcers affect many people around the world and their development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. Scutia buxifolia, commonly known as coronilha, has attracted the interest of the scientific community due to its pharmacological properties and its potential therapeutic applications. In this study, the preventive effects of the crude extract of Scutia buxifolia (ceSb) against gastric ulcer induced by 70% ethanol were evaluated in male Wistar rats. In addition, the composition of ceSb was clarified by high-performance liquid chromatography (HPLC). S. buxifolia extract (100, 200 and 400 mg/kg body weight) attenuated oxidative and histopathological features induced by ethanol. Moreover, all evaluated doses of ceSb caused significant (P<0.001 and P<0.0001) and dose-dependent increase in sulfhydryl groups (NPSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities. Furthermore, the administration of ceSb reversed the increase in lipid peroxidation produced by ethanol. The protective effect of the extract could be attributed to antioxidant compounds present in the ceSb, such as flavonoids and phenolic acids, which were quantified by HPLC. Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. These results indicate that S. buxifolia could have a beneficial role against ethanol toxicity by preventing oxidative stress and gastric tissue injury. PMID:26579405

  18. Evaluation of antioxidant and immuno-enhancing activities of Purslane polysaccharides in gastric cancer rats.

    PubMed

    Li, Yunqiao; Hu, Yanke; Shi, Shaojun; Jiang, Lei

    2014-07-01

    In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from plant or animal and used as a promising source of therapeutic agents for cancer. In this study, we examined the effects of Purslane polysaccharides (PPs) on the oxidative injury and immune status in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. PPs administration (200, 400 or 800mg/kg body weight) could not only increase the body weight, peripheral white blood cells (WBC) count, thymus and spleen indexes, but also remarkably promote splenocytes proliferation of gastric cancer rats. Furthermore, the production of serum cytokines in gastric cancer rats, such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-?) was enhanced by PPs treatment. Besides, treatment with PPs was found to provide a dose-dependent protection against MNNG-induced oxidative injury by enhancing SOD, CAT, GSH-Px activities of gastric cancer rats. Taken together, we concluded that enhancement of antioxidants and immune response might be responsible for the anticancer effect of PPs in gastric cancer. PMID:24768972

  19. Mycoplasma hyorhinis Activates the NLRP3 Inflammasome and Promotes Migration and Invasion of Gastric Cancer Cells

    PubMed Central

    Yao, Xiaomin; Xing, Yue; Wang, Xun; Zhong, Jin; Meng, Guangxun

    2013-01-01

    Background Mycoplasma hyorhinis (M.hyorhinis, M.hy) is associated with development of gastric and prostate cancers. The NLRP3 inflammasome, a protein complex controlling maturation of important pro-inflammatory cytokines interleukin (IL)-1? and IL-18, is also involved in tumorigenesis and metastasis of various cancers. Methodology/Principal Findings To clarify whether M.hy promoted tumor development via inflammasome activation, we analyzed monocytes for IL-1? and IL-18 production upon M.hy challenge. When exposed to M.hy, human monocytes exhibited rapid and robust IL-1? and IL-18 secretion. We further identified that lipid-associated membrane protein (LAMP) from M.hy was responsible for IL-1? induction. Applying competitive inhibitors, gene specific shRNA and gene targeted mice, we verified that M.hy induced IL-1? secretion was NLRP3-dependent in vitro and in vivo. Cathepsin B activity, K+ efflux, Ca2+ influx and ROS production were all required for the NLRP3 inflammasome activation by M.hy. Importantly, it is IL-1? but not IL-18 produced from macrophages challenged with M.hy promoted gastric cancer cell migration and invasion. Conclusions Our data suggest that activation of the NLRP3 inflammasome by M.hy may be associated with its promotion of gastric cancer metastasis, and anti-M.hy therapy or limiting NLRP3 signaling could be effective approach for control of gastric cancer progress. PMID:24223129

  20. Sensitivity and Specificity of Hypnosis Effects on Gastric Myoelectrical Activity

    PubMed Central

    Enck, Paul; Weimer, Katja; Muth, Eric R.; Zipfel, Stephan; Martens, Ute

    2013-01-01

    Objectives The effects of hypnosis on physiological (gastrointestinal) functions are incompletely understood, and it is unknown whether they are hypnosis-specific and gut-specific, or simply unspecific effects of relaxation. Design Sixty-two healthy female volunteers were randomly assigned to either a single session of hypnotic suggestion of ingesting an appetizing meal and an unappetizing meal, or to relax and concentrate on having an appetizing or unappetizing meal, while the electrogastrogram (EGG) was recorded. At the end of the session, participants drank water until they felt full, in order to detect EGG-signal changes after ingestion of a true gastric load. During both conditions participants reported their subjective well-being, hunger and disgust at several time points. Results Imagining eating food induced subjective feelings of hunger and disgust as well as changes in the EGG similar to, but more pronounced than those seen with a real gastric water load during both hypnosis and relaxation conditions. These effects were more pronounced when imagining an appetizing meal than with an unappetizing meal. There was no significant difference between the hypnosis and relaxation conditions. Conclusion Imagination with and without hypnosis exhibits similar changes in subjective and objective measures in response to imagining an appetizing and an unappetizing food, indicating high sensitivity but low specificity. PMID:24358287

  1. Loss of TFF1 promotes Helicobacter pylori-induced ?-catenin activation and gastric tumorigenesis

    PubMed Central

    Soutto, Mohammed; Romero-Gallo, Judith; Krishna, Uma; Piazuelo, M. Blanca; Washington, M. Kay; Belkhiri, Abbes; Peek, Richard M.; El-Rifai, Wael

    2015-01-01

    Using in vitro and in vivo models, we investigated the role of TFF1 in suppressing H. pylori-mediated activation of oncogenic ?-catenin in gastric tumorigenesis. A reconstitution of TFF1 expression in gastric cancer cells decreased H. pylori-induced ?-catenin nuclear translocation, as compared to control (p < 0.001). These cells exhibited significantly lower ?-catenin transcriptional activity, measured by pTopFlash reporter, and induction of its target genes (CCND1 and c-MYC), as compared to control. Because of the role of AKT in regulating ?-catenin, we performed Western blot analysis and demonstrated that TFF1 reconstitution abrogates H. pylori-induced p-AKT (Ser473), p-?-catenin (Ser552), c-MYC, and CCND1 protein levels. For in vivo validation, we utilized the Tff1-KO gastric neoplasm mouse model. Following infection with PMSS1 H. pylori strain, we detected an increase in the nuclear staining for ?-catenin and Ki-67 with a significant induction in the levels of Ccnd1 and c-Myc in the stomach of the Tff1-KO, as compared to Tff1-WT mice (p < 0.05). Only 10% of uninfected Tff1-KO mice, as opposed to one-third of H. pylori-infected Tff1-KO mice, developed invasive adenocarcinoma (p = 0.03). These findings suggest that loss of TFF1 could be a critical step in promoting the H. pylori-mediated oncogenic activation of ?-catenin and gastric tumorigenesis. PMID:25980439

  2. Effect of peptide YY on gastric motor and secretory activity in vagally innervated and denervated corpus pouch dogs.

    PubMed

    Zai, H; Haga, N; Fujino, M A; Itoh, Z

    1996-03-22

    In this study, we examined the mechanism by which constant intravenous infusion of physiological doses of PYY affects gastric secretion and motility in the vagally innervated (Pavlov) and denervated (Heidenhain) corpus pouch. As a result, only in the Heidenhain pouch, PYY at a dose of 100 pmol/kg-h significantly inhibited gastric secretion in the interdigestive and postprandial states. A dose of 300 pmol/kg-h inhibited the gastric secretion in both types of pouch, but inhibition in the Pavlov pouch was less than in the Heidenhain pouch. The inhibitory effect of PYY on phase III contractile activity was dose-dependent and significant, except in the Heidenhain pouch, and no dose of PYY had any effect on postprandial gastric motility. After all, vagal denervation enhanced the inhibitory effect of PYY on gastric secretion, but abolished the inhibitory effect on phase III contractile activity. Our findings strongly suggest that the inhibitory effect of PYY on gastric secretion is in part mediated by a non-vagal pathway and the inhibitory effect of PYY on gastric motor activities is completely dependent on vagal innervation, but the vagus nerve acts as an inhibitory modulator of the inhibitory effect of PYY on gastric secretion. PMID:8701034

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

    PubMed Central

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

    2015-01-01

    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. [BMB Reports 2015; 48(6): 324-329] PMID:25047444

  4. Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping

    PubMed Central

    Du, Peng; Cheng, Leo K.; Egbuji, John U.; Lammers, Wim J. E. P.; Windsor, John A.; Pullan, Andrew J.

    2010-01-01

    Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm2) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3–4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 ± 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies. PMID:20595620

  5. TIPE2 functions as a metastasis suppressor via negatively regulating ?-catenin through activating GSK3? in gastric cancer.

    PubMed

    Wu, Jie; Zhang, Haitao; Xu, Chun; Xu, Hong; Zhou, Xiumin; Xie, Yufeng; Tao, Min

    2016-01-01

    Tumor necrosis factor (TNF)-?-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is a novel anti-inflammatory factor involved in maintaining immune homeostasis. Accumulating evidence has also shown that TIPE2 displays tumor-suppressive effects in several tumor types. Previous studies revealed that TIPE2 inhibits hepatocellular carcinoma metastasis by repressing Ral and Rac1 GTPases. However, its antimetastatic activity and underlying mechanism in other human cancers is largely unknown. We investigated TIPE2 in AGS, HGC-27 and SGC-7901 human gastric cancer cells compared with GES-1 normal human gastric mucous epithelial cells. We demonstrated that TIPE2 was expressed in GES-1 gastric mucous epithelial cells but lost in all three types of gastric cancer cells. We then performed a gain-of-function study by adenovirus-mediated TIPE2 overexpression (AdVTIPE2) and investigated the effects of TIPE2 on migration and invasion of AGS human gastric cancer cells. Wound healing and Transwell invasion assays showed that forced expression of TIPE2 markedly suppressed the gastric cancer cell migration and invasion in vitro. Mechanistically, TIPE2 remarkably reduced the total levels of pAKT, pGSK3? and ?-catenin as well as the nuclear level of ?-catenin in gastric cancer cells. The TIPE2-elicited antimetastatic effect in gastric cancer was closely associated with the inhibition of AKT signaling and enhancement of GSK3? activity followed by the degradation and decreased translocation to nucleus of ?-catenin. These results provide the first compelling evidence that TIPE2 suppresses gastric cancer metastasis via downregulating ?-catenin signaling through inhibiting AKT and activating GSK3?, indicating that TIPE2 is a promising therapeutic target for human gastric cancer metastasis. PMID:26530498

  6. Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer.

    PubMed

    Yang, Mei; Huang, Chang-Zhi

    2015-11-01

    The mortality rate of gastric cancer worldwide is as high as 70%, despite the development of novel therapeutic strategies. One reason for the high mortality is the rapid and uninhibited spread of the disease, such that the majority of patients are diagnosed at a stage when efficient therapeutic treatment is not available. Therefore, in-depth research is needed to investigate the mechanism of gastric cancer metastasis and invasion to improve outcomes and provide biomarkers for early diagnosis. The mitogen-activated protein kinase (MAPK) signaling pathway is widely expressed in multicellular organisms, with critical roles in multiple biological processes, such as cell proliferation, death, differentiation, migration, and invasion. The MAPK pathway typically responds to extracellular stimulation. However, the MAPK pathway is often involved in the occurrence and progression of cancer when abnormally regulated. Many studies have researched the relationship between the MAPK signaling pathway and cancer metastasis and invasion, but little is known about the important roles that the MAPK signaling pathway plays in gastric cancer. Based on an analysis of published data, this review aims to summarize the important role that the MAP kinases play in the invasion and metastasis of gastric cancer and attempts to provide potential directions for further research and clinical treatment. PMID:26556994

  7. Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer

    PubMed Central

    Yang, Mei; Huang, Chang-Zhi

    2015-01-01

    The mortality rate of gastric cancer worldwide is as high as 70%, despite the development of novel therapeutic strategies. One reason for the high mortality is the rapid and uninhibited spread of the disease, such that the majority of patients are diagnosed at a stage when efficient therapeutic treatment is not available. Therefore, in-depth research is needed to investigate the mechanism of gastric cancer metastasis and invasion to improve outcomes and provide biomarkers for early diagnosis. The mitogen-activated protein kinase (MAPK) signaling pathway is widely expressed in multicellular organisms, with critical roles in multiple biological processes, such as cell proliferation, death, differentiation, migration, and invasion. The MAPK pathway typically responds to extracellular stimulation. However, the MAPK pathway is often involved in the occurrence and progression of cancer when abnormally regulated. Many studies have researched the relationship between the MAPK signaling pathway and cancer metastasis and invasion, but little is known about the important roles that the MAPK signaling pathway plays in gastric cancer. Based on an analysis of published data, this review aims to summarize the important role that the MAP kinases play in the invasion and metastasis of gastric cancer and attempts to provide potential directions for further research and clinical treatment. PMID:26556994

  8. Leptin activates STAT and ERK2 pathways and induces gastric cancer cell proliferation

    SciTech Connect

    Pai, Rama . E-mail: rpai@uci.edu; Lin Cal; Tran, Teresa; Tarnawski, Andrzej . E-mail: atarnawski@yahoo.com

    2005-06-17

    Although leptin is known to induce proliferative response in gastric cancer cells, the mechanism(s) underlying this action remains poorly understood. Here, we provide evidence that leptin-induced gastric cancer cell proliferation involves activation of STAT and ERK2 signaling pathways. Leptin-induced STAT3 phosphorylation is independent of ERK2 activation. Leptin increases SHP2 phosphorylation and enhances binding of Grb2 to SHP2. Inhibition of SHP2 expression with siRNA but not SHP2 phosphatase activity abolished leptin-induced ERK2 activation. While JAK inhibition with AG490 significantly reduced leptin-induced ERK2, STAT3 phosphorylation, and cell proliferation, SHP2 inhibition only partially reduced cancer cell proliferation. Immunostaining of gastric cancer tissues displayed local overexpression of leptin and its receptor indicating that leptin might be produced and act locally in a paracrine or autocrine manner. These findings indicate that leptin promotes cancer growth by activating multiple signaling pathways and therefore blocking its action at the receptor level could be a rational therapeutic strategy.

  9. Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, S. H.; Stern, R. M.; Koch, K. L.

    1992-01-01

    This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.

  10. Effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells

    PubMed Central

    Sun, Li; Wang, Xu

    2003-01-01

    AIM: To investigate the effects of allicin on both telomerase activity and apoptosis in gastric cancer SGC-7901 cells. METHODS: The gastric cancer SGC-7901 adenocarcinoma cells were treated with allicin and the cell cycle, inhibitory rate, apoptosis, telomerase activity and morphologic changes were studied by MTT assay, flow cytometry (FCM), TRAP-PCR-ELISA assay, light microscope, electron microscope respectively. Results were compared with that of AZT (3’-Azido-3’-deoxythymidine). RESULTS: SGC-7901 cells were suppressed after exposure to allicin of 0.016 mg/mL, 0.05 mg/mL, and 0.1 mg/mL for 48 h. Compared with the control, the difference was significant (P < 0.05). Allicin could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P < 0.05). Allicin could inhibit telomerase activity in a time-dependent and dose-dependent pattern. After exposure to allicin at 0.016 mg/mL for 24 hours, SGC-7901 cells showed typical morphologic change. CONCLUSION: Allicin can inhibit telomerase activity and induce apoptosis of gastric cancer SGC-7901 cells. Allicin may be more effective than AZT. PMID:12970878

  11. Regulation of Gastric Electrical and Mechanical Activity by Cholinesterases in Mice

    PubMed Central

    Worth, Amy A; Forrest, Abigail S; Peri, Lauren E; Ward, Sean M; Hennig, Grant W; Sanders, Kenton M

    2015-01-01

    Background/Aims Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. Methods Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. Results Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 ?M) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (> 1 ?M) caused aberrant contractile frequency and propagation and ectopic pacemaking. Conclusions Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns. PMID:25843073

  12. Phorbol ester stimulates secretory activity while inhibiting receptor-activated aminopyrine uptake by gastric glands

    SciTech Connect

    Brown, M.R.; Chew, C.S.

    1986-03-05

    Both cyclic AMP-dependent and -independent secretagogues stimulate pepsinogen release, respiration and H/sup +/ secretory activity (AP uptake) in rabbit gastric glands. 12-O-tetradecanoylphorbol-13-acetate (T), a diacyglycerol analog, activates protein kinase C (PKC) and stimulates secretion in many systems. T stimulated respiration and pepsinogen release by glands and increased AP uptake by both glands and purified parietal cells. However, T reduced AP uptake by glands stimulated with carbachol (C) or histamine (H) with an apparent IC/sub 50/ of 1 nM. Preincubation with T for 30 min produced maximum inhibition which was not reversed by removal of T. T accelerated the decline of the transient C peak while the late steady state response to H was most inhibited. H-stimulated AP uptake was also inhibited by 50 ..mu..g/ml 1-oleoyl-2-acetyl-glycerol, a reported PKC activator, but not by the inactive phorbol, 4..cap alpha..-phorbol-12,13-didecanoate. In contrast, T potentiated AP uptake by glands stimulated with submaximal doses of dibutyryl cyclic AMP. These results suggest inhibition by T is a specific effect of PKC activators. The differing effects of T on secretion indicators may result from a dual action of T on receptor and post-receptor intracellular events.

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

    PubMed

    Yang, Yun; Bai, Zhi-Gang; Yin, Jie; Wu, Guo-Cong; Zhang, Zhong-Tao

    2014-07-01

    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

  14. Stimulation of gastric acid secretion by rabbit parietal cell A2B adenosine receptor activation.

    PubMed

    Arin, Rosa María; Vallejo, Ana Isabel; Rueda, Yuri; Fresnedo, Olatz; Ochoa, Begoña

    2015-12-15

    Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four G protein-coupled receptors. The renewed interest in the adenosine A2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A2 adenosine receptor subtype(s) on the cell surface. Recently, we confirmed A2BR expression in native, nontransformed parietal cells at rest by using flow cytometry and confocal microscopy. In this study, we show that A2BR is functional in primary rabbit gastric parietal cells, as indicated by the fact that agonist binding to A2BR increased adenylate cyclase activity and acid production. In addition, both acid production and radioligand binding of adenosine analogs to isolated cell membranes were potently blocked by selective A2BR antagonists, whereas ligands for A1, A2A, and A3 adenosine receptors failed to abolish activation. We conclude that rabbit gastric parietal cells possess functional A2BR proteins that are coupled to Gs and stimulate HCl production upon activation. Whether adenosine- and A2BR-mediated functional responses play a role in human gastric pathophysiology is yet to be elucidated. PMID:26468208

  15. Baicalein inhibits the invasion of gastric cancer cells by suppressing the activity of the p38 signaling pathway.

    PubMed

    Yan, Xi; Rui, Xiaojiang; Zhang, Kai

    2015-02-01

    Baicalein, one of the major flavonoids in Scutellaria baicalensis, has been used in anti-inflammatory and anticancer therapies for a long time. However, the antimetastatic effects and related mechanism(s) in gastric cancer remain unclear. In the present study, we tested the hypothesis that administration of baicalein may inhibit the proliferation, motility and invasion of human gastric cancer cell lines by regulating the p38 signaling pathway. In the present study, we found that baicalein could inhibit migration and invasion of gastric cancer cells. Additionally, after treating with baicalein for 24 h, the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in gastric cancer cells were reduced in a dose-dependent manner. Moreover, baicalein clearly reduced the phosphorylated levels of p38. Combined treatment with p38 activator partially blocked the antimetastatic effects of baicalein, while p38 inhibitor (SB203580) and baicalein resulted in a synergistic reduction in MMP-2 and -9 expression; the invasive ability of gastric cancer cells was also inhibited. In conclusion, baicalein inhibits gastric cancer cell invasion and metastasis by reducing cell motility and migration via suppression of the p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for gastric cancer. PMID:25502212

  16. Cetuximab-induced insulin-like growth factor receptor I activation mediates cetuximab resistance in gastric cancer cells.

    PubMed

    Li, Xin; Xu, Ling; Li, Heming; Zhao, Lei; Luo, Ying; Zhu, Zhitu; Liu, Yunpeng; Qu, Xiujuan

    2015-06-01

    Epidermal growth factor receptor (EGFR) and insulin?like growth factor receptor?I (IGF?IR) are frequently overexpressed in gastric cancer cells. However, these cells are resistant to the anti?EGFR monoclonal antibody cetuximab. The aim of the present study was to determine whether cetuximab resistance in gastric cancer cells resulted from activation of the IGF?IR signaling pathway by cetuximab. The results demonstrated that EGFR phosphorylation was markedly inhibited in gastric cancer cell lines (SGC7901 and MGC803) which possessed functional K?ras and BRAF following treatment with cetuximab. However, cetuximab treatment did not diminish cell viability; by contrast, IGF?IR activation was observed. Knockdown of IGF?IR or the use of an IGF?IR inhibitor were found to increase the sensitivity of gastric cancer cells to cetuximab. Furthermore, cetuximab induced phosphorylation of the non?receptor tyrosine kinase c?steroid receptor co?activator (Src). Treatment of gastric cancer cells with a Src inhibitor was shown to significantly reduce cetuximab?induced phosphorylation of IGF?IR as well as Src, which resulted in enhanced sensitivity to cetuximab treatment. In conclusion, the results of the present study demonstrated that cetuximab?induced IGF?IR activation was involved in cetuximab resistance in gastric cancer cells and that Src was an important mediator for IGF?IR activation. PMID:25625229

  17. The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation.

    PubMed

    Kikuchi, Yoshinao; Kunita, Akiko; Iwata, Caname; Komura, Daisuke; Nishiyama, Takashi; Shimazu, Kazuhiro; Takeshita, Kimiko; Shibahara, Junji; Kii, Isao; Morishita, Yasuyuki; Yashiro, Masakazu; Hirakawa, Kosei; Miyazono, Kohei; Kudo, Akira; Fukayama, Masashi; Kashima, Takeshi G

    2014-03-01

    Overexpression of periostin (POSTN), an extracellular matrix protein, has been observed in several cancers. We investigated the importance of POSTN in gastric cancer. Genome-wide gene expression analysis using publicly available microarray data sets revealed significantly high POSTN expression in cancer tissues from stage II-IV gastric cancer, compared with background normal tissues. The POSTN/vimentin mRNA expression ratio was highly associated with gene groups that regulate the cell cycle and cell proliferation. IHC showed that periglandular POSTN deposition, comprising linear deposition abutting the glandular epithelial cells in normal mucosa, disappeared during intestinal gastric cancer progression. Stromal POSTN deposition was also detected at the invasive front of intestinal-type and diffuse-type cancers. In situ hybridization confirmed POSTN mRNA in cancer-associated fibroblasts, but not in tumor cells themselves. POSTN enhanced the in vitro growth of OCUM-2MLN and OCUM-12 diffuse-type gastric cancer cell lines, accompanied by the activation of ERK. Furthermore, coinoculation of gastric cancer cells with POSTN-expressing NIH3T3 mouse fibroblast cells facilitated tumor formation. The OCUM-2MLN orthotopic inoculation model demonstrated that tumors of the gastric wall in Postn(-/-) mice were significantly smaller than those in wild-type mice. Ki-67 and p-ERK positive rates were both lower in Postn(-/-) mice. These findings suggest that POSTN produced by cancer-associated fibroblasts constitutes a growth-supportive microenvironment for gastric cancer. PMID:24418260

  18. Allicin induces apoptosis in gastric cancer cells through activation of both extrinsic and intrinsic pathways.

    PubMed

    Zhang, Wenlu; Ha, Minwen; Gong, Yuehua; Xu, Ying; Dong, Nannan; Yuan, Yuan

    2010-12-01

    Allicin is an active compound derived from garlic that has been shown to have antitumor properties in vitro. The current study was designed to explore the effects and the underlying mechanism of allicin on gastric cancer cells. The MTT assay was used to detect cell viability. Transmission electron microscopy, Rh123 and propidium iodide staining, annexin V/FITC assay and the mitochondrial membrane potential were used to assess for the presence of apoptosis. Immunocytochemistry, western blot analysis, and Q-RT-PCR were used to detect gene expression. We found that allicin reduced cell viability in a dose- and time-dependent manner, partly through induction of apoptosis in gastric cancer cells. At the molecular level, allicin induced cytochrome c release from the mitochondria and increased caspase-3, -8, and -9 activation, with concomitant upregulation of bax and fas expression in the tumor cells. Allicin treatment inhibited proliferation and induced apoptosis in SGC-7901 cancer cells. Both intrinsic mitochondrial and extrinsic Fas/FasL-mediated pathways of apoptosis occur simultaneously in SGC-7901 cells following allicin treatment. Data from the current study demonstrated that allicin should be further investigated as a novel cancer preventive or therapeutic agent in control of gastric cancer, with potential uses in other tumor types. PMID:21042755

  19. Activation of JNK by TPA promotes apoptosis via PKC pathway in gastric cancer cells

    PubMed Central

    Chen, Yan; Wu, Qiao; Song, Si-Yang; Su, Wen-Jin

    2002-01-01

    AIM: JNK cascade plays an important role in cell proliferation, differentiation and apoptosis. However, the exact function of JNK cascade for apoptosis induction remains largely unknown. In this study, the role of JNK activation stimulated by TPA in the process of apoptosis induction and its signaling transduction pathway in gastric cancer cells were investigated and determined. METHODS: Expressions of mRNA and protein were detected by Northern blot and Western blot. Transcription activity was measured by transient transfection and CAT assay. Apoptotic cells were displayed through staining the nucleus with DAPI and were observed under fluorescence microscope. The apoptotic index was determined by counting 1000 cells randomly. RESULTS: JNK protein was stimulated rapidly by TPA, and reached its highest peak within 3 hr, then decreased in a time-dependent manner, but the expression level of JNK protein induced by TPA was always keeping higher than that in untreated cells. Similar pattern was seen in c-jun mRNA level induced by TPA. TPA significantly activated the transcriptional activity of activator protein-1 with a TPA-dose-dependent manner. Furthermore, activation of JNK was mediated through PKC pathway. Treatment of cells with PKC specific inhibitor, Wortmannin, led to repression of JNK even in the presence of TPA. More importantly, all these effects were associated with induction of apoptosis in gastric cancer cells. TPA inducted apoptosis obviously in gastric cancer cells. The apoptotic cells became smaller and rounded, and their nuclei became condensation and fragmentation with brightly stained chromatin. However, suppression of JNK by PKC specific inhibitor, Wortmannin, resulted in the decrease of apoptosis induced by TPA in a time-dependent manner, apoptotic index dramatically decreased from 32.56% to 8.71%. CONCLUSION: TPA stimulates JNK cascade, including up-regulation of JNK protein expression level and c-jun mRNA expression level, and activation of activator protein-1 transcriptional activity. Activation of JNK is mediated through PKC pathway, which has an association with induction of apoptosis by TPA. Thus, activation of JNK via PKC pathway may represent one of important mechanisms for TPA to induce apoptosis in gastric cancer cells. PMID:12439916

  20. Antioxidative Activity of Flavonoids from Abrus cantoniensis against Ethanol-Induced Gastric Ulcer in Mice.

    PubMed

    Li, Hui; Song, Zi-Jing; Dai, Yan-Ping; Zhang, Su-Li; He, Xin; Guo, Chang-Run; Zhang, Wen-Jun; Wang, Jiao-Ying; Zhang, Chun-Feng; Wang, Chong-Zhi; Yuan, Chun-Su

    2015-07-01

    The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83?µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67?mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (p<0.001). Significant differences were found in the levels of superoxide dismutase, catalase, glutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment. PMID:26039267

  1. Intrathoracic gastric activity of Tc-99m sestamibi in a patient with gastric pull-up for esophageal cancer.

    PubMed

    Alabed, Yazan; Probst, Stephan; Rakheja, Rajan; Crelinsten, Gordon; Hickeson, Marc

    2009-09-01

    A 69-year-old man with remote gastric pull-up was evaluated with a 2-day stress-rest dypiridamole Tc-99m sestamibi myocardial perfusion imaging, where significant tracer uptake was noted in the posterior mediastinum related to enterogastric reflux of sestamibi. These ancillary findings were suggestive of a noncardiac etiology of the patient's atypical chest pain. This case highlights the value of examining the raw projection images for incidental findings that may be present during myocardial perfusion imaging. PMID:19692833

  2. Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis

    PubMed Central

    Suh, Yun-Suhk; Yu, Jieun; Kim, Byung Chul; Choi, Boram; Han, Tae-Su; Ahn, Hye Seong; Kong, Seong-Ho; Lee, Hyuk-Joon; Kim, Woo Ho; Yang, Han-Kwang

    2015-01-01

    Purpose The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis. Materials and Methods Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ? 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients. Results CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393). Conclusion DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC. PMID:25687870

  3. 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

  4. MicroRNA-19a mediates gastric carcinoma cell proliferation through the activation of nuclear factor-?B

    PubMed Central

    YANG, FAN; WANG, HONGJIAN; JIANG, ZHENYU; HU, ANXIANG; CHU, LISHA; SUN, YILING; HAN, JUNQING

    2015-01-01

    In gastric carcinoma, the nuclear factor-?B (NF-?B) signaling pathway is highly active, and the constitutive activation of NF-?B prompts malignant cell proliferation. MicroRNAs are considered to be important mediators in the regulation of the NF-?B signaling pathway. The present study predominantly focussed on the effects of microRNA (miR)-19a on NF-?B activation. Reverse transcription-quantitative polymerase chain reaction was used to quantify the relative levels of miR-19a in gastric carcinoma cells. MTT assays were used to determine the effect of miR-19a on cellular proliferation. To detect the activation of NF-?B, western blotting was performed to measure the protein levels of NF-?B and the products of its downstream target genes. To define the target genes, luciferase reporter assays were used. miR-19a was found to be markedly upregulated in gastric carcinoma cells. The overexpression of miR-19a resulted in proliferation and enhanced migratory capabilities of the MGC-803 gastric carcinoma cell line. The results of the western blot analysis demonstrated that the protein levels of p65 increased when the MGC-803 cells were transfected with miR-19a mimics. In addition, the downstream target genes of miR-19a, including intercellular adhesion molecule, vascular cell adhesion molecule and monocyte chemoattractant protein-1, were upregulated. The results of the luciferase assay indicated that I?B-? was the target gene of miR-19a. Therefore, the results of the present study suggested that miR-19a enhances malignant gastric cell proliferation by constitutively activating the NF-?B signaling pathway. PMID:26239140

  5. 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

  6. Role of ghrelin-induced phosphatidylinositol 3-kinase activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori.

    PubMed

    Slomiany, B L; Slomiany, A

    2014-06-01

    A peptide hormone, ghrelin, is recognized as an important modulator of gastric mucosal inflammatory responses to Helicobacter pylori through the regulation of Src/Akt-dependent activation of constitutive nitric oxide synthase (cNOS) by phosphorylation. In this study, we report on the role of phosphatidylinositol 3-kinase (PI3K) in the processes of Src/Akt activation in gastric mucosal cells exposed to H. pylori LPS. We demonstrate that cNOS activation through phosphorylation induced by ghrelin is associated with PI3K activation which occurs upstream of cSrc, and that PI3K is required for cSrc activation of Akt. We show further that ghrelin-induced activation of PI3K, as well as that of Src and Akt, was susceptible to suppression by the inhibitors of phospholipase C (U73122) and protein kinase C (BIM). Both these inhibitors also blocked the ghrelin-induced membrane translocation of PI3K and cSrc, whereas the inhibitor of PI3K (LY294002) blocked only the membrane translocation of cSrc. Collectively, our findings suggest that the modulatory influence of ghrelin in countering gastric mucosal responses to H. pylori LPS relies on PI3K activation that depends on PLC/PKC signaling pathway, and that PI3K activity is required for the induction of cSrc/Akt activation. PMID:24057979

  7. The antisecretory factors: inducible proteins which modulate secretion in the small intestine.

    PubMed

    Lönnroth, I; Lange, S; Skadhauge, E

    1988-01-01

    1. Cholera toxin and glucose induce the synthesis of antisecretory factors (ASF) of isoelectric points 5.0 and 4.3, respectively, and of a molecular mass of ca 60,000. 2. ASF, in nanogram amounts, inhibit intestinal secretion induced by cholera toxin, Campylobacter toxin, E. coli heat-stable toxin, C. difficile toxin A, and Dinophysis toxin. 3. Intraspinal injection of cholera toxin and glucose induces the synthesis of pituitary ASF much more effectively than does either peroral or intranasal administration. 4. Cholera toxin and glucose seem to act synergistically while inducing ASF. 5. Vagotomy abolishes both the intestinal effects of ASF and the peroral, but not the intraspinal induction of pituitary ASF. 6. ASF has no effect on ion transport across isolated intestinal mucosa from either pig or hen. 7. The results suggest that both the induction and the intestinal effects of ASF are mediated via the central and intestinal nervous system. PMID:2902968

  8. 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...

  9. 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

  10. Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration

    SciTech Connect

    Osawa, Hiroyuki; Ohnishi, Hirohide . E-mail: hohnishi@jichi.ac.jp; Takano, Koji; Noguti, Takasi; Mashima, Hirosato; Hoshino, Hiroko; Kita, Hiroto; Sato, Kiichi; Matsui, Hirofumi; Sugano, Kentaro

    2006-06-02

    Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca{sup 2+}]{sub i}). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca{sup 2+}]{sub i}, activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system.

  11. Vasoactive intestinal peptide represses activation of tumor-associated macrophages in gastric cancer via regulation of TNF?, IL-6, IL-12 and iNOS.

    PubMed

    Chen, Lu; Yuan, Weijie; Chen, Zhikang; Wu, Shaobin; Ge, Jie; Chen, Jinxiang; Chen, Zihua

    2015-10-01

    Vasoactive intestinal peptide (VIP) has been regarded as deactivator for macrophages. However, the depressive effect of VIP on tumor-associated macrophages (TAM) has not been recognized. In the present study, we investigated the effect of VIP on gastric cancer via TAM by suppressing expression levels of TNF?, IL-6, IL-12 and iNOS. Real-time PCR was carried out to examine the expression of CD68 to determine the levels of TAM. The effect of VIP on cell activities was assayed by proliferation assay, colony formation and flow cytometry analysis. The co-culture of TAM and human gastric cancer cell line MKN-45 were performed to understand whether the VIP affects the gastric cancer cells via TAM. Further, the tumor formation in a nude mouse model and VIP injection were performed to illustrate the effect on tumor progression in vivo. CD68 was high expressed in gastric cancer indicating high level of TAM in gastric cancer. Treatment with VIP significantly depressed TAM activation. Moreover, the expression of TNF?, IL-6, IL-12 and iNOS in TAM were depressed by VIP treatment, and the VIP treated TAM depressed gastric cancer cells. The experiment in the nude mouse model also suggested that by injection with TAM+VIP, the tumor volume and tumor weight were both decreased significantly. These data suggest that treatment with VIP inhibits gastric cancer. PMID:26314485

  12. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers.

    PubMed

    Katsha, Ahmed; Arras, Janet; Soutto, Mohammed; Belkhiri, Abbes; El-Rifai, Wael

    2014-12-01

    Aurora kinase A is a frequently amplified and overexpressed gene in upper gastrointestinal adenocarcinomas (UGCs). Using in vitro cell models of UGCs, we investigated whether AURKA can regulate Signal Transducer and Activator of Transcription 3 (STAT3). Our data indicate that overexpression of AURKA in FLO-1 and AGS cells increase STAT3 phosphorylation at the Tyr705 site, whereas AURKA genetic depletion by siRNA results in decreased phosphorylation levels of STAT3 in FLO-1 and MKN45 cells. Immunofluorescence analysis showed that AURKA overexpression enhanced STAT3 nuclear translocation while AURKA genetic knockdown reduced the nuclear translocation of STAT3 in AGS and FLO-1 cells, respectively. Using a luciferase reporter assay, we demonstrated that AURKA expression induces transcriptional activity of STAT3. Pharmacological inhibition of AURKA by MLN8237 reduced STAT3 phosphorylation along with down-regulation of STAT3 pro-survival targets, BCL2 and MCL1. Moreover, by using clonogenic cells survival assay, we showed that MLN8237 single dose treatment reduced the ability of FLO-1 and AGS cells to form colonies. Additional experiments utilizing cell models of overexpression and knockdown of AURKA indicated that STAT3 upstream non-receptor tyrosine kinase Janus kinase 2 (JAK2) is mediating the effect of AURKA on STAT3. The inhibition of JAK2 using JAK2-specific inhibitor AZD1480 or siRNA knockdown, in presence of AURKA overexpression, abrogated the AURKA-mediated STAT3 activation. These results confirm that the AURKA-JAK2 axis is the main mechanism by which AURKA regulates STAT3 activity. In conclusion, we report, for the first time, that AURKA promotes STAT3 activity through regulating the expression and phosphorylation levels of JAK2. This highlights the importance of targeting AURKA as a therapeutic approach to treat gastric and esophageal cancers. PMID:24953013

  13. Lycopene Enhances Antioxidant Enzyme Activities and Immunity Function in N-Methyl-N?-nitro-N-nitrosoguanidine–Induced Gastric Cancer Rats

    PubMed Central

    Luo, Cong; Wu, Xian-Guo

    2011-01-01

    To investigate anticancer effect of lycopene, we examined the effects of lycopene on the oxidative injury and immunity activities of N-methyl-N?-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. The animals were divided into five groups. Group I served as the normal control and was given corn oil orally for 20 weeks. Group II were induced with MNNG 200 mg/kg body weight by oral gavage at days 0 and 14, and saturated NaCl (1 mL per rats) was given once every three days for four weeks until the end of the experimental period. Group III, IV and V were posttreated with lycopene (50, 100 and 150 mg/kg body weight, dissolved in corn oil) from the sixth week of MNNG (as in group II) induction up to the end of the experimental period. In the presence of MNNG, MDA and immunity levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) antioxidant activities were decreased in the treated rats compared with normal control rats. Administration of lycopene to gastric carcinoma-induced rats largely up-regulated the redox status and immunity activities to decrease the risk of cancer compared to group II. We conclude that up-regulation of antioxidants and immunity by lycopene treatment might be responsible for the anticancer effect in gastric carcinoma. PMID:21686188

  14. Role of ghrelin-induced cSrc activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori.

    PubMed

    Slomiany, B L; Slomiany, A

    2011-08-01

    A peptide hormone, ghrelin, is recognized as an important modulator of gastric mucosal inflammatory responses to H. pylori through the regulation of nitric oxide synthase (NOS) system. As cSrc kinase plays a major role in transduction of signals that regulate the activity of NOS isozyme system, we investigated the influence of H. pylori LPS on the processes associated with Src activation in gastric mucosal cells. The LPS-induced drop in constitutive (c) cNOS activity and up-regulation in inducible (i) iNOS was associated with the suppression in cSrc kinase activity that was reflected in a decrease in its phosphorylation at Tyr?¹?. Further, the countering effect of ghrelin on the LPS-induced changes in cSrc activity and the extent of its phosphorylation was accompanied by a marked reduction in the activity of iNOS and an increase in cNOS activation through phosphorylation at Ser¹¹??. Moreover, the effect of ghrelin on cSrc activation and its Tyr?¹? phosphorylation was associated with the kinase S-nitrosylation that was susceptible to the blockage by cNOS inhibition. Our findings suggest that up-regulation in iNOS with H. pylori infection leads to disturbances in cNOS phosphorylation that exerts the detrimental effect on the processes of cSrc activation through cNOS-mediated S-nitrosylation. We also show that ghrelin attenuation of H. pylori-induced gastric mucosal inflammatory responses involves the enhancement in cSrc activation, elicited by the kinase S-nitrosylation and the increase in its phosphorylation at Tyr?¹?. PMID:21516493

  15. Gastric cancer

    SciTech Connect

    Douglass, H.O. )

    1988-01-01

    This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer.

  16. CXCL1 promotes tumor growth through VEGF pathway activation and is associated with inferior survival in gastric cancer.

    PubMed

    Wei, Zhe-Wei; Xia, Guang-Kai; Wu, Ying; Chen, Wei; Xiang, Zhen; Schwarz, Roderich E; Brekken, Rolf A; Awasthi, Niranjan; He, Yu-Long; Zhang, Chang-Hua

    2015-04-10

    The chemokine (C-X-C motif) ligand 1 (CXCL1) regulates tumor-stromal interactions and tumor invasion. However, the precise role of CXCL1 on gastric tumor growth and patient survival remains unclear. In the current study, protein expressions of CXCL1, vascular endothelial growth factor (VEGF) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in primary tumor tissues from 98 gastric cancer patients were measured by immunohistochemistry (IHC). CXCL1 overexpressed cell lines were constructed using Lipofectamine 2000 reagent or lentiviral vectors. Effects of CXCL1 on VEGF expression and local tumor growth were evaluated in vitro and in vivo. CXCL1 was positively expressed in 41.4% of patients and correlated with VEGF and p-STAT3 expression. Higher CXCL1 expression was associated with advanced tumor stage and poorer prognosis. In vitro studies in AGS and SGC-7901 cells revealed that CXCL1 increased cell migration but had little effect on cell proliferation. CXCL1 activated VEGF signaling in gastric cancer (GC) cells, which was inhibited by STAT3 or chemokine (C-X-C motif) receptor 2 (CXCR2) blockade. CXCL1 also increased p-STAT3 expression in GC cells. In vivo, CXCL1 increased xenograft local tumor growth, phospho-Janus kinase 2 (p-JAK2), p-STAT3 levels, VEGF expression and microvessel density. These results suggested that CXCL1 increased local tumor growth through activation of VEGF signaling which may have mechanistic implications for the observed inferior GC survival. The CXCL1/CXCR2 pathway might be potent to improve anti-angiogenic therapy for gastric cancer. PMID:25641338

  17. 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

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

    PubMed

    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

  19. Testing biological activity of model Maillard reaction products: studies on gastric smooth muscle tissues.

    PubMed

    Argirova, Mariana D; Stefanova, Iliyana D; Krustev, Athanas D; Turiiski, Valentin I

    2010-03-01

    Water-soluble Maillard reaction products obtained from five different model systems were investigated for their effects upon the mechanical activity of rat gastric smooth muscle. Most of the total Maillard reaction products applied at concentration of 1.5 mg/ml evoked contractions; among them the product obtained from arginine and glucose (Arg-Glc) produced the most powerful contractions. The product obtained from glycine and ascorbic acid (Gly-AsA) was the only one that brought about relaxation response. The high molecular weight fractions (>3,500 Da) isolated from the reaction systems Arg-Glc and Gly-AsA demonstrated effects similar in type and amplitude to those evoked by non-fractioned reaction products. The results obtained suggest that moieties of molecules acting upon the muscle tonus originate mainly from lysine and arginine residues; that these structures are available in both low and high molecular pools in similar concentrations, and most likely these fragments act upon membrane-located cellular structures involved in calcium transport. PMID:19350367

  20. Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia

    PubMed Central

    Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-ichiro; Mizushima, Tohru

    2015-01-01

    Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the ?-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

  1. Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

    PubMed

    Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-Ichiro; Mizushima, Tohru

    2015-01-01

    Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the ?-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

  2. Wnt/?-Catenin Signaling Enhances Cyclooxygenase-2 (COX2) Transcriptional Activity in Gastric Cancer Cells

    PubMed Central

    Nuñez, Felipe; Bravo, Soraya; Cruzat, Fernando; Montecino, Martín; De Ferrari, Giancarlo V.

    2011-01-01

    Background Increased expression of the cyclooxygenase-2 enzyme (COX2) is one of the main characteristics of gastric cancer (GC), which is a leading cause of death in the world, particularly in Asia and South America. Although the Wnt/?-catenin signaling pathway has been involved in the transcriptional activation of the COX2 gene, the precise mechanism modulating this response is still unknown. Methodology/Principal Findings Here we studied the transcriptional regulation of the COX2 gene in GC cell lines and assessed whether this phenomenon is modulated by Wnt/?-catenin signaling. We first examined the expression of COX2 mRNA in GC cells and found that there is a differential expression pattern consistent with high levels of nuclear-localized ?-catenin. Pharmacological treatment with either lithium or valproic acid and molecular induction with purified canonical Wnt3a significantly enhanced COX2 mRNA expression in a dose- and time-dependent manner. Serial deletion of a 1.6 Kbp COX2 promoter fragment and gain- or loss-of-function experiments allowed us to identify a minimal Wnt/?-catenin responsive region consisting of 0.8 Kbp of the COX2 promoter (pCOX2-0.8), which showed maximal response in gene-reporter assays. The activity of this pCOX2-0.8 promoter region was further confirmed by site-directed mutagenesis and DNA-protein binding assays. Conclusions/Significance We conclude that the pCOX2-0.8 minimal promoter contains a novel functional T-cell factor/lymphoid enhancer factor (TCF/LEF)-response element (TBE Site II; -689/-684) that responds directly to enhanced Wnt/?-catenin signaling and which may be important for the onset/progression of GC. PMID:21494638

  3. Role of calcium-activated potassium currents in CNP-induced relaxation of gastric antral circular smooth muscle in guinea pigs

    PubMed Central

    Guo, Hui-Shu; Cai, Zheng-Xu; Zheng, Hai-Feng; Li, Xiang-Lan; Cui, Yi-Feng; Wang, Zuo-Yu; Xu, Wen-Xie; Lee, Sang-Jin; Kim, Young-Chul

    2003-01-01

    AIM: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs. METHODS: Spontaneous contraction of gastric smooth muscle was recorded by a four-channel physiograph. The whole cell patch-clamp technique was used to record calcium-activated potassium currents and membrane potential in the gastric myocytes isolated by collagenase. RESULTS: C-type natriuretic peptide (CNP) markedly inhibited the spontaneous contraction in a dose-dependent manner in gastric circular smooth muscle in guinea pigs. Ly83583, an inhibitor of guanylate cyclase, weakened CNP-induced inhibition on spontaneous contraction but Zaparinast, an inhibitor of cGMP sensitive phosphoesterase, potentiated CNP-induced inhibition in gastric circular smooth muscles. The inhibitory effects of CNP on spontaneous contraction were blocked by tetrathylammonium (TEA), a nonselective potassium channel blocker. C N P hyperpolarized membrane potential from -60.0 mV ± 2.0 mV to -68.3 mV ± 3.0 mV in a single gastric myocyte. CNP increased calcium-activated potassium currents (IK(ca)) in a dose-dependent manner in gastric circular myocytes. CNP also increased the spontaneously transient outward currents (STOCs). Ly83583 partly blocked CNP-induced increase of calcium-activated potassium currents, but Zaparinast potented the effect. CONCLUSION: CNP inhibits spontaneous contraction, and potassium channel may be involved in the process in gastric circular smooth muscle of guinea pigs. CNP-induced increase of IK(ca) is mediated by a cGMP dependent pathway. PMID:12970905

  4. Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2).

    PubMed

    Lin, Jinfeng; Sun, Zhaorui; Zhang, Wei; Liu, Hongmei; Shao, Danbing; Ren, Yi; Wen, Yanfang; Cao, Liping; Wolfram, Joy; Yang, Zhizhou; Nie, Shinan

    2015-06-01

    The rapid repair of gastric mucosa is critical upon exposure to injurious agents. Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain peptides, which play an important role in the cytoprotection of gastric epithelium. However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear. In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose- and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway. Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury. PMID:25776570

  5. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents.

    PubMed

    Olatunji, Opeyemi J; Chen, Hongxia; Zhou, Yifeng

    2015-01-01

    The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and interleukin-1? (IL-1?) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-?, IL-6, and IL-1? in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-?B in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers. PMID:26694339

  6. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-?-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  7. Antisecretory factor peptide AF-16 inhibits the secreted autotransporter toxin-stimulated transcellular and paracellular passages of fluid in cultured human enterocyte-like cells.

    PubMed

    Nicolas, Valérie; Liévin-Le Moal, Vanessa

    2015-03-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of D-[1-(14)C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-?-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  8. Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats.

    PubMed

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2014-02-01

    Antisecretory drugs such as histamine H?-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole. The effects of the drugs on intestinal motility and mucus distribution/content were also examined. Male Wistar rats (180-220 g) were used. Each drug was administered orally under fed conditions. Diclofenac (1-10 mg/kg) produced multiple lesions in the small intestine dose-dependently. Both ranitidine (30 mg/kg) and omeprazole (100 mg/kg) significantly increased the intestinal lesions induced by low doses (3 and 6 mg/kg) of diclofenac. Misoprostol (0.03-0.3 mg/kg), irsogladine (3-30 mg/kg), and rebamipide (30-300 mg/kg), as well as mucin (30-300 mg/kg) inhibited the formation of intestinal lesions caused by a high dose (10 mg/kg) of diclofenac alone and prevented the exacerbation of diclofenac-induced lesions by antisecretory drugs. Diclofenac (10 mg/kg) markedly increased the intestinal motility and decreased the mucosal mucus, and the decrease of mucus was significantly inhibited by the MPAs. These results indicate the usefulness of the MPAs for the treatment of intestinal lesions induced by NSAIDs alone or by coadministration with antisecretory drugs, and suggest that mucus plays an important role in the protection of intestinal mucosa by the MPAs. PMID:24254524

  9. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    SciTech Connect

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF{beta} enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells. Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGF{beta} might be an important pathway of gastric cancer cell proliferation by TGF{beta}.

  10. PGE2 secretion from organ cultured gastric mucosa: correlation with cyclooxygenase activity and endogenous substrate release.

    PubMed

    Preclik, G; Strange, E F; Ditschuneit, H

    1992-06-01

    In gastrointestinal research the in vitro release of prostaglandins from incubated or cultured biopsies is a widely used method to estimate prostaglandin synthesis. We therefore investigated the rate limiting mechanisms of PGE2 release in organ cultured gastric mucosa of the rabbit, determining PGE2 secretion from organ cultured mucosal biopsies by radioimmunoassay and prostaglandin synthesizing capacity by in vitro incubation of mucosal homogenate or microsomes with [14C]-arachidonic acid. Freshly taken biopsies secreted PGE2 at an initial high rate, that decreased during the following 4 hrs of culture. This PGE2 release was dose dependently reduced by inhibitors of the prostaglandin cyclooxygenase. 5mM acetylsalicylic acid (ASA) maximally suppressed PGE2 secretion to 7% of controls, and the inhibition by ASA was quantitatively similar at every given culture period. PGE2 release was markedly increased by carbenoxolone but was only slightly activated by extracellular calcium and the Ca(++)-ionophore A23187. However, Ca++/A23187 were unable to maintain PGE2 secretion at the initial rate. PGE2 secretion was undisturbed in calcium-free medium but was reduced to 50-60% of controls by excess EDTA. The intracellular calcium chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N',-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) similarly inhibited PGE2 release to 72% of controls. In contrast, PGE2 release was unaffected by the intracellular calcium antagonist 3,4,5-trimethylene-bis(4-formylpyridinium bromide) dioxime (TMB-8), the calmodulin antagonists N-(6-aminohexyl)-1-5-chloro-1-naphthalenesulfonamide (W-7) and calmidazolium (compound R24571) or various direct inhibitors of endogenous arachidonic acid release like tetracaine, bromophenacyl bromide, neomycin or low dose quinacrine, indicating that the reduction of PGE2 release by EDTA or BAPTA may be mediated by mechanisms different from substrate release. In contrast, an inhibition of PGE2 secretion by quinacrine at high concentrations (greater than or equal to 0.8 mM) was attributed to a direct inhibition of the prostaglandin cyclooxygenase, similar to ASA. Finally, the reduction of the prostaglandin synthesizing capacity by ASA was strongly correlated with the inhibition of PGE2 secretion, also at low concentrations and minor degrees of inhibition. From these data we conclude, that the activity of the prostaglandin cyclooxygenase is rate limiting for PGE2 secretion from organ cultured mucosal biopsies rather than arachidonic acid release by a phospholipase A2. This should be considered for interpretation of studies based on prostaglandin release from cultured mucosa. PMID:1410519

  11. Gastric Adenocarcinoma

    PubMed Central

    Dicken, Bryan J.; Bigam, David L.; Cass, Carol; Mackey, John R.; Joy, Anil A.; Hamilton, Stewart M.

    2005-01-01

    Objective: This update reviews the epidemiology and surgical management, and the controversies of gastric adenocarcinoma. We provide the relevance of outcome data to surgical decision-making and discuss the application of gene-expression analysis to clinical practice. Summary Background Data: Gastric cancer mortality rates have remained relatively unchanged over the past 30 years, and gastric cancer continues to be one of the leading causes of cancer-related death. Well-conducted studies have stimulated changes to surgical decision-making and technique. Microarray studies linked to predictive outcome models are poised to advance our understanding of the biologic behavior of gastric cancer and improve surgical management and outcome. Methods: We performed a review of the English gastric adenocarcinoma medical literature (1980–2003). This review included epidemiology, pathology and staging, surgical management, issues and controversies in management, prognostic variables, and the application of outcome models to gastric cancer. The results of DNA microarray analysis in various cancers and its predictive abilities in gastric cancer are considered. Results: Prognostic studies have provided valuable data to better the understanding of gastric cancer. These studies have contributed to improved surgical technique, more accurate pathologic characterization, and the identification of clinically useful prognostic markers. The application of microarray analysis linked to predictive models will provide a molecular understanding of the biology driving gastric cancer. Conclusions: Predictive models generate important information allowing a logical evolution in the surgical and pathologic understanding and therapy for gastric cancer. However, a greater understanding of the molecular changes associated with gastric cancer is needed to guide surgical and medical therapy. PMID:15621988

  12. Inhibition of gastric H+,K+-ATPase activity by flavonoids, coumarins and xanthones isolated from Mexican medicinal plants.

    PubMed

    Reyes-Chilpa, Ricardo; Baggio, Cristiane Hatsuko; Alavez-Solano, Dagoberto; Estrada-Muñiz, Elizabeth; Kauffman, Frederick C; Sanchez, Rosa I; Mesia-Vela, Sonia

    2006-04-21

    Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency. The xanthones inhibited the H+,K+-ATPase with IC50 values ranging from 47 microM to 1.6 mM. Coumarins inhibited H+,K+-ATPase with IC50 values of 110 and 638 microM. IC50 values for the flavonoids ranged from 9.6 to 510 microM among which minimiflorin was the most potent. The results suggest that H+,K+-ATPase is sensitive to inhibition by several types of structurally different natural compounds. The potency of the effects on gastric H+,K+-ATPase depends on the presence, position and number of hydroxyls groups in the molecule. Collectively, these results suggest a potential for important pharmacological and toxicological interactions by these types of natural products at the level of H+,K+-ATPase which may explain, at least in part, the gastroprotective properties, indicated by traditional medicine, of the plants from which these compounds were isolated. PMID:16314059

  13. Role of nitrosation in the mutagenic activity of coal dust: a postulation for gastric carcinogenesis in coal miners

    SciTech Connect

    Whong, W.Z.; Long, R.; Ames, R.G.; Ong, T.M.

    1983-12-01

    The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system. Coal dust solvent extracts were either nonmutagenic or very weakly mutagenic with S9 activation. High mutagenic activities, however, were found when extracts of bituminous, subbituminous, and lignite coal dusts were reacted with nitrite under an acidic condition. Formation of mutagens from coal dust extracts by nitrosation was highest at pH 3.2 and decreased with increasing pH in the reation mixture. Mutagenic activity appeared to be independent of metabolic activation. The mutagens formed from nitrosation of coal dust extracts induced frameshift mutations. The results reported here may have possible implications for the explanation of an elevated incidence of gastric cancer in coal miners.

  14. Gastric Microbiota.

    PubMed

    Ianiro, Gianluca; Molina-Infante, Javier; Gasbarrini, Antonio

    2015-09-01

    After the discovery of Helicobacter pylori in 1983, the stomach was no longer considered a sterile environment. In 2015, evolving data shows that H. pylori is not the only inhabitant of the gastric mucosa. Using culture-independent methods of analysis, a non-H. pylori microbial community has been recently observed in the human stomach, the so-called human gastric microbiota, along with H. pylori itself. Increasing evidence supports the hypothesis that although H. pylori may be the most relevant, it is not the only local bacterial culprit leading to gastric diseases. Further studies are warranted to offer a better picture of the role and functions of gastric microbiota and to identify the best therapeutic modulators of gut microbiota for the management of gastric diseases. PMID:26372828

  15. 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

  16. A comparative study of anti-gastric cancer activity between aqueous extract and ethanol extract of Folium Cordylines Fruticosae.

    PubMed

    Liu, Shaojun; Cao, Dongbo; Xiao, Zhiming; Liu, Fen; Wang, Xiaoyan; Zhao, Lian; Tian, Li; Shen, Shourong

    2013-01-01

    The active components in Folium Cordylines Fruticosae were extracted by heat reflux method. The solvents used were distilled water and ethanol. The effects of two types of extracts on gastric cancer cells were compared; dry extract yields were calculated, as well as the inhibition rates of gastric cancer MGC-803 cell proliferation and the colony cell counts. The micro-Kjeldahl method was used to measure the cell protein contents and to make a comprehensive comparison. The results showed that the MGC-803 cell inhibition rates of three different concentrations (32.5, 75 and 150 mg/ml) of ethanol extracts increased with the increase of concentration, which was 48.9% at a concentration of 150 mg/ml; aqueous extract of Folium Cordylines Fruticosae had very low inhibitory activity at a low concentration (32.5 mg/ml), which was remained at about 20%. After being affected by two types of extracts, cells had uneven sizes, with very low brightness, while the normal cells presented a uniform full form, with high definition. PMID:24146505

  17. [Proliferative activity in gastric cancer with Ki-67 and propidium iodide: analysis by flow cytometry].

    PubMed

    Kimura, H; Yonemura, Y; Ohyama, S; Kamata, T; Yamaguchi, A; Miwa, K; Miyazaki, I

    1992-04-01

    Growth fractions in the cell cycle were demonstrated by flow cytometry with monoclonal antibody Ki-67 for gastric cancer. By setting the cut off line at the lowest channel number of S-phase, the Ki-67 labeling rate was calculated by Ki-DNA dual fluorescence analysis. In addition to 32 gastric cancers, we examined three cell lines (Colo 320, NUGC4 and MKN28) and compared the result with the BrdUrd labeling rate. The G0G1 ratio obtained with BrdUrd was generally correlated with the G0 + G1 ratio obtained with Ki-67. The S-phase fractions obtained with Ki-67, however were a little different from those obtained with BrdUrd because of the existence of S0. The mean Ki-67 labeling rate of gastric cancer was 45.1% (16.2-66.3%). Fifteen cases received Ki-67 immunohistochemical study in the same samples. The results of flow cytometric analysis were parallel to those of microscopic study, and a correlation line: y = 0.626x + 15.9145, r = 0.8031, (p less than 0.001) was obtained. Ki-67 antibodies may provide useful information on cell kinetics. PMID:1603045

  18. 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.

  19. Glutamine Deprivation Causes Hydrogen Peroxide-induced Interleukin-8 Expression via Jak1/Stat3 Activation in Gastric Epithelial AGS Cells

    PubMed Central

    Lee, Yun Mi; Kim, Mi Jung; Kim, Youngha; Kim, Hyeyoung

    2015-01-01

    Background: The Janus kinase (Jak)/Signal transducers of activated transcription (Stat) pathway is an upstream signaling pathway for NF-?B activation in Helicobacter pylori-induced interleukin (IL)-8 production in gastric epithelial AGS cells. H. pylori activates NADPH oxidase and produces hydrogen peroxide, which activates Jak1/Stat3 in AGS cells. Therefore, hydrogen peroxide may be critical for IL-8 production via Jak/Stat activation in gastric epithelial cells. Glutamine is depleted during severe injury and stress and contributes to the formation of glutathione (GSH), which is involved in conversion of hydrogen peroxide into water as a cofactor for GSH peroxidase. Methods: We investigated whether glutamine deprivation induces hydrogen peroxide-mediated IL-8 production and whether hydrogen peroxide activates Jak1/Stat3 to induce IL-8 in AGS cells. Cells were cultured in the presence or absence of glutamine or hydrogen peroxide, with or without GSH or a the Jak/Stat specific inhibitor AG490. Results: Glutamine deprivation decreased GSH levels, but increased levels of hydrogen peroxide and IL-8, an effect that was inhibited by treatment with GSH. Hydrogen peroxide induced the activation of Jak1/Stat3 time-dependently. AG490 suppressed hydrogen peroxide- induced activation of Jak1/Stat3 and IL-8 expression in AGS cells, but did not affect levels of reactive oxygen species in AGS cells. Conclusions: In gastric epithelial AGS cells, glutamine deprivation increases hydrogen peroxide levels and IL-8 expression, which may be mediated by Jak1/Stat3 activation. Glutamine supplementation may be beneficial for preventing gastric inflammation by suppressing hydrogen peroxide-mediated Jak1/Stat3 activation and therefore, reducing IL-8 production. Scavenging hydrogen peroxide or targeting Jak1/Stat3 may also prevent oxidant-mediated gastric inflammation. PMID:26473156

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

    SciTech Connect

    Ma, Gui-Fen; Chen, Shi-Yao; Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai ; Sun, Zhi-Rong; Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng; Ma, Li-Li; Lian, Jing-Jing; Song, Dong-Li

    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.

  1. Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis

    PubMed Central

    Nagase, Lisa; Hayashi, Takeru; Senda, Toshiya; Hatakeyama, Masanori

    2015-01-01

    Infection with cagA-positive Helicobacter pylori is critically associated with the development of gastric cancer. The cagA-encoded CagA is delivered into gastric epithelial cells via type IV secretion, where it interacts with and thereby deregulates the pro-oncogenic phosphatase SHP2. East Asian CagA and Western CagA are two major CagA species produced by H. pylori circulating in East Asian countries and in the rest of the world, respectively. The SHP2 binding site of Western CagA, termed the EPIYA-C segment, variably duplicates and infection with H. pylori carrying Western CagA with multiple EPIYA-C segments is a distinct risk factor of gastric cancer. Here we show that duplication of EPIYA-C from one to two or more increases SHP2 binding of Western CagA by more than one hundredfold. Based on the decisive difference in SHP2 binding, Western CagA can be divided into two types: type I CagA carrying a single EPIYA-C segment and type II CagA carrying multiple EPIYA-C segments. Gastric epithelial cells expressing type II CagA acquire the ability to invade extracellular matrices, a malignant cellular trait associated with deregulated SHP2. A big leap in SHP2 binding activity may therefore provide molecular basis that makes type II Western CagA a distinct gastric cancer risk. PMID:26507409

  2. Gastric culture

    MedlinePLUS

    Gastric culture is a test to check a child's stomach contents for the bacteria that cause tuberculosis (TB). ... is placed in a special dish called a culture medium and watched for the growth of bacteria.

  3. Jak1/Stat3 Is an Upstream Signaling of NF-?B Activation in Helicobacter pylori-Induced IL-8 Production in Gastric Epithelial AGS Cells

    PubMed Central

    Cha, Boram; Lim, Joo Weon

    2015-01-01

    Helicobacter pylori (H. pylori) induces the activation of nuclear factor-kB (NF-?B) and cytokine expression in gastric epithelial cells. The Janus kinase/signal transducers and activators of transcription (Jak/Stat) cascade is the inflammatory signaling in various cells. The purpose of the present study is to determine whether H. pylori-induced activation of NF-?B and the expression of interleukin-8 (IL-8) are mediated by the activation of Jak1/Stat3 in gastric epithelial (AGS) cells. Thus, gastric epithelial AGS cells were infected with H. pylori in Korean isolates (HP99) at bacterium/cell ratio of 300:1, and the level of IL-8 in the medium was determined by enzyme-linked immonosorbent assay. Phospho-specific and total forms of Jak1/Stat3 and I?B? were assessed by Western blot analysis, and NF-?B activation was determined by electrophoretic mobility shift assay. The results showed that H. pylori induced the activation of Jak1/Stat3 and IL-8 production, which was inhibited by a Jak/Stat3 specific inhibitor AG490 in AGS cells in a dose-dependent manner. H. pylori-induced activation of NF-?B, determined by phosphorylation of I?B? and NF-?B-DNA binding activity, were inhibited by AG490. In conclusion, Jak1/Stat3 activation may mediate the activation of NF-?B and the expression of IL-8 in H. pylori-infected AGS cells. Inhibition of Jak1/Stat3 may be beneficial for the treatment of H. pylori-induced gastric inflammation, since the activation of NF-?B is inhibited and inflammatory cytokine expression is suppressed. PMID:25837197

  4. Anti-tumor Activity of Ferulago angulata Boiss. Extract in Gastric Cancer Cell Line via Induction of Apoptosis

    PubMed Central

    Heidari, Shafagh; Akrami, Hassan; Gharaei, Roghaye; Jalili, Ali; Mahdiuni, Hamid; Golezar, Elham

    2014-01-01

    Ferulago angulata Boiss. known in Iran as Chavir, has some bioactive compounds having antioxidant activity. Because of its antioxidant activities, it sounded Chavir extract can be a good candidate for finding chemopreventive agents having inductive apoptosis properties on cancer cells. In this study, the cytotoxic effects and proapoptotic activities of Chavir’s leaf and flower extracts were investigated on human adenocarcinoma gastric cell line (AGS). The ferric reducing antioxidant power (FRAP) assay was used to determine antioxidant activity of the extract. Cytotoxic effects of the extract were performed by trypan blue and neutral red assays. For apoptosis detection, we used Annexin V staining, flow cytometry and DNA fragmentation assays. The FRAP assay results showed that antioxidant activity of leaf extract was higher than flower extract. Cytotoxicity and apoptosis–inducing activity of flower and leaf extracts changed coordinately, indicating the cytotoxicity of chavir extracts is due probably to induce apoptosis. Our results revealed that the cytotoxic effects of F. angulate Boiss. extracts on AGS cell line is close to some other plant extracts such as Rhus verniciflua Stokes (RVS) and Scutellaria litwinowii. This is the first study on cytotoxic and apoptosis–inducing effects of chavir leaf and flower extracts against AGS cell line. The Further investigation can be identification of the agent(s) by which these effects is observed. PMID:25587323

  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 Central

    Bimczok, Diane; Kao, John Y.; Zhang, Min; Cochrun, Steven; Mannon, Peter; Peter, Shajan; Wilcox, Charles M.; Mönkemüller, Klaus E.; Harris, Paul R.; Grams, Jayleen M.; Stahl, Richard D.; Smith, Phillip D.; Smythies, Lesley E.

    2014-01-01

    Despite the high prevalence of chronic gastritis caused by H. 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, 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 retinol 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 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. Influence of habitual physical activity on gastric emptying in healthy males and relationships with body composition and energy expenditure.

    PubMed

    Horner, Katy M; Byrne, Nuala M; Cleghorn, Geoffrey J; King, Neil A

    2015-08-14

    Although a number of studies have examined the role of gastric emptying (GE) in obesity, the influences of habitual physical activity level, body composition and energy expenditure (EE) on GE have received very little consideration. In the present study, we compared GE in active and inactive males, and characterised relationships with body composition (fat mass and fat-free mass) and EE. A total of forty-four males (active n 22, inactive n 22; BMI 21-36 kg/m2; percentage of fat mass 9-42%) were studied, with GE of a standardised (1676 kJ) pancake meal being assessed by the [13C]octanoic acid breath test, body composition by air displacement plethysmography, RMR by indirect calorimetry, and activity EE (AEE) by accelerometry. The results showed that GE was faster in active compared with inactive males (mean half-time (t 1/2): active 157 (sd 18) and inactive 179 (sd 21) min, P< 0.001). When data from both groups were pooled, GE t 1/2 was associated with percentage of fat mass (r 0.39, P< 0.01) and AEE (r - 0.46, P< 0.01). After controlling for habitual physical activity status, the association between AEE and GE remained, but not that for percentage of fat mass and GE. BMI and RMR were not associated with GE. In summary, faster GE is considered to be a marker of a habitually active lifestyle in males, and is associated with a higher AEE level and a lower percentage of fat mass. The possibility that GE contributes to a gross physiological regulation (or dysregulation) of food intake with physical activity level deserves further investigation. PMID:26168984

  8. [Gastric emptying].

    PubMed

    Güller, R

    1977-03-01

    Gastric emptying can be measured by three basically different means: Intubation -x-ray - Isotopes, X-ray methods may be neglected as they do not permit quantitative measurement of the exptying process. Intubation methods offer the advantage of exact determinations of emptying rates, but disadvantages are the limitation to liquid meals and patient discomfort. Radioisotopes can be used as marker both of liquid and solid foodstuffs with minimal patient discomfort. However problems often neglected wtih isotopes are reliability of their attachement to the marked meal and radiation dose to the probands. The most important indications of measuring gastric emptying is determination of alterations induced by peptic ulcer surgery and drugs. PMID:871058

  9. Investigation of Antiulcer and Antioxidant Activity of Juniperus phoenicea L. (1753) Essential Oil in an Experimental Rat Model.

    PubMed

    Ben Ali, Manel Jema?; Guesmi, Fatma; Harrath, Abdel Halim; Alwasel, Saleh; Hedfi, Amor; Ncib, Sana; Landoulsi, Ahmed; Aldahmash, Badr; Ben-Attia, Mossadok

    2015-01-01

    Juniperus phoenicea is a tree of the Cupressaceae family that is popularly known in the south of Tunisia because of its wide application in herbal medicine, including the use of its leaves to treat many diseases such as diarrhea, rheumatism, and intestinal disorders. The aim of this study was to evaluate the ulceroprotective and antioxidant activity of essential oil extracted from the leaves of J. phoenicea (EOJp) against hydrogen chloride (HCl)/ethanol-induced ulcers in rats. The antiulcer activities of 50, 75 and 100?mg/kg body weight (b.w.) EOJp were investigated on 0.3?M HCl/ethanol-induced ulcers in rats. The essential oil yield was 0.69% with 48 compounds; ?-pinene was the principal component (20.24%). In vivo pretreatment with EOJp given orally provided dose-dependent protection against HCl/ethanol-induced gastric ulcers in rats. Furthermore, pretreatment with EOJp significantly decreased malondialdehyde (MDA) content and increased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). The activity of the antiulcerogenic EOJp could be from synergistic antioxidant and anti-secretory effects. Oral use of EOJp has excellent preventive effects on induced gastric ulcers comparable to those of the proton pump inhibitor (PPI) omeprazole. PMID:26521824

  10. 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

  11. A Bio-Guided Fractionation to Assess the Inhibitory Activity of Calendula officinalis L. on the NF-?B Driven Transcription in Human Gastric Epithelial Cells

    PubMed Central

    Colombo, Elisa; Sangiovanni, Enrico; D'Ambrosio, Michele; Bosisio, Enrica; Ciocarlan, Alexandru; Fumagalli, Marco; Guerriero, Antonio; Harghel, Petru; Dell'Agli, Mario

    2015-01-01

    Calendula officinalis L. has been largely known for its topical anti-inflammatory properties; however, there are no experimental evidences about its antiphlogistic effect at the gastric level. To investigate whether marigold might exert an activity against gastric inflammation, a CH2Cl2 extract obtained from C. officinalis flowers was evaluated in vitro on the NF-?B pathway. The lipophilic extract demonstrated a significant inhibitory effect on the NF-?B driven transcription. The identification of active compounds was conducted by a bio-guided fractionation of the extract that afforded 16 fractions. Fraction J exhibited a concentration-dependent inhibitory activity on the NF-?B driven transcription and significantly contributed to the antiphlogistic effect showed by CH2Cl2 extract. The main components of fraction J were loliolide and the fucoside acetates of ?-eudesmol and viridiflorol. HPLC analysis of fractions D and E led to the identification and isolation of triterpene esters that showed a concentration-dependent inhibition of the NF-?B driven transcription, with faradiol-3-myristate and the corresponding aglycone being the most active compounds. The present study provides some experimental evidences that Calendula officinalis L. may exert an anti-inflammatory activity on the gastric district by the inhibition of the NF-?B system, identifying the compounds responsible, at least in part, for the observed effect. PMID:26491463

  12. A Novel Proteomics-Based Clinical Diagnostics Technology Identifies Heterogeneity in Activated Signaling Pathways in Gastric Cancers

    PubMed Central

    Kim, Sung; Liu, Xinjun; Lee, Tani; Kim, Kyoung-Mee; Do, In-Gu; Park, Joon Oh; Park, Se Hoon; Jang, Jiryeon; Hoe, Nicholas; Harvie, Gulia; Kuller, Anne; Jain, Anjali; Meyer, Gary; Leesman, Glen; Park, Young Suk; Choi, Min Gew; Sohn, Tae Sung; Bae, Jae Moon; Lim, Ho Yeong; Singh, Sharat; Kang, Won Ki

    2013-01-01

    Purpose The aim of this study was to utilize the proteomics-based Collaborative Enzyme Enhanced Reactive (CEER) immunoassay to investigate protein tyrosine phosphorylations as diagnostic markers in gastric cancers (GCs). Experimental Design Protein lysates from fresh-frozen 434 advanced stage GCs were analyzed for phosphorylation of HER1, HER2, p95HER2, HER3, cMET, IGF1R and PI3K. The pathway activation patterns were segregated based on the tumor HER2 status. Hierarchical clustering was utilized to determine pathway coactivations in GCs. Prognostic value of pathway activation patterns was determined by correlating disease-free survival times of the various GC subgroups using Kaplan-Meier survival analysis. CEER was also used to determine the presence of tyrosine phosphorylated signaling cascades in circulating tumor cells (CTCs) and ascites tumor cells (ATCs). Results Utilizing a novel diagnostics immunoassay, CEER, we demonstrate the presence of p95HER2 and concomitantly activated signaling pathways in GC tumor tissues, CTCs and ATCs isolated from GC patients for the first time. p95HER2 is expressed in ?77% of HER2(+) GCs. Approximately 54% of GCs have an activated HER1, HER2, HER3, cMET or IGF1R and demonstrate a poorer prognosis than those where these receptor tyrosine kinases (RTKs) are not activated. Hierarchical clustering of RTKs reveals co-clustering of phosphorylated HER1:cMET, HER2:HER3 and IGF1R-PI3K. Coactivation of HER1 with cMET renders GCs with a shorter disease-free survival as compared to only cMET activated GCs. Conclusions Our study highlights the utility of a novel companion diagnostics technology, CEER that has strong implications for drug development and therapeutic monitoring. CEER is used to provide an increased understanding of activated signaling pathways in advanced GCs that can significantly improve their clinical management through accurate patient selection for targeted therapeutics. PMID:23372746

  13. Antioxidant activity and ultrastructural changes in gastric cancer cell lines induced by Northeastern Thai edible folk plant extracts

    PubMed Central

    2013-01-01

    Background Phytochemical products have a critical role in the drug discovery process. This promising possibility, however, necessitates the need to confirm their scientific verification before use. Hence, this study aims to evaluate (1) the antioxidant activity, (2) cytotoxicity potential, and (3) the effect on ultrastructural alteration in gastric cancer cell lines through exposure to fractions of three local Northeastern Thai edible plants. Methods Plants, Syzygium gratum, Justicia gangetica and Limnocharis flava were extracted with ethyl acetate, and each crude extract analysed for their total phenolics content by Folin-Ciocalteu method. Their antioxidant activity was assessed using the ABTS system. The extracts were then assayed for cytotoxicity on two gastric cancer cell lines Kato-III and NUGC-4, and compared with Hs27 fibroblasts as a control using the MTT assay. The cell viability (%), IC50 values, as well as the ultrastructural alterations were evaluated after treatment with one way analysis of variance (ANOVA). Results The total phenolic values of the ethyl acetate extracts were well correlated with the antioxidant capacity, with extracted product of S. gratum displaying the highest level of antioxidant activity (a 10-fold greater response) over J. gangetica and L. flava respectively. Exposure of S. gratum and J. gangetica extracts to normal cell lines (Hs27) resulted in marginal cytotoxicity effects. However, through a dose-dependent assay S. gratum and J. gangetica extracts produced cytotoxicological effects in just over 75 percent of Kato-III and NUGC-4 cell lines. In addition, apoptotic characteristic was shown under TEM in both cancer cell lines with these two extracts, whereas characteristics of autophagy was found in cell lines after post exposure to extracts from L. flava. Conclusions From these three plants, S. gratum had the highest contents of phenolic compounds and antioxidant capacity. All of them found to contain compound(s) with cytotoxicity in vitro on cancer cells but not on normal cell lines as resolved in tissue culture and ultrastructural analysis. This is the first report to show the effect on cellular alteration as apoptosis of an ethyl acetate extract of S. gratum and J. gangetica. Further studies are now focused on individual isolates and their function, prioritizing on S. gratum and J. gangetica for the development of novel therapeutics and combatants against cancer. PMID:23497063

  14. 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

  15. Impact of the availability of active cytotoxic agents on the survival of patients with advanced gastric cancer

    PubMed Central

    CHO, BYUNG HA; HAN, HYE SOOK; KWON, JIHYUN; HAN, JOUNG-HO; YOON, SOON MAN; KIM, DAE HOON; YUN, HYO YUNG; LEE, KI HYEONG; YOUN, SEI JIN; KIM, SEUNG TAIK

    2015-01-01

    Several cytotoxic agents, including fluoropyrimidines, platinums, taxanes and irinotecan, are effective in the treatment of advanced gastric cancer (AGC). However, the effect of the availability of cytotoxic agents on survival has not yet been evaluated. Therefore, the present study assessed the impact of the availability of active cytotoxic agents on the survival of patients with AGC. The records of 216 patients with newly diagnosed AGC that were treated with palliative chemotherapy between March 2002 and November 2012 at Chungbuk National University Hospital were reviewed. For the present study, the patients were divided according to the availability of active cytotoxic agents over the course of treatment: Group 1 received fluoropyrimidine and platinum; group 2 received fluoropyrimidine, platinum and taxane or irinotecan; and group 3 received fluoropyrimidine, platinum, taxane and irinotecan. The median overall survival times for groups 1, 2 and 3 were 6.3, 9.9 and 14.3 months, respectively (P<0.0001). Multivariate analysis revealed that the Eastern Cooperative Oncology Group (ECOG) performance status and the availability of active cytotoxic agents were independent prognostic factors, as the hazard ratios for mortality were 3.25 for patients with an ECOG performance status of 2–3 [95% confidence interval (CI), 1.99–5.30; P<0.0001], 0.58 for patients in group 2 (95% CI, 0.42–0.80; P=0.0009), and 0.40 for patients in group 3 (95% CI, 0.28–0.58; P<0.0001). The present study reveals that the availability of active cytotoxic agents is associated with an improved survival time in patients with AGC.

  16. Gastric Carcinoids

    PubMed Central

    Borch, Kurt; Ahrén, Bo; Ahlman, Håkan; Falkmer, Sture; Granérus, Göran; Grimelius, Lars

    2005-01-01

    Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. PMID:15973103

  17. Green and black tea inhibit cytokine-induced IL-8 production and secretion in AGS gastric cancer cells via inhibition of NF-?B activity.

    PubMed

    Gutierrez-Orozco, Fabiola; Stephens, Brian R; Neilson, Andrew P; Green, Rodney; Ferruzzi, Mario G; Bomser, Joshua A

    2010-10-01

    Consumption of tea is associated with a reduced risk for several gastrointestinal cancers. Inflammatory processes, such as secretion of IL-8 from the gastric epithelium in response to chronic chemokine or antigen exposure, serve both as a chemoattractant for white blood cells and a prerequisite for gastric carcinogenesis. In this study, the gastric adenocarcinoma cell line AGS was used to investigate the effect of green tea extract, black tea extract, and epigallocatechin gallate (EGCG), the most abundant catechin in tea, on cytokine-induced inflammation. AGS cells were stimulated with interleukin-1? (IL-1?) to initiate inflammation, followed by exposure to either tea extracts or EGCG. We found that both green and black tea extracts at concentrations of 20 and 2?µM total catechins, respectively, significantly (p < 0.05) inhibited IL-1?-induced IL-8 production and secretion to a similar extent. Treatment of AGS cells with EGCG (8?µM) produced similar reductions in IL-1?-induced IL-8 production and secretion. Inhibition of NF-?B activity was found to be responsible, in part, for these observed effects. Our findings demonstrate that both green and black tea extracts with distinctly different catechin profiles, are capable of disrupting the molecular link between inflammation and carcinogenesis via inhibition of NF-?B activity in AGS cells. PMID:20506079

  18. Gastric anti-ulcer and cytoprotective effect of selenium in rats

    SciTech Connect

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

    1988-01-01

    Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl was significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.

  19. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys

    SciTech Connect

    Danquechin Dorval, E.; Mueller, G.P.; Eng, R.R.; Durakovic, A.; Conklin, J.J.; Dubois, A.

    1985-08-01

    The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. The authors investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. They measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) /sup 60/Co total body irradiation. In addition to causing vomiting, total body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive beta-endorphin.

  20. Effect of ionizing radiation on gastric secretion and gastric motility in monkeys

    SciTech Connect

    Dorval, E.D.; Mueller, G.P.; Eng, R.R.; Durakovic, A.; Conklin, J.J.

    1985-08-01

    The prodromal syndrome of radiation sickness is characterized by nausea and vomiting but the pathophysiology and the treatment of this entity is largely unknown. The authors investigated this problem by determining the effects of ionizing radiation on gastric function with and without administration of the dopamine antagonist domperidone. They measured gastric electrical control activity (waves per minute), fractional emptying rate (percent per minute), acid output (microequivalents per minute), and plasma levels of immunoreactive Beta-endorphin. Twelve conscious, chair-adapted rhesus monkeys were studied twice before, once immediately after, and once 2 days after a single 800-cGy (800 rads) /sup 60/Co total-body irradiation. In addition to causing vomiting, total-body irradiation transiently suppressed gastric electrical control activity, gastric emptying and gastric secretion, while increasing plasma levels of immunoreactive Beta-endorphin. Domperidone had no effect on vomiting or gastric function either before or after irradiation, but it significantly increased plasma immunoreactive Beta endorphin.

  1. 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 ...

  2. ?-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-?B in H. pylori-Infected Gastric Epithelial AGS Cells

    PubMed Central

    Choi, Ji Hyun; Cho, Soon Ok

    2016-01-01

    The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. ?-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether ?-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-?B in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without ?-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-?B-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-?B in AGS cells, which was inhibited by ?-lipoic acid. In conclusion, ?-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation. PMID:26632410

  3. ?-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-?B in H. pylori-Infected Gastric Epithelial AGS Cells.

    PubMed

    Choi, Ji Hyun; Cho, Soon Ok; Kim, Hyeyoung

    2016-01-01

    The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. ?-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether ?-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-?B in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without ?-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-?B-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-?B in AGS cells, which was inhibited by ?-lipoic acid. In conclusion, ?-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation. PMID:26632410

  4. In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats

    PubMed Central

    Al Batran, Rami; Al-Bayaty, Fouad; Jamil Al-Obaidi, Mazen M.; Abdualkader, Abdualrahman Mohammed; Hadi, Hamid A.; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2013-01-01

    Background The current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats. Methodology/Principal Findings Sprague Dawley rats were separated into 7 groups. Groups 1–2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4–7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2–7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4–7. Groups 3–7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests. Conclusion Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2). PMID:23724090

  5. 1,8-Naphthyridine Derivatives: A Review of Multiple Biological Activities.

    PubMed

    Madaan, Alka; Verma, Ritu; Kumar, Vivek; Singh, Anu T; Jain, Swatantra K; Jaggi, Manu

    2015-12-01

    The 1,8-naphthyridine group of compounds have gained special attention of researchers on account of their demonstrating a variety of interesting biological activities. A wide range of biological properties establishes them as potent scaffolds in therapeutic and medicinal research. The broad spectrum of activities primarily includes antimicrobial, antiviral, anticancer, anti-inflammatory, and analgesic activities. 1,8-Naphthyridine derivatives have also exhibited potential applications in neurological disorders such as Alzheimer's disease, multiple sclerosis, and depression. In addition, these synthetic derivatives have been found to possess activities such as anti-osteoporotic (?(v)?(3) antagonists), anti-allergic, antimalarial, gastric antisecretory, bronchodilator, anticonvulsant, anti-hypertensive, platelet aggregation inhibition, anti-oxidant, EGFR inhibition, protein kinase inhibition, ionotropic agent, ?-3 antagonist, MDR modulator, adenosine receptor agonist, adrenoceptor antagonist, and pesticide activities. In spite of the widespread application of the 1,8-naphythyridine scaffolds, only a limited number of review articles are available till date. In this review, we attempt to compile and discuss the key data available in the literature for the multiple biological activities of 1,8-naphthyridine derivatives, in a chronological manner. This review compilation (with 199 references) may be helpful in understanding the diverse biological properties of 1,8-naphthyridines and provide insights into their mechanism of action. This may direct future research in the synthesis of new derivatives and exploring this scaffold for other possible biological activities. PMID:26548568

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

    PubMed

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

    2011-12-01

    The cytostatic potential of the new duplex drug 2'-deoxy-5-fluorouridylyl-(5'5')-3'-C-ethynylcytidine (5FdU(5'-5')ECyd) was evaluated in comparison to those of 5-fluorouracil (5FU), 2'-deoxy-5-fluorourindine (5FdU), 3'-C-ethynylycytidine (ECyd), cisplatin, an equimolar mixture of 5FdU + ECyd and a three component-mixture of 0.75 ?M epirubicin/0.90 ?M cisplatin/3.0 ?M 5FU (ECF) by incubation of the two human gastric adenocarcinoma cell lines 23132/87 and MKN-45. The molar composition of ECF was taken from data of a triple combination chemotherapy for human gastric cancer. Time and dose depending inhibition of cell growth was determinated using the CASY technology. A growth decrease of both cell lines from 100% to about 20% was observed by treatment with ECF over a course of 14 days. This result provided basis to estimate the cytostatic potential of all tested drugs and combinations thereof. Corresponding high activities in respect to ECF were achieved by incubation of 23132/87 cells with single drugs 49 ?M 5FU, 10 ?M cisplatin, 3.4 ?M 5FdU, 0.65 ?M ECyd, the mixture 0.32 ?M 5FdU + 0.32 ?M ECyd and 0.32 ?M 5FdU(5'-5')ECyd. The less sensitive MKN-45 cells require a 1.5-4 fold higher dose of the standard chemotherapeutics in order to achieve an equivalent cytostatic effect, in respect to the 23132/87 cell line,. However, the effect of the duplex drugs on MKN-45 cells was gained with a 5-fold lower dose than ECF. Due to its high cytostatic potential the duplex drug, which covalently links two active anticancer compounds, could be a new therapeutic alternative for chemotherapy in gastric cancer, currently treated with different combinations. PMID:20596746

  7. Inhibitory effect of withaferin A on Helicobacter pylori?induced IL?8 production and NF??B activation in gastric epithelial cells.

    PubMed

    Kim, Green; Kim, Tae-Hyoun; Kang, Min-Jung; Choi, Jin-A; Pack, Da-Young; Lee, Ik-Rae; Kim, Min-Gyu; Han, Sang-Seop; Kim, Bo-Yeon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Jae; Park, Jong-Hwan

    2016-01-01

    Withaferin A (WA), a withanolide purified from Withania somnifera, has been known to exert anti-inflammatory effects. The present study sought to determine the effects of WA on Helicobacter (H.) pylori-mediated inflammation in the AGS gastric epithelial cell line. Cellular production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) was measured by ELISA. Western blot analysis was performed to determine the activation of nuclear factor (NF)-?B and mitogen-activated protein kinases (MAPKs) as well as hypoxia-inducible factor 1? stabilization. Bacterial growth was also examined by measuring the optical density. Pre-treatment or co-treatment with WA efficiently reduced IL-8 production by AGS cells in response to H. pylori infection. H. pylori-induced activation of NF-?B, but not MAPKs, was also inhibited by pre-treatment of WA in the cells. However, WA did not affect VEGF production and HIF-1? stabilization induced by H. pylori in AGS cells. In addition, WA did not influence the growth of H. pylori, suggesting that the anti-inflammatory effect of WA was not due to any bactericidal effect. These findings indicate that WA is a potential preventive or therapeutic agent for H. pylori-mediated gastric inflammation. PMID:26647855

  8. 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. PMID:26064948

  9. A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model

    PubMed Central

    2012-01-01

    Background The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants. Methods A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants. Results The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual plant extracts and the mixed extracts of 5 plants exhibited weak to moderate antibacterial activity against four G-ve bacteria. Despite Ozoroa insignis being toxic to mice at doses above 1000 mg/kg body wt, the other plant extracts and the combined extract of the 5 plants were tolerated by mice up to 5000 mg/kg body wt. The brine shrimp test results showed the same pattern of toxicity with Ozoroa insignis being the most toxic (LC50?=?10.63 ?g/ml). Phytochemical tests showed that the combined extract of the five plants contained tannins, saponins, steroids, cardiac glycosides, flavonoids and terpenoids. Flavonoids, tannins and terpenoids are known to have antioxidant activity. Conclusion The combined extract of the five plants exhibited a dose-dependent protective activity in the rat ethanol-HCl gastric ulcer model. The extracts also exhibited weak antibacterial activity against four Gram negative bacteria and low acute toxicity in mice and brine shrimps. Although the results support claims by traditional healers who use a decoction of the five plants for treatment of peptic ulcers, more models of gastric ulceration and proper animal toxicity studies are needed to validate possible clinical use of the polyherbal extract. It is also evident that the doses of the crude extracts showing protection of the gastric mucosa are too large for realistic translation to direct clinical application, but further studies using bioassay guided fractionation are important to either identify more practical fractions or active compound/s. PMID:23031266

  10. Stages of Gastric Cancer

    MedlinePLUS

    ... Gastric) Cancer Prevention Stomach (Gastric) Cancer Screening Age, diet, and stomach disease can affect the risk of ... may be used alone or to carry drugs, toxins , or radioactive material directly to cancer cells. For ...

  11. 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

  12. 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

  13. Superior antitumor activity of trastuzumab combined with capecitabine plus oxaliplatin in a human epidermal growth factor receptor 2-positive human gastric cancer xenograft model

    PubMed Central

    HARADA, SUGURU; YANAGISAWA, MIEKO; KANEKO, SAORI; YOROZU, KEIGO; YAMAMOTO, KANAME; MORIYA, YOICHIRO; HARADA, NAOKI

    2015-01-01

    In the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction cancer, it has been reported that the combination of trastuzumab with capecitabine plus cisplatin, or with 5-fluorouracil (5-FU) plus cisplatin, significantly increased overall survival compared with chemotherapy alone (ToGA trial). In addition, adjuvant therapy with capecitabine plus oxaliplatin (XELOX) improved the survival of patients who received curative D2 gastrectomy (CLASSIC trial). However, the efficacy of the combination of trastuzumab with XELOX for patients with HER2-positive gastric cancer remains unknown. The aim of this study, was to investigate the efficacy of the combination of trastuzumab with XELOX in a HER2-positive human gastric cancer xenograft model. Combination treatment with these three agents (trastuzumab 20 mg/kg, capecitabine 359 mg/kg and oxaliplatin 10 mg/kg), was found to exhibit a significantly stronger antitumor activity in NCI-N87 xenografts compared with either trastuzumab or XELOX alone. In this model, treatment with trastuzumab alone or trastuzumab plus oxaliplatin enhanced the expression of thymidine phosphorylase (TP), a key enzyme in the generation of 5-FU from capecitabine in tumor tissues. In in vitro experiments, trastuzumab induced TP mRNA expression in NCI-N87 cells. In addition, NCI-N87 cells co-cultured with the natural killer (NK) cell line CD16(158V)/NK-92 exhibited increased expression of TP mRNA. When NCI-N87 cells were cultured with CD16(158V)/NK-92 cells in the presence of trastuzumab, the mRNA expression of cytokines reported to have the ability to induce TP was upregulated in tumor cells. Furthermore, a medium conditioned by CD16(158V)/NK-92 cells also upregulated the expression of TP mRNA in NCI-N87 cells. These results suggest that trastuzumab promotes TP expression, either by acting directly on NCI-N87 cells, or indirectly via a mechanism that includes trastuzumab-mediated interactions between NK and NCI-N87 cells. Therefore, the combination of trastuzumab with XELOX may be a potent therapy for HER2-positive gastric cancer. PMID:26623038

  14. 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

  15. Prostaglandin Analogous and Antioxidant Activity Mediated Gastroprotective Action of Tabernaemontana divaricata (L.) R. Br. Flower Methanolic Extract against Chemically Induced Gastric Ulcers in Rats

    PubMed Central

    Mat Jais, Abdul Manan; Afreen, Adiba

    2013-01-01

    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses—125, 250, and 500?mg/kg—orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization—high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous. PMID:24350249

  16. Optimization of 1,3,4-benzotriazepine-based CCK(2) antagonists to obtain potent, orally active inhibitors of gastrin-mediated gastric acid secretion.

    PubMed

    McDonald, Iain M; Black, James W; Buck, Ildiko M; Dunstone, David J; Griffin, Eric P; Harper, Elaine A; Hull, Robert A D; Kalindjian, S Barret; Lilley, Elliot J; Linney, Ian D; Pether, Michael J; Roberts, Sonia P; Shaxted, Mark E; Spencer, John; Steel, Katherine I M; Sykes, David A; Walker, Martin K; Watt, Gillian F; Wright, Laurence; Wright, Paul T; Xun, Wei

    2007-06-28

    Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor antagonist, a process of optimization has afforded further compounds of this type that maintain the nanomolar affinity for recombinant, human CCK2 receptors and high selectivity over CCK1 receptors observed in the initial lead but display more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo. Moreover, this has largely been achieved without altering their potency at wild-type canine and rat receptors, as judged by their displacement of [125I]-BH-CCK-8S in a radioligand binding assay and by their activity in an isolated, perfused rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro- [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most effective compound stemming from this approach, proving to be a potent inhibitor of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous bolus as well as by enteral administration. PMID:17536796

  17. Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

    NASA Technical Reports Server (NTRS)

    Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

  18. Targeting receptor tyrosine kinases in gastric cancer

    PubMed Central

    Morishita, Asahiro; Gong, Jian; Masaki, Tsutomu

    2014-01-01

    Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies. PMID:24782606

  19. Helicobacter pylori in gastric corpus of patients 20 years after partial gastric resection

    PubMed Central

    Kirsch, Christian; Madisch, Ahmed; Piehler, Petja; Bayerdörffer, Ekkehard; Stolte, Manfred; Miehlke, Stephan

    2004-01-01

    AIM: To determine the long-term prevalence of Helicobacter pylori (H pylori) gastritis in patients after partial gastric resection due to peptic ulcer, and to compare the severity of H pylori-positive gastritis in the corpus mucosa between partial gastrectomy patients and matched controls. METHODS: Endoscopic biopsies were obtained from 57 patients after partial gastric resection for histological examination using hematoxylin/eosin and Warthin-Starry staining. Gastritis was graded according to the updated Sydney system. Severity of corpus gastritis was compared between H pylori-positive partial gastrectomy patients and H pylori-positive duodenal ulcer patients matched for age and gender. RESULTS: In partial gastrectomy patients, surgery was performed 20 years (median) prior to evaluation. In 25 patients (43.8%) H pylori was detected histologically in the gastric remnant. Gastric atrophy was more common in H pylori-positive compared to H pylori-negative partial gastrectomy patients (P < 0.05). The severity of corpus gastritis was significantly lower in H pylori-positive partial gastrectomy patients compared to duodenal ulcer patients (P < 0.01). There were no significant differences in the activity of gastritis, atrophy and intestinal metaplasia between the two groups. CONCLUSION: The long-term prevalence of H pylori gastritis in the gastric corpus of patients who underwent partial gastric resection due to peptic ulcer disease is comparable to the general population. The expression of H pylori gastritis in the gastric remnant does not resemble the gastric cancer phenotype. PMID:15300905

  20. 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.

  1. Primary gastric tuberculosis mimicking gastric cancer

    PubMed Central

    Eray, ?smail Cem; Rencüzo?ullar?, Ahmet; Yalav, Orçun; Dalc?, Kubilay; Kakil, Erdem; Ba??r, Emine; Parsak, Cem Kaan

    2015-01-01

    A 42-year-old female patient with no previous known diseases who had complaints of postprandial epigastric pain and weight loss and who could not be diagnosed by endoscopic biopsy, although gastric cancer was suspected radiologically and endoscopically, was diagnosed with primary gastric tuberculosis by laparotomy and frozen section. Following anti-tuberculosis treatment, a complete clinical, radiological, and endoscopic response was achieved. PMID:26504425

  2. 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

  3. 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.

  4. Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice

    PubMed Central

    Jaccob, Ausama Ayoob

    2015-01-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. Materials and Methods: A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex. PMID:26401392

  5. Gastric mucosal mast cells in atopic subjects.

    PubMed

    Bagnato, G F; Di Cesare, E; Caruso, R A; Gulli, S; Cugliari, A; Morabito Lo Prete, A; Previti, M; Muscarà, M; Bottari, M

    1995-04-01

    Intragastral allergen provocation under endoscopic control (IPEC) allows direct observation of gastric mucosa reactions after contact with inhalant allergens that reach the stomach. We selected patients with proved atopy to Parietaria but without clinical and endoscopic signs of gastric disease, and we tested them with the specific inhalant allergen during IPEC, recording gastric macroscopic reaction and mucosal mast-cell changes in biopsy specimens. All atopic patients showed visible changes in gastric mucosa quantified as IPEC score. Mast-cell numbers detected in atopic patients (135.4 +/- 102.6/mm2 of stromal area) were significantly higher than in nonatopic subjects (59.8 +/- 25.4/mm2; P < 0.03) and were positively correlated to atopic IPEC score (P < 0.01). In addition, 6/12 atopics who had both higher mast-cell counts and IPEC score showed an intraepithelial distribution of gastric mast cells which displayed ultrastructural features of partial degranulation. It is likely that changes observed in our patients with allergy to Parietaria reflect a subclinical activation of mast cells in the gastric mucosa. PMID:7573815

  6. Treatment of gastric cancer

    PubMed Central

    Orditura, Michele; Galizia, Gennaro; Sforza, Vincenzo; Gambardella, Valentina; Fabozzi, Alessio; Laterza, Maria Maddalena; Andreozzi, Francesca; Ventriglia, Jole; Savastano, Beatrice; Mabilia, Andrea; Lieto, Eva; Ciardiello, Fortunato; De Vita, Ferdinando

    2014-01-01

    The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4th most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status PMID:24587643

  7. Effect of caffeine on ibuprofen-induced gastric mucosal damage in rats.

    PubMed

    Koyama, R; Kataoka, H; Tanaka, Y; Nakatsugi, S; Furukawa, M

    1999-07-01

    During investigations on the effect of caffeine on ibuprofen-induced gastric mucosal lesions in rats, we have found that caffeine (p.o.) inhibits the development of ibuprofen-induced gastric lesions in a dose-dependent manner (ED50 18.4 mg kg(-1)). To investigate this protective effect of caffeine, we have studied the effect of caffeine on HCl-ethanol-induced gastric mucosal lesions with or without indomethacin pretreatment. Caffeine inhibited the development of HCl-ethanol-induced gastric lesions with and without indomethacin pretreatment. These results indicate that caffeine did not act as a mild irritant but, on the contrary, had protective effects. We measured the gastric mucosal prostaglandin E2 (PGE2) concentrations and gastric mucosal blood flow, as representative protective factors for gastric mucosa. Caffeine did not affect the gastric mucosal PGE2 concentrations 4h after administration of ibuprofen. However, topical administration of caffeine resulted in an increase in gastric mucosal blood flow, as measured by laser Doppler flowmetry. We investigated the gastric acid secretion and gastric mucosal myeloperoxidase activity as representative aggressive factors for gastric mucosa. When caffeine was administered intraduodenally in pylorus-ligated rats, gastric acid secretion decreased in a dose-dependent manner, with an ED50 of 44.9 mg kg(-1). Caffeine decreased ibuprofen-induced gastric myeloperoxidase activity in a dose-dependent manner, with an ED50 of 9.1 mg kg(-1). These findings indicate that caffeine, at least in rats, may inhibit the development of acute gastric mucosal injury. The mechanisms underlying the protective actions of caffeine are unclear, but may be related in part to an increase in gastric mucosal blood flow and suppression of neutrophil activation. PMID:10467957

  8. Long Non-Coding RNA LSINCT5 Predicts Negative Prognosis and Exhibits Oncogenic Activity in Gastric Cancer

    PubMed Central

    Xu, Mi-Die; Qi, Peng; Weng, Wei-Wei; Shen, Xiao-Han; Ni, Shu-Juan; Dong, Lei; Huang, Dan; Tan, Cong; Sheng, Wei-Qi; Zhou, Xiao-Yan; Du, Xiang

    2014-01-01

    Abstract Long non-coding RNAs (lncRNAs) are recently discovered RNA transcripts that are aberrantly expressed in many tumor types. Numerous studies have suggested that lncRNAs can be utilized for cancer diagnosis and prognosis. LSINCT5 (long stress-induced non-coding transcript 5) is dramatically upregulated in breast and ovarian cancer and affects cellular proliferation. However, the expression pattern of LSINCT5 in gastrointestinal cancer and the association between aberrant expression of LSINCT5 in gastrointestinal cancer and malignancy, metastasis, or prognosis remain unknown. LSINCT5 expression was detected in gastrointestinal cancer and paired adjacent normal tissue samples or cell lines using reverse transcription quantitative PCR (RT-qPCR). We also investigated the potential relationship between tumor LSINCT5 levels and clinicopathological features of gastrointestinal cancer. Finally, we assessed whether LSINCT5 influences in vitro cell proliferation. The expression of LSINCT5 is significantly upregulated in gastrointestinal cancer tissues and cell lines relative to their normal counterparts. In addition, increased LSINCT5 expression was correlated with a larger tumor size, deeper tumor depth, and advanced clinical stage. Kaplan–Meier analysis indicated that gastric cancer (GC) and colorectal cancer (CRC) patients with higher LSINCT5 expression levels have worse disease-free survival (DFS) and disease-specific survival (DSS) rates. Moreover, multivariate analysis revealed that increased expression of LSINCT5 is an independent predictor of DFS and DSS rates in GC patients. The ectopic expression of LSINCT5 in gastrointestinal cancer cell lines resulted in an increase in cellular proliferation; conversely, knock down of LSINCT5 significantly inhibited proliferation. These results suggest that LSINCT5 may represent a novel prognostic indicator and a target for gene therapy in gastrointestinal cancer. PMID:25526476

  9. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    SciTech Connect

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-04-18

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.

  10. Gastric Emptying Assessment in Frequency and Time Domain Using Bio-impedance: Preliminary Results

    NASA Astrophysics Data System (ADS)

    Huerta-Franco, R.; Vargas-Luna, M.; Hernández, E.; Córdova, T.; Sosa, M.; Gutiérrez, G.; Reyes, P.; Mendiola, C.

    2006-09-01

    The impedance assessment to measure gastric emptying and in general gastric activity has been reported since 1985. The physiological interpretation of these measurements, is still under research. This technique usually uses a single frequency, and the conductivity parameter. The frequency domain and the Fourier analysis of the time domain behavior of the gastric impedance in different gastric conditions (fasting state, and after food administration) has not been explored in detail. This work presents some insights of the potentiality of these alternative methodologies to measure gastric activity.

  11. Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia

    PubMed Central

    Shin, Seung Hwan; Jung, Da Hyun; Kim, Jie-Hyun; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan

    2015-01-01

    Purpose There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms. Materials and Methods We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36). Results Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041). Conclusion Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia. PMID:26580072

  12. 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.; Cho, C.H.; Sung, J.J.Y.

    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.

  13. Dietary monosodium glutamate enhances gastric secretion.

    PubMed

    Khropycheva, Raisa; Uneyama, Hisayuki; Torii, Kunio; Zolotarev, Vasiliy

    2009-01-01

    Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT(3) receptors in the gastric mucosa. PMID:20224184

  14. Pathobiology of Helicobacter pylori-Induced Gastric Cancer.

    PubMed

    Amieva, Manuel; Peek, Richard M

    2016-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  15. 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; Chang, Chi-Sen; Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan ; Ho, Wei-Chi; Liao, Sheng-You; Lin, Wea-Lung; Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan ; Wang, Chau-Jong; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan

    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.

  16. Hereditary Diffuse Gastric Cancer

    MedlinePLUS

    ... with the syndrome is recommended. What are the estimated cancer risks associated with HDGC? Not everyone who ... the lifetime risk for diffuse gastric cancer is estimated to be 70% to 80% for men and ...

  17. 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

  18. Gastric Sleeve Surgery

    MedlinePLUS

    ... or "sleeve" out of the rest. The new, banana-shaped stomach is much smaller than the original ... of your stomach, leaving you with a smaller banana-shaped stomach called the gastric sleeve. Because it's ...

  19. 2-[[(4-Amino-2-pyridyl)methyl]sulfinyl]benzimidazole H+/K+-ATPase inhibitors. The relationship between pyridine basicity, stability, and activity.

    PubMed

    Ife, R J; Dyke, C A; Keeling, D J; Meenan, E; Meeson, M L; Parsons, M E; Price, C A; Theobald, C J; Underwood, A H

    1989-08-01

    The benzimidazole sulfoxide class of antisecretory H+/K+-ATPase inhibitors need to possess high stability under neutral physiological conditions yet rearrange rapidly at low pH to the active sulfenamide 2. Since the initial reaction involves internal nucleophilic attack by the pyridine nitrogen, control of the pyridine pKa is critical. In this paper we show that by utilizing the powerful electron-donating effect of a 4-amino substituent on the pyridine, moderated by the electron-withdrawing effect of a 3- or 5-halogen substituent, a combination of high potency (as inhibitors of histamine-stimulated gastric acid secretion) and good stability under physiological conditions can be obtained. Furthermore, the role of the steric interaction between the 3/5-substituents and the 4-substituent in modifying the electron-donating ability of the 4-amino group is exemplified, and additional factors affecting stability are identified. One compound, in particular, 2-[[(3-chloro-4-morpholino-2- pyridyl)methyl]sulfinyl]-5-methoxy-(1H)-benzimidazole (3a, SK&F 95601), was chosen for further development and evaluation in man. PMID:2547073

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

    PubMed

    Gomathy, G; Venkatesan, D; Palani, S

    2015-11-01

    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

  1. Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats.

    PubMed

    Ji, Cheng-Xue; Fan, Dong-Sheng; Li, Wei; Guo, Liang; Liang, Zi-Liang; Xu, Rui-Ming; Zhang, Jian-Jun

    2012-09-15

    The effects of acute systemic administration of duloxetine, amitriptyline, mirtazapine and fluoxetine were compared in experimental models of gastric ulcer in rats. Compared with the vehicle control group, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), mirtazapine (10 and 20 mg/kg, i.p.) and fluoxetine (5 and 10 mg/kg, i.p.) significantly protected against water-immersion plus restraint stress-induced gastric lesions, as evidenced by dose-dependent decrease in ulcer index and score for intraluminal bleeding. Duloxetine (20 mg/kg, i.p.), amitriptyline (10 and 20 mg/kg, i.p.), fluoxetine (10 and 20 mg/kg, i.p.) and mirtazapine (5, 10 and 20 mg/kg, i.p.) significantly decreased indomethacin (30 mg/kg, i.p.)-induced gastric lesions and intraluminal bleeding. In reserpine (25 mg/kg, i.p.)-induced gastric ulcer experiment, duloxetine (5, 10 and 20 mg/kg, i.p.), amitriptyline (5, 10 and 20 mg/kg, i.p.), fluoxetine (10 mg/kg, i.p.) and mirtazapine (5 mg/kg, i.p.) significantly attenuated gastric lesions and intraluminal bleeding. These results (a) highlighted the relationship in correlating antiulcer effect of drugs from different antidepressant classes across various animal gastric ulcer models and (b) suggested that antidepressants that differently affected both norepinephrine and serotonin levels (such as duloxetine, amitriptyline and mirtazapine) had more potent and efficacious antiulcer effect in various gastric ulcer animal models than drugs that only affected serotonin level (such as fluoxetine). PMID:22789173

  2. CT of Gastric Emergencies.

    PubMed

    Guniganti, Preethi; Bradenham, Courtney H; Raptis, Constantine; Menias, Christine O; Mellnick, Vincent M

    2015-01-01

    Abdominal pain, nausea, and vomiting are common presenting symptoms among adult patients seeking care in the emergency department, and, with the increased use of computed tomography (CT) to image patients with these complaints, radiologists will more frequently encounter a variety of emergent gastric pathologic conditions on CT studies. Familiarity with the CT appearance of emergent gastric conditions is important, as the clinical presentation is often nonspecific and the radiologist may be the first to recognize gastric disease as the cause of a patient's symptoms. Although endoscopy and barium fluoroscopy remain important tools for evaluating patients with suspected gastric disease in the outpatient setting, compared with CT these modalities enable less comprehensive evaluation of patients with nonspecific complaints and are less readily available in the acute setting. Endoscopy is also more invasive than CT and has greater potential risks. Although the mucosal detail of CT is relatively poor compared with barium fluoroscopy or endoscopy, CT can be used with the appropriate imaging protocols to identify inflammatory conditions of the stomach ranging from gastritis to peptic ulcer disease. In addition, CT can readily demonstrate the various complications of gastric disease, including perforation, obstruction, and hemorrhage, which may direct further clinical, endoscopic, or surgical management. We will review the normal anatomy of the stomach and discuss emergent gastric disease with a focus on the usual clinical presentation, typical imaging appearance, and differentiating features, as well as potential imaging pitfalls. (©)RSNA, 2015. PMID:26562229

  3. The intestinal phase of gastric secretion.

    PubMed Central

    Kester, R. C.

    1975-01-01

    The intestinal phase hormone, elaborated by the jejunum in response to an intestinal meal or simple distension, produces profound gastric hypersecretion when it escapes hepatic degradation through a portacaval anastomosis. The hormone is released within 30 min of the application of the stimulus and rapidly reaches peak concentration in the portal blood. Intravenous infusion into a donor dog of active portal plasma from a shunted, intestinally fed dog stimulates gastric acid secretion after a delay of approximately 1 h, and requires a mean 1 1/2 h to stimulate peak secretion, which suggests that intermediate steps may be necessary before the hormone can effectively stimulate the parietal cell mass. The pig develops portacaval-shunt-related gastric acid hypersecretion in response to food comparable to that observed in the dog and in man. Porcine jejunal mucosa is thus an appropriate source for isolation of the intestinal phase hormone. Pig intestinal mucosal extract contains a heat-stable acidic peptide which is a potent stimulator of gastric acid secretion. Administration of crude intestinal mucosal extract elicits gastric acid secretion after a brief delay, again indicating that some intermediate reactions occur before the target organ--the parietal cell mass--is stimulated. PMID:1147535

  4. Gastric Adenocarcinoma Presenting with Gastric Outlet Obstruction in a Child

    PubMed Central

    Al-Hussaini, Abdulrahman; AlGhamdi, Salem; Al-Kasim, Fawaz; Habib, Zakaria; Ourfali, Nouri

    2014-01-01

    Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5?cm × 2?cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction. PMID:24707411

  5. Parenteral adjuvant activities of Escherichia coli heat-labile toxin and its B subunit for immunization of mice against gastric Helicobacter pylori infection.

    PubMed

    Weltzin, R; Guy, B; Thomas, W D; Giannasca, P J; Monath, T P

    2000-05-01

    The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric challenge with H. pylori. Control mice were immunized orally with urease plus LT, a regimen shown previously to protect against H. pylori gastric infection. Parenteral immunization using either LT or LTB as adjuvant protected mice against H. pylori challenge as effectively as oral immunization and enhanced urease-specific immunoglobulin G (IgG) responses in serum as effectively as aluminum hydroxide adjuvant. LT and LTB had adjuvant activity at subtoxic doses and induced more consistent antibody responses than those observed with oral immunization. A mixture of a low dose of LT and a high dose of LTB stimulated the highest levels of protection and specific IgG in serum. Urease-specific IgG1 and IgG2a antibody subclass responses were stimulated by all immunization regimens tested, but relative levels were dependent on the adjuvant used. Compared to parenteral immunization with urease alone, LT preferentially enhanced IgG1, while LTB or the LT-LTB mixture preferentially enhanced IgG2a. Parenteral immunization using LT or LTB as adjuvant also induced IgA to urease in the saliva of some mice. These results show that LT and LTB stimulate qualitatively different humoral immune responses to urease but are both effective parenteral adjuvants for immunization of mice against H. pylori infection. PMID:10768972

  6. Wireless Gastric Stimulators Smitha Rao1

    E-print Network

    Chiao, Jung-Chih

    ,000 suffering from severe forms of the disorder (2012). At least 20% of people with type-1 diabetes develop GP and it can occur in type-2 diabetes as well [1, 2]. Gastroparesis is characterized by the abnormal amplitude and frequency of the gastric slow waves [3] affecting myoelectrical activities in stomach. Drug therapies

  7. The Role of Gastrokine 1 in Gastric Cancer

    PubMed Central

    Yoon, Jung Hwan; Choi, Won Suk; Kim, Olga

    2014-01-01

    Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-?B signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastric-specific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression. PMID:25328759

  8. Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer.

    PubMed

    Lee, Hyunseung; Lee, Ju-Hee; Jung, Kyung Hee; Hong, Soon-Sun

    2010-10-01

    Gastric cancer is often diagnosed in locally advanced or metastatic stages, which preludes a poor prognosis. As only 10% of patients with advanced gastric cancer treated with chemotherapy survive 2 years, new approaches for preventing and controlling the disease are required. We therefore, assessed in gastric cancer cells the chemotherapeutic potential and mechanism of deguelin, a rotenoid of the flavonoid family isolated from several plant species. The effect of deguelin on the proliferation and apoptosis in the gastric cancer cells were assessed by MTT and flow cytometry. The growth of gastric cancer cells (SNU-484, AGS and MKN-28) was inhibited by deguelin in a dose-dependent manner. G2/M phase arrest was induced by deguelin in gastric cancer cells. deguelin (1 microM) induced chromatin condensation and DNA fragmentation. Also the exposure to 1 microM deguelin resulted in the increase in early-apoptotic cells (Annexin V-positive/Propidium iodide-negative) after 24 h, compared to the cells in the control medium (31 versus 12%). Deguelin-induced apoptosis involved the caspase-9 and caspase-3 pathways in gastric cancer cells. Akt phosphorylation, hypoxia-inducible factor-1alpha accumulation, and vascular endothelial growth factor expression in gastric cancer cells was inhibited by deguelin. Taken together, deguelin showed anticancer activity in gastric cancer cells, which is correlated with the inhibition of angiogenesis and induction of apoptosis. Deguelin may be a potential agent in inhibiting the progression of gastric cancer by virtue of its activity on these crucial cell characteristics. PMID:20811676

  9. Gastric Electrical Stimulation

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this analysis was to assess the effectiveness, safety and cost-effectiveness of gastric electrical stimulation (GES) for the treatment of chronic, symptomatic refractory gastroparesis and morbid obesity. Background Gastroparesis - Epidemiology Gastroparesis (GP) broadly refers to impaired gastric emptying in the absence of obstruction. Clinically, this can range from the incidental detection of delayed gastric emptying in an asymptomatic person to patients with severe nausea, vomiting and malnutrition. Symptoms of GP are nonspecific and may mimic structural disorders such as ulcer disease, partial gastric or small bowel obstruction, gastric cancer, and pancreaticobiliary disorders. Gastroparesis may occur in association with diabetes, gastric surgery (consequence of peptic ulcer surgery and vagotomy) or for unknown reasons (idiopathic gastroparesis). Symptoms include early satiety, nausea, vomiting, abdominal pain and weight loss. The majority of patients with GP are women. The relationship between upper gastrointestinal symptoms and the rate of gastric emptying is considered to be weak. Some patients with markedly delayed gastric emptying are asymptomatic and sometimes, severe symptoms may remit spontaneously. Idiopathic GP may represent the most common form of GP. In one tertiary referral retrospective series, the etiologies in 146 GP patients were 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson’s disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction and 6% miscellaneous causes. The true prevalence of digestive symptoms in patients with diabetes and the relationship of these symptoms to delayed gastric emptying are unknown. Delayed gastric emptying is present in 27% to 58% of patients with type 1 diabetes and 30% with type 2 diabetes. However, highly variable rates of gastric emptying have been reported in type 1 and 2 diabetes, suggesting that development of GP in patients with diabetes is neither universal nor inevitable. In a review of studies examining gastric emptying in patients with diabetes compared to control patients, investigators noted that in many cases the magnitude of the delay in gastric emptying is modest. GP may occur as a complication of a number of different surgical procedures. For example, vagal nerve injury may occur in 4% to 40% of patients who undergo laparoscopic fundoplication1 for gastroesophageal reflux disease. The prevalence of severe, refractory GP is scantily reported in the literature. Using data from a past study, it has been estimated that the prevalence of severe, symptomatic and refractory GP in the United States population is 0.017%. Assuming an Ontario population of 13 million, this would correspond to approximately 2,000 people in Ontario having severe, symptomatic, refractory GP. The incidence of severe refractory GP estimated by the United States Food and Drug Administration (FDA) is approximately 4,000 per year in the United States. This corresponds to about 150 patients in Ontario. Using expert opinion and FDA data, the incidence of severe refractory GP in Ontario is estimated to be about 20 to 150 per year. Treatment for Gastroparesis To date, there have been no long-term studies confirming the beneficial effects of maintaining euglycemia on GP symptoms. However, it has been suggested that consistent findings of physiologic studies in healthy volunteers and diabetes patients provides an argument to strive for near-normal blood glucose levels in affected diabetes patients. Dietary measures (e.g., low fibre, low fat food), prokinetic drugs (e.g., domperidone, metoclopramide and erythromycin) and antiemetic or antinausea drugs (e.g, phenothiazines, diphenhydramine) are generally effective for symptomatic relief in the majority of patients with GP. For patients with chronic, symptomatic GP who are refractory to drug treatment, surgical options may include jejunostomy tube for feeding, gastrotomy tube for stomach decompression and pyloroplasty for gastric emptying. Few small studies

  10. MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ

    PubMed Central

    Zuo, Q-F; Zhang, R; Li, B-S; Zhao, Y-L; Zhuang, Y; Yu, T; Gong, L; Li, S; Xiao, B; Zou, Q-M

    2015-01-01

    Gastric cancer (GC) is a biologically heterogeneous disease accompanying various genetic and epigenetic alterations, and the molecular mechanisms underlying this disease are complex and not completely understood. Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in GC tumorigenesis, but the role of specific miRNAs involved in this disease remains elusive. MiR-141 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely unclear. Here we found that the expression of miR-141 was significantly reduced in GC compared with paired adjacent normal tissues and was significantly correlated with a more aggressive phenotype of GC in patients. Ectopic expression of miR-141 mimics in GC cell lines resulted in reduced proliferation, invasion and migration, and inhibition of miR-141 in GC cell lines promoted cell proliferation, invasion and migration in vitro. We further demonstrated that miR-141 acted as tumor suppressors through targeting transcriptional co-activator with PDZ-binding motif (TAZ) in GC. Moreover, the inverse relationship between miR-141 and its target was verified in patients and xenograft mice. Finally, overexpression of miR-141 suppressed tumor growth and pulmonary metastasis in nude mice. Take together, we identified that miR-141 is a potent tumor suppressor in the stomach, and its growth inhibitory effects are, in part, mediated through its downstream target gene, TAZ. These findings implied that miR-141 might be employed as novel prognostic markers and therapeutic targets of GC. PMID:25633292

  11. Eradication of gastric cancer is now both possible and practical.

    PubMed

    Shiotani, Akiko; Cen, Putao; Graham, David Y

    2013-12-01

    In 1994, Helicobacter pylori was declared a human carcinogen. Evidence has now accumulated to show that at least 95% of gastric cancers are etiologically related to H. pylori. An extensive literature regarding atrophic gastritis and its effects on acid secretion, gastric microflora, and its tight association with gastric cancer has been rediscovered, confirmed, and expanded. Methods to stratify cancer risk based on endoscopic and histologic findings or serologic testing of pepsinogen levels and H. pylori testing have been developed producing practical primary and secondary gastric cancer prevention strategies. H. pylori eradication halts progressive mucosal damage. Cure of the infection in those with non-atrophic gastritis will essentially prevent subsequent development of gastric cancer. For all, the age-related progression in cancer risk is halted and likely reduced as eradication reduces or eliminates mucosal inflammation and reverses or reduces H. pylori-associated molecular events such aberrant activation-induced cytidine deaminase expression, double strand DNA breaks, impaired DNA mismatch repair and aberrant DNA methylation. Those who have developed atrophic gastritis/gastric atrophy however retain some residual risk for gastric cancer which is proportional to the extent and severity of atrophic gastritis. Primary and secondary cancer prevention starts with H. pylori eradication and cancer risk stratification to identify those at higher risk who should also be considered for secondary cancer prevention programs. Japan has embarked on population-wide H. pylori eradication coupled with surveillance targeted to those with significant remaining risk. We anticipate that countries with high gastric cancer burdens will follow their lead. We provide specific recommendations on instituting practical primary and secondary gastric cancer prevention programs as well identifying research needed to make elimination of gastric cancer both efficient and cost effective. PMID:23876852

  12. Neural mechanisms of reflex facilitation and inhibition of gastric motility to stimulation of various skin areas in rats.

    PubMed Central

    Kametani, H; Sato, A; Sato, Y; Simpson, A

    1979-01-01

    1. Experiments were performed on chloralose-urethane anaesthetized rats to determine the involvement of extrinsic gastric autonomic nerves in reflex facilitation and inhibition of gastric motility when mechanical nociceptive stimulation was delivered to either hind paw or abdominal skin, respectively. 2. After bilaterally sectioning the splanchnic nerves in vagal intact animals, the reflex facilitation of gastric motility produced by hind paw stimulation persisted, but the reflex inhibition previously produced by abdominal skin stimulation disappeared. 3. Hind paw stimulation increased efferent activity of the gastric branch of the vagus nerve, but stimulation of abdominal skin had little influence. 4. Bilateral vagotomy in splanchnic nerve intact animals did not influence the gastric reflex inhibition by abdominal skin stimulation, but either abolished gastric reflex facilitation produced by hind paw stimulation or reversed the reflex facilitation response to slight reflex inhibition. 5. Efferent activity of the gastric sympathetic nerve was greatly increased by abdominal skin stimulation, and was either slightly increased or not influenced by hind paw stimulation. 6. It was concluded that reflex increase of efferent activity of the gastric vagi was responsible for the gastric motility facilitation produced by hind paw stimulation, and also that reflexly increased efferent activity of the gastric sympathetic nerves resulted in gastric motility inhibition produced by abdominal skin stimulation. It is suggested efferents are inhibitory. 7. After spinal transection at the cervical level, the reflex facilitation of gastric motility previously produced by stimulation of a hind paw was completely abolished, or reversed to slight reflex inhibition, while reflex inhibition of gastric motility produced by stimulation of abdominal skin remained. It was concluded that the gastric reflex inhibition was a spinal reflex. 8. Interaction between reflex facilitation and inhibition of gastric motility during simultaneous stimulation of both hind paws and abdominal skin was observed as partial cancellation of each effect by the other. However, sympathetic reflex inhibition of gastric motility seemed to be much stronger than the vagal reflex facilitatory effect. PMID:512950

  13. Enzymatic sulfation of mucus glycoprotein in gastric mucosa

    SciTech Connect

    Liau, Y.H.; Carter, S.R.; Gwozdzinski, K.; Nadziejko, C.; Slomiany, A.; Slomiany, B.L.

    1986-05-01

    Among the posttranslational modifications that mucus glycoprotein undergo prior to secretion into the gastric lumen is the process of sulfation of the carbohydrate chains. These sulfate groups impart strongly negative charge to nucus glycoprotein and are thought to play a major role in the maintenance of gastric mucosal integrity. The authors report here the presence and some properties of an enzyme involved in the sulfation of gastric mucus glycoprotein. The sulfotransferase activity which catalyzes the transfer of sulfate ester group from PAPS to mucus glycoprotein was located in the detergent extracts of the microsomal fraction of rat gastric mucosa. Optimum enzymatic activity for sulfation of gastric mucin was obtained using 0.5% Triton X-100 and 25mM NaF at a pH of 6.8. ATP, ADP, MgCl/sub 2/ and MnCl/sub 2/ at concentrations examined were inhibitory. Under optimal conditions, the rate of sulfate incorporation was proportional to the microsomal enzyme protein concentration up to 50..mu..g and remained constant with time of incubation for at least 1h. The apparent Km value of the enzyme for gastric mucus glycoprotein was 8.3 x 10/sup -6/M. The /sup 35/S-labeled product of the enzyme reaction cochromatographed on Bio-Gel A-50 with gastric mucin, and gave on CsCl equilibrium density gradient centrifugation a band at the density of 1.48 in which the /sup 35/S label coincided with the glycoprotein.

  14. Effect of gastric acid suppressants on human gastric motility

    PubMed Central

    Parkman, H; Urbain, J; Knight, L; Brown, K; Trate, D; Miller, M; Maurer, A; Fisher, R

    1998-01-01

    Background—The effect of histamine H2 receptor antagonists on gastric emptying is controversial. ?Aims—To determine the effects of ranitidine, famotidine, and omeprazole on gastric motility and emptying. ?Patients and methods—Fifteen normal subjects underwent simultaneous antroduodenal manometry, electrogastrography (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of fasting manometry and EGG recording, subjects received either intravenous saline, ranitidine, or famotidine, followed by another 30 minutes recording and then three hours of postprandial recording after ingestion of a radiolabelled meal. Images were obtained every 10-15 minutes for three hours to measure gastric emptying and assess antral contractility. Similar testing was performed after omeprazole 20 mg daily for one week. ?Results—Fasting antral phase III migrating motor complexes (MMCs) were more common after ranitidine (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%) compared with placebo (4/14, 29%; p<0.05). Postprandially, ranitidine, famotidine, and omeprazole slowed gastric emptying, increased the amplitude of DAS contractions, increased the EGG power, and increased the antral manometric motility index. ?Conclusions—Suppression of gastric acid secretion with therapeutic doses of gastric acid suppressants is associated with delayed gastric emptying but increased antral motility. ?? Keywords: gastric motility; gastric emptying; histamine H2 receptor antagonists; proton pump inhibitors; gastric acid secretion; scintigraphy PMID:9536950

  15. TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway

    PubMed Central

    Wei, Lunshou; Li, Yan; Suo, Zhimin

    2015-01-01

    Aims: This study was designed to investigate the effects of Tetraspanin 8 (TSPAN8) overexpression and TSPAN8 suppression on gastric cancer cell proliferation and invasion. Furthermore, whether extracellular-signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway was involved in TSPAN8’s function on gastric cancer cells was examined. Methods: The expression of TSPAN8 in human gastric cancer tissues and gastric cancer cell lines was detected using real-time PCR and western blot analysis. TSPAN8-pcDNA3.1 plasmid or TSPAN8 siRNA was transfected into the gastric cancer cell lines to overexpress or suppress TSPAN8. Cells were treated with U0126 to inhibit ERK MAPK pathway. Cell proliferation and invasion were assessed by MTT and transwell-matrigel assay. Results: TSPAN8 was overexpressed in human gastric cancer tissues and gastric cancer cell lines compared with the normal. TSPAN8 overexpression promoted cell proliferation and invasion, while TSPAN8 suppression inhibited cell proliferation and invasion. TSPAN8 could activate the ERK MAPK pathway in gastric cancer cells, and MEK-ERK inhibition reversed the effects of TSPAN8 overexpression on cell proliferation and invasion. Conclusion: This study firstly demonstrated that TSPAN8 promotes gastric cancer cell growth and metastasis at least partially through the activation of ERK MAPK pathway. These findings provided a novel molecular basis for the understanding and treatment of gastric cancer. PMID:26309511

  16. Mouse models of gastric carcinogenesis.

    PubMed

    Yu, Sungsook; Yang, Mijeong; Nam, Ki Taek

    2014-06-01

    Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field. PMID:25061535

  17. Companion diagnostics for the targeted therapy of gastric cancer

    PubMed Central

    Yoo, Changhoon; Park, Young Soo

    2015-01-01

    Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer. PMID:26494953

  18. Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    PubMed

    Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W; Dubeykovskaya, Zinaida A; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R; Setlik, Wanda; Gershon, Michael D; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G; Friedman, Richard A; Konieczny, Stephen F; Worthley, Daniel L; Korinek, Vladimir; Wang, Timothy C

    2015-12-14

    The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche. PMID:26585400

  19. 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

  20. Models of gastric emptying.

    PubMed Central

    Stubbs, D F

    1977-01-01

    Some empirical and theoretical models of the emptying behaviour of the stomach are presented. The laws of Laplace, Hooke, and Poisseuille are used to derive a new model of gastric emptying. Published data on humans are used to test the model and evaluate empirical constants. It is shown that for meals with an initial volume of larger than or equal to 300 ml, the reciprocal of the cube root of the volume of meal remaining is proportional to the time the meal is in the stomach.For meals of initial volume of less than 300 ml the equation has to be corrected for the fact that the 'resting volume' of gastric contents is about 28 ml. The more exact formula is given in the text. As this model invokes no neural or hormonal factors, it is suggested that the gastric emptying response to the volume of a meal does not depend on these factors. The gastric emptying response to the composition of the meal does depend on such factors and a recent model of this process is used to evaluate an empirical constant. PMID:856678

  1. Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

    PubMed Central

    Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

    2015-01-01

    AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal metaplasia score of specimen from the greater curvature of the upper body. The type of gastritis changed from antrum-predominant gastritis to corpus-predominant gastritis with age in both populations. CONCLUSION: Gastric cancer was located in the upper part of the stomach in half of the Mongolian patients; Mongolian patients were infected with non-East-Asian-type H. pylori. PMID:26217093

  2. Allicin induces apoptosis of the MGC-803 human gastric carcinoma cell line through the p38 mitogen-activated protein kinase/caspase-3 signaling pathway.

    PubMed

    Zhang, Xuecheng; Zhu, Yong; Duan, Wei; Feng, Chen; He, Xuan

    2015-04-01

    Gastric cancer is one of the most common forms of malignant tumor, and the development of anti?gastric cancer drugs with minimal toxicity is of clinical importance. Allicin is extracted from Allium sativum (garlic). Recent research, including clinical experiments, has shown that garlic has anticancer and tumor suppressive effects. The present study aimed to investigate the effects of allicin on the MGC?803 human gastric carcinoma cell line, and to further explore the possible mechanisms of its tumor suppressor effects. The effects of allicin on the MGC?803 cells were initially examined using an 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide assay. Hoechst staining was also used, in order to demonstrate the impact of allicin on MGC?803 cell apoptosis. In addition, western blot analysis was performed to determine the abnormal expression levels of apoptosis?associated proteins, following the treatment of MGC?803 cells with allicin. Western blotting was also used to investigate the specific mechanisms underlying allicin?induced apoptosis of MGC?803 cells. The rate of MGC?803 apoptosis was significantly increased, when the concentration and treatment time of allicin were increased. Hoechst staining detected an enhanced rate of apoptosis, and enhanced expression levels of cleaved caspase 3 were determined by western blotting. Notably, the protein expression levels of p38 were increased when the MGC?803 cells were treated with allicin. The results of the present study suggest that allicin may inhibit the proliferation and induce the apoptosis of MGC?803 human gastric carcinoma cells, and this may partially be achieved through the enhanced expression of p38 and cleaved caspase 3. PMID:25523417

  3. NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36.

    PubMed

    Gao, Xinyan; Qiao, Yongfa; Jia, Baohui; Jing, Xianghong; Cheng, Bin; Wen, Lei; Tan, Qiwen; Zhou, Yi; Zhu, Bing; Qiao, Haifa

    2012-01-01

    Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynaptic ?-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36. PMID:23118791

  4. 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

  5. [Indications for surgical treatment of hard scarring gastric ulcers].

    PubMed

    Durleshter, V M; Korochanskaia, N V; Serikova, S N

    2014-01-01

    It was done the comparative analysis of the morphofunctional state of the upper gastrointestinal tract between 350 patients with effective conservative treatment and 104 patients with hard scarring gastric ulcers. The analysis identified the predictors of ineffective medical treatment and led to deliver the indications for timely surgical treatment. It was identified the next indications for planned organ-preserving surgical treatment of patients with hard scarring gastric ulcers: penetrating and non-healing ulcers with large or gigantic size in case of the adequate medical therapy, high-grade dysplasia and colonic metaplasia of the gastric epithelium in the borders or fundus of the ulcer,ulcers combination with fixed cardio-fundal or fundo-corporal hiatal hernias; hypotonic-hypokinetic type of the gastric and duodenal activity with the development of gastrostasis and pronounced duodenogastric reflux. PMID:24781063

  6. Helicobacter pylori in gastric carcinogenesis

    PubMed Central

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  7. Helicobacter pylori in gastric carcinogenesis.

    PubMed

    Ahn, Hyo Jun; Lee, Dong Soo

    2015-12-15

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori (H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to the occurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cagA and vacA are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis. PMID:26690981

  8. 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

  9. [Primary gastric lymphoma].

    PubMed

    Guerrera, C; Marzola, R; Fabi, P; Salomoni, C; Zandi, G; Pozza, E; Rubbini, M; Ortolani, M

    1990-10-01

    Primary gastric lymphoma (P.G.L.), though rare, is nevertheless the most frequent non-epithelial neoplasm of the stomach. The Authors report their experience based on 18 cases of lymphoma observed from 1975 throughout 1989. Diagnostic and therapeutic problems related to the disease are stressed, uncertain in the results the former, still discussed the latter. The crucial role of surgery, either diagnostic or therapeutic, even in advanced stages, is underlined. PMID:2288849

  10. 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

  11. Experimental gastric ulcers induced by immobilization and electric shock of rats and their pharmacotherapy

    NASA Technical Reports Server (NTRS)

    Zabrodin, O. N.

    1980-01-01

    The mechanism of development of experimental gastric ulcers, induced in rats by combined immobilization and electric shock, was analyzed pharmacologically with peripheral neurotropic agents. It is concluded that: (1) The most marked preventive effect in the development of the experimentally induced gastric ulcers was displayed by agents capable of blocking the ascending activation system of the reticular formation. (2) Sympathetic fibers, which disrupt the trophism of the gastric wall, form the efferent portion of the reflex arc. (3) Gastric secretion does not appear to be the primary cause of ulceration.

  12. Pharmacological evidence for the participation of NO-cGMP-KATP pathway in the gastric protective effect of curcumin against indomethacin-induced gastric injury in the rat.

    PubMed

    Díaz-Triste, Nadia Estela; González-García, Martha Patricia; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2014-05-01

    Curcumin, main compound obtained from rizhoma of Curcuma longa, shows antitumoral, antioxidant, anticarcinogenic and gastric protective properties. Recently, it has been demonstrated that curcumin exerts its gastric protective action due to an increase in gastric nitric oxide (NO) levels. However, it is unknown whether these increased NO levels are associated with activation of intracellular signaling pathways. Thus, the purpose of this study was to investigate the role of NO-cGMP-KATP pathway in the gastric protective effect of curcumin during indomethacin-induced gastric injury in the rat. Adult female Wistar rats were gavaged with curcumin (3-300mg/kg, p.o.) or omeprazole (30mg/kg, p.o.) 30min before indomethacin insult (30mg/kg, p.o.). Other groups of rats were administered L-NAME (70mg/kg, i.p.; inhibitor of nitric oxide synthase), ODQ (10mg/kg, i.p.; inhibitor of soluble guanylate cyclase) or glibenclamide (1mg/kg, i.p.; blocker of ATP-sensitive potassium (KATP) channels) 30min before curcumin (30mg/kg, p.o.). 3h after indomethacin administration, rats were sacrificed and gastric injury was evaluated by determining total damaged area. A sample of gastric tissue was harvested and processed to quantify organic nitrite levels. Curcumin significantly protected against indomethacin-induced gastric injury and this effect was comparable to gastroprotective effect by omeprazole. L-NAME, ODQ and glibenclamide significantly prevented the curcumin-mediated gastric protective effect in the indomethacin-induced gastric injury model. Furthermore, curcumin administration induced a significant increase in gastric nitric oxide levels as compared to vehicle administration. Our results show for the first time that curcumin activates NO/cGMP/KATP pathway during its gastro protective action. PMID:24607410

  13. [Effect of prednisolone on the basal gastric secretion in laboratory rats depending on functional state of the stomach adrenoreceptors].

    PubMed

    Trefilov, A B

    2002-04-01

    Activation of the stomach adrenoreceptors with adrenaline resulting in inhibition of fundal glands promotes stimulating effect of prednisolone glucocorticosteroid action on basal gastric secretion. PMID:12058541

  14. 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.

  15. Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer

    PubMed Central

    Mei, Hong; Pu, Jiarui; Xiang, Xuan; Jiao, Wanju; Song, Huajie; Qu, Hongxia; Huang, Kai; Zheng, Liduan; Tong, Qiangsong

    2015-01-01

    Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory lectin, in human cancers. Our previous studies have implicated the potential roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated the functions, downstream targets, and clinical significance of ITLN1 in the progression of gastric cancer. We demonstrated that ITLN1 increased the levels of hepatocyte nuclear factor 4 alpha (HNF4?), resulting in suppression of nuclear translocation and transcriptional activity of ?-catenin in gastric cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor-kappa B, a transcription factor repressing the HNF4? expression, in gastric cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1 suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro and in vivo. In addition, restoration of HNF4? expression prevented the gastric cancer cells from ITLN1-mediated changes in these biological features. In clinical gastric cancer tissues, HNF4? expression was positively correlated with that of ITLN1. Patients with high ITLN1 or HNF4? expression had greater survival probability. Taken together, these data indicate that ITLN1 suppresses the progression of gastric cancer through up-regulation of HNF4?, and is associated with improved survival in patients with gastric cancer. PMID:25965823

  16. Gastroprotective Effect of Selenium on Ethanol-Induced Gastric Damage in Rats

    PubMed Central

    Kim, Jeong-Hwan; Park, Shin-Hyung; Nam, Soo-Wan; Choi, Yung-Hyun

    2012-01-01

    In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 ?g/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 ?g/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging. PMID:22754328

  17. Gastroprotective effect of selenium on ethanol-induced gastric damage in rats.

    PubMed

    Kim, Jeong-Hwan; Park, Shin-Hyung; Nam, Soo-Wan; Choi, Yung-Hyun

    2012-01-01

    In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 ?g/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 ?g/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging. PMID:22754328

  18. Separation and characteristics of two histaminocytes from rat gastric mucosa.

    PubMed

    Lemmi, C A

    1984-02-01

    To determine the properties of rat gastric cells involved in histamine metabolism (histaminocytes), fundic mucosa was enzymatically dispersed prior to separation by sedimentation methods. The distribution of histamine content, histidine decarboxylase (HDC) activity and incorporation of radioactive histidine metabolites were used to determine the characteristics of various populations of gastric cells. All activities measured, as well as most of the dispersed gastric cells, occurred in a narrow range of density between 1.083 and 1.091 g/ml. Velocity sedimentation showed that two populations of histaminocytes can be distinguished. One population has a higher sedimentation rate, suggesting a larger size, contains histamine, HDC activity and incorporates radioactive metabolites. Another population, in fractions with lower sedimentation rates, contains little histamine, has a higher HDC activity than the previous population and also incorporates radiolabelled histidine metabolites. For the first time, two populations of viable histaminocytes have been separated that differ in their biochemical properties. PMID:6711385

  19. AKT plays a crucial role in gastric cancer

    PubMed Central

    SASAKI, TAKAMITSU; YAMASHITA, YUICHI; KUNIYASU, HIROKI

    2015-01-01

    The AKT protein is involved in the phosphatidylinositol-3 kinase signaling pathway and is a vital regulator of survival, proliferation and differentiation in various types of cells. Helicobacter pylori infection induces epithelial cell proliferation and oxidative stress in chronic gastritis. These alterations lead to telomere shortening, resulting in the activation of telomerase. AKT, in particular, is activated by H. pylori-induced inflammation. AKT then promotes the expression of human telomerase reverse transcriptase, which encodes a catalytic subunit of telomerase, and induces telomerase activity, an essential component of the process of carcinogenesis. AKT activation is increased in gastric mucosa with carcinogenic properties and is associated with the low survival of patients with gastric cancer. The findings of the present study suggest that AKT is pivotal in gastric carcinogenesis and progression.

  20. Effect of leucine 13-motilin (KW5139) on early gastric stasis after pylorus-preserving pancreatoduodenectomy.

    PubMed Central

    Matsunaga, H; Tanaka, M; Naritomi, G; Yokohata, K; Yamaguchi, K; Chijiwa, K

    1998-01-01

    OBJECTIVE: To test a hypothesis that exogenously administered motilin would improve early gastric stasis after pylorus-preserving pancreatoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Prolonged gastric stasis is a frequent complication after PPPD. We demonstrated that this might at least in part be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. METHODS: Ten patients with a mean age of 54 years (range, 33-70) who underwent PPPD were studied. An assembly of manometric tubes was placed in the gastric antrum and jejunum (neoduodenum) at surgery. A gastrostomy tube was added for drainage and volume measurements of the gastric juice. After baseline recording, saline as a placebo was given intravenously on day 14 and 0.5 microg/kg of KW5139 (leucine-13 motilin) was given on days 17 and 18 every 2 hours, 6 times a day. The daily volume of gastric juice output and a gastric motility index were measured. RESULTS: The mean period until the first appearance of phase III activity in the stomach was 41 +/- 2 days. The injection of saline did not change the gastric motility index (7.3 +/- 1.1 to 7.1 +/- 1.3 mmHg; p = 0.72). In contrast, motilin resulted in a significant increase in the gastric motility index (7.5 +/- 1.0 to 17.7 +/- 2.0 mmHg; p < 0.001). The saline injection produced no change in the daily gastric juice output (1175 +/- 140 to 1393 +/- 193 mL; p = 0.09). Motilin significantly decreased the gastric juice output (1387 +/- 157 to 934 +/- 142 mL; p = 0.01). CONCLUSIONS: These data indicate that KW5139 is a safe and effective prokinetic drug for the treatment of early gastric stasis after PPPD. PMID:9563538

  1. Is endoscopic resection of gastric gastrointestinal stromal tumors safe?

    PubMed

    Waterman, Alyson L; Grobmyer, Stephen R; Cance, William G; Hochwald, Steven N

    2008-12-01

    Gastric gastrointestinal stromal tumors (GIST) commonly present as an incidental finding on upper gastrointestinal endoscopy. Advances in endoscopic technology have allowed some to perform attempted excision of these lesions endoscopically. The oncologic implications of such an approach remain unclear. A-74-year-old man initially presented with an incidental finding of a 1.6 x 1.8-cm c-kit-positive gastrointestinal stromal tumor with low mitotic activity in the gastric fundus. The patient underwent an attempted endoscopic resection of this mass resulting in incomplete excision and gastric perforation. There was immediate conversion to a celiotomy and the patient underwent partial gastrectomy; there was no evidence of metastatic GIST. Three years later, the patient was noted to have an asymptomatic large pelvic mass (4 x 7 cm) on CT scan and was referred for evaluation. Subsequent surgical exploration revealed a single mass adherent to the pelvic sidewall that was resected. Subsequent pathology demonstrated a c-kit-positive GIST consistent with metastatic disease. Eighteen months later, the patient remains free of disease. Complications from endoscopic resection of gastric GIST may be associated with peritoneal dissemination of disease. This should be considered when formulating a strategy for management of gastric GIST. Complete transperitoneal excision (either open or laparoscopic) with clear margins and without tumor rupture remains the gold standard for management of gastric GIST. PMID:19097534

  2. Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells.

    PubMed

    Lu, Yan-Jie; Geng, Zhi-Jun; Sun, Xiao-Yan; Li, Yu-Hong; Fu, Xiao-Bing; Zhao, Xiang-Yang; Wei, Bo

    2015-10-01

    The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the ?2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that ?2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as ?-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and ?-catenin. Isoprenaline stimulation of ?2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting ?2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression. PMID:26253173

  3. Resveratrol: A potential challenger against gastric cancer

    PubMed Central

    Zulueta, Aida; Caretti, Anna; Signorelli, Paola; Ghidoni, Riccardo

    2015-01-01

    Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here. PMID:26457023

  4. Resveratrol: A potential challenger against gastric cancer.

    PubMed

    Zulueta, Aida; Caretti, Anna; Signorelli, Paola; Ghidoni, Riccardo

    2015-10-01

    Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here. PMID:26457023

  5. Hereditary aspects of gastric cancer.

    PubMed

    Keller, G

    2002-10-01

    Although the etiology of gastric cancer and the mechanisms involved in its carcinogenesis are still poorly understood, dietary habits and life style as well as bacterial infections have been suggested to be important in the tumorigenic process. However, there is also an increasing evidence that a genetic predisposition in at least a subset of patients, plays an important role. Germline mutations in the E-cadherin gene have been described to be the molecular genetic cause of an hereditary diffuse type gastric cancer syndrome. In addition, gastric cancer is observed more frequently in association with some hereditary tumor syndromes which are mainly characterized by tumors in other organs. This article will summarize recent findings about the hereditary diffuse type gastric cancer syndrome and about gastric cancer in association with hereditary tumor syndromes with a known molecular genetic basis. PMID:12417969

  6. 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

  7. Gastric and ectopic varices.

    PubMed

    Henry, Zachary; Uppal, Dushant; Saad, Wael; Caldwell, Stephen

    2014-05-01

    Although often considered together, gastric and ectopic varices represent complications of a heterogeneous group of underlying diseases. Commonly, these are known to arise in patients with cirrhosis secondary to portal hypertension; however, they also arise in patients with noncirrhotic portal hypertension, most often secondary to venous thrombosis of the portal venous system. One of the key initial assessments is to define the underlying condition leading to the formation of these portal-collateral pathways to guide management. In the authors' experience, these patients can be grouped into distinct although sometimes overlapping conditions, which can provide a helpful conceptual basis of management. PMID:24679501

  8. Electrical bioimpedance and other techniques for gastric emptying and motility evaluation

    PubMed Central

    Huerta-Franco, María Raquel; Vargas-Luna, Miguel; Montes-Frausto, Juana Berenice; Flores-Hernández, Corina; Morales-Mata, Ismael

    2012-01-01

    The aim of this article is to identify non-invasive, inexpensive, highly sensitive and accurate techniques for evaluating and diagnosing gastric diseases. In the case of the stomach, there are highly sensitive and specific methods for assessing gastric motility and emptying (GME). However, these methods are invasive, expensive and/or not technically feasible for all clinicians and patients. We present a summary of the most relevant international information on non-invasive methods and techniques for clinically evaluating GME. We particularly emphasize the potential of gastric electrical bioimpedance (EBI). EBI was initially used mainly in gastric emptying studies and was essentially abandoned in favor of techniques such as electrogastrography and the gold standard, scintigraphy. The current research evaluating the utility of gastric EBI either combines this technique with other frequently used techniques or uses new methods for gastric EBI signal analysis. In this context, we discuss our results and those of other researchers who have worked with gastric EBI. In this review article, we present the following topics: (1) a description of the oldest methods and procedures for evaluating GME; (2) an explanation of the methods currently used to evaluate gastric activity; and (3) a perspective on the newest trends and techniques in clinical and research GME methods. We conclude that gastric EBI is a highly effective non-invasive, easy to use and inexpensive technique for assessing GME. PMID:22368782

  9. 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

  10. 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

  11. Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

    PubMed Central

    Kang, Jung-Woo; Yun, Nari; Han, Hae-Jung; Kim, Jeom-Yong; Kim, Joo-Young; Lee, Sun-Mee

    2014-01-01

    Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101) on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-?B, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-?B translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators. PMID:25610477

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

    SciTech Connect

    Wu, William Ka Kei; Lee, Chung Wa; Cho, Chi Hin; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong ; Chan, Francis Ka Leung; Yu, Jun; Sung, Joseph Jao Yiu

    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.

  13. Absence of ras gene mutations in early gastric carcinomas.

    PubMed Central

    Craanen, M E; Blok, P; Top, B; Boerrigter, L; Dekker, W; Offerhaus, G J; Tytgat, G N; Rodenhuis, S

    1995-01-01

    The aims of this study were to assess the prevalence and type of activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes in a series of early gastric carcinomas in white patients and to correlate these ras gene mutations, if any, with the histological type (Lauren classification), the type of growth pattern, and with the Helicobacter pylori status. Haematoxylin and eosin and Giemsa stained sections from 45 formalin fixed, paraffin wax embedded early gastric carcinomas were used to assess the Lauren type, the type of growth pattern, and the antral H pylori status. DNA was extracted according to standard procedures. Mutations at codon 12 of the Ki-ras gene were examined with a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) method and dot blot hybridisation with allele-specific 32P-labelled oligodeoxynucleotide (ASO) probes. All other ras genes were analysed with specific PCR amplification and dot blot hybridisation with ASO probes. Mutations were detected by overnight autoradiography at -70 degrees C. Some 20 intestinal-type and 25 diffuse-type early gastric carcinomas were seen. According to growth pattern, there were 24 small mucosal type early gastric carcinomas, five superficial spreading type early gastric carcinomas, and 16 penetrating type early gastric carcinomas (four penetrating A type, 12 penetrating B type). H pylori was found in the antral mucosa of 28 early gastric carcinomas (62%). Activating ras gene mutations were not found. It was discovered that activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes do not play a part in the development of early gastric carcinomas in white subjects, irrespective of Lauren type. Moreover, differences in biological behaviour between early carcinomas with different types of growth pattern are not related to these ras gene mutations. Finally, H pylori positive and H pylori negative gastric carcinomas cannot be discriminated on the basis of ras gene mutational analysis. Images Figure 2 PMID:8537044

  14. 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

  15. 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

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

    PubMed Central

    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

  17. Treatment Option Overview (Gastric Cancer)

    MedlinePLUS

    ... Gastric cancer is a disease in which malignant (cancer) cells form in the lining of the stomach. The ... diagnosed, tests are done to find out if cancer cells have spread within the stomach or to other ...

  18. General Information about Gastric Cancer

    MedlinePLUS

    ... Gastric cancer is a disease in which malignant (cancer) cells form in the lining of the stomach. The ... diagnosed, tests are done to find out if cancer cells have spread within the stomach or to other ...

  19. Neonatal zygomycosis with gastric perforation.

    PubMed

    Mathur, N B; Gupta, Aashima

    2013-07-01

    Zygomycosis is a rare infection in neonates. The clinical presentation is non-specific and diagnosis most often is made at autopsy. Surgical debridement performed early improves survival. We report a case of neonatal zygomycosis with gastric perforation. PMID:23942436

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

    SciTech Connect

    Pandi, Narayanan Sathiya 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.

  1. 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

  2. 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

  3. Genetics and gastric cancer susceptibility

    PubMed Central

    Lu, Yan; Lu, Fang; Zeng, Sha; Sun, Suqing; Lu, Li; Liu, Lifeng

    2015-01-01

    Gastric cancer has high morbidity and mortality in China. It is ranked first in malignant tumors of the digestive system. Its etiology and pathogenesis are still unclear, but they may be associated with a variety of factors. Genetic susceptibility genes have become a research hotspot in China. Elucidating the genetic mechanisms of gastric cancer can facilitate achieving individualized prevention and developing more effective methods to reduce clinical adverse consequences, which has important clinical significance. Genetic susceptibility results from the influence of genetic factors or specific genetic defects that endow an individual’s offspring with certain physiological and metabolic features that are prone to certain diseases. Currently, studies on the genetic susceptibility genes of gastric cancer have become a hotspot. The purpose is to screen for the etiology of gastric cancer, search for gene therapy methods, and ultimately provide a scientific basis for the prevention and control of gastric cancer. This article reviews the current progress of studies on genetic susceptibility genes for gastric cancer. PMID:26309491

  4. DBGC: A Database of Human Gastric Cancer

    PubMed Central

    Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

  5. Statistical processing for gastric slow-wave identification.

    PubMed

    Grant, M S; Williams, R D

    2002-07-01

    Successful identification of gastric slow waves in canine gastric electrical activity (GEA) data was achieved using a statistical data-processing procedure based on the multiple linear regression (MLR) curve fitting technique. Both distal and proximal waveforms were identified, first by construction of separate orthonormal bases from pre-selected sets of representative distal and proximal gastric slow waves (GSWs). Respective basis matrices were used to fit proximal and distal data to an MLR data model. Residual waveforms were computed from the original and 'fitted' waveforms and used in identifying GSWs in the data. Canine GEA data were split into 1,800-point blocks, and each 245-point data segment in a block was processed to identify the GSWs. Gastric slow waves were located in the data using a residual mean-squared error (MSE) threshold and, for distal GEA data, the minimum value of the main distal waveform peak. All threshold values were determined empirically and were set to detect GSWs while limiting false matches. Identification rates of 95% and 99% for proximal and distal GSWs, respectively, represent a significant improvement over those obtained in a previous study in which the same data were analysed using linear signal-processing methods. The use of the method presented in this paper for real-time identification of GSWs in conjunction with an implantable gastric pacer unit appears promising. Because the technique is inherently customisable, results obtained in this study should also be applicable to human subjects. PMID:12227630

  6. 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

  7. Behavior of almond oil bodies during in vitro gastric and intestinal digestion.

    PubMed

    Gallier, Sophie; Singh, Harjinder

    2012-05-01

    An aqueous suspension of almond oil bodies (about 10% lipids) was prepared and subjected to in vitro gastric (with pepsin) and intestinal (with bile salts and pancreatin) digestion, simulating fasting conditions. The physicochemical and structural changes of the almond oil body emulsion were examined. The almond oil body emulsion behaved similarly to a protein-stabilized emulsion, with flocculation of the oil bodies occurring under gastric conditions. Proteins, peptides, and phospholipids covered the surface of the oil bodies throughout gastric digestion. Under intestinal conditions, bile salts displaced the interfacial peptides and phospholipids, and disrupted the flocs. Gastric pepsinolysis of almond proteins was a prerequisite for their digestion in the duodenum. The oil body membrane had a negative impact on the efficiency of gastric digestion, and long chain fatty acids, the main lipolytic products, accumulated at the surface of the oil bodies and therefore limited the activity of pancreatic lipase. PMID:22354453

  8. 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.

  9. Sodium bicarbonate treatment prevents gastric emptying delay caused by acute exercise in awake rats.

    PubMed

    Silva, Moisés T B; Palheta-Junior, Raimundo C; Sousa, Daniel F; Fonseca-Magalhães, Patrícia A; Okoba, Willy; Campos, Caio P S; Oliveira, Ricardo B; Magalhães, Pedro J C; Santos, Armenio A

    2014-05-01

    Physical exercise, mainly after vigorous activity, may induce gastrointestinal dysmotility whose mechanisms are still unknown. We hypothesized that physical exercise and ensuing lactate-related acidemia alter gastrointestinal motor behavior. In the present study, we evaluated the effects of short-term exercise on gastric emptying rate in awake rats subjected to 15-min swimming sessions against a load equivalent to 5% of their body weight. After 0, 10, or 20 min of exercise testing, the rats were gavage fed with 1.5 ml of a liquid test meal (0.5 mg/ml of phenol red in 5% glucose solution) and euthanized 10 min postprandially to measure fractional gastric dye recovery. In addition to inducing acidemia and increasing blood lactate levels, acute exercise increased (P < 0.05) gastric retention. Such a phenomenon presented a positive correlation (P < 0.001) between blood lactate levels and fractional gastric dye recovery. Gastric retention and other acidbase-related changes were all prevented by NaHCO3 pretreatment. Additionally, exercise enhanced (P < 0.05) the marker's progression through the small intestine. In anesthetized rats, exercise increased (P < 0.05) gastric volume, measured by a balloon catheter in a barostat system. Compared with sedentary control rats, acute exercise also inhibited (P < 0.05) the contractility of gastric fundus strips in vitro. In conclusion, acute exercise delayed the gastric emptying of a liquid test meal by interfering with the acid-base balance. PMID:24557800

  10. PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

    PubMed Central

    Song, Zongchang; Liu, Wenying; Xiao, Yu; Zhang, Minghui; Luo, Yan; Yuan, Weiwei; Xu, Yu; Yu, Guanzhen; Hu, Yide

    2015-01-01

    PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer. PMID:26252227

  11. Expression of Jagged1 predicts postoperative clinical outcome of patients with gastric cancer

    PubMed Central

    Liu, Hao; Zhang, Heng; Shen, Zhenbin; Wang, Xuefei; Wang, Zhenglin; Xu, Jiejie; Sun, Yihong

    2015-01-01

    Background: Clinical significance of Notch1 activation in gastric cancer has been elucidated in our previous study, but the role of its ligands remains obscure. This study aims to evaluate the prognostic value of Jagged1 expression in patients with gastric cancer. Methods: We examined Jagged1 expression in tumor and nontumor tissues in retrospectively enrolled 302 patients with gastric cancer undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of Jagged1 expression and its association with clinicopathological features. We created a predictive nomogram by integrating Jagged1 expression with the TNM staging system for overall survival of gastric cancer patients. Results: Jagged1 expression in gastric cancer was decreased compared with that in nontumor tissues. Low expression of Jagged1 in tumor and nontumor both predicted a dismal outcome. The Jagged1 risk derived from Jagged1 expression in tumor/nontumor tissue gave a further discrimination for the prognosis of gastric cancer patients. By Cox multivariate analysis, the Jagged1 risk was defined as an independent prognostic factor. The generated nomogram performed well in predicting the 3- and 5-year overall survival of gastric cancer patients. Conclusion: Jagged1 is a potential prognostic biomarker for overall survival, which could be integrated with TNM stage to give a better risk stratification for gastric cancer patients.

  12. Gastric lactobezoar - a rare disorder?

    PubMed

    Heinz-Erian, Peter; Gassner, Ingmar; Klein-Franke, Andreas; Jud, Veronika; Trawoeger, Rudolf; Niederwanger, Christian; Mueller, Thomas; Meister, Bernhard; Scholl-Buergi, Sabine

    2012-01-01

    Gastric lactobezoar, a pathological conglomeration of milk and mucus in the stomach of milk-fed infants often causing gastric outlet obstruction, is a rarely reported disorder (96 cases since its first description in 1959). While most patients were described 1975-1985 only 26 children have been published since 1986. Clinically, gastric lactobezoars frequently manifest as acute abdomen with abdominal distension (61.0% of 96 patients), vomiting (54.2%), diarrhea (21.9%), and/or a palpable abdominal mass (19.8%). Respiratory (23.0%) and cardiocirculatory (16.7%) symptoms are not uncommon. The pathogenesis of lactobezoar formation is multifactorial: exogenous influences such as high casein content (54.2%), medium chain triglycerides (54.2%) or enhanced caloric density (65.6%) of infant milk as well as endogenous factors including immature gastrointestinal functions (66.0%), dehydration (27.5%) and many other mechanisms have been suggested. Diagnosis is easy if the potential presence of a gastric lactobezoar is thought of, and is based on a history of inappropriate milk feeding, signs of acute abdomen and characteristic features of diagnostic imaging. Previously, plain and/or air-, clear fluid- or opaque contrast medium radiography techniques were used to demonstrate a mass free-floating in the lumen of the stomach. This feature differentiates a gastric lactobezoar from intussusception or an abdominal neoplasm. Currently, abdominal ultrasound, showing highly echogenic intrabezoaric air trapping, is the diagnostic method of choice. However, identifying a gastric lactobezoar requires an investigator experienced in gastrointestinal problems of infancy as can be appreciated from the results of our review which show that in not even a single patient gastric lactobezoar was initially considered as a possible differential diagnosis. Furthermore, in over 30% of plain radiographs reported, diagnosis was initially missed although a lactobezoar was clearly demonstrable on repeat evaluation of the same X-ray films. Enhanced diagnostic sensitivity would be most rewarding since management consisting of cessation of oral feedings combined with administration of intravenous fluids and gastric lavage is easy and resolves over 85% of gastric lactobezoars. In conclusion, gastric lactobezoar is a disorder of unknown prevalence and is nowadays very rarely published, possibly because of inadequate diagnostic sensitivity and/or not yet identified but beneficial modifications of patient management. PMID:22216886

  13. Treatment Options by Stage (Gastric Cancer)

    MedlinePLUS

    ... Gastric) Cancer Prevention Stomach (Gastric) Cancer Screening Age, diet, and stomach disease can affect the risk of ... may be used alone or to carry drugs, toxins , or radioactive material directly to cancer cells. For ...

  14. Endoscopic appearance of irradiated gastric mucosa.

    PubMed

    De Sagher, L I; Van den Heule, B; Van Houtte, P; Engelholm, L; Balikdjan, D; Bleiberg, H

    1979-09-01

    Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds. PMID:488012

  15. Oxidative DNA damage accumulation in gastric carcinogenesis

    PubMed Central

    Farinati, F; Cardin, R; Degan, P; Rugge, M; Di, M; Bonvicini, P; Naccarato, R

    1998-01-01

    Background—Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role. ?Aims—In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy. ?Patients—Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls. ?Methods—Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed. ?Results—8OHdG concentrations (mean number of adducts/105 dG residues) were significantly higher in chronic atrophic gastritis (p=0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p=0.02), intestinal metaplasia (p=0.035), and H pylori infection (p=0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r=0.53, p=0.002). ?Conclusions—Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation. ?? Keywords: free radicals; oxidative DNA damage; gastric carcinogenesis; precancerous changes; peroxidative damage PMID:9577340

  16. 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

  17. 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

  18. Osteopetrorickets due to Snx10 Deficiency in Mice Results from Both Failed Osteoclast Activity and Loss of Gastric Acid-Dependent Calcium Absorption

    PubMed Central

    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.

    2015-01-01

    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-deficent 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

  19. 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

  20. [Gastric volvulus: diagnosis and management].

    PubMed

    Bedioui, Heykal; Bensafta, Zoubeir

    2008-03-01

    Gastric volvulus is defined as an abnormal rotation of all or part of the stomach around one of its axes. It is a diagnostic emergency and therapeutic challenge because in acute forms it may lead to gastric strangulation with a high risk of ischemia and necrosis. Organoaxial and mesentericoaxial volvulus are distinguished according to the direction of rotation. The most common cause of gastric volvulus is hiatal hernia, but the principal predisposing factor is ligamentous laxity. The diagnosis is suspected when erect chest radiograph images show a high air-fluid level in the chest. Moreover a barium swallow is essential to confirm the diagnosis. Nonetheless, a computed tomography (CT) scan now provides a comprehensive description of the thoracic lesion, including stomach vitality. Gastric volvulus requires surgical treatment, specifically volvulus reduction, reintegration of the stomach into the abdominal cavity in cases of intrathoracic migration, and correction of causal factors. Resection of the hernial sac and the role of gastropexy for preventing recurrence remain controversial. Advances in laparoscopic surgery have made possible a laparoscopic approach to most cases of chronic gastric volvulus. PMID:17587536

  1. Docosahexaenoic acid, an omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury.

    PubMed

    Pineda-Peña, Elizabeth Arlen; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2012-12-15

    Previous studies have shown gastroprotective effect of fish oil in several experimental models. However, the mechanisms and active compounds underlying this effect are not fully understood. Fish oil has several components; among them, one of the most studied is docosahexaenoic acid (DHA), which is an omega-3 long-chain polyunsaturated fatty acid. The aim of this study was to examine the gastroprotective effect of DHA as a pure compound in a rat model of indomethacin-induced gastric injury as well as elucidate some of the mechanism(s) behind DHA's gastroprotective effect. Indomethacin was orally administered to induce an acute gastric injury (3, 10 and 30mg/kg). Omeprazol (a proton pump inhibitor, 30mg/kg, p.o.) and DHA (3, 10, 30mg/kg, p.o.) were gavaged 30 and 120min, respectively, before indomethacin insult (30mg/kg p.o.). Three hours after indomethacin administration, rats were sacrificed, gastric injury was evaluated by determining the total damaged area. A sample of gastric tissue was harvested and processed to quantify prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) levels by enzyme-linked immunosorbent assay. Indomethacin produced gastric injury in dose-dependent manner. DHA protected against indomethacin-induced gastric damage, and this effect was comparable with omeprazol's gastroprotective effect. DHA did not reverse the indomethacin-induced reduction of PGE(2) gastric levels. In contrast, DHA partially prevented the indomethacin-induced increase in LTB(4) gastric levels. This is the first report demonstrating DHA's gastroprotective effect as a pure compound. Furthermore, the results reveal that the gastroprotective effect is mediated by a decrease in gastric LTB(4) levels in indomethacin-induced gastric damage. PMID:23063544

  2. Gastric secretion--from Pavlov's nervism to Popielski's histamine as direct secretagogue of oxyntic glands.

    PubMed

    Konturek, S J

    2003-12-01

    Gastric acid and pepsin secretions result from the interplay of neurohormonal factors with stimulatory and inhibitory actions on oxyntic glands. At the turn of XIX century, the notion of nervism or entire neural control of digestive functions, developed by Pavlov prevailed. However, in the second part of XX century, hormonal control has been thought to play a major role in the mechanism of gastric secretion, especially gastrin, which was isolated and synthesized in 1964 by Gregory. Polish traces in gastroenterological history started with the discovery of histamine, a non-nervous and non-gastrin compound in oxyntic mucosa by L. Popielski in 1916, who found that this amine is the most potent and direct stimulant of gastric acid secretion. This histamine concept was supported by leading American gastroenterologists such as A.C. Ivy, championed later by C.F. Code, and clinically applied for testing gastric secretion by K. Kowalewski. Recently, it received a strong support from pharmacological research when J. Black designed H(2)-receptors antagonists, which were first discovered by M.I. Grossman and S.J. Konturek to inhibit not only histamine-, but also meal- and vagally-induced gastric acid secretion, thus reinforcing the notion of the crucial significance of histamine in the control of gastric secretion as the final common chemostimulator. In conclusion, Polish traces appear to be substantial in gastric history due: 1) to discovery by Popielski that histamine is a major, direct stimulus of gastric secretion; 2) to clinical application of this agent by Kowalewski in testing maximal gastric secretory activity; and 3) to clinical use of histamine H(2)-antagonists in control of gastric acid secretion and treatment of peptic ulcers. PMID:15075464

  3. 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

  4. Obstructing Gastric Carcinoma Complicating Pregnancy

    PubMed Central

    Sims, Edward H.; Schlater, Theodore L.; Sims, Maureen; Lou, Mary Ann

    1980-01-01

    Although gastric cancer has not been reported in association with pregnancy, the authors encountered it in a paraplegic young pregnant woman presenting with gastric outlet obstruction. Fiberoptic gastroscopy and biopsy provided the surprising tissue diagnosis. Ultrasound was helpful in assessing the size and position of the fetus. Intravenous fluid therapy and total parenteral nutrition enabled the authors to correct the negative nitrogen balance and metabolic derangement, and to improve the operative risk to both the mother and the fetus. Cesarean section delivered a viable baby. A high gastrectomy relieved the patient of her obstruction and tumor burden. Although the long-term prognosis of gastric cancer remains grim, having saved the mother and the baby through such an ordeal is a rewarding experience. PMID:7373660

  5. Megaduodenum associated with gastric strongyloidiasis.

    PubMed

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

    2015-01-01

    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 10kg 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

  6. Evolution of Gastric Cancer Treatment: From the Golden Age of Surgery to an Era of Precision Medicine

    PubMed Central

    Choi, Yoon Young; Noh, Sung Hoon

    2015-01-01

    Gastric cancer imposes a global health burden. Although multimodal therapies have proven to benefit patients with advanced diseases after curative surgery, the prognosis of most advanced cancer patients still needs to be improved. Surgical extirpation is the mainstay of gastric cancer treatment. Indeed, without curative surgery, variations and combinations of chemotherapy and/or radiation cannot bring clinically meaningful success. Centered around D2 surgery, adjuvant and peri-operative multimodal therapies have improved survival in a certain group of gastric cancer patients. Moving toward a personalized cancer therapy era, molecular targeted strategies have been tested in clinical trials for gastric cancer. With some success and failures, we have learned valuable lessons regarding the biology of gastric cancer and the clinical relevance of biological therapies in addition to conventional treatments. Future treatment of gastric cancer will be shifted to molecularly tailored and genome information-based personalized therapy. Collaboration across disciplines and actively adopting emerging anti-cancer strategies, along with in-depth understanding of molecular and genetic underpinnings of tumor development and progression, are imperative to realizing personalized therapy for gastric cancer. Although many challenges remain to be overcome, we envision that the era of precision cancer medicine for gastric cancer has already arrived and anticipate that current knowledge and discoveries will be transformed into near-future clinical practice for managing gastric cancer patients. PMID:26256958

  7. The G-protein-coupled bile acid receptor Gpbar1 (TGR5) suppresses gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway.

    PubMed

    Guo, Cong; Su, Jia; Li, Zhijun; Xiao, Rui; Wen, Jianxun; Li, Yanyan; Zhang, Meng; Zhang, Xueting; Yu, Donna; Huang, Wendong; Chen, Wei-Dong; Wang, Yan-Dong

    2015-10-27

    Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles in regulation of energy homeostasis and glucose metabolism. Here we show that TGR5 is a suppressor of gastric cancer cell proliferation and migration through antagonizing STAT3 signaling pathway. We firstly show that TGR5 activation greatly inhibited proliferation and migration of human gastric cancer cells and strongly induced gastric cancer cell apoptosis. We then found that TGR5 activation antagonized STAT3 signaling pathway through suppressing the phosphorylation of STAT3 and its transcription activity induced by lipopolysaccharide (LPS) or interleukin-6. TGR5 overexpression with ligand treatment inhibited gene expression mediated by STAT3. It suggests that TGR5 antagonizes gastric cancer proliferation and migration at least in part by inhibiting STAT3 signaling. These findings identify TGR5 as a suppressor of gastric cancer cell proliferation and migration that may serve as an attractive therapeutic tool for human gastric cancer. PMID:26417930

  8. Gastric Motility Following Ingestion of a Solid Meal in a Cohort of Adult Asthmatics

    PubMed Central

    Pathmeswaran, Arunasalam; de Silva, Arjuna Priyadharshin; Dassanayake, Anuradha Supun; Ranasinha, Channa Dhammika; de Silva, Hithanadura Janaka

    2013-01-01

    Background/Aims Asthmatics have abnormal esophageal motility and increased prevalence of gastroesophageal reflux disease (GERD). The contribution of gastric motility is less studied. We studied gastric myoelectrical activity, gastric emptying (GE) and their association with GERD symptoms and vagal function in adult asthmatics. Methods Thirty mild, stable asthmatics and 30 healthy controls underwent real-time ultrasonography and 1 hour pre- and post-prandial cutaneous electrogastrography, following a test meal (480 kcal, 60% carbohydrate, 20% protein, 20% fat and 200 mL water). The percentage of normal slow waves and arrhythmias, dominant frequency and power, frequency of antral contractions, gastric emptying rate (GER) and antral motility index (MI) was calculated. Twenty-seven asthmatics underwent gastroscopy and in all subjects GERD symptoms were assessed by a validated questionnaire. Vagal function parameters were correlated with gastric motility parameters. Results The asthmatics (37% male; 34.8 ± 8.4 years) and controls (50% male; 30.9 ± 7.7 years) were comparable. None had endoscopic gastric pathological changes. Twenty asthmatics described GERD symptoms. Twenty-two (73.3%) asthmatics showed a hypervagal response. Compared to controls, asthmatics had delayed GER and lower MI, lower percentage of normal gastric slow waves, more gastric dysrythmias and failed to increase the post-prandial dominant power. There was no correlation of GE and cutaneous electrogastrography parameters with presence of GERD symptoms or with vagal function. Conclusions Asthmatics showed abnormal gastric myoelectrical activity, delayed GE and antral hypomotility in response to a solid meal compared to controls. There was no association with vagal function or GERD symptom status. PMID:23875103

  9. 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

  10. Gastroprotective and Antioxidant Effects of Lobaria pulmonaria and Its Metabolite Rhizonyl Alcohol on Indomethacin-Induced Gastric Ulcer.

    PubMed

    Atalay, Fadime; Odabasoglu, Fehmi; Halici, Mesut; Cakir, Ahmet; Cadirci, Elif; Aslan, Ali; Aydin Berktas, Ozlem; Kazaz, Cavit

    2015-11-01

    Two lichen metabolites, rhizonaldehyde (1) and rhizonyl alcohol (2), were isolated from the acetone extract of Lobaria pulmonaria by chromatographic methods, and their chemical structures were determined by UV/VIS, IR, and 1D- and 2D-NMR spectroscopic methods. The gastroprotective and in vivo antioxidant activities of extracts of L. pulmonaria and its metabolites, 1 and 2, were investigated in indomethacin-induced ulcer models in rats. The gastric lesions were significantly reduced by acetone, hexane, and CHCl3 extracts, with 75.3-41.5% inhibition. Rhizonyl alcohol (2) significantly reduced the gastric lesions with an inhibition rate of 84.6-42.8%, whereas rhizonaldehyde (1) significantly increased the gastric lesions. Antioxidant parameters and myeloperoxidase activities were also evaluated in the gastric tissues of the rats. Indomethacin caused oxidative stress, which resulted in lipid peroxidation in gastric tissues by decreasing the levels of the antioxidants as compared to healthy rat tissues. In contrast to indomethacin, all extracts and rhizonyl alcohol (2) caused a significant decrease in lipid peroxidation levels and an increase in antioxidant parameters, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase, and reduced glutathione in gastric tissues. The administration of rhizonyl alcohol (2) also resulted in a decrease in gastric myeloperoxidase activity increased by indomethacin. The gastroprotective effect of rhizonyl alcohol (2) can be attributed to its antioxidant properties and its suppressing effect on neutrophil infiltration into gastric tissues. PMID:26567953

  11. 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.

  12. Gastric juice acidity in upper gastrointestinal diseases

    PubMed Central

    Lu, Pei-Jung; Hsu, Ping-I; Chen, Chung-Hsuan; Hsiao, Michael; Chang, Wei-Chao; Tseng, Hui-Hwa; Lin, Kung-Hung; Chuah, Seng-Kee; Chen, Hui-Chun

    2010-01-01

    AIM: To search the independent factors determining gastric juice acidity and to investigate the acidity of gastric juices in various benign and malignant upper gastrointestinal diseases. METHODS: Fasting gastric juice acidity of 165 healthy subjects and 346 patients with esophageal ulcer (n = 21), gastric ulcer (n = 136), duodenal ulcer (n = 100) or gastric cancer (n = 89) were measured and compared. Additionally, gastric specimens were taken from the antrum and body for rapid urease test and histological examination. RESULTS: Multivariate analysis revealed that bile stain of gastric juice, high acute inflammatory score of the corpus, and atrophy of the corpus were independent risk factors for the development of gastric hypoacidity with odds ratios of 3.1 (95% CI: 1.3-7.3), 3.1 (95% CI: 1.2-7.9) and 3.5 (95% CI: 1.3-9.2). Esophageal ulcer and duodenal ulcer patients had a lower pH level (1.9 and 2.1 vs 2.9, both P < 0.05) of gastric juices than healthy subjects. In contrast, gastric ulcer and gastric cancer patients had a higher pH level (3.4 and 6.6 vs 2.9, both P < 0.001) than healthy controls. Hypoacidity existed in 22%, 5%, 29%, 5% and 88% of healthy subjects, esophageal ulcer, gastric ulcer, duodenal ulcer and gastric cancer patients, respectively. CONCLUSION: Bile reflux, atrophy and dense neutrophil infiltrate of the corpus are three independent factors determining the acidity of gastric juice. PMID:21086570

  13. Remote ischemic postconditioning protects against gastric mucosal lesions in rats

    PubMed Central

    Wang, Tao; Zhou, Ye-Ting; Chen, Xin-Nian; Zhu, An-Xiang; Wu, Bo-Hua

    2014-01-01

    AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury. METHODS: Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h. Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36), or sham treatment (n = 36). Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO). Additional samples were processed for histologic analysis by hematoxylin and eosin staining. Blood samples were similarly collected to determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor (TNF)-? and interleukin (IL)-10. RESULTS: The pathologic changes in gastric tissue induced by IR were observed by light microscopy. Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion (5.85 ± 0.22 vs 7.72 ± 0.43; P < 0.01). In addition, RIP treatment decreased the serum activities of LDH (3.31 ± 0.32 vs 6.46 ± 0.03; P < 0.01), CK (1.94 ± 0.20 vs 4.54 ± 0.19; P < 0.01) and the concentration of TNF-? (53.82 ± 0.85 vs 88.50 ± 3.08; P < 0.01), and elevated the concentration of IL-10 (101.46 ± 5.08 vs 99.77 ± 4.32; P < 0.01) induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation in MDA (3.79 ± 0.29 vs 6.39 ± 0.81) content, XOD (7.81 ± 0.75 vs 10.37 ± 2.47) and MPO (0.47 ± 0.05 vs 0.82 ± 0.03) activities, and decrease in SOD (4.95 ± 0.32 vs 3.41 ± 0.38; P < 0.01) activity in the gastric tissue as measured at 6 h. CONCLUSION: RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions. PMID:25071347

  14. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    SciTech Connect

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  15. 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

  16. Antiadhesive property of microalgal polysaccharide extract on the binding of Helicobacter pylori to gastric mucin.

    PubMed

    Loke, Mun Fai; Lui, Sook Yin; Ng, Bee Ling; Gong, Min; Ho, Bow

    2007-07-01

    The emergence of antibiotic-resistant Helicobacter pylori is of concern in the treatment of H. pylori-associated gastroduodenal diseases. As the organism was reported to bind gastric mucin, we used porcine gastric mucin as substrate to assess the antiadhesive property of polysaccharides derived from Spirulina (PS), a commercially available microalga, against the binding of H. pylori to gastric mucin. Results show that polysaccharides prevented H. pylori from binding to gastric mucin optimally at pH 2.0, without affecting the viability of either bacteria or gastric epithelial cells, thus favouring its antiadhesive action in a gastric environment. Using ligand overlay analysis, polysaccharide was demonstrated to bind H. pylori alkyl hydroperoxide reductase (AhpC) and urease, which have shown here to possess mucin-binding activity. An in vivo study demonstrated that bacteria load was reduced by >90% in BALB/c mice treated with either Spirulina or polysaccharides. It is thus suggested that polysaccharides may function as a potential antiadhesive agent against H. pylori colonization of gastric mucin. PMID:17521357

  17. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

    PubMed Central

    Magalhães, Ana; Marcos-Pinto, Ricardo; Nairn, Alison V.; Rosa, Mitche dela; Ferreira, Rui M.; Junqueira-Neto, Susana; Freitas, Daniela; Gomes, Joana; Oliveira, Patrícia; Santos, Marta R.; Marcos, Nuno T.; Xiaogang, Wen; Figueiredo, Céu; Oliveira, Carla; Dinis-Ribeiro, Mário; Carneiro, Fátima; Moremen, Kelley W.; David, Leonor; Reis, Celso A.

    2015-01-01

    Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local proinflammatory signature with significantly higher TNF-? levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity. PMID:26144047

  18. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.

    PubMed

    Magalhães, Ana; Marcos-Pinto, Ricardo; Nairn, Alison V; Dela Rosa, Mitche; Ferreira, Rui M; Junqueira-Neto, Susana; Freitas, Daniela; Gomes, Joana; Oliveira, Patrícia; Santos, Marta R; Marcos, Nuno T; Xiaogang, Wen; Figueiredo, Céu; Oliveira, Carla; Dinis-Ribeiro, Mário; Carneiro, Fátima; Moremen, Kelley W; David, Leonor; Reis, Celso A

    2015-09-01

    Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-? levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity. PMID:26144047

  19. Novel therapy for advanced gastric cancer

    PubMed Central

    Zhang, Yue; Wu, Shenhong

    2015-01-01

    Gastric cancer (GC) is a common lethal malignancy. Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States. Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease. The median overall survival (OS) is less than one year for advanced GC patients; thus, there is an urgent unmet need to develop novel therapy for GC. Although multiple targeted agents were studied, only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit (5.2 mo vs 3.8 mo, P = 0.047) as a single agent; 2.2 mo improvement of survival (9.6 mo vs 7.4 mo, P = 0.017) when combined with paclitaxel in previously treated advanced GC patients. It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab. Even with limited success, targeted therapy may be improved by developing new biomarkers. Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials. More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities. PMID:26600926

  20. The etiology of gastric cancer.

    PubMed

    Forman, D

    1991-01-01

    We review recent evidence concerning risk factors for gastric cancer. An overview of analytical studies shows convincing evidence of a protective effect of fruit and vegetables. The specific protective constituents have not been firmly established, but micronutrients, especially ascorbic acid, are probably of importance. Other dietary factors that show a consistent pattern of effect in different studies are the moderate risks associated with high intake of preserved foods and salt. Evidence also indicates that gastric cancer is associated with tobacco consumption, although even in continuing heavy smokers the risk does not exceed two fold. Another non-dietary factor of potential importance is infection with the bacterium, Helicobacter (Campylobacter) pylori. The model of Correa and co-workers currently offers the best working hypothesis to explain the etiology of gastric cancer. Although the endogenous synthesis of N-nitroso compounds is central to the model, it is not yet clear what the rate-limiting steps are. Exposure to nitrate per se does not directly cause gastric cancer. PMID:1855854

  1. Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

    PubMed

    Lee, I-C; Baek, H-S; Kim, S-H; Moon, C; Park, S-H; Kim, S-H; Shin, I-S; Park, S-C; Kim, J-C

    2015-03-01

    This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-? (TNF-?) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-? and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities. PMID:24972622

  2. Inhibitory effect of octreotide on gastric cancer growth via MAPK pathway

    PubMed Central

    Wang, Chun-Hui; Tang, Cheng-Wei; Liu, Chun-Lun; Tang, Li-Ping

    2003-01-01

    AIM: Somatostatin and its analogues may suppress the growth of various tumor cells. However, the effect of octreotide on growth of gastric adenocarcinoma is still largely unknown. This study was to explore if octreotide could inhibit the growth of gastric adenocarcinoma and its probable mechanisms. METHODS: Proliferation of gastric cancer cell line affected by octreotide was determined by 3H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotopically in stomach, nude mice were administrated octreotide for 8 weeks. The mRNA of somatostatin receptor in the SGC-7901 cells was detected by reverse transcription polymerase chain reaction technique. Extracellular signal-regulated protein kinase and c-Fos in gastric cancer tissues were measured by immunohistochemistry and Western blot. Activator protein-1 binding activity was examined by electrophoretic mobility sift assay. RESULTS: 3H-thymidine incorporation into SGC-7901 cells was significantly decreased by octreotide in a concentration dependent manner. Either size or weight of tumors treated with octreotide was significantly reduced in vivo. The inhibition rate for tumor was 62.3% in octreotide group. The genes of somatostatin receptors 2 and 3 were expressed in SGC-7901 gastric cancer cell lines. Extracellular signal-regulated protein kinase and c-Fos protein level were decreased in gastric adenocarcinoma treated with octreotide. Moreover, fetal calf serum stimulated activator protein-1 binding activity could be suppressed by octreotide potentially. CONCLUSION: Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms underlying the effect of octreotide on the growth of gastric adenocarcinoma. PMID:12970873

  3. 64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

    ClinicalTrials.gov

    2015-11-02

    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

  4. Advances in gastric cancer prevention

    PubMed Central

    Giordano, Antonio; Cito, Letizia

    2012-01-01

    Gastric cancer is a multifactorial neoplastic pathology numbering among its causes both environmental and genetic predisposing factors. It is mainly diffused in South America and South-East Asia, where it shows the highest morbility percentages and it is relatively scarcely diffused in Western countries and North America. Although molecular mechanisms leading to gastric cancer development are only partially known, three main causes are well characterized: Helicobacter pylori (H. pylori) infection, diet rich in salted and/or smoked food and red meat, and epithelial cadherin (E-cadherin) mutations. Unhealthy diet and H. pylori infection are able to induce in stomach cancer cells genotypic and phenotypic transformation, but their effects may be crossed by a diet rich in vegetables and fresh fruits. Various authors have recently focused their attention on the importance of a well balanced diet, suggesting a necessary dietary education starting from childhood. A constant surveillance will be necessary in people carrying E-cadherin mutations, since they are highly prone in developing gastric cancer, also within the inner stomach layers. Above all in the United States, several carriers decided to undergo a gastrectomy, preferring changing their lifestyle than living with the awareness of the development of a possible gastric cancer. This kind of choice is strictly personal, hence a decision cannot be suggested within the clinical management. Here we summarize the key points of gastric cancer prevention analyzing possible strategies referred to the different predisposing factors. We will discuss about the effects of diet, H. pylori infection and E-cadherin mutations and how each of them can be handled. PMID:23061031

  5. Gastric parietal cell autoantigen: physical, chemical and biological properties

    PubMed Central

    Ward, H. A.; Nairn, R. C.

    1972-01-01

    The properties of the gastric parietal cell autoantigen have been further investigated using mucosal subcellular fractions and gastric sections. Sucrose density layer ultracentrifugation of a microsomal preparation from bovine abomasum fundus (gastric) mucosa allowed the separation of an antigenic smooth membrane fraction, providing further evidence that the antigen is associated with smooth cytoplasmic membranes. Both hydrophobic and polar bonds appear to be concerned with maintenance of antigenic structure. Protein and lipid are essential components of the antigen. Lipid extracted with chloroform–methanol was inactive. The lipid-free protein retained slight activity which was increased on recombination with the lipid. The results suggest that the antigen is a lipoprotein. Enzymatic and chemical treatments showed that RNA and carbohydrate are not concerned in the antigenicity, which was also not dependent upon thiol groups, disulphide bonds or metal ions. Attempts to subfractionate an antigenic 6 M urea extract of bovine gastric microsomes by gel filtration and electrophoresis led to recovery of antigenic material without further resolution. An immunoadsorption–elution experiment gave promise of this being a useful method for purification of the antigen. ImagesFig. 1Fig. 2 PMID:4556010

  6. Duodenogastric reflux and gastric stump carcinoma.

    PubMed

    Kondo, Ken

    2002-01-01

    Gastric stump carcinoma after gastric surgery for benign disease is now widely recognized as a distinct clinical entity. The stump carcinoma was often found to be localized to the anastomosis, known to be the site with severe duodenogastric reflux. For this reason, duodenogastric reflux, including the reflux of bile and pancreatic juice, after a Billroth II procedure for benign disease is frequently discussed as an important factor related to the development of stump carcinoma. Many experiments have implicated bile acids, the main component of the duodenal juice, in gastric carcinogenesis. In particular, rat models without the use of the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), showed adenocarcinoma in the remnant stomach that was related to the severity of duodenogastric reflux. However, human data are, inevitably, much less consistent. Whether the incidence of stump carcinoma is higher than that of gastric carcinoma in general is still controversial. Concerning the histogenesis of stump carcinoma after benign disease, a relationship between gastritis cystica polyposa (GCP) and gastric type adenocarcinoma has been suggested. Recently, the population at risk of gastric stump carcinoma for benign disease has been diminishing significantly, and the incidence of gastric stump carcinoma after surgery for malignant disease has been increasing. The influence of duodenogastric reflux in the gastric remnant after malignant disease may differ from its influence in the gastric remnant after benign disease. Further clinical study is needed to elucidate the pathogenetic factors involved in gastric stump carcinoma. PMID:12021855

  7. The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population.

    PubMed

    Du, Mulong; Wang, Weizhi; Jin, Hua; Wang, Qiaoyan; Ge, Yuqiu; Lu, Jiafei; Ma, Gaoxiang; Chu, Haiyan; Tong, Na; Zhu, Haixia; Wang, Meilin; Qiang, Fulin; Zhang, Zhengdong

    2015-10-13

    The HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA, is involved in pathogenesis and progress of multiple tumors. Its ectopic expression and biological functions have been observed in gastric cancer. In this study, we conducted a two-stage case-control study to evaluate whether genetic variations of HOTAIR were associated with gastric cancer risk. We identified that a single nucleotide polymorphism (SNP) rs4759314 was significantly associated with the increased gastric cancer risk with an odds ratio (OR) of 1.39 [95% confidence interval (CI) = 1.13-1.71, P = 0.002] in the combined sets. Further functional experiments revealed the allele-specific effects on HOTAIR and HOXC11 expressions in gastric cancer tissues, of which HOTAIR and HOXC11 expressions of individuals carrying with AG genotype were much higher than those with AA genotype; similarly, the effects occurred in intronic promoter activities, of which the promoter activity of G allele was more pronounced than that of A allele. Interestingly, we identified a novel potential oncogene HOXC11 in gastric cancer pathogenesis with differential expression in gastric cancer tissues by association analysis with candidate gene strategy. These results suggest that SNP rs4759314 of HOTAIR acts as a potential biomarker for predicting gastric cancer, and the role of HOXC11 in gastric cancer etiology is warranted to further investigation. PMID:26384301

  8. 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

  9. Regulation of gastric motility and blood flow during acute nociceptive stimulation of the paraspinal muscles in urethane-anaesthetised rats.

    PubMed

    Piché, Mathieu; Watanabe, Nobuhiro; Hotta, Harumi

    2014-01-01

    The aim of this study was to examine gastric motility and blood flow during nociceptive hypertonic saline injections (HS) in paraspinal muscles of urethane-anaesthetised rats. Gastric pressure was not affected by HS in intact or vagotomised conditions. After cervical spinalisation, it was decreased by injections at T13 or L6 but not T2. Moreover, HS injections at T13 produced greater gastric pressure decreases compared with L6 and T2 and increased gastric sympathetic nerve activity. Blood pressure and gastric blood flow were decreased by T13 injections in spinal cord intact but not spinalised rats. Besides, isotonic saline injections (non-nociceptive) produced non-significant or marginal effects. These results indicate that gastric motility is decreased by nociceptive input from paraspinal muscles in spinalised rats through activation of the gastric sympathetic nerve. Although gastric blood flow was also decreased by nociceptive stimulation at T13 in spinal cord intact rats, these changes seem to depend on blood pressure. PMID:24037728

  10. Deregulation of MUC4 in gastric adenocarcinoma: potential pathobiological implication in poorly differentiated non-signet ring cell type gastric cancer

    PubMed Central

    Senapati, S; Chaturvedi, P; Sharma, P; Venkatraman, G; Meza, J L; El-Rifai, W; Roy, H K; Batra, S K

    2008-01-01

    MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n=45) and gastric adenocarcinoma (n=83; P<0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P<0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein. PMID:18781152

  11. Anti-proliferation effects of Twist gene silencing in gastric cancer SGC7901 cells

    PubMed Central

    Zhang, Hui; Gong, Jian; Kong, Di; Liu, Hong-Yi

    2015-01-01

    AIM: To study the role of Twist gene in gastric cancer by gene silencing, including the potential of induction of apoptosis, cell cycle arrest, and proliferation inhibition in human malignant gastric SGC7901 cells. METHODS: The expression level of Twist in gastric cancer samples was measured by immunohistochemistry. The effects of Twist gene silencing were detected at both mRNA and protein levels by RT-PCR and Western blot. We also evaluated the cell proliferation and apoptosis by CCK-8 assay and flow cytometry. We determined the activity of caspase-3 and caspase-9 with a caspase activity assay kit. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion ability was evaluated by wound scratch assay and Boyden chamber assay. RESULTS: Twist protein was highly expressed in gastric cancer samples. Twist gene silencing significantly induced apoptosis, cell cycle arrest at G0/G1 phase, proliferation inhibition, and reduced the ability of migration and invasion in human gastric cancer SGC7901 cells. Meanwhile, both caspase-3 and caspase-9 were activated. CONCLUSION: The Twist gene could serve as a potential molecular target for gene therapy of gastric cancer with targeted small interfering RNA. PMID:25780290

  12. 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

  13. Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

    ClinicalTrials.gov

    2013-06-03

    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

  14. STAT3 and STAT1 mediate IL-11–dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice

    PubMed Central

    Ernst, Matthias; Najdovska, Meri; Grail, Dianne; Lundgren-May, Therese; Buchert, Michael; Tye, Hazel; Matthews, Vance B.; Armes, Jane; Bhathal, Prithi S.; Hughes, Norman R.; Marcusson, Eric G.; Karras, James G.; Na, Songqing; Sedgwick, Jonathon D.; Hertzog, Paul J.; Jenkins, Brendan J.

    2008-01-01

    Deregulated activation of STAT3 is frequently associated with many human hematological and epithelial malignancies, including gastric cancer. While exaggerated STAT3 signaling facilitates an antiapoptotic, proangiogenic, and proproliferative environment for neoplastic cells, the molecular mechanisms leading to STAT3 hyperactivation remain poorly understood. Using the gp130Y757F/Y757F mouse model of gastric cancer, which carries a mutated gp130 cytokine receptor signaling subunit that cannot bind the negative regulator of cytokine signaling SOCS3 and is characterized by hyperactivation of the signaling molecules STAT1 and STAT3, we have provided genetic evidence that IL-11 promotes chronic gastric inflammation and associated tumorigenesis. Expression of IL-11 was increased in gastric tumors in gp130Y757F/Y757F mice, when compared with unaffected gastric tissue in wild-type mice, while gp130Y757F/Y757F mice lacking the IL-11 ligand–binding receptor subunit (IL-11R?) showed normal gastric STAT3 activation and IL-11 expression and failed to develop gastric tumors. Furthermore, reducing STAT3 activity in gp130Y757F/Y757F mice, either genetically or by therapeutic administration of STAT3 antisense oligonucleotides, normalized gastric IL-11 expression and alleviated gastric tumor burden. Surprisingly, the genetic reduction of STAT1 expression also reduced gastric tumorigenesis in gp130Y757F/Y757F mice and coincided with reduced gastric inflammation and IL-11 expression. Collectively, our data have identified IL-11 as a crucial cytokine promoting chronic gastric inflammation and associated tumorigenesis mediated by excessive activation of STAT3 and STAT1. PMID:18431520

  15. Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells

    PubMed Central

    Lu, Jing Nan; Lee, Won Sup; Nagappan, Arulkumar; Chang, Seong-Hwan; Choi, Yung Hyun; Kim, Hye Jung; Kim, Gon Sup; Ryu, Chung Ho; Shin, Sung Chul; Jung, Jin-Myung; Hong, Soon Chan

    2015-01-01

    Background: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells. Methods: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells. Results: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein. Conclusions: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP. PMID:25853103

  16. Cancer Gastric Chemoprevention: Isolation of Gastric Tumor-Initiating Cells.

    PubMed

    Mori, Federica; Canu, Valeria; Lorenzon, Laura; Garofalo, Alfredo; Blandino, Giovanni; Strano, Sabrina

    2016-01-01

    Gastric cancer is an important healthcare problem and represents the second leading cause of death for malignant disease worldwide. In the Western world, the diagnosis is done at late stage when treatments can be only palliative. Searches for new therapeutic regimens as well as for new biomarkers are in progress.To reduce cancer mortality is crucial the prevention of the lesion at earlier stages. Therefore, new bullets to prevention are needed.Nowadays, studies relating to different kinds of tumor are unanimous in considering cancer stem cells (CSCs) as "the core" of the tumor and the responsible of tumor chemoresistance and relapse.This chapter aims to provide the instructions to (1) isolate, (2) grow, and (3) validate, both in vivo and in vitro, the gastric CSC subpopulation. PMID:26608296

  17. 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

  18. 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

  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. 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.

  1. Gene therapy for gastric cancer: A review

    PubMed Central

    Zhang, Chao; Liu, Zhan-Kui

    2003-01-01

    Gastric cancer is common in China, and its early diagnosis and treatment are difficult. In recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. The present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer. PMID:14606062

  2. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer.

    PubMed

    Ji, Runbi; Zhang, Bin; Zhang, Xu; Xue, Jianguo; Yuan, Xiao; Yan, Yongmin; Wang, Mei; Zhu, Wei; Qian, Hui; Xu, Wenrong

    2015-08-01

    Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer. PMID:26091251

  3. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    SciTech Connect

    Li, Weifeng Huang, Huimin; Niu, Xiaofeng 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.

  4. [Rare causes of acute gastric hemorrhage].

    PubMed

    Petrova, N N

    1975-06-01

    According to the author's findings rare causes of acute gastric hemorrhages (the Mallory-Weiss syndrome, cancerous lesions of the gastrointestinal organs, excluding the stomach, esophageal and duodenal diverticulum, prolapse of gastric mucosa into the duodenum, necrosis of the gastric wall, its traumatic rupture, the Rendu-Osler disease, rupture of the renal artery aneurysm) made 3.2% of other causes. Profuse hemorrhage was noted in 12 of 32 patients under consideration. In 8 of 32 patients (25%) the diagnosis was established only at autopsy. In other more frequent causes of acute gastric hemorrhage the diagnosis proved to be feasible in 90-95% of cases. PMID:1080309

  5. Gastric pseudolymphoma. A challenging clinical problem.

    PubMed Central

    Orr, R K; Lininger, J R; Lawrence, W

    1984-01-01

    Gastric pseudolymphoma is a benign inflammatory condition that is usually associated with chronic gastric ulcer and often mimics gastric carcinoma or malignant lymphoma. Our experience with 12 histologically documented gastric pseudolymphomas at the Medical College of Virginia is presented with an emphasis on the approach to both diagnosis and surgical management. Preoperative diagnoses in this series ranged from benign gastric ulcer to gastric cancer. Treatment was by gastric resection in all cases and it included, as a minimum, antrectomy and excision of the lesion with an adequate gross margin. Of 11 cases with adequate follow-up, there are eight asymptomatic patients without recurrence and one patient who died of other causes without recurrence 5 years after gastrectomy. One patient developed recurrent pseudolymphoma in the proximal gastric remnant 39 months after a distal subtotal gastrectomy for pseudolymphoma. Another patient subsequently developed Hodgkin's disease of the gastric remnant, with regional lymph node and liver involvement, and died 35 months after the earlier subtotal gastrectomy for pseudolymphoma. Our clinical experience with this confusing and uncommon entity is compared with that previously reported in the medical literature. Images FIG. 1. FIG. 2. FIG. 3. FIG. 4. FIG. 5. PMID:6465973

  6. 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

  7. 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

  8. 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

  9. Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats.

    PubMed

    Wu, Chiu-Lung; Hung, Chen-Road; Chang, Full-Young; Pau, K-Y Francis; Wang, Paulus S

    2003-04-01

    The effects of oxytocin (OT) on gastric emptying, gastrointestinal transit, and plasma levels of cholecystokinin (CCK) were studied in female rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na(2)(51)CrO(4). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for CCK radioimmunoassay. After administration of OT (0.2-0.8 mg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas the plasma concentration of CCK was increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT- induced inhibition of gastric emptying and gastrointestinal transit. However, administration of atosiban alone had no effect on gastric emptying and gastrointestinal transit. The selective CCK(1) receptor antagonists, devazepide and lorglumide, effectively attenuated the OT-induced inhibition of gastric emptying and gastrointestinal transit. L-365, 260, a selective CCK(2) receptor antagonist, did not alter the OT-induced inhibition of gastric emptying and gastrointestinal transit. These results suggest that OT inhibits gastric emptying and gastrointestinal transit in female rats via a mechanism involving CCK stimulation and CCK(1) receptor activation. PMID:12690433

  10. MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box-binding homeobox 2

    PubMed Central

    DU, YING; WANG, LINGFEI; WU, HONGHAI; ZHANG, YIYIN; WANG, KAN; WU, DINGTING

    2015-01-01

    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

  11. Acupuncture and gastric acid studies.

    PubMed

    Sodipo, J O; Falaiye, J M

    1979-01-01

    The effects of therapeutic acupuncture on gastric acid secretion on pain relief in chronic duodenal ulcer patients were studied. Ten adult Nigerian patients with clinical, endoscopic as well as radiological evidence of duodenal ulcer constituted the "Ulcer Group." Four other patients who gave history of dyspepsia formed the "Dyspeptic Group." Pentagastrin stimulation test was performed on all subjects pre- and post-acupuncture therapy. The classical Chinese acupuncture loci were employed. The mean Basal Acid Output (BAO) in the duodenal ulcer group was markedly reduced from 4.04 +/- 1.01 mMols/hour to 1.05 +/- 2.5 mMols/hour. The mean Maximal Acid Output (MAO) was lowered from 34.72 +/- 13.81 mMols/hour to 15.34 +/- 4.01 mMols/hour. The difference was statistically significant (P less than 0.001). It is more probable, therefore, that the relief of pain is attributable to the therapeutic inhibition of gastric hyperacidity in our patients. Thus, though pain relief has been previously demonstrated in response to acupuncture, the results of this investigation have gone further to show that acupunture achieves symptomatic relief through therapeutic gastric depression in duodenal ulcer patients. PMID:44432

  12. 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

  13. Activation of Helicobacter pylori CagA by tyrosine phosphorylation is essential for dephosphorylation of host cell proteins in gastric epithelial cells.

    PubMed

    Püls, Jurgen; Fischer, Wolfgang; Haas, Rainer

    2002-02-01

    Helicobacter pylori type I strains harbour the cag pathogenicity island (cag-PAI), a 37 kb sequence,which encodes the components of a type IV secretion system. CagA, the first identified effector protein of the cag-PAI, is translocated into eukaryotic cells and tyrosine phosphorylated (CagAP-tyr) by a host cell tyrosine kinase. Translocation of CagA induces the dephosphorylation of a set of phosphorylated host cell proteins of unknown identity. CagA proteins of independent H. pylori strains vary in sequence and thus in the number and composition of putative tyrosine phosphorylation motifs (TPMs). The CagA protein of H. pylori strain J99 (CagAJ99) does not carry any of three putative tyrosine phosphorylation motifs (TPM-A, TPM-B or TPM-C) predicted by the MOTIF algorithm in CagA proteins. CagA,n is not tyrosine phosphorylated and is inactive in the dephosphorylation of host cell proteins. By site-specific mutagenesis,we introduced a TPM-C into CagA,. by replacing a single lysine with a tyrosine. This slight modification resulted in tyrosine phosphorylation of CagAJ99 and host cell protein dephosphorylation. In contrast, the removal of the indigenous TPM-C from CagAP12 did not abolish its tyrosine phosphorylation, suggesting that further phosphorylated sites are present in CagAP12. By generation of hybrid CagA proteins, a phosphorylation of the most N-terminal TPM-A could be excluded. Our data suggest that tyrosine phosphorylation at TPM-C is sufficient, but not exclusive,to activate translocated CagA. Activated CagAPtr might either convert into a phosphatase itself or activate a cellular phosphatase to dephosphorylate cellular phosphoproteins and modulate cellular signalling cascades of the host. PMID:11936078

  14. 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

  15. Duodeno-gastric reflux and gastric adenomas: a scintigraphic study in patients with familial adenomatous polyposis.

    PubMed Central

    Spigelman, A D; Granowska, M; Phillips, R K

    1991-01-01

    To test whether the presence of gastric adenomas (dysplasia) was associated with gastric reflux of duodenal contents, six patients with familial adenomatous polyposis (FAP) who had gastric adenomas and nine matched FAP patients without gastric adenomas underwent scintigraphic duodeno-gastric reflux scanning. Reflux was graded 0-6, where 0 = no reflux, 1 = intermittent reflux into antrum only, 2 = prolonged reflux into antrum only, 3 = intermittent reflux into body, 4 = prolonged reflux into body, 5 = intermittent reflux into body and fundus, and 6 = prolonged reflux into body and fundus. FAP patients with gastric adenomas had more severe reflux (median 6, range 4-6) than did controls (median 3, range 0-6; P = 0.009, Mann-Whitney U test). These results are consistent with a role for bile in the development of gastric adenomatous polyps and suggest that bile is involved in the dysplasia-carcinoma sequence. PMID:1653358

  16. Gastroprotective Potential of Dalbergia sissoo Roxb. Stem Bark against Diclofenac-Induced Gastric Damage in Rats

    PubMed Central

    Khan, Muhammad Israr; Khan, Muhammad Rashid

    2013-01-01

    Objectives Dalbergia sissoo Roxb. stem bark possesses anti-inflammatory, antipyretic, and antioxidant properties. This plant is used traditionally in the Indian system of medicine to treat emesis, ulcers, leucoderma, dysentery, stomach complaints, and skin disorders. This study was conducted to evaluate the antiulcer effects of D. sissoo stem bark methanol extract (DSME) against the diclofenac sodium-induced ulceration in rat. Methods The DSME (200 mg/kg and 400 mg/kg body weight) was orally administered to rats once a day for 10 days in diclofenac-treated rats. The gastroprotective effects of DSME were determined by assessing gastric-secretory parameters such as volume of gastric juice, pH, free acidity, and total acidity. Biochemical studies of gastric mucosa were conducted to estimate the levels of nonprotein sulfhydryls (NP-SHs), lipid peroxidation [thiobarbituric acid reactive substances (TBARSs)], reduced glutathione (GSH), hydrogen peroxide (H2O2), levels of scavenging antioxidants, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and myeloperoxidase (MPO). Moreover, adherent mucus content and histological studies were performed on stomach tissues. Results Administration of DSME significantly decreased the ulcer index, TBARSs, H2O2, and MPO activity in gastric mucosa of the ulcerated rats. Activities of enzymic antioxidants, CAT, SOD, GSH-Px, GST and GSH, and NP-SH contents were significantly increased with DSME administration in the gastric mucosa of diclofenac-treated rats. Volume of gastric juice, total and free acidity were decreased, whereas pH of the gastric juice was increased with the administration of DSME + diclofenac. Our results show that DSME administration is involved in the prevention of ulcer through scavenging of free radicals. Results of histopathological studies supported the gastroprotective activities of DSME. Conclusion The results of this study showed that DSME exhibit potential gastroprotective activity probably due to its antioxidant and cytoprotection ability. PMID:24298443

  17. Gastric digestion of ?-lactalbumin in adult human subjects using capsule endoscopy and nasogastric tube sampling.

    PubMed

    Sullivan, Louise M; Kehoe, Joseph J; Barry, Lillian; Buckley, Martin J M; Shanahan, Fergus; Mok, K H; Brodkorb, André

    2014-08-28

    In the present study, structural changes in the milk protein ?-lactalbumin (?-LA) and its proteolysis were investigated for the potential formation of protein-fatty acid complexes during in vivo gastric digestion. Capsule endoscopy allowed visualisation of the digestion of the test drinks, with nasogastric tubes allowing sampling of the gastric contents. A total of ten healthy volunteers had nasogastric tubes inserted into the stomach and ingested test drinks containing 50 g/l of sucrose and 25 g/l of ?-LA with and without 4 g/l of oleic acid (OA). The samples of gastric contents were collected for analysis at 3 min intervals. The results revealed a rapid decrease in the pH of the stomach of the subjects. The fasting pH of 2·31 (SD 1·19) increased to a pH maxima of pH 6·54 (SD 0·29) after ingestion, with a subsequent decrease to pH 2·22 (SD 1·91) after 21 min (n 8). Fluorescence spectroscopy and Fourier transform IR spectroscopy revealed partial protein unfolding, coinciding with the decrease in pH below the isoelectric point of ?-LA. The activity of pepsin in the fasting state was found to be 39 (SD 12) units/ml of gastric juice. Rapid digestion of the protein occurred: after 15 min, no native protein was detected using SDS-PAGE; HPLC revealed the presence of small amounts of native protein after 24 min of gastric digestion. Mirocam® capsule endoscopy imaging and video clips (see the online supplementary material) revealed that gastric peristalsis resulted in a heterogeneous mixture during gastric digestion. Unfolding of ?-LA was observed during gastric transit; however, there was no evidence of a cytotoxic complex being formed between ?-LA and OA. PMID:24967992

  18. Modeling human development and disease in pluripotent stem cell-derived gastric organoids

    PubMed Central

    McCracken, Kyle W.; Catá, Emily M.; Crawford, Calyn M.; Sinagoga, Katie L.; Schumacher, Michael; Rockich, Briana E.; Tsai, Yu-Hwai; Mayhew, Christopher N.; Spence, Jason R.; Zavros, Yana; Wells, James M.

    2014-01-01

    Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world’s population and are largely due to chronic H. pylori infection1–3. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis4, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells (hPSCs). We identified that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signaling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signaling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signaling and induction of epithelial proliferation. Together, these studies describe a novel and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease. PMID:25363776

  19. A potential role for Helicobacter pylori heat shock protein 60 in gastric tumorigenesis

    SciTech Connect

    Lin, Chen-Si; School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan ; He, Pei-Juin; Tsai, Nu-Man; Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung; Wu, Ming-Shiang; Wu, Chang-Jer; Cheng, Tain-Lu; Liao, Kuang-Wen

    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.

  20. GM130 regulates epithelial-to-mesenchymal transition and invasion of gastric cancer cells via snail

    PubMed Central

    Zhao, Jianquan; Yang, Chun; Guo, Shujun; Wu, Yonggang

    2015-01-01

    Gastric cancer is one of the most common causes of digestive tract tumor. Despite of recent advances in surgical techniques and development of adjuvant therapy, the underlying mechanisms of gastric cancer remain poorly understood and relevant insight into novel treatment strategies using gene target remains incomplete. Recently, several studies report that epithelial to mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors; however, the molecular mechanisms underlying this transition are unknown. As a cis-Golgi matrix protein, GM130 plays an important role in cell cycle progression and transport of protein in the secretory pathway. In this study, we found that GM130 expression has a positive correlation with the pathological differentiation and tumor node metastasis (TNM) stage of gastric cancer. High GM130 expression levels also predict shorter overall survival of gastric cancer patients. RNA interference-mediated knockdown of GM130 expression increased epithelial marker (E-cadherin) and decreased mesenchymal marker (N-cadherin and vimentin) expression in gastric cancer cells, suppressing cell invasion, and tumor formation. Furthermore, we found that GM130 upregulated expression of the key EMT regulator Snail (SNAI1), which mediated EMT activation and cell invasion by GM130. Taken together, our study indicates GM130 may be a promising therapeutic biomarker for gastric cancer.

  1. The current status and future perspectives of laparoscopic surgery for gastric cancer

    PubMed Central

    Ahn, Sang-Hoon

    2011-01-01

    Gastric cancer is most common cancer in Korea. Surgery is still the main axis of treatment. Due to early detection of gastric cancer, the innovation of surgical instruments and technological advances, gastric cancer treatment is now shifting to a new era. One of the most astonishing changes is that minimally invasive surgery (MIS) is becoming more dominant treatment for early gastric cancer. These MIS are represented by endoscopic resection, laparoscopic surgery, robotic surgery, single-port surgery and natural orifice transluminal endoscopic surgery. Among them, laparoscopic gastrectomy is most actively performed in the field of surgery. Laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer (EGC) has already gained popularity in terms of the short-term outcomes including patient's quality of life. We only have to wait for the long-term oncologic results of Korean Laparoscopic Gastrointestinal Surgery Study Group. Upcoming top issues following oncologic safety of LADG are function-preserving surgery for EGC, application of laparoscopy to advanced gastric cancer and sentinel lymph node navigation surgery. In the aspect of technique, laparoscopic surgery at present could reproduce almost the whole open procedures. However, the other fields mentioned above need more evidences and experiences. All these new ideas and attempts provide technical advances, which will minimize surgical insults and maximize the surgical outcomes and the quality of life of patients. PMID:22066116

  2. Ets1 as a marker of malignant potential in gastric carcinoma

    PubMed Central

    Yu, Yong; Zhang, Yi-Chu; Zhang, Wen-Zhu; Shen, Li-Song; Hertzog, Paul; Wilson, Trevor J; Xu, Da-Kang

    2003-01-01

    AIM: Ets1 proto-oncogene is a transcription factor involved in the activation of several genes of tumor invasion and metastasis. We aimed to determine the relationship between the extent and intensity of Ets1 expression and patients’ clinicopathological factors in gastric carcinoma. METHODS: Immunohistochemical analysis was performed for gastric tumor paraffin-embedded sections, followed by image analysis. RESULTS: Ets1 was not expressed in the normal gastric epithelium and its surrounding cells. The percentage of Ets1 expressing cells detected increased significantly in both epithelial tumor and stromal cells from high T classification, lymph node metastasis positive, clinical advanced-stage groups (P < 0.001). The level of Ets1 staining in epithelial tumor cells also reflected the degree of cell differentiation. The percentage of epithelial and stromal cells expressing Ets1 was significantly correlated with the presence of lymph node metastasis (P = 0.014 and P < 0.001 respectively). Ets1 expression was not observed in tissue samples from patients with benign gastric ulcers. CONCLUSION: Ets1 protein expression in epithelial tumor cells reflects the degree of differentiation, and the percentage of Ets1 positive tumor and stromal cells correlates with lymph node metastasis. Thus Ets1 is a valuable marker of malignant potential in terms of invasiveness and metastasis of gastric carcinoma. It is also possible that inhibition of Ets1 is a potential avenue for therapy in gastric cancer. PMID:14562368

  3. Effect of smoking on failure of H. pylori therapy and gastric histology in a high gastric cancer risk area of Colombia

    PubMed Central

    Camargo, M Constanza; Piazuelo, M Blanca; Mera, Robertino M; Fontham, Elizabeth TH; Delgado, Alberto G; Yepez, M Clara; Ceron, Cristina; Bravo, Luis E; Bravo, Juan C; Correa, Pelayo

    2014-01-01

    Summary It has been proposed that eradication of Helicobacter pylori infection is a sound strategy for gastric cancer prevention. Several factors including smoking have been associated to treatment failure rates. This study aimed to evaluate the smoking effect on the efficacy of H. pylori therapy, as well as on the histological parameters in the gastric mucosa from subjects from a high gastric cancer risk area. Two-hundred-sixty-four Colombian subjects with gastric precancerous lesions who participated in a chemoprevention trial, received anti-H. pylori treatment at baseline and had data recorded on cigarette use, were included in this study. A detailed histopathological assessment of the gastric mucosa was performed in biopsies taken before any intervention. H. pylori eradication was assessed in gastric biopsies at 36 months post-treatment. The overall eradication rate was 52.3%; rates of 41.3% and 57.1% were observed for active-smokers and non-smokers, respectively. Multivariate logistic regression analysis showed that smokers had a 2-fold higher probability of failure in Helicobacter pylori eradication than non-smokers (OR: 2.0; 95% CI: 1.01–3.95). At baseline, active-smokers had a higher score of intestinal metaplasia compared to non-smokers. In the corpus mucosa, active- smokers showed lower scores of H. pylori density, total inflammation, neutrophil infiltration, and mucus depletion than non-smokers. In the antrum, no significant differences were observed between active-smokers and non-smokers. In summary, in patients who smoked, H. pylori treatment was less effective. Smoking cessation may benefit H. pylori eradication rates. PMID:18254262

  4. The biological relevance of gastric neuroendocrine tumors.

    PubMed Central

    Klöppel, G.; Clemens, A.

    1996-01-01

    Gastric neuroendocrine tumors were originally thought to have a low incidence (three percent). Since endoscopic diagnostic procedures have become clinical routine, they are now found more frequently (relative incidence up to 41 percent). In recent years, classifications have been developed that attempt to consider the biological relevance of these tumors. Four types of gastric neuroendocrine tumor may be distinguished: Type 1 gastric neuroendocrine tumor is most common. It is associated with chronic atrophic fundus gastritis, hypergastrinemia and often with pernicious anemia. Usually it is multicentric and smaller than one cm, does not produce any symptoms and has an excellent prognosis. Type 2 gastric neuroendocrine tumor is second in frequency. It has no association with other diseases, is solitary and has no predilection for a particular localization. It may be larger than 1 cm, produce a carcinoid syndrome or Zollinger-Ellison syndrome and have a metastasis rate of up to 30 percent. Type 3 gastric neuroendocrine tumor is rare and always associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I. It occurs as multiple lesions in the gastric body fundus and has a lower metastatic rate than type 2 gastric neuroendocrine tumor. Type 4 gastric neuroendocrine tumor corresponds to a small-cell carcinoma. PMID:9041691

  5. Nutrition and Gastric Cancer Risk: An Update

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data from epidemiologic, experimental, and animal studies indicate that diet plays an important role in the etiology of gastric cancer. High intake of fresh fruit and vegetable, lycopene and lycopene-containing food products, and potentially vitamin C and selenium may reduce the risk for gastric can...

  6. Anticancer effect of adenosine on gastric cancer via diverse signaling pathways

    PubMed Central

    Tsuchiya, Ayako; Nishizaki, Tomoyuki

    2015-01-01

    Extracellular adenosine induces apoptosis in a variety of cancer cells via intrinsic and extrinsic pathways. In the former pathway, adenosine uptake into cells triggers apoptosis, and in the latter pathway, adenosine receptors mediate apoptosis. Extracellular adenosine also induces apoptosis of gastric cancer cells. Extracellular adenosine is transported into cells through an adenosine transporter and converted to AMP by adenosine kinase. In turn, AMP activates AMP-activated protein kinase (AMPK). AMPK is the factor responsible for caspase-independent apoptosis of GT3-TKB gastric cancer cells. Extracellular adenosine, on the other hand, induces caspase-dependent apoptosis of MKN28 and MKN45 gastric cancer cells by two mechanisms. Firstly, AMP, converted from intracellularly transported adenosine, initiates apoptosis, regardless of AMPK. Secondly, the A3 adenosine receptor, linked to Gi/Gq proteins, mediates apoptosis by activating the Gq protein effector, phospholipase C?, to produce inositol 1,4,5-trisphosphate and diacylglycerol, which activate protein kinase C. Consequently, the mechanisms underlying adenosine-induced apoptosis vary, depending upon gastric cancer cell types. Understand the contribution of each downstream target molecule of adenosine to apoptosis induction may aid the establishment of tailor-made chemotherapy for gastric cancer. PMID:26494951

  7. JWA reverses cisplatin resistance via the CK2—XRCC1 pathway in human gastric cancer cells

    PubMed Central

    Xu, W; Chen, Q; Wang, Q; Sun, Y; Wang, S; Li, A; Xu, S; Røe, O D; Wang, M; Zhang, R; Yang, L; Zhou, J

    2014-01-01

    Gastric cancer is the third most common malignancy in China, with a median 5-year survival of only 20%. Cisplatin has been used in first-line cancer treatment for several types of cancer including gastric cancer. However, patients are often primary resistant or develop acquired resistance resulting in relapse of the cancer and reduced survival. Recently, we demonstrated that the reduced expression of base excision repair protein XRCC1 and its upstream regulator JWA in gastric cancerous tissues correlated with a significant survival benefit of adjuvant first-line platinum-based chemotherapy as well as XRCC1 playing an important role in the DNA repair of cisplatin-resistant gastric cancer cells. In the present study, we demonstrated the role of JWA in cisplatin-induced DNA lesions and aquired cisplatin resistance in five cell-culture models: gastric epithelial cells GES-1, cisplatin-sensitive gastric cancer cell lines BGC823 and SGC7901, and the cisplatin-resistant gastric cancer cell lines BGC823/DDP and SGC7901/DDP. Our results indicated that JWA is required for DNA repair following cisplatin-induced double-strand breaks (DSBs) via XRCC1 in normal gastric epithelial cells. However, in gastric cancer cells, JWA enhanced cisplatin-induced cell death through regulation of DNA damage-induced apoptosis. The protein expression of JWA was significantly decreased in cisplatin-resistant cells and contributed to cisplatin resistance. Interestingly, as JWA upregulated XRCC1 expression in normal cells, JWA downregulated XRCC1 expression through promoting the degradation of XRCC1 in cisplatin-resistant gastric cancer cells. Furthermore, the negative regulation of JWA to XRCC1 was blocked due to the mutation of 518S/519T/523T residues of XRCC1, and indicating that the CK2 activated 518S/519T/523T phosphorylation is a key point in the regulation of JWA to XRCC1. In conclusion, we report for the first time that JWA regulated cisplatin-induced DNA damage and apoptosis through the CK2—P-XRCC1—XRCC1 pathway, indicating a putative drug target for reversing cisplatin resistance in gastric cancer. PMID:25476899

  8. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province

    PubMed Central

    Cai, Lin; Yu, Shun-Zhang; Zhang, Zuo-Feng

    2001-01-01

    AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group (6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significan difference between the two groups (two-tailed Fisher’s exact test, P = 0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2 (OR = 7.34) than indivduals in control group (?² = 4.597, for trend P = 0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province. PMID:11854903

  9. Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer

    PubMed Central

    Park, Jong-Lyul; Kim, Mirang; Song, Kyu-Sang; Kim, Seon-Young

    2015-01-01

    MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer. PMID:26523130

  10. Gastroprotective effect of methanolic extract of Gomphrena celosioides on indomethacin induced gastric ulcer in Wistar albino rats

    PubMed Central

    Oluwabunmi, Ige Janet; Abiola, Tijani

    2015-01-01

    Context: Gastric ulcer is one of the most prevalent gastrointestinal disorders. A number of studies have been carried out to determine the efficacy of herbal medicines in the treatment of gastric ulcer. Objectives: The present study was undertaken to evaluate the anti-ulcerogenic activity of methanol extract of Gomphrena celosioides (GC) in male Wistar rats. Materials and Methods: The rats were divided into eight groups, methanol extract of GC was administered orally, for seven consecutive to five groups. On the 7th day, indomethacin was administered to induce gastric ulceration. Gastric secretions were collected and analyzed. Results: Animals pretreated with GC extract showed a significant reduction in ulcer score, ulcer index, gastric volume, and gastric total acidity in indomethacin-induced ulcer models in a dose dependent manner when compared to the ulcerated control group. Conclusion: The study revealed gastroprotective activity of the extract in dose-dependent manner. Methanol extract of the leaves of GC was significantly effective in protecting the gastric mucosa against indomethacin-induced ulcers at all the dose level studied. PMID:25664267

  11. Abnormal intragastric distribution of food during gastric emptying in functional dyspepsia patients.

    PubMed Central

    Troncon, L E; Bennett, R J; Ahluwalia, N K; Thompson, D G

    1994-01-01

    Although delayed gastric emptying is found in some patients with functional dyspepsia, there seems to be little relation between rate of emptying and symptoms. This study examined the hypothesis that food maldistribution rather than gastric stasis may equate to symptoms in such patients and used scintigraphic techniques to quantify the partition of gastric contents between proximal and distal stomach during gastric emptying. Eleven patients with functional dyspepsia characterised by chronic severe postprandial bloating without organic abnormality, and 12 healthy volunteers, ingested a standard meal labelled with technetium-99M (99mTc). Serial images of the gastric area in anterior and posterior projections were taken for 90 minutes, regions of interest for proximal, distal, and total stomach were defined, and activity time curves were derived from the geometric means of anterior and posterior counts. Total emptying in patients (median: 46 minutes; range: 30-76) was not significantly different from controls (45 minutes; 28-58) and only three showed delayed gastric emptying. In controls, food remained predominantly in the proximal half of the stomach after ingestion and then redistributed to the distal half. In the patients, however, initial activity in the proximal half after ingestion (48%; 40-65) was significantly lower (p < 0.05) than in controls (60%; 39-73) and distributed more fully to the distal half of the stomach with a peak distal activity (56%; 34-58), which was consistently higher than in controls (36%; 33-42) (p < 0.05). It is concluded that this subgroup of functional dyspepsia patients show abnormal intragastric distribution of food, independent of gastric emptying rate. Images Figure 1 PMID:8150341

  12. Mechanism of UES relaxation initiated by gastric air distension.

    PubMed

    Lang, Ivan M; Medda, Bidyut K; Shaker, Reza

    2014-08-15

    The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa. PMID:24970778

  13. Mechanism of UES relaxation initiated by gastric air distension

    PubMed Central

    Medda, Bidyut K.; Shaker, Reza

    2014-01-01

    The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa. PMID:24970778

  14. [Gastrointestinal hormones and blood circulation in the gastric mucosa].

    PubMed

    Koch, H

    1976-03-01

    The gastrointestinal hormones influence gastric mucosal blood flow in different ways. Gastrin, secretin and pancreocymin increase gastric mucosal blood flow, glucagon, vip and somatostatin decrease it. Motilin has a special position. Given alone motilin improves gastric mucosal blood flow, wheras it reduces gastric mucosal blood flow after previous administration of pentagastrin or histamin. PMID:960910

  15. A strategy for oral chemotherapy via dual pH-sensitive polyelectrolyte complex nanoparticles to achieve gastric survivability, intestinal permeability, hemodynamic stability and intracellular activity.

    PubMed

    Deng, Liandong; Dong, Hongxu; Dong, Anjie; Zhang, Jianhua

    2015-11-01

    Efficient oral administration of anticancer agents requires a nanocarrier to long survive in the stomach, effectively penetrate across the small intestine, tightly retain the drug during bloodstream and quickly release drug in tumor cells. Herein a kind of dual pH-sensitive polyelectrolyte complex nanoparticles (CNPs) was developed by employing electrostatic interaction between positively charged chitosan (CS) and negative poly (l-glutamic acid) grafted polyethylene glycol-doxorubicin conjugate nanoparticles (PG-g-PEG-hyd-DOX NPs) with acid-labile hydrazone linkages. The obtained NPs and CNPs were characterized for their morphology, particle size, ?-potential, pH-sensitivity under the simulated physiological conditions, drug release, as well as in vivo antitumor activity and biodistribution. The results indicated that CNPs can remain intact structure in pH range from 3.0 to 6.5. After detaching CS layer due to the pH-induced deprotonation with increasing pH to 7.4 in the mucus layer of the small intestine, the inner NPs would be released and effectively absorbed into blood circulation via opening the tight junctions by CS. PG-g-PEG-hyd-DOX NPs with demonstrated long-circulating properties can be accumulated in the tumor via EPR effect and dump the drug within tumor cells by acid-cleavage of hydrazone bonds between PG-g-PEG and DOX, achieving high therapeutic efficacy and low systemic toxicity. These results suggest that the design presented here, combining the functions of the gastrointestinal pH-sensitive electrostatic complex and intracellular acid-sensitive macromolecular prodrugs NPs, can sequentially overcome the biological barriers of oral anticancer drug delivery, which thus provides a promising nanomedicine platform for oral chemotherapy. PMID:26515259

  16. Targeted therapy for gastric cancer.

    PubMed

    Smyth, Elizabeth C; Cunningham, David

    2012-09-01

    For patients with advanced gastric cancer, traditional double or triplet cytotoxic chemotherapy regimens result in a median survival of 9-11 months. As combination therapy is associated with increased survival, but also increased toxicity in a patient population whose performance status often compromised by their malignancy, development of more effective and less toxic treatment choices is mandated. Emerging data from gene expression profiling suggests that differences in pathological appearance and clinical behavior may be due the presence of unique molecular phenotypes. Characterization of the gastric cancer genomic landscape reveals the presence of multiple alterations in expression of receptor tyrosine kinases, which in conjunction with their ligands and downstream effector molecules represent potentially druggable pathways for future drug development. Treatment of HER2 positive gastric cancer with trastuzumab has led to significant gains in overall survival, and further manipulation of this pathway using the novel anti-HER2 directed agents pertuzumab and T-DM1 in addition to dual EGFR/HER2 blockade with lapatinib may yield positive results. In contrast, targeting of the EGFR pathway in combination with chemotherapy in unselected patients has not been fruitful to date, with no significant gains over standard chemotherapy yet demonstrated. Similarly, use of the anti-angiogenic monoclonal antibody bevacizumab was not successful in a large global randomized trial; however intriguing regional variations were seen with respect to efficacy of this drug, leading to calls for a second, regionally stratified study. Careful selection of patient subsets will become a key factor in future clinical trials, as novel targeted agents such as those targeting the MET/HGF and FGFR axes move forward into clinical development. It is hoped that treatment of patients in such molecularly defined groups is will lead to significant gains in survival compared to current treatment paradigms. PMID:22552927

  17. A Direct Role for Secretory Phospholipase A2 and Lyso-Phosphatidylcholine in the Mediation of Lipopolysaccharide-induced Gastric Injury

    PubMed Central

    Dial, Elizabeth J.; Tran, Duy M.; Romero, Jimmy J.; Zayat, Mayssa; Lichtenberger, Lenard M.

    2010-01-01

    Background & Aims Endotoxemia from sepsis can injure the GI tract through mechanisms that have not been fully elucidated. We have shown that lipopolysaccharide (LPS) induces an increase in gastric permeability in parallel with the luminal appearance of secretory phospholipase A2 (sPLA2) and its product, lyso-phosphatidylcholine (lyso-PC). We proposed that sPLA2 acted on the gastric hydrophobic barrier, composed primarily of PC, to degrade it and produce lyso-PC, an agent that is damaging to the mucosa. In the present study we have tested whether lyso-PC and/or sPLA2 have direct damaging effects on the hydrophobic barriers of synthetic and mucosal surfaces. Methods Rats were administered LPS (5 mg/kg, ip), and gastric contents were collected 5 h later for analysis of sPLA2 and lyso-PC content. Using these measured concentrations, direct effects of sPLA2 and lyso-PC were determined on: 1) surface hydrophobicity as detected with an artificial PC surface and with intact gastric mucosa (contact angle analysis); and 2) cell membrane disruption of gastric epithelial cells (AGS). Results Both lyso-PC and sPLA2 increased significantly in the collected gastric juice of LPS-treated rats. Using similar concentrations to the levels in gastric juice, the contact angle of PC-coated slides declined after incubation with either pancreatic sPLA2 or lyso-PC. Similarly, gastric contact angles seen in control rats were significantly decreased in sPLA2 and lyso-PC treated rats. Additionally, we observed dose-dependent injurious effects of both lyso-PC and sPLA2 in gastric AGS cells. Conclusions An LPS-induced increase in sPLA2 activity in the gastric lumen, and its product lyso-PC, are capable of directly disrupting the gastric hydrophobic layer and may contribute to gastric barrier disruption and subsequent inflammation. PMID:19940811

  18. Robotic gastrectomy for gastric cancer.

    PubMed

    Son, Taeil; Hyung, Woo Jin

    2015-09-01

    Robotic surgery for gastric cancer overcomes technical difficulties with laparoscopic gastrectomy. Its benefits include reduced intraoperative bleeding and shorter hospital stays; it is also easier to learn. Because accuracy increases during lymphadenectomy, a larger number of lymph nodes is likely to be retrieved using robotic gastrectomy. Higher costs and longer operation times have hindered the widespread adaptation and use of robotic surgery. In this review, we summarize the current status and issues regarding robotic gastrectomy. J. Surg. Oncol. 2015; 112:271-278. © 2015 Wiley Periodicals, Inc. PMID:26031408

  19. Molecular events in gastric carcinogenesis

    PubMed Central

    Mahu, C; Purcarea, AP; Gheorghe, CM; Purcarea, MR

    2014-01-01

    Abstract Gastric cancer represents an important problem for the public health, being one of the main causes of mortality. At present, it represents the second cause of mortality due to cancer, after the bronchopulmonary cancer in men and the fourth cause of mortality in women. Important progresses have been made in the last couple of years in determining the neoplastic etiopathogenesis, but it cannot be affirmed that the genetic mutations chain, which leads to the appearance of the malignant cell, has been fully understood. PMID:25408758

  20. Gastritis, nitrosamines, and gastric cancer

    SciTech Connect

    Stemmermann, G.N.; Mower, H.

    1981-01-01

    Gastritis is associated with peptic ulcer, gastroenterostomy, pernicious anemia, and exposure to nitrosamines. Once established, the process may be self-perpetuating, resulting in atrophy, metaplasia, dysplasia, and neoplasia. This can be explained by the process of endogenous nitrosation of amines in the inflamed gastric mucosa. Evidence is presented to support this hypothesis. Several drugs given parenterally have been identified as mutagenic nitroso compounds in homogenates of human and canine antral mucosa. Nitrite for this process is apparently derived from the inflamed mucosa. Different amines appear to be nitrosated at different places in the antrum, suggesting the presence of site-specific enzymes that control these reactions.

  1. [Bilateral chylothorax after gastric surgery].

    PubMed

    Medina, E; Anguiano, M P; Agudo, O; Lobo, J; Tihista, J A; Alonso, I; Calvo, A

    2005-01-01

    Chylothorax is a lymphatic effusion of chylous in the pleural space due to thoracic duct obstruction or injury. The most frequent aetiology is cancer; it is also related to chest trauma and iatrogenic. We describe the case of bilateral chylothorax in a 76-year-old woman, right predominant, during the post-operational phase of gastric surgery. This presented itself with respiratory insufficiency and tachycardia without initial haemodynamic compromise. It presented a favourable evolution after conservative treatment, cessation of oral intake and TPN and chest tube during 10 to 14 days. PMID:16421622

  2. Pneumobilia with gastric outlet obstruction.

    PubMed

    Kakked, Gaurav A; Bhatt, Nikita R; Bhatt, Rajiv

    2015-01-01

    Complications of peptic ulcer disease (PUD) like gastric outlet obstruction (GOO) and biliary fistula have become extremely rare with the advent of proton-pump inhibitors.This is a case of PUD presenting with GOO, a cholecystoduodenal fistula discovered incidentally on upper gastrointestinal endoscopy, and the presence of pneumobilia on a contrast-enhanced CT of the abdomen. A gastrojejunostomy with internal pyloric exclusion was performed. Since the patient did not have any signs of biliary tract disease,we decided not to operate on the fistula to prevent injury to the bile duct. The patient had an uneventful recovery. PMID:26552878

  3. Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis

    PubMed Central

    Chen, Sheng-Liang; Mo, Jian-Zhong; Cao, Zhi-Jun; Chen, Xiao-Yu; Xiao, Shu-Dong

    2005-01-01

    AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis. METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory and simultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile reflux positive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including active inflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance >0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH >4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance >0.14) and 11 patients (7 men and 4 women, mean age 46.2 years, range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH >4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region, and has no influence on acid-exposing status of gastric mucosa in patients with dyspepsia or chronic gastritis. PMID:15884134

  4. MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

    PubMed Central

    2013-01-01

    Background MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. Methods We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. Results MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. Conclusion In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer. PMID:24053468

  5. Effects of celecoxib on acid-challenged gastric mucosa of rats: comparison with metamizol and piroxicam.

    PubMed

    Berenguer, Bettina; Alarcón De La Lastra, Catalina; Motilva, Virginia; La Casa, Carmen; Herrerias, Juan Manuel; Pozo, David; Calero, María José Martin

    2004-06-01

    Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies. PMID:15309881

  6. Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers

    PubMed Central

    Nur Azlina, Mohd Fahami; Ibrahim, Ibrahim Abdel Aziz

    2015-01-01

    This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-? and IL1-? expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-? and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-?. PMID:26465592

  7. Relationship between gastric cancer and blood trace metal levels

    SciTech Connect

    Saito, K.; Fujimoto, S.; Sasaki, T.; Kurasaki, M.; Kaji, H.

    1981-06-01

    The metal concentrations in whole blood, blood plasma and blood cells of the patients were compared with those of normal subjects. Significantly lower levels of Cd, Mn, Pb and Zn in whole blood of the patients were found. The Cu levels in the blood cells and Zn levels in the blood plasma of patients were of definitely lower levels than those of the normal subjects. Superoxide dismutase (SOD), catale (CAT), glutathione peroxidase (GPX) and delta aminolevulinic dehydratase (ALAD) metal enzymes were assayed in the 30 patients and in 24 normal subjects matches in age to the patients. SOD levels in blood cells of the patients were definitely lower than those of the normal subjects. The CAT activities showed a significantly higher level in the stage II and a significantly lower level in the stage IV and metastatic groups. The activities of GPX and ALAD did not show any significant difference between the patients with gastric cancer and the normal subjects. There were significant negative correlations between CAT activity in whole blood and Cu level in whole blood and blood plasma; also, positive correlations between Zn level and in whole blood and CAT activity, and between Zn level and GPX activity in patients with gastric cancer. Moreover there were positive correlations between Zn level and SOD level in the blood cells and also a negative correlation between Zn level in blood cells and GPX activity in whole blood. These correlations suggested that there may be some important relationship between the metabolism of superoxide anion in gastric cancer patients and advanced cancer.

  8. Effect of ethanol upon gastric emptying.

    PubMed Central

    Kaufman, S E; Kaye, M D

    1979-01-01

    The effect of ethanol upon gastric emptying in healthy human subjects was studied by measuring the gastric emptying rates of three 750 ml meals, the osmolalities, energy densities, and pH of which were similar. Meal A, which contained 80 ml alcohol, emptied more rapidly than meal B, which contained 40 ml ethanol and 63.3 g dextrose; and meal B emptied more rapidly than meal C, which contained 126.6 g dextrose but no ethanol. The slower rate of emptying of the dextrose meal (C) was not due to an increased gastric secretory rate, as serial measurements of gastric pH were substantially and significantly higher with this than with the other two meals; nor was it due to a greater degree of duodenogastric reflux, as serial measurements of gastric bile acid concentrations were similar for the three meals. We conclude that the duodenal osmoreceptor mechanism is relatively insensitive to ethanol; that the relationship between energy density and gastric emptying rate does not hold in the case of ethanol; and that the gastro-oesophageal reflux which occurs in response to ethanol is not due to impairment of gastric emptying. PMID:39879

  9. Current status of proximal gastric vagotomy.

    PubMed Central

    Schirmer, B D

    1989-01-01

    Proximal gastric vagotomy is nearing its twentieth year in clinical use as an operation for peptic ulcer disease. No other acid-reducing operation has undergone as much scrutiny or study. At this time, the evidence of such studies and long-term follow-up strongly supports the use of proximal gastric vagotomy as the treatment of choice for chronic duodenal ulcer in patients who have failed medical therapy. Its application in treating the complications of peptic ulcer disease, which recently have come to represent an increasingly greater percentage of all operations done for peptic ulcer disease, is well-tested. However, initial series suggest that it should probably occupy a prominent role in treating some of these complications, particularly in selected patients, in the future. The operation has the well-documented ability to reduce gastric acid production, not inhibit gastric bicarbonate production, and also minimally inhibit gastric motility. The combination of these physiologic results after proximal gastric vagotomy, along with preservation of the normal antropyloroduodenal mechanism of gastrointestinal control, serve to allow patients with proximal gastric vagotomy the improved benefits of significantly fewer severe gastrointestinal side effects than are seen after other operations for peptic ulcer disease. PMID:2644897

  10. Recognition of gastric cancer by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Xu, Ming; Ma, Jun; Qu, Yefei; Mao, Weizheng; Zheng, Ronger

    2009-08-01

    The purpose of this study was to explore near-infrared (NIR) Raman spectroscopy for distinguishing cancer from normal gastric tissue. In our study, a total of 236 Raman spectra of mucosa from 43 gastric cancer patients were obtained by NIR Raman spectroscopy system with an excitation wavelength of 785 nm. After pretreatment, a comparison of the Raman spectra between cancer and normal tissues occurred. It was found that the gastric cancerous mucosa showed lower intensities at around 748, 944, and 1520cm-1, while higher at 807 and 1661cm-1, compared with normal tissue. And there was only one peak at 1022cm-1 in the spectra of normal mucosa, while there were two peaks at 1022 and 1052cm-1 in the spectra of cancerous mucosa. Support Vector Machine (SVM) was employed to classify Raman spectra between cancer and normal gastric tissues. A sensitivity of 88.2%, a specificity of 91.9%, and an overall diagnostic accuracy of 90.3% were achieved for discriminating gastric cancer from normal tissues with a Radial Basic Function (RBF) SVM algorithm. The experimental results show that Raman spectra differed significantly between cancerous and normal gastric tissue, which provides the experimental basis for the diagnosis of gastric cancer by Raman spectroscopy technology. And RBF SVM algorithm can give the well generalized classification performance for the samples, which expands the application of mathematical algorithms in the classification.

  11. [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

  12. Chemoprevention of gastric cancer: current status.

    PubMed

    Xia, Harry Hua-Xiang; Wong, Benjiamin Chun-Yu; Lam, Shiu-Kum

    2003-01-01

    The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer. PMID:12667378

  13. Viscous fingering of HCI through gastric mucin

    NASA Astrophysics Data System (ADS)

    Bhaskar, K. Ramakrishnan; Garik, Peter; Turner, Bradley S.; Bradley, James Douglas; Bansil, Rama; Stanley, H. Eugene; Lamont, J. Thomas

    1992-12-01

    THE HCI in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium1-4 and acts as a diffusion barrier5,6 Bicarbonate ions secreted by the gastric epithelium7 are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface8-10. How does HCI, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCI through solutions of pig gastric mucin produces viscous fingering patterns11-18 dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCI neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCI secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HC1 in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.

  14. 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

  15. Effect of GABA and baclofen on gastric mucosal protective factors.

    PubMed

    Abbas, W R; Maiti, R N; Goel, R K; Bhattacharya, S K

    1998-02-01

    GABA and baclofen (BAC), a GABA-mimetic agent, were investigated for antiulcerogenic activity. Orally administered GABA (100 mg/kg) and BAC (10 mg/kg) showed significant ulcer protection when given either alone for one day or for 4 days, or when given together with aspirin (ASP; 200 mg/kg x 3 days) in their 4 days treatment time in pylorus-ligated rats. Both the drugs showed a tendency to increase acid and decrease peptic output, and increased gastric mucus secretion in terms of total carbohydrate to protein ratio (TC:P) in both the above treatment groups. ASP tended to decrease acid and increase peptic output and significantly decreased TC:P ratio. Both GABA and BAC tended to reverse aspirin-induced effects, though they had little per se effect on TC:P ratio of gastric mucosal glycoproteins except an increase in sialic acid content both after one day or four days treatment. No, per se, effect on cell shedding (DNA and protein content of gastric juice) or cell proliferation (DNA/mg protein) was noted with GABA or BAC but the enhanced cell shedding induced by ASP was attenuated by them. ASP was found to enhance cell proliferation. However, neither of drug showed any effect on cell proliferation when given either alone or in combination with ASP. The antiulcerogenic effect of GABA and BAC may be due to their predominant effects on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding or mucosal damage. PMID:9754049

  16. 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

  17. An integrated approach of predicted miR-34a targets identifies a signature for gastric cancer

    PubMed Central

    TANG, TIANTIAN; SU, RONGJIAN; WANG, BAOQUAN; ZHANG, YUNLI

    2015-01-01

    microRNA-34a (miRNA/miR-34a) functions as a tumor suppressor gene in gastric cancer and may be involved in system-wide regulatory networks. To clarify the expression of all predicted target genes of this miRNA, a comprehensive and systematic analysis of miR-34a-target genes in gastric cancer was conducted in the present study. In the initial analysis, the potential functions, pathways and networks of gastric cancer-associated molecules and miR-34a targets were identified. In the final integrative analysis of gastric cancer-associated miR-34a targets, 30 hub genes were identified using overlap calculations, indicating that miR-34a may be significant in the development and progression of gastric cancer through the Smad signaling pathway, the cell cycle, the mitogen-activated protein kinase signaling pathway, apoptosis, the Notch signaling pathway and other pathways. The present study provides a bioinformatic analysis of miR-34a-targets in gastric cancer, describes numerous target genes and novel coregulatory networks, and may provide an opportunity to identify a critical regulatory network for predicting the molecular mechanisms of miR-34a in the development and progression of gastric cancer.

  18. Frequent amplification of AIB1, a critical oncogene modulating major signaling pathways, is associated with poor survival in gastric cancer

    PubMed Central

    Sui, Fang; Lu, Rong; He, Qingyuan; Yang, Qi; Lv, Hongjun; Shi, Bingyin; Hou, Peng

    2015-01-01

    Amplified in breast cancer 1 (AIB1) is a member of p160 steroid receptor coactivator (SRC) family that mediates the transcriptional activities of nuclear receptors and other transcription factors. It acts as a major oncogene in diverse cancers, whereas biological function of AIB1 in gastric cancer remains largely unclear. This study was designed to explore the role of AIB1 in gastric tumorigenesis and its potential as a useful prognostic marker and therapeutic target in this cancer. Our data demonstrated that AIB1 was significantly up-regulated in gastric cancer tissues as compared with control subjects. Moreover, AIB1 amplification was found in 47 of 133 (35.3%) gastric cancer cases, but not in control subjects. AIB1 amplification was positively associated with its protein expression, and was significantly correlated with poor patient survival. AIB1 knockdown in gastric cancer cells dramatically inhibited cell proliferation, invasiveness and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Mechanically, AIB1 promotes gastric cancer cell proliferation, survival and invasiveness through modulating major signaling pathways such as ErbB and Wnt/?-catenin pathways. Collectively, these findings suggest that AIB1 plays an important role in the pathogenesis of gastric cancer and represents a potential prognostic marker and therapeutic target for this cancer. PMID:25970779

  19. Gastric Cancer: New Drugs – New Strategies

    PubMed Central

    Schulte, Nadin; Ebert, Matthias P; Härtel, Nicola

    2014-01-01

    Background Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed. Summary The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways. Key Message The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways. Practical Implications Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under development.

  20. Diabetes and gastric cancer: the potential links.

    PubMed

    Tseng, Chin-Hsiao; Tseng, Farn-Hsuan

    2014-02-21

    This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer. PMID:24587649

  1. A case report of localized gastric amyloidosis

    PubMed Central

    Wu, Dan; Lou, Jian-Ying; Chen, Jian; Fei, Lun; Liu, Gui-Jie; Shi, Xiao-Yu; Lin, Han-Ting

    2003-01-01

    AIM: To elucidate the clinical and laboratory features of localized gastric amyloidosis via a rare report along with a review of related literatures. METHODS: The clinical manifestations, laboratory results and surgical treatment of a female patient with localized gastric amyloidosis in our hospital were summarized. The relevant literatures were reviewed on the etiology, clinical features, diagnosis, treatment and prognosis of this disease. RESULTS: The patient was lack of specific clinical manifestations and positive laboratory results. Prior to the treatment, she was suspected to be of malignization from gastric ulcer by both gastroscopy and endoscopic ultrasonography, which was denied by the gastric biopsy. The patient was treated with subtotal gastrectomy and clearance of perigastric lymph nodes. The postoperative pathological diagnosis determined the lesion to be the deposition of amyloid materials in the gastric mucosa, submucosa and blood vessel walls with intestinal metaplasia and atrophy of the gastric glands, in which no malignant tumor was found. Congo red staining with prior potassium permanganate incubation confirmed the AA type of amyloid in this case. Multiple biopsies from esophagus, remnant stomach, duodenum, colon and bone marrow in the follow-up survey showed no amyloidal deposition in these tissues and organs. Up to the present, no signs of recurrence have been found in this patient. CONCLUSION: Localized gastric amyloidosis, being rare in incidence, should be considered in the differentiation of gastric tumors, in which biopsy is the only means to confirm the diagnosis. Currently, surgical resection of pathological tissue and circumambient lymph nodes may be a preferable therapeutic strategy for the localized amyloidosis to prevent possible complications. Although with a benign prognosis, gastric amyloidosis possesses a recurrent tendency as suggested by the literatures. PMID:14606114

  2. Do calories or osmolality determine gastric emptying

    SciTech Connect

    Shafer, R.B.; Levine, A.S.; Marlette, J.M.; Morley, J.E.

    1984-01-01

    Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) and gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals.

  3. Diabetes and gastric cancer: The potential links

    PubMed Central

    Tseng, Chin-Hsiao; Tseng, Farn-Hsuan

    2014-01-01

    This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer. PMID:24587649

  4. Gastric bypass reduces fat intake and preference

    PubMed Central

    Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R.; Spector, Alan C.; Olbers, Torsten; Lutz, Thomas A.

    2011-01-01

    Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation. PMID:21734019

  5. Effect of pancreatic juice on basal pancreatic and gastric secretion in dogs.

    PubMed Central

    Magee, D F; Naruse, S

    1982-01-01

    1. The effect of duodenal infusion of pancreatic juice on basal pancreatic and gastric secretion was studied in five conscious dogs provided with pancreatic fistulae, gastric fistulae and Heidenhain fundic pouches. 2. Pancreatic juice and trypsin stimulated a pancreatic secretion rich in protein. 3. Autodigested juice without proteolytic activities also stimulated the secretion. Boiling the juice or addition of trypsin inhibitor to the juice diminished the augmented secretion. 4. It seems, therefore, that trypsin is necessary even in proteolytically inactive autodigested juice for pancreatic stimulation. 5. In dogs, unlike rats and pigs, basal pancreatic secretion is not under negative feed-back control by duodenal tryptic activity. 6. Basal gastric secretion was not significantly changed by duodenal infusion of pancreatic juice. PMID:7175754

  6. 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

  7. Proteasome inhibitor MG-132 lowers gastric adenocarcinoma TMK1 cell proliferation via bone morphogenetic protein signaling

    SciTech Connect

    Wu, William Ka Kei; Sung, Joseph Jao Yiu; Yu Le; Cho, C.H.

    2008-06-27

    Proteasome inhibitor is a novel class of cancer therapeutics, of which the mechanism of action is not fully understood. It is reported that proteasome inhibitor enhances bone morphogenetic protein (BMP) signaling in osteoblasts to stimulate bone formation. BMP signaling is also an important tumor-suppressing pathway in gastric carcinogenesis. We therefore sought to determine the anti-mitogenic effect of proteasome inhibition in relation to BMP signaling in gastric cancer cells. Results showed that proteasome inhibitor MG-132 significantly suppressed the proliferation and the colony-forming ability of gastric cancer TMK1 cells. In this connection, MG-132 activated BMP signaling, manifested as an increase in Smad1/5/8 phosphorylation and up-regulation of p21{sup Waf1/Cip1} mRNA and protein expression. Knockdown of BMP receptor II by RNA interference abolished Smad1/5/8 phosphorylation, p21{sup Waf1/Cip1} induction, and the inhibition of cell proliferation induced by MG-132. Further analysis revealed that MG-132 up-regulated the expression of BMP1 and BMP4 and suppressed the expression of Smad6. Knockdown of Smad6 also mimicked the effect of MG-132 on BMP signaling. Collectively, these findings suggest that inhibition of proteasome suppresses gastric cancer cell proliferation via activation of BMP signaling. This discovery may open up a novel therapeutic avenue to proteasome inhibitors for the management of gastric cancer.

  8. Comparison of the effects of glucagon and atropine sulfate on gastric emptying.

    PubMed

    Chernish, S M; Brunelle, R R; Rosenak, B D; Ahmadzai, S

    1978-12-01

    Six asymptomatic adult males cooperated in a study of gastric emptying. Each subject was given a test meal of 500 ml. of 3.5% glucose on a fasting stomach. Ten minutes prior to the meal each was given either 1 mg atropine sulfate, placebo, or 2 mg. glucagon, double-blind and crossover. Each drug was given twice, intravenously, in a random order. The meal was removed by a Salem sump tube half an hour after ingestion. When compared to placebo, the active drugs significantly (P less than 0.05) slowed gastric emptying; atropine sulfate was more effective (P less than 0.05) than glucagon. The active drugs significantly (P 0.05) decreased total gastric acid secretion and total gastric chloride as compared to placebo. Glucagon significantly (P 0.05) increased the blood glucose concentration as compared to placebo. These results indicate that both glucagon and atropine sulfate slow the gastric emptying of a liquid sugar meal from the stomach. PMID:369361

  9. Clinical significance of MET in gastric cancer

    PubMed Central

    Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC. PMID:26600931

  10. Overexpression of PI3K p110? contributes to acquired resistance to MET inhibitor, in MET-amplified SNU-5 gastric xenografts

    PubMed Central

    Ji, Fujian; Liu, Xuanwen; Wu, Yuanyu; Fang, Xuedong; Huang, Guomin

    2015-01-01

    Gastric cancer is one of the most virulent malignant diseases and is the second leading cause of cancer mortality in the world. The receptor tyrosine kinase MET is constitutively activated in many gastric cancers and its expression is strictly required for survival of some gastric cancer cells. Targeting gastric cancers with amplified or abnormally activated MET may have therapeutic benefit based on nonclinical and emerging clinical findings. However, one of the major problems of therapies targeting tyrosine kinases is that many tumors are not responsive to treatment or eventually develop resistance to the drugs. This study aims to understand the mechanisms of MET resistance in gastric SNU-5 xenografts which developed resistance to PHA665752, a MET inhibitor, through long-period tyrosine kinase inhibitor exposure. In the current study, we found that PI3K p110? is overexpressed in PHA665752-resistant SNU-5 xenografts. These findings showed that high PI3K p110? expression contributes to tyrosine kinase inhibitor resistance. In addition, we reported the development of a carcinogen-induced gastric cancer model that recapitulates PI3K p110? expression in human disease, which will serve as a useful model to study PI3K p110?’s biology and its effectiveness as a novel biomarker and a molecular target for gastric cancer. Ultimately, PI3K p110? represents a novel target for gastric cancer. PMID:26543351

  11. 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

  12. IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

    PubMed Central

    Sun, Guoming; Zhuo, Wei; Zhong, Jing; Qian, Cuijuan; Wang, Lan; Wang, Liangjing; Si, Jianmin; Chen, Shujie

    2013-01-01

    Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element “TTAT”. Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients. PMID:24386080

  13. The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis

    PubMed Central

    Huang, Tzu-Ting; Fang, Wen-Liang; Huang, Kuo-Hung; Lee, Hsin-Chen; Chi, Chin-Wen; Yeh, Tien-Shun

    2015-01-01

    Gastric carcinoma is one of the most common malignancies and the third highest cause of global cancer-related death. Notch2 receptor intracellular domain (N2IC), the activated form of Notch2 receptor, enhances gastric carcinogenesis. MicroRNAs (miRNAs) act as either oncogenes or tumor suppressors in tumorigenesis and cross-talk with Notch pathways. Herein, microRNA-23b (miR-23b) was identified as a Notch2 receptor-related miRNA and its role in gastric carcinogenesis was investigated. Levels of miR-23b in stomach adenocarcinoma samples were down-regulated, whereas those of Notch2 receptor, v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1), and E2F1 transcripts were up-regulated. Results also showed that N2IC down-regulated miR-23b expression in gastric cancer cells through up-regulating E2F1. The miR-23b inhibited gastric tumorigenesis including growth, viability, epithelial-mesenchymal transition, and abilities of colony formation, migration, invasion, and tumorsphere formation. Mechanistically, miR-23b suppressed tumor progression and pluripotency gene expression and affected tumorsphere ultra-structure in gastric cancer cells via targeting Notch2 receptor or Ets1. Furthermore, miR-23b diminished the xenografted tumor growth and lung metastasis of SC-M1 gastric cancer cells through Notch2 pathway. Our results suggest that Notch2 pathway and miR-23b interplay in a reciprocal regulation loop in gastric cancer cells and this axis plays an important role in gastric carcinogenesis. PMID:26041881

  14. PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion

    PubMed Central

    Wang, G; Zhang, Q; Song, Y; Wang, X; Guo, Q; Zhang, J; Li, J; Han, Y; Miao, Z; Li, F

    2015-01-01

    Actin protrusion at the cell periphery is central to the formation of invadopodia during tumor cell migration and invasion. Although RUFY3 (RUN and FYVE domain containing 3)/SINGAR1 (single axon-related1)/RIPX (Rap2 interacting protein X) has an important role in neuronal development, its pathophysiologic role and relevance to cancer are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which RUFY3 involves in gastric cancer cell migration and invasion. Here, our data show that overexpression of RUFY3 leads to the formation of F-actin-enriched protrusive structures at the cell periphery and induces gastric cancer cell migration. Furthermore, P21-activated kinase-1 (PAK1) interacts with RUFY3, and promotes RUFY3 expression and RUFY3-induced gastric cancer cell migration; inhibition of PAK1 attenuates RUFY3-induced SGC-7901 cell migration and invasion. Importantly, we found that the inhibitory effect of cell migration and invasion is significantly enhanced by knockdown of both PAK1 and RUFY3 compared with knockdown of RUFY3 alone or PAK1 alone. Strikingly, we found significant upregulation of RUFY3 in gastric cancer samples with invasive carcinoma at pathologic TNM III and TNM IV stages, compared with their non-tumor counterparts. Moreover, an obvious positive correlation was observed between the protein expression of RUFY3 and PAK1 in 40 pairs of gastric cancer samples. Therefore, these findings provide important evidence that PAK1 can positively regulate RUFY3 expression, which contribute to the metastatic potential of gastric cancer cells, maybe blocking PAK1-RUFY3 signaling would become a potential metastasis therapeutic strategy for gastric cancer. PMID:25766321

  15. Effect and prognostic significance of the KAI1 gene in human gastric carcinoma

    PubMed Central

    GUO, JING; FAN, KAI-XI; XIE, LI; XIAO, JIA-JIA; CHEN, KAI; HUI, LI-NA; XU, ZHONG-FA

    2015-01-01

    The present study aimed to explore the effect and mechanism of the Kangai 1 (KAI1) gene in regulating the migration and invasion of gastric carcinoma cells, and the prognostic significance of this gene in gastric cancer patients. Immunohistochemistry and in situ hybridization were used to investigate the role of KAI1 in the progression and prognosis of gastric cancer. The pEGFP-N1-KAI1 plasmid was transfected into human gastric carcinoma SGC7901 cells using liposomes. The effect of transfection with the KAI1 gene was measured using a reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR) assay. The Transwell chamber assay was used to study the metastatic and invasive ability of SGC7901 cells. Gastric cancer metastasis-associated genes, including hypoxia-inducible factor (HIF)-1?, matrix metalloproteinase (MMP)-2, MMP-9, basic fibroblast growth factor (bFGF), and urease plasminogen activator (uPA) were measured by RT-sqPCR prior to and following transfection with the KAI1 gene. The expression of KAI1 protein and mRNA was associated with the differentiation degree of gastric cancer, presence of lymph node metastasis, tumor-node-metastasis stage, depth of invasion and the survival time of patients. The migratory and invasive abilities of SGC7901 cells were significantly decreased subsequent to transfection with the KAI1 gene, and the expression of bFGF and uPA was downregulated. It was concluded that the tumor suppressor gene KAI1 inhibits the migration and invasion of gastric carcinoma cells, possibly by suppressing the expression of uPA. Patients that expressed KAI1 may demonstrate an improved prognosis.

  16. Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro.

    PubMed

    Sharma, S A; Tummuru, M K; Miller, G G; Blaser, M J

    1995-05-01

    Gastric infection with Helicobacter pylori activates a mucosal inflammatory response by mononuclear cells and neutrophils that includes expression of cytokines interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and IL-8. In this study, we analyzed the IL-8 response of human gastric cancer cell lines (Kato III, AGS, and MKN28) to H. pylori infection in vitro. IL-8 mRNA expression was detected by reverse transcription-PCR amplification of RNA extracted from epithelial cells after incubation with different H. pylori wild-type and mutant strains, and IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Exposure to viable H. pylori induced IL-8 mRNA and protein synthesis in all three gastric cell lines but not in nongastric epithelial cell lines. Heat-killed H. pylori and a crude cytotoxin preparation did not induce significant IL-8 secretion. IL-8 mRNA peaked between 2 and 4 h postinfection, and IL-8 protein production was maximal 24 h postinfection. Exposure of gastric carcinoma cells to other gastrointestinal bacteria, such as Pseudomonas aeruginosa, Campylobacter jejuni, and Escherichia coli, but not Campylobacter fetus, induced IL-8 synthesis. Wild-type strains that expressed the vacuolating cytotoxin (Tox+) and a cytotoxin-associated gene (cagA) product (CagA+) induced significantly more IL-8 than did CagA- Tox- strains. However, there was no decrease in IL-8 induction by isogenic mutants of CagA-, Tox-, or Cag- Tox- strains or by a mutant lacking the urease subunits. These results indicate that exposure to H. pylori and other gram-negative organisms that do not colonize the gastric mucosa induces IL-8 production by gastric carcinoma cells in vitro. Although the CagA+ Tox+ phenotype of H. pylori is associated with enhanced IL-8 production by gastric cell lines, other bacterial constituents are clearly essential. PMID:7729872

  17. Primary gastric rupture in 47 horses (1995-2011).

    PubMed

    Winfield, Laramie S; Dechant, Julie E

    2015-09-01

    The purpose of this retrospective case-control study was to identify factors associated with primary gastric rupture and to investigate if there were differences between etiologies of primary gastric rupture. Compared to the general colic population, Quarter horses were under-represented and Friesians and draft breeds were over-represented in 47 cases of primary gastric ruptures. Horses with primary gastric rupture typically presented with severe clinical and clinicopathological derangements. There were 24 idiopathic gastric ruptures, 20 gastric impaction associated ruptures, and 3 perforating gastric ulcers. Thoroughbred horses were over-represented in the idiopathic gastric rupture group compared to other breeds and etiologies. This study suggests the presence of important breed predispositions for development of gastric rupture. Further study is necessary to identify if these predispositions are associated with management factors or breed-specific disorders. PMID:26345205

  18. Enterogastric reflux and gastric clearance of refluxate in normal subjects and in patients with and without bile vomiting following peptic ulcer surgery.

    PubMed Central

    Mackie, C; Hulks, G; Cuschieri, A

    1986-01-01

    A noninvasive scintigraphic technique was used to estimate enterogastric reflux and subsequent gastric evacuation of refluxate in 35 normal, healthy subjects and 55 patients previously treated by vagotomy or partial gastrectomy. Reflux was provoked by a milk drink and quantitated by counting 99Tcm-EHIDA activity within the gastric area during gamma camera imaging. Seven normal subjects (20%) showed reflux of 5-18% of initial activity (mean: 10%), with peak values occurring at 5-30 minutes (mean: 14 minutes) following the milk. Gastric evacuation of activity in these subjects was monoexponential (r = 0.993, T1/2 = 24.1 minutes). Reflux occurred more frequently than normal in patients with truncal vagotomy and drainage (22/28 patients) and partial gastrectomy (20/21 patients). All of 16 patients with Billroth II anastomoses exhibited reflux, which was excessive compared with refluxing normal subjects (mean: 25%; p less than 0.01) and occurred later into the study (mean: 34 minutes; p less than 0.01). Ten of 11 asymptomatic patients showed reflux of similar amounts of activity (mean: 21%) compared with 16 patients who complained of bile vomiting (mean: 22%). However, asymptomatic patients exhibited gastric evacuation of refluxate at a rate similar to that of refluxing normal subjects, while bile vomiters showed significant gastric retention of refluxate at 25-30 minutes following peak gastric activity (p less than 0.05). This result confirms that post-operative bile vomiting is essentially a problem of gastric emptying. PMID:3767485

  19. Biochemical mechanisms on species differences in gastric carcinogenesis.

    PubMed

    Chen, J; Barnes, W S; Maiello, J; Weisburger, J H

    1984-01-01

    The biochemical denitrosation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in tissues from four strains of rat, inbred Buffalo, Lewis, B-N, and the random-bred Sprague-Dawley, with different sensitivities to MNNG-induced gastric carcinomas was investigated as a possible explanation for the species/strain differences in MNNG-induced carcinogenesis. An analytical HPLC method was developed to assay denitrosation of MNNG to N-methyl-N'-nitroguanidine (MNG) by cytosolic, microsomal, mitochondrial, and nuclear cell fractions. All the activity was contained in the microsomal and cytosolic fractions, with the major portion occurring in the cytosol. The activity in both fractions was NADPH-dependent, but denitrosation was not reduced by inhibitors of the cytochrome P-450 system. Denitrosation of MNNG post-mitochondrial supernatant (S9) fractions from liver, glandular stomach mucosa, and duodenal mucosa of the four rat strains was determined. In all strains, denitrosation activities were highest in liver. Comparisons between the three strains most sensitive to MNNG-induced gastric carcinogenesis indicated no large differences for any tissue. However, Buffalo, the most resistant strain, did have a higher level of denitrosating activity in all three tissues, which is consistent with the hypothesis that higher levels of detoxifying enzymes may lead to a decreased incidence of tumors. On the other hand, denitrosation accounts for less than 3% of the MNNG that disappears during the incubation period so that the relevance of denitrosation as a mechanism in strain-specific sensitivity to MNNG-induced gastric carcinoma requires additional studies. PMID:6746704

  20. Gastric Emptying Rates for Selected Athletic Drinks

    ERIC Educational Resources Information Center

    Coyle, Edward F.; And Others

    1978-01-01

    The intent of this research was to compare the rate of gastric emptying of three commercially available athletic drinks with water and, in doing so, to determine their relative contributions of water, electrolytes, and carbohydrate to the body. (JD)

  1. 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.

  2. Weighing the Options: Gastric Sleeve Surgery

    MedlinePLUS

    ... the roux-en-y gastric bypass is the malnutrition. The patients who undergo that procedure must take ... within reason, and not have to worry about malnutrition. Well, essentially, everyone will be able to eat ...

  3. Helicobacter pylori Infection and Gastric Adenocarcinoma

    PubMed Central

    Correa, Pelayo; Piazuelo, M Blanca

    2011-01-01

    Gastric adenocarcinoma is the second leading cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the strongest recognized risk factor for gastric adenocarcinoma. This bacterial species colonizes the stomach of more than half of the world’s population; however, only a very small proportion of infected subjects develop adenocarcinoma. H. pylori causes a chronic gastritis that may last decades, and a multistep precancerous process is recognized for the most frequent histologic type of gastric adenocarcinoma: the intestinal type. The severity and long-term outcome of this infection is modulated by an increasing list of bacterial, host, and environmental factors, which interplay in a complex manner. Identification of individuals at high risk for gastric cancer that may enter a surveillance program and intervention during the precancerous process is the most suitable strategy for decreasing mortality due to this malignancy. PMID:21857882

  4. 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.

  5. "Gastric cytoprotection" is still relevant.

    PubMed

    Szabo, Sandor

    2014-12-01

    Although Andre Robert's historic article on "gastric cytoprotection" in 1979 introduced this new name and concept, gastroprotective drugs (e.g. sofalcone, sucralfate), which prevent and/or accelerate healing of gastric ulcers without inhibiting acid secretion, were known in Japan before or around that time. But since Robert's studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal research for more than 30 years. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate, despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide counteract virtually any form of gastroprotection. In Robert's terms of "prevention of chemically induced acute mucosal lesions," so far no single mechanism could explain the beneficial effects of diverse protective agents, but I argue that these two endogenous substances (i.e. PG, SH), in addition to histamine, are the main mechanistic mediators of acute gastroprotection: PG and histamine, because as mediators of acute inflammation, they increase vascular permeability (VP), and SH scavenge free radicals. This is contrary to the search for a single mechanism of action, long focused on enhanced secretion of mucus and/or bicarbonate that may contribute but cannot explain all forms of gastroprotection. Nevertheless, based on research work of the last 30 years, in part from our lab, a new mechanistic explanation of gastroprotection may be formulated: it's a complex but orderly and evolution-based physiologic response of the gastric mucosa under pathologic conditions. Namely, one of the first physiologic defense responses of any organ is inflammation that starts with rapid vascular changes (e.g. increased VP and blood flow), followed by cellular events (e.g. infiltration by acute and chronic inflammatory cells). Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. "adaptive cytoprotection"). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective, that is, a key element in the complex pathophysiologic response during acute gastroprotection. Over the years, "gastroprotection" was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence "gastric cytoprotection" research is still relevant. PMID:25521744

  6. [Gastritis associated with duodeno-gastric reflux].

    PubMed

    Diarra, M; Konate, A; Traore, C B; Drabo, M; Soukho, A espouse Diarra; Kalle, A; Dembele, M; Traore, H A; Maiga, M Y

    2007-01-01

    Our main objective was to study gastritis associated to duodeno-gastric reflux. It is about a longitudinal study case/witness, paired according to the sex and the age. It was unrolled from February 2005 to January 2006 in the digestive diseases department of the hospital Gabriél Touré, and endoscopic centers of Promenade des Angevins, and clinique Farako. The patients profited from an upper digestive endoscopy to appreciate endoscopic aspect of gastritis associated to bile in the stomach mucus lake. The gastric biopsies were systematic. This study included 50 patients having gastritis associated to bile in gastric mucus lake compared to 50 patients having gastritis associated to clearly gastric mucus lake. The sex-ratio was 1.26 in favour of men. The average age of the patients was of 41.30 +/- 15.43 years. On the symptomatic hand, fetid breath was significantly met in duodeno-gastric reflux (p = 0.013). Potash consumption in the "tô" (millet cake) was significantly reported in gastritis associated to bile in gastric mucus lake (p = 0.042). The endoscopic aspects were comparable. Histological aspects of nonatrophic chronic gastritis were significantly mint in witnesses as well into the antrum as into the fundus (p = 0.0001 and p = 0.00023). The reactional gastritis aspect was the prerogative of duodenogastric reflux (p ranging between 10(-6) and 3.10 (-6). Helicobacter pylori infection was found comparable in the two groups (p = 0.297). Dysplasia although rare was found only in gastritis associated to duodeno-gastric reflux. Gastritis associated to bile in gastric mucus does not se,nm to have specific clinical, endoscopic and histological presentation. However the presence of dysplasia must have an attentive monitoring. PMID:19434982

  7. Epigenetic alterations in gastric cancer (Review)

    PubMed Central

    FU, DU-GUAN

    2015-01-01

    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

  8. Multicentric Type 3 Gastric Neuroendocrine Tumors

    PubMed Central

    Lee, Sang Hoon; Moon, Dochang; Lee, Hee Seung; Lee, Choong-kun; Jeon, Yong Duk; Park, Ji Hye; Kim, Hyunki

    2015-01-01

    A 50-year-old woman with incidentally detected multiple gastric polyps and biopsy-proven neuroendocrine tumor (NET) was referred to our hospital. More than 10 polypoid lesions (less than 15 mm) with normal gastric mucosa were detected from the gastric body to the fundus. The serum level of gastrin was within the normal limits. There was no evidence of atrophic changes on endoscopy and serologic marker as pepsinogen I/II ratio. Computed tomography of the abdomen and pelvis revealed no evidence of metastatic lesions. She refused surgery, and we performed endoscopic polypectomy for almost all the gastric polyps that were greater than 5 mm. Although the histological examination revealed that all the removed polys were diagnosed as NET G1, three of them extended to the lateral or vertical resection margins, while two exhibited lymphovascular invasion. A follow-up upper endoscopy that was performed 6 months after the diagnosis showed multiple remnant gastric polyps that were suggestive of remnant gastric NET. PMID:26473128

  9. [On epidemiology of gastric cancer (author's transl)].

    PubMed

    Wolff, G; Läuter, J

    1976-01-01

    257 stomach cancer patients and 766 controls were interviewed using a standardized questionnaire for 35 variables. The two groups were compared by multivariate variance analysis. This analysis results in a combination of 20 variables significantly connected with gastric cancer. The rankorder of the most prominent variables is as follows: no food intolerance, higher alcohol consumption, living place near Berlin, occupation labourer, early loss of teeth, car driving, no gallstones, smoking and age. It can be assumed that these variables are of aetiological importance. In the aetiology of gastric cancer, exogenous cancerogens seem to play a more important role than endogenous factors. In two further multivariate variance analysis, control group is divided into persons with and persons without chronic gastritis verified by blind gastric biopsy and compared with gastric cancer patients, too. A fourth analysis is limited to female only. The results of the three last mentioned analysis are similar to those of the first one and also similar to results from other countries based on univariate analysis. The computed combination of variables was used for diagnosis of gastric cancer by discriminance analysis in the persons forming the material for this study. This diagnosis was correct in 71% of gastric cancer patients and in 72% of control persons. PMID:962497

  10. Unusual endoscopic findings of gastric neuroendocrine tumor.

    PubMed

    Kishi, Kazuhiro; Fujisawa, Akihiko; Horikita, Minoru; Nakai, Yoshihiro; Ooshimo, Kazushi; Kishi, Fumiko; Kimura, Masako; Lin, Chun-Che; Takayama, Tetsuji

    2015-01-01

    Gastric neuroendocrine tumor (NET) is sometimes found as a submucosal tumor on upper gastrointestinal endoscopy. Gastric NET with malignant profile and neuroendocrine carcinoma (NEC) show various forms which are difficult to distinguish from gastric cancer and other disease. We report a case of a cauliflower-shaped NET of the stomach. A 61-year-old man was referred to our hospital with a complaint of abdominal fullness. Upper gastrointestinal endoscopic examination revealed an unusual, whitish cauliflower-shaped tumor that belongs to Borrmann type I on the lesser curvature of the gastric antrum. Histological examination of the biopsy specimen revealed NET G2, because the tumor cells were CD56- and synaptophysin-positive by immunohistochemical analysis. A distal gastrectomy with D2 lymphadenectomy was performed. A recurrence in the liver was revealed by follow up computed tomography after 11 months from operation. Combined chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP) was treated. The patient achieved a partial response, but he died after 31 months from gastrectomy. There is no independent, large-scaled prospective study and no standard treatment for gastric NETs with distant metastases. Our case is reported with a literature review of the treatment of metastatic gastric NET G2. PMID:26399359

  11. Cyanoacrylate Injection Versus Band Ligation in the Endoscopic Management of Acute Gastric Variceal Bleeding

    PubMed Central

    Qiao, Weiguang; Ren, Yutang; Bai, Yang; Liu, Side; Zhang, Qiang; Zhi, Fachao

    2015-01-01

    Abstract The evidence for optimal endoscopic management of bleeding gastric varices is lacking. The clinical outcome is controversial in trials comparing cyanoacrylate injection and band ligation. To help guide endoscopic decisions regarding acute gastric variceal bleeding, a meta-analysis was conducted. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ScienceDirect were searched for all randomized controlled trials (RCTs) containing the 2 interventions. The main outcomes evaluated in the meta-analysis were active bleeding control, blood transfusion, rebleeding, recurrence of varices, complications, and survival. Three RCTs were identified, which included 194 patients with active gastric variceal bleeding from Taiwan and Romania. Active bleeding control was achieved in 46 of 49 (93.9%) patients in the cyanoacrylate injection group, compared with 35 of 44 (79.5%) in the band ligation group (P?=?0.032), for a pooled odds ratio of 4.44 (95% confidence interval, 1.14–17.30). Rebleeding rate was comparable in type 2 gastroesophageal varices (GOV2) between the 2 interventions (35.7% vs 34.8%, P?=?0.895), but cyanoacrylate injection seemed superior for reducing rebleeding rate in type 1 gastroesophageal varices (GOV1, 26.1% vs 47.7%, P?=?0.035) and type 1 isolated gastric varices (IGV1, 17.6% vs 85.7%, P?=?0.015). Cyanoacrylate injection was also superior in controlling recurrence of gastric varices to band ligation (36.0% vs 66.0%, P?=?0.002). There was no difference in complications or mortality between the 2 interventions. The major limitation of this meta-analysis is the small number of studies/patients included. Compared with band ligation, injection cyanocrylate have an advantage in the control of acute gastric variceal bleeding, also with lower recurrence rate and rebleeding (except GOV2). The limited amount of studies included attenuates the strength of this meta-analysis; therefore, more high-quality RCTs are needed. PMID:26469912

  12. Mechanosensitive enteric neurons in the guinea pig gastric corpus

    PubMed Central

    Mazzuoli-Weber, Gemma; Schemann, Michael

    2015-01-01

    For long it was believed that a particular population of enteric neurons, referred to as intrinsic primary afferent neuron (IPAN)s, encodes mechanical stimulation. We recently proposed a new concept suggesting that there are in addition mechanosensitive enteric neurons (MEN) that are multifunctional. Based on firing pattern MEN behaved as rapidly, slowly, or ultra-slowly adapting RAMEN, SAMEN, or USAMEN, respectively. We aimed to validate this concept in the myenteric plexus of the gastric corpus, a region where IPANs were not identified and existence of enteric sensory neurons was even questioned. The gastric corpus is characterized by a particularly dense extrinsic sensory innervation. Neuronal activity was recorded with voltage sensitive dye imaging after deformation of ganglia by compression (intraganglionic volume injection or von Fry hair) or tension (ganglionic stretch). We demonstrated that 27% of the gastric neurons were MEN and responded to intraganglionic volume injection. Of these 73% were RAMEN, 25% SAMEN, and 2% USAMEN with a firing frequency of 1.7 (1.1/2.2), 5.1 (2.2/7.7), and of 5.4 (5.0/15.5) Hz, respectively. The responses were reproducible and stronger with increased stimulus strength. Even after adaptation another deformation evoked spike discharge again suggesting a resetting mode of the mechanoreceptors. All MEN received fast synaptic input. Fifty five percent of all MEN were cholinergic and 45% nitrergic. Responses in some MEN significantly decreased after perfusion of TTX, low Ca++/high Mg++ Krebs solution, capsaicin induced nerve defunctionalization and capsazepine indicating the involvement of TRPV1 expressing extrinsic mechanosensitive nerves. Half of gastric MEN responded to intraganglionic volume injection as well as to ganglionic stretch and 23% responded to stretch only. Tension-sensitive MEN were to a large proportion USAMEN (44%). In summary, we demonstrated for the first time compression and tension-sensitive MEN in the stomach; many of them responded to one stimulus modality only. Their proportions and the basic properties were similar to MEN previously identified by us in other intestinal region and species. Unlike in the intestine, the responsiveness of some gastric MEN is enhanced by extrinsic TRPV1 expressing visceral afferents. PMID:26578888

  13. Hypercapnia counteracts captopril-induced depression of gastric mucosal oxygenation.

    PubMed

    Vollmer, Christian; Schwartges, Ingo; Behmke, Robert; Bauer, Inge; Picker, Olaf

    2013-09-01

    Hypercapnia (HC) increases systemic oxygen delivery (DO2) and gastric mucosal oxygenation. However, it activates the renin-angiotensin-aldosterone system (RAAS), which conversely reduces mesenteric perfusion. The aims of this study were to evaluate the effect of RAAS inhibition during normocapnia and HC on oral and gastric mucosal oxygenation (?HbO2) and to assess the effect of blood pressure under these circumstances. Five dogs were repeatedly anesthetized to study the effects of ACE inhibition (ACE-I; 5?mg/kg captopril, followed by 0.25?mg/kg per h) on ?HbO2 (reflectance spectrophotometry) and hemodynamic variables during normocapnia (end-tidal CO2=35?mmHg) and HC (end-expiratory carbon dioxide (etCO2)=70?mmHg). In the control group, the dogs were subjected to HC alone. To exclude the effects of reduced blood pressure, in one group, blood pressure was maintained at baseline values via titrated phenylephrine (PHE) infusion during HC and additional captopril infusion. ACE-I strongly reduced gastric ?HbO2 from 72±2 to 65±2% and mean arterial pressure (MAP) from 64±2 to 48±4?mmHg, while DO2 remained unchanged. This effect was counteracted in the presence of HC, which increased gastric ?HbO2 from 73±3 to 79±6% and DO2 from 15±2 to 22±4?ml/kg per min during ACE-I without differences during HC alone. However, MAP decreased similar to that observed during ACE-I alone from 66±3 to 47±5?mmHg, while left ventricular contractility (dPmax) increased from 492±63 to 758±119?mmHg/s. Titrated infusion of PHE had no additional effects on ?HbO2. In summary, our data suggest that RAAS inhibition reduces gastric mucosal oxygenation in healthy dogs. HC not only abolishes this effect, but also increases ?HbO2, DO2, and dPmax. The increase in ?HbO2 during ACE-I under HC is in accordance with our results independent of blood pressure. PMID:23757508

  14. 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

  15. Relation between gastric acid output, Helicobacter pylori, and gastric metaplasia in the duodenal bulb.

    PubMed Central

    Harris, A W; Gummett, P A; Walker, M M; Misiewicz, J J; Baron, J H

    1996-01-01

    BACKGROUND: Factors that determine gastric metaplasia in the duodenal bulb are ill defined. It is more common and extensive in the presence of high acid output and possibly in the presence of Helicobacter pylori. However, no quantitative relation between acid output and the extent of gastric metaplasia has been demonstrated and its relation to H pylori is uncertain. AIM: To determine the relation between H pylori infection and acid output and the presence and extent of gastric metaplasia in the duodenal bulb. subjects: H pylori positive and negative patients with duodenal ulcer and healthy controls were studied. METHODS: Quadrantic duodenal bulb biopsy specimens were taken and the presence and extent of gastric metaplasia determined using a computer enhanced image intensifier. Basal and stimulated acid outputs were measured. RESULTS: gastric metaplasia was significantly (p < 0.05 more common and significantly (p < 0.05) greater in extent in patients with duodenal ulcer than in controls. Neither the prevalence or extent of gastric metaplasia was affected by H pylori status. There were significant (p < 0.01) direct correlations between acid output and extent of gastric metaplasia. CONCLUSIONS: Prevalence and extent of gastric metaplasia are not related to H pylori in controls, or in patients with duodenal ulcer. Rather, high acid response to gastrin may be more important. Images Figure 1 PMID:8944558

  16. [Inhibition of histamine-sensitive adenylate cyclase system of human gastric mucosa by cimetidine (author's transl)].

    PubMed

    Simon, B; Kather, H

    1977-12-01

    Human gastric mucosa contains a histamin-sensitive adenylate cyclase system. The activation of this enzyme system by histamine is competititively inhibited by the H2-receptor blocking agent cimetidine. Our results underscore the rational basis for the use 0f H2-receptor antagonists in the therapy of peptic ulcer. PMID:593028

  17. [Effect of the dry aspen bark extract on the gastric secretory function].

    PubMed

    Krylova, S G; Zueva, E P; Razina, T G; Amosova, E N; Gridneva, V I; Turetskova, V F

    2000-01-01

    Dry aspen (Populus tremula L.) bark extract exhibits antiulcerogenic activity as demonstrated by the results of experiments using the models of gastric ulcers in rats according to H. Shay. The cytoprotective action of the dry aspen bark extract was also demonstrated in experiments on dogs with fistula according to Basov. PMID:11109522

  18. Gastrokine 1 induces senescence and apoptosis through regulating telomere length in gastric cancer.

    PubMed

    Yoon, Jung Hwan; Seo, Ho Seok; Choi, Won Seok; Kim, Olga; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

    2014-11-30

    The present study aims to investigate whether gastrokine 1 (GKN1) induces senescence and apoptosis in gastric cancer cells by regulating telomere length and telomerase activity. Telomere length, telomerase activity, and hTERT expression decreased significantly in AGSGKN1 and MKN1GKN1 cells. Both stable cell lines showed increased expression of TRF1 and reduced expression of the hTERT and c-myc proteins. In addition, TRF1 induced a considerable decrease in cell growth, telomerase activity, and expression of hTERT mRNA and protein. GKN1 completely counteracted the effects of c-myc on cell growth, telomere length, and telomerase activity. Interestingly, GKN1 directly bound to c-myc and down-regulated its expression as well as inhibited its binding to the TRF1 protein and a hTERT promoter. Furthermore, GKN1 triggered senescence, followed by apoptosis via up-regulating the p53, p21, p27, and p16 proteins and down-regulating Skp2. Telomere length in 35 gastric cancers was shortened significantly compared with the corresponding gastric mucosae, whereas GKN1 expression was inversely correlated with telomere length and c-myc and hTERT mRNA expression. Taken together, these results suggest that GKN1 may shorten telomeres by acting as a potential c-myc inhibitor that eventually leads to senescence and apoptosis in gastric cancer cells. PMID:25344918

  19. Gastrokine 1 induces senescence and apoptosis through regulating telomere length in gastric cancer

    PubMed Central

    Yoon, Jung Hwan; Seo, Ho Seok; Choi, Won Seok; Kim, Olga; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

    2014-01-01

    The present study aims to investigate whether gastrokine 1 (GKN1) induces senescence and apoptosis in gastric cancer cells by regulating telomere length and telomerase activity. Telomere length, telomerase activity, and hTERT expression decreased significantly in AGSGKN1 and MKN1GKN1 cells. Both stable cell lines showed increased expression of TRF1 and reduced expression of the hTERT and c-myc proteins. In addition, TRF1 induced a considerable decrease in cell growth, telomerase activity, and expression of hTERT mRNA and protein. GKN1 completely counteracted the effects of c-myc on cell growth, telomere length, and telomerase activity. Interestingly, GKN1 directly bound to c-myc and down-regulated its expression as well as inhibited its binding to the TRF1 protein and a hTERT promoter. Furthermore, GKN1 triggered senescence, followed by apoptosis via up-regulating the p53, p21, p27, and p16 proteins and down-regulating Skp2. Telomere length in 35 gastric cancers was shortened significantly compared with the corresponding gastric mucosae, whereas GKN1 expression was inversely correlated with telomere length and c-myc and hTERT mRNA expression. Taken together, these results suggest that GKN1 may shorten telomeres by acting as a potential c-myc inhibitor that eventually leads to senescence and apoptosis in gastric cancer cells. PMID:25344918

  20. 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

  1. 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

  2. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer

    PubMed Central

    Graham, David Y

    2014-01-01

    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

  3. Dietary agonists of TRPV1 inhibit gastric acid secretion in mice.

    PubMed

    Okumi, Hirokuni; Tashima, Kimihito; Matsumoto, Kenjiro; Namiki, Takao; Terasawa, Katsutoshi; Horie, Syunji

    2012-11-01

    Capsaicin and 6-gingerol, pungent components of chilli pepper and ginger, are known as dietary agonists of transient receptor potential vanilloid-1. Transient receptor potential vanilloid-1 nerve fibers are recognized to play a role in gastric mucosal integrity in rats. In the present studies, we examined the acute effects of peroral administration of capsaicin and 6-gingerol on gastric acid secretion in conscious mice. These agents were given p.?o. 30?min before the pylorus was ligated. Oral administration of capsaicin (1.0-100?mg/kg) or 6-gingerol (1.5-50?mg/kg) significantly and dose-dependently inhibited basal acid secretion. Pretreatment with BCTC, a transient receptor potential vanilloid-1 antagonist, significantly reversed the reduced basal acid secretion by capsaicin or 6-gingerol. The combination of the lowest doses of capsaicin and 6-gingerol markedly inhibited basal acid secretion in conscious mice and this was also significantly reversed by BCTC. Moreover, the combination of the maximal dose of capsaicin and 6-gingerol inhibited basal acid secretion only to the level of a single administration of the maximal dose of capsaicin. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on the inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1. In separate experiments, intraduodenal administration of either capsaicin (30?mg/kg) or 6-gingerol (15?mg/kg), whose doses were observed to have a significant inhibitory effect by oral administration, tended to inhibit basal acid secretion compared with the vehicle. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1, and oral administration of transient receptor potential vanilloid-1 agonists directly stimulates transient receptor potential vanilloid-1 in the gastric lumen, resulting in a potent reduction of gastric acid secretion. PMID:23047250

  4. Plasma Selenium Measurements in Subjects from Areas with Contrasting Gastric Cancer Risks in Colombia

    PubMed Central

    Camargo, Maria Constanza; Burk, Raymond F.; Bravo, Luis E.; Piazuelo, Maria B.; Hill, Kristina E.; Fontham, Elizabeth T.; Motley, Amy K.; Yepez, Maria C.; Mora, Yolanda; Schneider, Barbara G.; Correa, Pelayo

    2008-01-01

    Background An inverse association between selenium status and incidence of different neoplasias including gastric cancer has been reported. This pilot study aimed to determine and compare selenium status in two Colombian populations with different gastric cancer risks: a high-risk area in the volcanic region of the Andes Mountains and a low-risk area on the Pacific coast. Methods Eighty nine adult males were recruited in the outpatient clinics of two public hospitals (44 and 45 from high- and low-risk areas, respectively) and provided a blood sample. Seventy one (79.8%) participants underwent upper gastrointestinal endoscopy. Plasma selenium was assayed using a fluorometric method, selenoprotein-P by ELISA, and glutathione peroxidase activity by a spectrophometric method. Histological diagnosis and Helicobacter pylori infection were evaluated in gastric biopsy samples. Unpaired samples t-test and linear regression analyses were used for statistical analyses. Results Although none of the subjects in either of the two geographic areas was selenium deficient, the level of plasma selenium was significantly lower in men from the high-risk area compared with those from the low-risk area. Levels of selenoprotein-P and glutathione peroxidase activity were similar between groups after adjustment for confounders. Selenium measurements were not associated with histopathological diagnosis. Conclusions The high incidence of gastric cancer in the Andean region of Colombia is unlikely to be explained by selenium deficiency. We cannot exclude, however, that suboptimal selenium levels may exist in the gastric mucosa of subjects in the high-risk area. Therefore, the benefit of selenium supplementation in gastric cancer prevention cannot be dismissed. PMID:18375257

  5. Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice

    PubMed Central

    Wang, Fang-Yan; Liu, Jia-Ming; Luo, Hai-Hua; Liu, Ai-Hua; Jiang, Yong

    2015-01-01

    AIM: To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively. METHODS: One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1?, tumor necrosis factor (TNF)-?, leukotriene B4 (LTB4) and 6-keto-PGF-1? (degradation product of PGI2) in the gastric tissue. RESULTS: Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-?, TNF-? and LBT4 decreased, while 6-keto-PGF-1? increased with pretreatment by C. butyricum in all three GU models. CONCLUSION: Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits. PMID:26217085

  6. Challenges of deciphering gastric cancer heterogeneity

    PubMed Central

    Hudler, Petra

    2015-01-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  7. Challenges of deciphering gastric cancer heterogeneity.

    PubMed

    Hudler, Petra

    2015-10-01

    Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively. PMID:26457012

  8. Familial gastric cancer: genetic susceptibility, pathology, and implications for management.

    PubMed

    Oliveira, Carla; Pinheiro, Hugo; Figueiredo, Joana; Seruca, Raquel; Carneiro, Fátima

    2015-02-01

    Familial gastric cancer comprises at least three major syndromes: hereditary diffuse gastric cancer, gastric adenocarcinoma and proximal polyposis of the stomach, and familial intestinal gastric cancer. The risk of development of gastric cancer is high in families affected b-y these syndromes, but only hereditary diffuse gastric cancer is genetically explained (caused by germline alterations of CDH1, which encodes E-cadherin). Gastric cancer is also associated with a range of several cancer-associated syndromes with known genetic causes, such as Lynch, Li-Fraumeni, Peutz-Jeghers, hereditary breast-ovarian cancer syndromes, familial adenomatous polyposis, and juvenile polyposis. We present contemporary knowledge on the genetics, pathogenesis, and clinical features of familial gastric cancer, and discuss research and technological developments, which together are expected to open avenues for new genetic testing approaches and novel therapeutic strategies. PMID:25638682

  9. Gastric Carcinosarcoma and 18F-FDG PET/CT.

    PubMed

    Li, Beilei; Zhang, Yiqiu; Hou, Jun; Cai, Liang; Zhou, Jianwei; Shi, Hongcheng

    2015-11-01

    Gastric carcinosarcoma is a rare, malignant neoplasm that simultaneously comprises mixed epithelial and mesenchymal elements. In the present study, we report a case of gastric carcinosarcoma composed of rhabdomyosarcoma and adenocarcinoma on F-FDG PET/CT. PMID:26359557

  10. The effect of gender on Helicobacter pylori and gastric cancer

    E-print Network

    Sheh, Alexander

    2011-01-01

    Gastric cancer is the 2nd leading cause of cancer death worldwide and the 4th most commonly diagnosed cancer worldwide. Helicobacter pylori infection is the major risk factor of gastric cancer, and as such, this bacterium ...

  11. TGF-? induces fascin expression in gastric cancer via phosphorylation of smad3 linker area

    PubMed Central

    Li, Liling; Cao, Fang; Liu, Baoan; Luo, Xiaojuan; Ma, Xin; Hu, Zhongliang

    2015-01-01

    Background: Fascin is an actin-bundling protein critical for tumor invasion. TGF-? could induce fascin expression in gastric cancer cells. In this study, we attempted to explore the role of p-smad3L in the expression of fascin induced by TGF-? in gastric cancer cells. Methods: Pseudopodia were evaluated by immunofluorescence. Fascin expression was detected by RT-PCR and western blot. Smad3 siRNA was used to repress the endogenous smad3. The phosphorylations of smad3 linker region at sites s204, s208 and s213 were detected by western blot. The fascin promoter reporter activity was measured by dual luciferase assay. Results: TGF-? could increase the formation of pseudopodia and the expression of fascin in gastric cancer cells. Smad3 depletion abrogated the expression of fascin induced by TGF-?. The phosphorylation of smad3 linker region at serine 204, 208 and 213 was enhanced in gastric cancer cells after TGF-? treatment. The fascin promoter reporter activity was significantly enhanced with TGF-? treatment in both wild-type Smad3 group and Smad3EPSM group (P<0.05). Furthermore, the fascin promoter reporter activity in the wild-type Smad3 transfectant cells was significantly higher than that in Smad3EPSM cells (P<0.05). Conclusions: fascin expression induced by TGF-? depends on smad3, at least in part, depends on smad3 linker phosphorylation. PMID:26269751

  12. Adrenergic mechanism responsible for pathological alteration in gastric mucosal blood flow in rats with ulcer bleeding

    NASA Astrophysics Data System (ADS)

    Semyachkina-Glushkovskaya, O. V.; Pavlov, A. N.; Semyachkin-Glushkovskiy, I. A.; Gekalyuk, A. S.; Ulanova, M. V.; Lychagov, V. V.; Tuchin, V. V.

    2014-09-01

    The adrenergic system plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhage. Because the impaired gastric mucosal blood flow (GMBF) is the major cause of gastroduodenal lesions, including ulcer bleeding (UB), we studied the adrenergic mechanism responsible for regulation of GMBF in rats with a model of stress-induced UB (SUB) using the laser Doppler flowmetry (LDF). First, we examined the effect of adrenaline on GMBF in rats under normal state and during UB. In all healthy animals the submucosal adrenaline injection caused a decrease in local GMBF. During UB the submucosal injection of adrenaline was accompanied by less pronounced GMBF suppression in 30,3% rats with SUB vs. healthy ones. In 69,7% rats with SUB we observed the increase in local GMBF after submucosal injection of adrenaline. Second, we studied the sensitivity of gastric ?2-adrenoreceptors and the activity of two factors which are involved in ?2-adrenomediated vasorelaxation-KATP -channels and NO. The effects of submucosal injection of isoproterenol, ICI118551 and glybenclamide on GMBF as well as NO levels in gastric tissue were significantly elevated in rats with SUB vs. healthy rats. Thus, our results indicate that high activation of gastric ?2-adrenoreceptors associated with the increased vascular KATP -channels activity and elevated NO production is the important adrenergic mechanism implicated in the pathogenesis of UB.

  13. Anti-Inflammation Property of Syzygium cumini (L.) Skeels on Indomethacin-Induced Acute Gastric Ulceration

    PubMed Central

    Chanudom, Lanchakon; Tangpong, Jitbanjong

    2015-01-01

    Indomethacin, nonsteroidal anti-inflammatory drug (NSAIDs), induced gastric damage and perforation through the excess generation of reactive oxygen species (ROS). Syzygium cumini (L.) Skeels is commonly used as a medicinal plant and is claimed to have antioxidant activities. The effects of Syzygium cumini (L.) Skeels aqueous extract (SCC) on antifree radical, anti-inflammation, and antiulcer of SCC on indomethacin induced acute gastric ulceration were determined in our study. Scavenging activity at 50% of SCC is higher than ascorbic acid in in vitro study. Mice treated with indomethacin revealed mucosal hemorrhagic lesion and inhibited mucus content. Pretreatment with SCC caused discernible decrease in indomethacin induced gastric lesion and lipid peroxide content. In addition, oxidized glutathione (GSSG), glutathione peroxidase (GPx), nitric oxide (NO) levels, and gastric wall mucus were restored on acute treated mice model. Indomethacin induced inflammation by activated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-?) proinflammatory cytokines to release large amount of ROS/RNS which were ameliorated in mice pretreatment with SCC. SCC showed restoration of the imbalance of oxidative damage leading to amelioration of cyclooxygenase enzyme (COX). In conclusion, SCC acts as an antioxidant, anti-inflammation, and antiulcer against indomethacin. PMID:26633969

  14. Ablation of osteopontin suppresses N-methyl-N-nitrosourea and Helicobacter pylori-induced gastric cancer development in mice.

    PubMed

    Lee, Su-Hyung; Park, Jun-Won; Go, Du-Min; Kim, Hark Kyun; Kwon, Hyo-Jung; Han, Sang-Uk; Kim, Dae-Yong

    2015-12-01

    Several clinical studies have reported increased expression of osteopontin (OPN) in various types of human cancer, including gastric cancer. However, the precise mechanisms underlying tumor development remain unclear. In the present study, we investigated the pathogenic roles of OPN in Helicobacter pylori-induced gastric cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N-methyl-N-nitrosourea (MNU) and infected with H.pylori. Mice were killed 50 weeks after treatment, and stomach tissues were assessed by histopathological examination, immunohistochemistry, quantitative real-time RT-PCR and western blotting. To clarify the carcinogenic effects of OPN, we also conducted an in vitro study using AGS human gastric cancer cell line and THP-1 human monocytic cell line. The overall incidence of gastric tumors was significantly decreased in OPN KO mice compared with WT mice. Apoptotic cell death was significantly enhanced in OPN KO mice and was accompanied by upregulation of signal transducer and activator of transcription 1 (STAT1) and inducible nitric oxide synthase (iNOS). In vitro study, OPN suppression also caused STAT1 upregulation and iNOS overexpression in AGS and THP-1 cells, which resulted in apoptosis of AGS cells. In addition, a negative correlation was clearly identified between expression of OPN and iNOS in human gastric cancer tissues. Our data demonstrate that loss of OPN decreases H.pylori-induced gastric carcinogenesis by suppressing proinflammatory immune response and augmenting STAT1 and iNOS-mediated apoptosis of gastric epithelial cells. An important implication of these findings is that OPN actually contributes to the development of gastric cancer. PMID:26438603

  15. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice

    PubMed Central

    Kentish, Stephen J.; Frisby, Claudine L.; Kritas, Stamatiki; Li, Hui; Hatzinikolas, George; O’Donnell, Tracey A.; Wittert, Gary A.; Page, Amanda J.

    2015-01-01

    Aim Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice. Methods TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined. Results Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet. Conclusion TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity. PMID:26285043

  16. Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin

    PubMed Central

    Takabayashi, Kaoru; Kashiwagi, Kazuhiro; Kawata, Tetsuya; Sato, Toshiro; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Takaishi, Hiromasa; Hibi, Toshifumi; Ogata, Haruhiko; Yahagi, Naohisa; Kitagawa, Yuko; Shigematsu, Naoyuki; Kanai, Takanori

    2014-01-01

    The efficacy of conventional radiation therapy for gastric cancer is controversial. In this study, we evaluated the in vitro and in vivo effects of continuous low-dose-rate irradiation by I-125 seeds on different histological types of gastric cancer cell lines. Three human gastric cancer cell lines (MKN74, MKN45, and NUGC4) were treated with or without continuous low-dose irradiation by I-125 seeds in vitro and in vivo. Cell viability, apoptosis, caspase-3 assay, and cell-cycle distribution were examined in vitro. Body weight and tumor volumes of BALB/c nude mice bearing MKN74, MKN45, and NUGC4 gastric cancer xenografts were measured, and in vivo cell proliferation and apoptosis assays were performed by Ki67 and TUNEL staining, respectively. Continuous low-dose-rate irradiation by I-125 seeds reduced cell viability and induced cell apoptosis through the activation of caspase-3, and led to the accumulation of cells in the G2/M phase in vitro. It also suppressed the growth of gastric cancer xenografts in nude mice, while inhibiting cell proliferation and inducing apoptosis as demonstrated by Ki67 and TUNEL staining. Therefore, our data suggest that continuous low-dose-rate irradiation by I-125 seeds could be a promising new option for gastric cancer treatment, regardless of histological origin. PMID:24149371

  17. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo

    SciTech Connect

    Tan, Wei; Zhou, Wei; Yu, Hong-gang; Luo, He-Sheng; Shen, Lei

    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.

  18. The interplay between hydrogen ions, bicarbonate ions and osmolality in the anterior duodenum modulating gastric function in the conscious calf.

    PubMed

    Bell, F R; Nouri, M; Webber, D E

    1981-05-01

    1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975).2. Duodenal infusion of NaCl at a constant osmolality of 300 m-osmole/kg, but with pH ranging from 2.0 to 12.0, did not alter the high level of gastric emptying and secretion already reported for isotonic NaCl or NaHCO(3) alone (Bell & Mostaghni, 1975; Bell & Webber, 1979). Gastric function, therefore, is either unaffected by gastric chyme at pH 2.0-12.0 entering the duodenum, or else isotonicity is dominant over pH in activating duodenal receptors which increase motor activity.3. When the pH of the isotonic NaCl was reduced by the addition of HCl to below pH 2.0, inhibition of gastric function occurred in direct proportion to the amount of titratable acid present in the infusate. The H(+) moiety of isotonic duodenal infusates of pH < 2.0 dominates activation of osmoreceptors and so inhibits motor activity.4. When the same amount of acid but at differing concentrations and infusion rates was introduced into the duodenum uniform inhibition of gastric function occurred. This result indicates that duodenal acid receptors respond to acid concentration and flow rate to produce an integrated response in proportion to the amount (concentration x volume) of acid present.5. Isotonic NaHCO(3) solutions adjusted to pH 8.1-12.0 by the addition of NaOH, like isotonic NaCl infusions, did not affect gastric function until pH 11.0-12.0, when significant inhibition occurred. This inhibitory effect of isotonic NaHCO(3) at high pH is probably due to CO(3) (2-), since Na(2)CO(3) and Li(2)CO(3), but not LiCl, produce a similar inhibitory effect on gastric function.6. The inhibitory effect of carbonate gives some support to the existence of a CO(2)-sensor as suggested by Hunt & Knox (1972), whereby increased P(CO2) produced by intracellular or intercellular neutralization of CO(3) (2-) by duodenal H(+) activates acid receptors. But other experiments reported here, where simultaneous perfusion of HCl and excess NaHCO(3) produced a rise in intraluminal P(CO2), did not inhibit gastric function, which is contrary to the idea of a direct intraluminal effect of CO(2) on duodenal receptors.7. The pH, P(O2), P(CO2), HCO(3) (-) and base excess of venous blood showed no detectable change during duodenal infusion of either acidic or alkaline solutions. Metabolic acidosis or alkalosis, therefore, cannot be considered to play any part in controlling gastric function. The results thus corroborate the notion that the receptors controlling gastric function are localized in the intestinal mucosa.8. Our results suggest that interplay between acid and osmolality of gastric chyme occurs in the rostral part of the duodenum to produce a graded inhibitory effect which by negative feedback modulates the gastric effectors that normally activate smooth muscle, parietal cells and zymogen cells. PMID:6796673

  19. Gastric Cancer Regional Detection System.

    PubMed

    Ural, Berkan; Hardalaç, F?rat; Serhatlio?lu, Selami; ?lhan, Mustafa Necmi

    2016-01-01

    In this study, a novel system was created to localize cancerous regions for stomach images which were taken with computed tomography(CT). The aim was to determine the coordinates of cancerous regions which spread in the stomach area in the color space with using this system. Also, to limit these areas with a high accuracy ratio and to feedback to the user of this system were the other objectives. This integration was performed with using energy mapping, analysis methods and multiple image processing methods and the system which was consisted from these advanced algorithms was appeared. For this work, in the range of 25-40 years and when gender discrimination was insignificant, 30 volunteer patients were chosen. During the formation of the system, to exalt the accuracy to the maximum level, 2 main stages were followed up. First, in the system, advanced image processing methods were processed between each other and obtained data were studied. Second, in the system, FFT and Log transformations were used respectively for the first two cases, then these transformations were used together for the third case. For totally three cases, energy distribution and DC energy intensity analysis were done and the performance of this system was investigated. Finally, with using the system's unique algorithms, a non-invasive method was achieved to detect the gastric cancer and when FFT and Log transformation were used together, the maximum success rate was obtained and this rate was calculated as 83,3119 %. PMID:26553064

  20. Biochanin A Gastroprotective Effects in Ethanol-Induced Gastric Mucosal Ulceration in Rats

    PubMed Central

    Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Batran, Rami Al; Majid, Nazia Abdul; Khalifa, Shaden A. M.; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

    2015-01-01

    Background Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. Methodology The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. Conclusions This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level. PMID:25811625

  1. Expression analysis of apolipoprotein E and its associated genes in gastric cancer

    PubMed Central

    SHI, XIUMIN; XU, JIANTING; WANG, JIHAN; CUI, MEIZI; GAO, YUSHUN; NIU, HAITAO; JIN, HAOFAN

    2015-01-01

    Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate the genes and transcription factors that interact with ApoE during the development of gastric cancer. Using gene expression profiling, the BioGRID database and the transcriptional regulatory element database, gene expression and regulatory networks in gastric cancer tissues and adjacent normal tissues were analyzed. The data demonstrated that eight genes associated with ApoE were differentially expressed, with six of these upregulated and two downregulated. Functionally, these genes were involved in the JAK-STAT cascade, acute-phase response, acute inflammatory response, and the steroid hormone response. Among these ApoE-associated genes, expression of the signal transducer and activator of transcription 2 (STAT2) and STAT3 transcription factors was upregulated. To the best of our knowledge, this is the first study to demonstrate the network of ApoE-related genes and transcription factors in gastric cancer. Additional studies are required in order to confirm these data and to translate the results into the identification of clinical biomarkers and novel treatment strategies for gastric cancer. PMID:26622669

  2. Gastric function and its contribution to the postprandial metabolic response of the Burmese python Python molurus.

    PubMed

    Secor, Stephen M

    2003-05-01

    The large intact prey ingested by Burmese pythons require considerable processing by the stomach before passage into the small intestine. To investigate the function and cost of gastric digestion and its contribution to postprandial metabolic response for the Burmese python, I examined the rate of gastric digestion, the postprandial profile of gastric pH and the effects of decreasing gastric workload on the metabolic cost of digestion, referred to as specific dynamic action (SDA). Ingested meal mass (equivalent to 25% of snake body mass) was reduced by 18% within 1 day postfeeding, by which time intragastric pH had decreased from 7.5 to 2. Gastric pH was maintained at 1.5 for the next 5-7 days, after which it returned to 7.5. The SDA generated by digesting an intact rat meal was reduced by 9.1%, 26.0%, 56.5% and 66.8%, respectively, when pythons were fed steak, ground rat, liquid diet or ground rat directly infused into the small intestine. The production of HCl and enzymes and other gastric functions represent an estimated 55% of the python's SDA generated from the digestion of an intact rodent meal. Additional contributors to SDA include protein synthesis (estimated 26%), gastrointestinal upregulation (estimated 5%) and the activities of the pancreas, gallbladder, liver, kidneys and intestines during digestion (estimated 14%). Operating on a 'pay before pumping' principle, pythons must expend endogenous energy in order to initiate acid production and other digestive processes before ingested nutrients can be absorbed and channeled into metabolic pathways. PMID:12682094

  3. Primary Gastric Burkitt’s Lymphoma

    PubMed Central

    Mitra, Swarupa; Mehta, Anurag; Gupta, Sunil Kumar; Sharma, Anila; Louis, A. Robert; Sharma, Manoj Kumar; Saxena, Upasna; Simson, David K.; Dewan, Abhinav

    2014-01-01

    The primary gastrointestinal non-Hodgkin’s lymphoma, although rare, is among the most common extra-nodal lymphomas, considering that gastric lymphomas are more common than intestinal lymphomas. Burkitt’s lymphoma (BL) is an aggressive form of B-cell lymphoma that is typically endemic in Africa, while non-endemic cases are found in the rest of the world. Primary gastric BL is extremely rare and only around 50 cases have been reported worldwide. Here we present the case of a young HIV-negative male, who was referred to our department with a stage IV gastric BL. He was planned for palliative chemotherapy, but after the first cycle of chemotherapy he succumbed to the progression of the disease. PMID:25568743

  4. [Gastric teratoma disclosed by neonatal digestive hemorrhage].

    PubMed

    Tenenbaum, D; Scart, C; Brichon, P; Justrabo, E; Autissier, J M; Nivelon, J L

    1987-01-01

    A gastric teratoma diagnosed after a gastro-intestinal tract bleeding in a neonate is reported. The endogastric tumor was shown by gastric endoscopy. The tumor was pediculated and a simple tumorectomy was performed, without trouble later. Fifty-three other cases have been found in the literature. Most of them presented with abdominal distension and a palpable mass; diagnosis was always made after surgery and the diagnosis of mature gastric teratoma was confirmed by histological examination. These rare tumors are always of benign nature, but are often revealed by complications. Their frequency is less than 1% of infants teratoma and 85% are found in the first year of life; they are more frequent in males. PMID:3498931

  5. Treatment modalities for early gastric cancer

    PubMed Central

    Espinel, Jesús; Pinedo, Eugenia; Ojeda, Vanesa; del Rio, Maria Guerra

    2015-01-01

    Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with “standard” criteria can be successfully treated by EMR techniques. Those who meet “expanded” criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer. PMID:26380052

  6. Helicobacter pylori: gastric cancer and beyond

    PubMed Central

    Polk, D. Brent; Peek, Richard M.

    2010-01-01

    Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host–microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche. PMID:20495574

  7. Laparoscopic Resection of Symptomatic Gastric Diverticula

    PubMed Central

    Zelisko, Andrea; Rodriguez, John; El-Hayek, Kevin

    2014-01-01

    Gastric diverticula are rare and usually asymptomatic. This report, however, describes two examples of symptomatic gastric diverticula successfully treated by laparoscopic resection. Both patients were male and in their sixth decade of life. One patient was relatively healthy with no past medical history, whereas the other patient had chronic pain issues and at presentation was also undergoing evaluation for hyperaldosteronism. The patients presented with gastrointestinal symptoms, including nausea, emesis, abdominal pain, and change in bowel function. In both cases, a gastric diverticulum was identified by CT scan, and precise anatomic position was determined by upper endoscopy. After discussion with the treating teams, including a gastroenterologist and surgeon, surgical treatment and resection was elected. Successful laparoscopic removal was accomplished in both patients, and they were discharged home after tolerating liquid diets. Both patients reported resolution of their abdominal symptoms at follow-up. PMID:24680154

  8. Improving the outcomes in gastric cancer surgery

    PubMed Central

    Tegels, Juul JW; De Maat, Michiel FG; Hulsewé, Karel WE; Hoofwijk, Anton GM; Stoot, Jan HMB

    2014-01-01

    Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and five-year survival rates are poor, therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately, in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-, intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index (e.g., Charlson comorbidity index), assessment of nutritional status (e.g., short nutritional assessment questionnaire, nutritional risk screening - 2002) and frailty assessment (Groningen frailty indicator, Edmonton frail scale, Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential. Implementation of fast-track or enhanced recovery after surgery programs is showing promising results, although future studies have to determine what the exact optimal strategy is. Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection. Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far. Advances in postoperative care include optimal timing of oral diet, which has been shown to reduce hospital stay. In general, hospital volume, i.e., centralization, and clinical audits might further improve the outcome in gastric cancer surgery. In conclusion, progress has been made in improving the surgical treatment of gastric cancer. However, gastric cancer treatment is high risk surgery and many areas for future research remain. PMID:25320507

  9. Incidence and surgical importance of the posterior gastric artery.

    PubMed Central

    Suzuki, K; Prates, J C; DiDio, L J

    1978-01-01

    In a series of 61 adult cadavers, the posterior gastric artery was found in 38 (62.3%), originating from the superior aspect of the mid-third of the splenic artery. The posterior gastric artery, running behind the parietal peritoneum of the omental bursa, produced a peritoneal fold before reaching the posterior wall of the superior portion of the gastric body, near the cardiac region, and the fundus. Its high incidence, hidden origin, deep course, and distribution make this artery very important for surgical procedures relating to the stomach, pancreas, spleen, and celiac region. It may be crucial, especially if partial gastric resection of splenectomy have obliterated other gastric vessels. PMID:629615

  10. Helicobacter pylori infection, gastrin and cyclooxygenase-2 in gastric carcinogenesis

    PubMed Central

    Shao, Yun; Sun, Kun; Xu, Wei; Li, Xiao-Lin; Shen, Hong; Sun, Wei-Hao

    2014-01-01

    Gastric cancer is one of the most frequent neoplasms and a main cause of death worldwide, especially in China and Japan. Numerous epidemiological, animal and experimental studies support a positive association between chronic Helicobacter pylori (H. pylori) infection and the development of gastric cancer. However, the exact mechanism whereby H. pylori causes gastric carcinogenesis remains unclear. It has been demonstrated that expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. In this review, we present the latest clinical and experimental evidence showing the role of gastrin and COX-2 in H. pylori-infected patients and their possible association with gastric cancer risk. PMID:25278683

  11. Neoadjuvant or adjuvant therapy for gastric cancer

    PubMed Central

    Quéro, Laurent; Guillerm, Sophie; Hennequin, Christophe

    2015-01-01

    Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. In the United States, where a limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In Europe, intensified perioperative chemotherapy is commonly administered. In Japan and South Korea, postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. Several ongoing trials are currently evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as well as the place of targeted therapeutic agents in the treatment of advanced gastric carcinoma. PMID:26306142

  12. Differential growth factor induction and modulation of human gastric epithelial regeneration

    SciTech Connect

    Tetreault, Marie-Pier; Chailler, Pierre; Rivard, Nathalie; Menard, Daniel . E-mail: Daniel.Menard@USherbrooke.ca

    2005-05-15

    While several autocrine/paracrine growth factors (GFs) can all stimulate epithelial regeneration in experimentally wounded primary gastric cultures, clinical relevance for their non-redundant cooperative actions in human gastric ulcer healing is suggested by the sequential pattern of GF gene induction in vivo. Using new HGE cell lines able to form a coherent monolayer with tight junctions as well as using primary human gastric epithelial cultures, we show that EGF, TGF{alpha}, HGF and IGFs accelerate epithelial restitution upon wounding, independently of the TGF{beta} pathway (as opposed to intestinal cells). However, they differently modulate cell behavior: TGF{alpha} exerts strong effects (even more than EGF) on cytoplasmic spreading and non-oriented protruding activity of bordering cells whereas HGF preferentially coordinates single lamella formation, cell elongation and migration into the wound. IGF-I and IGF-II rather induce the alignment of bordering cells and maintain a compact monolayer front. The number of mitotic cells maximally increases with EGF, followed by TGF{alpha} and IGF-I,-II. The current study demonstrates that GFs differentially regulate the regeneration of human gastric epithelial cells through specific modulation of cell shape adaptation, migration and proliferation, further stressing that a coordination of GF activities would be necessary for the normal progression of post-wounding epithelial repair.

  13. Antiulcer properties of Glycyrrhiza glabra L. extract on experimental models of gastric ulcer in mice

    PubMed Central

    Jalilzadeh-Amin, Ghader; Najarnezhad, Vahid; Anassori, Ehsan; Mostafavi, Mostafa; Keshipour, Hadi

    2015-01-01

    Glycyrrhiza glabra L. is used in folk medicine for treatment of stomach disorders including peptic ulcers. The hydroalcoholic extract of Glycyrrhiza glabra L. (HEGG) was evaluated for antiulcerogenic activity and acute toxicity profile in mice. Various doses of HEGG (50-200 mg/kg) were administered orally to animals of different groups. Omeprazole and cimetidine at doses of 30 and 100 mg/kg were used as positive controls, respectively. Stomach was opened along the greater curvature then ulceration index was determined examining the inner lining of stomach. Oral administration of the extract at 1600 mg/kg did not produce toxic symptoms and mortality in mice. 2950 mg/kg was determined as the oral LD50. The HEGG (50–200 mg/kg) showed a significant reduction in ulcer index in HCl/Ethanol-induced ulcer. G. glabra extract (50-150 mg/kg) showed antiulcer activity against indomethacin-induced gastric lesions dose dependently. The extract effectively inhibited formation of gastric lesions induced by ethanol. The extract (200 mg/kg) was more potent than omeprazole (30 mg/kg). HEGG reduced the ulcer index in hypothermic stress induced gastric ulcers in mice and the antiulcer effect was comparable to that of cimetidine. The results indicated that G. glabra hydroalcoholic extract exerted an antiulcergenic effect that could be associated with increase in gastric mucosal defensive factors. PMID:26664383

  14. RASSF10 is epigenetically silenced and functions as a tumor suppressor in gastric cancer

    SciTech Connect

    Wei, Ziran; Chen, Xia; Chen, Ji; Wang, Weimin; Xu, Xudong; Cai, Qingping

    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.

  15. 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

  16. [The role of gastric APUD system in progression of chronic Helicobacter gastritis].

    PubMed

    Osadchuk, M A; Sibiriaev, A A; Kireeva, N V; Kvetno?, I M

    2013-01-01

    The study included 60 patients with chronic Halicobacter gastritis (30 with chronic non-atrophic and 30 with atrophic Halicobacter gastritis (CNAHG and CAHG)). The control group was comprised of 15 practically healthy subjects. The aim of the work was to elucidate the role of Helicobacter infection, disturbances of regeneration, endothelin-1 and melatonin-secreting neuroendocrine cells of gastric antrum in progression of chronic Helicobacter gastritis (CHG). It was shown that CHG is due to H. pylori persistence and that patients with CNAHG undergo grade III microbial contamination while in CAHG patients atrophic changes are accompanied by metaplasia of gastric mucosa (GM) and inflammation of different severity. Patients with CNAHG has an increased number of melatonin-positive gastric cells and enhanced apoptotic activity of GM epitheliocytes. Patients with CAHG experience a reduction of melatonin-positive cells correlated with enhanced apoptotic activity of GM epitheliocytes. The number of endothelin-1 positive cells in patients with CNAHG and CAHG was similar to that in controls. Adequate eradication promoted normalization of the number of gastric endothelin-1 and melatonin-secreting neuroendocrine cells in patients with CHG. The apoptotic index reached the control value within 1 month after eradication in CNAHG patients but remained relatively high in CAHG patients. PMID:24159786

  17. Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

    PubMed Central

    de-Faria, Felipe Meira; Almeida, Ana Cristina Alves; Luiz-Ferreira, Anderson; Takayama, Christiane; Dunder, Ricardo José; da Silva, Marcelo Aparecido; Salvador, Marcos José; Abdelnur, Patrícia Verardi; Eberlin, Marcos Nogueira; Vilegas, Wagner; Toma, Walber; Souza-Brito, Alba Regina Monteiro

    2012-01-01

    Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property. PMID:22654592

  18. Risk of gastric cancer is associated with PRKAA1 gene polymorphisms in Koreans

    PubMed Central

    Kim, Yong-Dae; Yim, Dong-Hyuk; Eom, Sang-Yong; Moon, Sun In; Yun, Hyo-Yung; Song, Young-Jin; Youn, Sei-Jin; Hyun, Taisun; Park, Joo-Seung; Kim, Byung Sik; Lee, Jong-Young; Won, Hee Kwan; Kim, Heon

    2014-01-01

    AIM: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer. METHODS: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method. RESULTS: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. CONCLUSION: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer. PMID:25024613

  19. Prevalence of deleterious ATM germline mutations in gastric cancer patients.

    PubMed

    Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

    2015-12-01

    Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment. PMID:26506520

  20. [Three cases of pedunculated gastric hamartomatous inverted polyps resected endoscopically].

    PubMed

    Matsuoka, Junko; Itaba, Soichi; Makihara, Yasuaki; Murao, Hiroyuki; Umeno, Naruhiro; Minoda, Yosuke; Kaku, Toyoma; Kuniyoshi, Masami; Hamada, Tetsuo; Nakamura, Kazuhiko

    2015-06-01

    We report three cases of pedunculated gastric hamartomatous inverted polyps (HIPs) that were successfully treated by endoscopic polypectomy. The first case involved an 87-year-old woman with mild anemia. Esophagogastroduodenoscopy (EGD) revealed a pedunculated, reddish polyp located at the greater curvature of the upper stomach. The second case involved a 34-year-old woman in whom a pedunculated polyp was found at the gastric fundus during routine EGD. The third patient was a 59-year-old woman with epigastric discomfort. EGD revealed a pedunculated polyp in the gastric fundus. Polypectomy was successfully performed in all three cases. Histological examination revealed that the tumors comprised submucosal proliferation of cystically dilated gastric glands and hyperplastic glands;thus, we diagnosed gastric HIPs, which are rare and typically difficult to diagnose. Gastric HIPs should be considered in the differential diagnosis of elevated gastric lesions. PMID:26050726

  1. New satiety hormone nesfatin-1 protects gastric mucosa against stress-induced injury: mechanistic roles of prostaglandins, nitric oxide, sensory nerves and vanilloid receptors.

    PubMed

    Szlachcic, Alexandra; Sliwowski, Zbigniew; Krzysiek-Maczka, Gracjana; Majka, Jolanta; Surmiak, Marcin; Pajdo, Robert; Drozdowicz, Danuta; Konturek, Stanislaw J; Brzozowski, Tomasz

    2013-11-01

    Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible for satiety and are identified in the neurons and endocrine cells within the gut. These peptides have been implicated in the control of food intake; however, very little is known concerning its contribution to gastric secretion and gastric mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion and gastric lesions induced in rats by 3.5h of water immersion and restraint stress (WRS) were determined. Exogenous nesfatin-1 (5-40?g/kg i.p.) significantly decreased gastric acid secretion and attenuated gastric lesions induced by WRS, and this was accompanied by a significant rise in plasma NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO concentration, generation of PGE2 in the gastric mucosa, an overexpression of mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory cytokine IL-1? and TNF-? mRNAs. Nesfatin-1-induced protection was attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin, and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This study shows for the first time that nesfatin-1 exerts a potent protective action in the stomach of rats exposed to WRS and these effects depend upon decrease in gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the activation of vagal and sensory nerves and vanilloid receptors. PMID:23978788

  2. Gastric Mucosal Protection by Aegle Marmelos Against Gastric Mucosal Damage: Role of Enterochromaffin Cell and Serotonin

    PubMed Central

    Singh, Purnima; Dutta, Shubha R.; Guha, Debjani

    2015-01-01

    Background/Aims: Serotonin (5-hydroxytryptamine; 5-HT) released from enterochromaffin (EC) cells in gastric mucosa inhibits gastric acidity by increasing the gastric mucus secretion. In the present study, we evaluated the effect of aqueous extract of Aegle marmelos (AM) ripe fruit pulp (250 mg/kg body weight) on mean ulcer index (MUI), EC cells, 5-HT content, and adherent mucosal thickness of ulcerated gastric tissue in adult albino rats. Material and Methods: Ulceration was induced by using aspirin (500 mg/kg, p.o.), cerebellar nodular lesion and applying cold-restraint stress. Results: In all cases increased MUI in gastric tissue along with decreased EC cell count was observed with concomitant decrease of 5-HT content and adherent mucosal thickness (P < 0.05). Pretreatment with AM for 14 days decreased MUI, increased EC cell count, and 5-HT content as well as adherent mucosal thickness in all ulcerated group (P < 0.05). Conclusion: AM produces gastric mucosal protection mediated by increased EC cell count and 5-HT levels. PMID:25672237

  3. Effects of Different Local Moxibustion-Like Stimuli at Zusanli (ST36) and Zhongwan (CV12) on Gastric Motility and Its Underlying Receptor Mechanism

    PubMed Central

    Su, Yang-Shuai; Xin, Juan-Juan; Yang, Zhao-Kun; He, Wei; Shi, Hong; Wang, Xiao-Yu; Hu, Ling; Jing, Xiang-Hong; Zhu, Bing

    2015-01-01

    The aim of this study was to explore the “intensity-response” relationship in local moxibustion-like stimuli- (LMS-) modulated gastric motility and its underlying receptor mechanism. Based on the thermal pain threshold (43°C), 41°C, 43°C, and 45°C LMS were separately applied to ST36 or CV12 for 180?s among ASIC3 knockout (ASIC3?/?) mice, TRPV1 knockout (TRPV1?/?) mice, and their homologous wild-type C57BL/6 mice (n = 8 in each group). Gastric motility was continuously measured by an intrapyloric balloon, and the amplitude, integral, and frequency of gastric motility during LMS were compared with those of initial activities. We found that both 43°C and 45°C LMS at ST36 induced significantly facilitated effect of gastric motility (P < 0.05), while LMS at CV12 induced inhibited effects (P < 0.05). 41°C LMS had no significant impact on gastric motility. Compared with C57BL/6 mice, the facilitatory effect at ST36 and inhibitive effect of LMS at CV12 were decreased significantly in TRPV1?/? mice (P < 0.05; P < 0.01) but not changed markedly in ASIC3?/? mice (P > 0.05). These results suggest that there existed an “intensity-response” relationship between temperature in LMS and its effects on gastric motility. TRPV1 receptor played a crucial role in the LMS-modulated gastric motility. PMID:26246837

  4. Helicobacter pylori Antibody Titer and Gastric Cancer Screening

    PubMed Central

    Kishikawa, Hiroshi; Kimura, Kayoko; Takarabe, Sakiko; Kaida, Shogo; Nishida, Jiro

    2015-01-01

    The “ABC method” is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (?) PG (?)], Group B [H. pylori (+) PG (?)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (?) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered. PMID:26494936

  5. Integrated Proteomic and Genomic Analysis of Gastric Cancer Patient Tissues.

    PubMed

    Yan, Julia Fangfei; Kim, Hoguen; Jeong, Seul-Ki; Lee, Hyoung-Joo; Sethi, Manveen K; Lee, Ling Y; Beavis, Ronald C; Im, Hogune; Snyder, Michael P; Hofree, Matan; Ideker, Trey; Wu, Shiaw-Lin; Paik, Young-Ki; Fanayan, Susan; Hancock, William S

    2015-12-01

    V-erb-b2 erythroblastic leukemia viral oncogene homologue 2, known as ERBB2, is an important oncogene in the development of certain cancers. It can form a heterodimer with other epidermal growth factor receptor family members and activate kinase-mediated downstream signaling pathways. ERBB2 gene is located on chromosome 17 and is amplified in a subset of cancers, such as breast, gastric, and colon cancer. Of particular interest to the Chromosome-Centric Human Proteome Project (C-HPP) initiative is the amplification mechanism that typically results in overexpression of a set of genes adjacent to ERBB2, which provides evidence of a linkage between gene location and expression. In this report we studied patient samples from ERBB2-positive together with adjacent control nontumor tissues. In addition, non-ERBB2-expressing patient samples were selected as comparison to study the effect of expression of this oncogene. We detected 196 proteins in ERBB2-positive patient tumor samples that had minimal overlap (29 proteins) with the non-ERBB2 tumor samples. Interaction and pathway analysis identified extracellular signal regulated kinase (ERK) cascade and actin polymerization and actinmyosin assembly contraction as pathways of importance in ERBB2+ and ERBB2- gastric cancer samples, respectively. The raw data files are deposited at ProteomeXchange (identifier: PXD002674) as well as GPMDB. PMID:26435392

  6. Factors regulating gastric emptying in preterm infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVES: To determine whether osmolality, volume, or energy density affects gastric emptying rate (GE); whether simultaneously decreasing osmolality and increasing volume accelerates GE; and whether GE is related to any clinical and/or demographic characteristics. STUDY DESIGN: GE was measured us...

  7. Microarray analysis in gastric cancer: A review

    PubMed Central

    D’Angelo, Giovanna; Di Rienzo, Teresa; Ojetti, Veronica

    2014-01-01

    Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment. PMID:25232233

  8. NCI International EBV-Gastric Cancer Consortium

    Cancer.gov

    A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

  9. Cells of origin in human gastric neoplasms.

    PubMed

    Chen, C K; Parsa, I

    1983-12-01

    The epithelium of the surface mucosa of the human stomach is demonstrated to share an antigen (HP-DU-1) with human pancreatic ductal cell surface epithelium detectable by a murine monoclonal IgG. This marker was found to be characteristic of the epithelium of gastric surface mucosa and serves to distinguish these cells from the epithelium of gastric glands, the generative cell zone, the parietal and mucous neck cells. The absence of HP-DU-1 was confirmed in the epithelium of the small and large intestines, gall bladder, tracheobronchial trees, urinary bladder, intrahepatic bile ducts, prostatic and salivary glands. This surface marker was used to examine the participation of the surface mucosal cell in hyperplastic, pre-neoplastic and neoplastic lesions of the human gastric mucosa. Gastric hyperplastic polyps and polypoid hypertrophic gastritis were mainly composed of epithelium bearing HP-DU-1 antigens. In contrast epithelial cells of atrophic gastritis, atrophic gastritis with intestinal metaplasia, and adenocarcinoma of the stomach lacked this antigen. PMID:6360341

  10. Epidemiology of gastric cancer in Japan

    PubMed Central

    Inoue, M; Tsugane, S

    2005-01-01

    Despite its decreasing trend in Japan, gastric cancer remains an important public health problem. Although the age standardised rates of gastric cancer have been declining for decades, the absolute numbers are increasing because of the rapid aging of the population. A large proportion of Japanese gastric cancers are detected at an early stage, with a better overall survival rate. As with Western developed countries, a change in the social environment such as reduced salt use and increased fresh vegetable and fruit intake as well as improvement of food storage may play an important part in the decline. Differences in Helicobacter pylori infection rates between generations presumably have contributed to the generation related variation in the declining trends. It is expected that most gastric cancers in Japan may be preventable by lifestyle modification such as salt reduction and increased fruit and vegetable intake, together with avoidance of smoking and countermeasures against H pylori infection so that the level now evident in Western developed countries can be reached. PMID:15998815

  11. Gastric lymphoma presenting as phlegmonous gastritis.

    PubMed

    Harikumar, R; Pramod, K; Pushpa, M; Simi, K; Arun, G

    2007-01-01

    Phlegmonous gastritis is an uncommon local or diffuse bacterial infection of the stomach wall. It is an extremely rare disease with a fulminating course and a high mortality rate. A majority of cases are diagnosed only postmortem, and early diagnosis is crucial for survival. This used to be common in the preantibiotic era; a resurgence of cases has occurred of late due to the spread of acquired immunodeficiency syndrome. There are varying local and systemic associations like gastric ulcer, gastric carcinoma, post-therapeutic endoscopy, postsurgery, human immunodeficiency virus infection, malnutrition, Kaposi's sarcoma, myeloma, leukemia, Sjogren's syndrome, and glucocorticoid use. We report a case of phlegmonous gastritis in a 70-year-old lady associated with gastric lymphoma. She succumbed to death on the fifth day of hospitalization despite broad-spectrum antibiotic therapy. She could not be operated upon due to the onset of multiorgan dysfunction syndrome and multiple comorbidities. To our knowledge, gastric lymphoma presenting as phlegmonous gastritis has not been reported in published English literature. PMID:19065719

  12. The future of gastric cancer prevention.

    PubMed

    Correa, Pelayo; Piazuelo, M Blanca; Camargo, M Constanza

    2004-01-01

    Despite advances in surgical treatment and chemotherapy, gastric cancer remains a major global health burden. The most recent estimates show that it is the fourth most common cancer and the second most common cause of cancer deaths worldwide. Various etiologic factors have been linked with the disease. It is widely accepted that Helicobacter pylori infection and high salt intake are positively associated with this neoplastic process. Controversial associations have been found with smoking or drinking habits. In contrast, there is convincing evidence that the adequate consumption of fresh fruits and vegetables reduces the risk of gastric cancer. Prevention intervention trials involving antioxidant supplements and anti- H. pylori treatment have shown beneficial effects in preventing the progression of pathologic changes in the gastric mucosa. On the other hand, recent advances related to differences in the genotypes of the bacteria and in human cytokine polymorphisms would allow the design and implementation of large-scale screening programs to identify subjects at the highest risk of gastric cancer. Curing the infection in such subjects and supplying adequate amounts of antioxidants should prevent a neoplastic outcome, and this intervention should be monitored by endoscopic surveillance. PMID:15052434

  13. Sensor capsule for diagnosis of gastric disorders

    NASA Technical Reports Server (NTRS)

    Holen, J. T.

    1972-01-01

    Motility and pH sensor capsule is developed to monitor gastric acidity, pressure, and temperature. Capsule does not interfere with digestion. Sensor is capsule which includes pH electrode, Pitran pressure transducer, and thermistor temperature sensor all potted in epoxy and enclosed in high density polyethylene sheath.

  14. [Gastrectomy at the peak of gastric bleeding].

    PubMed

    Zaitsev, V T; Donets, N P; Derman, A I; Lagoda, A E; Boiko, V V; Taraban, I A

    1992-01-01

    The technique for performance of gastrectomy under conditions of emergency surgery permitting to shorten the duration of intervention and increase its effectiveness is presented. Gastrectomy was performed in 7 patients with gastric cancer complicated by profuse bleeding. All the patients are alive, no anastomotic suture failure occurred. PMID:1287331

  15. Effect of Helicobacter pylori Infection on the Composition of Gastric Microbiota in the Development of Gastric Cancer

    PubMed Central

    Cao, Lei; Yu, Jun

    2015-01-01

    Background Gastric cancer is one of the most common cancer types worldwide. In China, gastric cancer has become one of the major threats for public health, ranking second on incidence and third on cause of cancer death. Despite the common risk factors that promote the development of gastric cancer, the huge quantity of microorganism colonies within the gastrointestinal tract, particularly Helicobacter pylori infection, demonstrates a correlation with chronic inflammation and gastric carcinogenesis, as epidemiological studies have determined that H. pylori infection confers approximately 75% of the attributable risk for gastric cancer. Summary The current article draws an overview on the correlation between the microbiota, inflammation and gastric tumorigenesis. H. pylori infection has been identified as the main risk factor as it triggers epithelial barrier disruption, survival signaling as well as genetic/epigenetic modulation. Apart from H. pylori, the existence of a diverse and complex composition of microbiota in the stomach has been identified, which supports a role of microbiota in the development of gastric cancer. Moreover, metagenomics studies focused on the composition and function of the microbiota have associated microbiota with gastric metabolic diseases and even tumorigenesis. Apart from the gastric microbiota, inflammation is another identified contributor to cancer development as well. Key Message Though H. pylori infection and the non-H. pylori microbiota play a role in gastric cancer, the properties of gastric microbiota and mechanisms by which they participate in the genesis of gastric cancer are still not clearly depicted. Moreover, it remains to be understood how the presence of microbiota along with H. pylori infection affects the progress from gastric disease to cancer. Practical Implications This article summarized a clue of the current studies on microbiota, H. pylori infection and the progression from gastric disease to cancer. PMID:26673084

  16. Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers

    PubMed Central

    YI, RUOKUN; WANG, RUI; SUN, PENG; ZHAO, XIN

    2015-01-01

    Dragon-pearl tea is a type of green tea commonly consumed in Southwest China. In the present study, the antioxidative and anti-gastric ulcer effects of Dragon-pearl tea crude polyphenols (DTCP) were determined in vitro and in vivo. Treatment with 25, 50 or 100 µg/ml DTCP resulted in notable antioxidant effects in vitro, which manifested as 2,2-diphenyl-1-picrylhydrazyl and OH radical-scavenging activity. Furthermore, using an in vivo mouse model, DTCP was shown to reduce the gastric ulcer area in the stomach, in which the 200 mg/kg DTCP dose exhibited the most marked effect, with a gastric ulcer index inhibitory rate of 72.63%. In addition, DTCP was demonstrated to improve stomach acidity conditions in vivo by increasing the pH and reducing the level of gastric juice, as compared with the reserpine-induced gastric ulcer control mice. Furthermore, DTCP altered the serum levels of a number of oxidation-related biomolecules, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), lipid peroxidation (LPO) and catalase (CAT), to subsequently exert an anti-gastric ulcer effect. Treatment with 50, 100 and 200 mg/kg DTCP increased the SOD, GSH-Px and CAT levels and reduced the MDA and LPO levels in the mouse model of gastric ulcers. These serum level alterations resulted in the modified serum levels of prostaglandin E2 (PGE2) and nitric oxide (NO), which are associated with gastric mucosal protection. A reverse transcription-quantitative polymerase chain reaction (RT-PCR) assay is a molecular biology experiment which could determine the changes of mRNA in tissues. Using the RT-PCR assay, DTCP was observed to increase the mRNA expression levels of certain genes associated with gastric ulcers: Epidermal growth factor, epidermal growth factor receptor, vascular endothelial growth factor and vascular endothelial growth factor receptor 1, while reducing gastrin expression levels. Therefore, the results indicated that DTCP induced a marked preventative effect on reserpine-induced gastric ulcers in vivo, as a result of its antioxidative capacity. PMID:26170959

  17. Endoscopic cyanoacrylate injection for the treatment of gastric varices in children

    PubMed Central

    Oh, Seak Hee; Kim, Seung Jin; Rhee, Kang Won; Kim, Kyung Mo

    2015-01-01

    AIM: To evaluate the efficacy and safety of N-butyl-2-cyanoacrylate in treating acute bleeding of gastric varices in children. METHODS: The retrospective study included 21 children with 47 episodes of active gastric variceal bleeding who were treated by endoscopic injection of N-butyl-2-cyanoacrylate at Asan Medical Center Children’s Hospital between August 2004 and December 2011. To reduce the risk of embolism, each injection consisted of 0.1-0.5 mL of 0.5 mL N-butyl-2-cyanoacrylate diluted with 0.5 or 0.8 mL Lipiodol. The primary outcome was incidence of hemostasis after variceal obliteration and the secondary outcome was complication of the procedure. RESULTS: The 21 patients experienced 47 episodes of active gastric variceal bleeding, including rebleeding, for which they received a total of 52 cyanoacrylate injections. Following 42 bleeding episodes, hemostasis was achieved after one injection and following five bleeding episodes it was achieved after two injections. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 mL (range: 0.1-0.5 mL). Injection achieved hemostasis in 45 of 47 (95.7%) episodes of acute gastric variceal bleeding. Eleven patients (52.4%) developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 mo (range: 1.0-39.2 mo). No treatment-related complications such as distal embolism were noted with the exception of abdominal pain in one patient (4.8%). Among four mortalities, one patient died of variceal rebleeding. CONCLUSION: Endoscopic variceal obliteration using a small volume of aliquots with repeated cyanoacrylate injection was an effective and safe option for the treatment of gastric varices in children. PMID:25759541

  18. Protective Effects of Capparis zeylanica Linn. Leaf Extract on Gastric Lesions in Experimental Animals.

    PubMed

    Sini, Karanayil R; Sinha, Barij N; Rajasekaran, Aiyolu

    2011-01-01

    The aim of the study was to study the anti-ulcer activity of the methanolic extract of the leaves of Capparis zeylanica Linn on experimental animal models. The methanol extract of Capparis zeylanica Linn. leaves was investigated for anti-ulcer activity against aspirin plus pylorus ligation induced gastric ulcer in rats. HCl-Ethanol induced ulcer in mice and indomethacin induced ulcer in rats at 200 mg/kg body weight p.o. A significant (p<0.01, p<0.001) anti-ulcer activity was observed in all the models. Pylorus ligation showed significant (p<0.01) reduction in gastric volume, free acidity and ulcer index as compared to control. It also showed 88.5% ulcer inhibition in HCl-ethanol induced ulcer and 83.78% inhibition in indomethacin induced ulcer. PMID:23407576

  19. Gene expression profiling of gastric mucosa in mice lacking CCK and gastrin receptors.

    PubMed

    Zhao, Chun-Mei; Kodama, Yosuke; Flatberg, Arnar; Beisvag, Vidar; Kulseng, Bård; Sandvik, Arne K; Rehfeld, Jens F; Chen, Duan

    2014-01-01

    The stomach produces acid, which may play an important role in the regulation of bone homeostasis. The aim of this study was to reveal signaling pathways in the gastric mucosa that involve the acid secretion and possibly the bone metabolism in CCK1 and/or CCK2 receptor knockout (KO) mice. Gastric acid secretion was impaired and the ECL cell signaling pathway was inhibited in CCK2 receptor KO mice but not in CCK1 receptor KO mice. However, in CCK1+2 receptor double KO mice the acid secretion in response to pylorus ligation-induced vagal stimulation and the ECL cell pathway were partially normalized, which was associated with an up-regulated pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1). The basal part of the gastric mucosa expressed parathyroid hormone-like hormone (PTHLH) in a subpopulation of likely ECL cells (and possibly other cells) and vitamin D3 1? hydroxylase probably in trefoil peptide2-immunoreactive cells. In conclusion, mice lacking CCK receptors exhibited a functional shift from the gastrin-CCK pathways to the neuronal pathway in control of the ECL cells and eventually the acid secretion. Taking the present data together with previous findings, we suggest a possible link between gastric PTHLH and vitamin D and bone metabolism. PMID:25160855

  20. Dietary, non-microbial intervention to prevent Helicobacter pylori-associated gastric diseases.

    PubMed

    Han, Young-Min; Park, Jong-Min; Jeong, Migyeong; Yoo, Jun-Hwan; Kim, Won-Hee; Shin, Seok-Pyo; Ko, Weon-Jin; Hahm, Ki-Baik

    2015-06-01

    Since the discovery of Helicobacter pylori (H. pylori) infection as the major cause of gastroduodenal disorders including acute and chronic gastritis, gastroduodenal ulcer, chronic atrophic gastritis, and gastric cancer almost three decades ago, the possibility of preventing these clinical diseases through eradicating H. pylori has been the focus of active research, but soon debate in the scientific community, though eradication opens the feasibility of cancer prevention and the removal of bacteria significantly prevents development or recurrence of peptic ulcer diseases and some clinical diseases, was proposed due to uncertainty in either achievement of complete eradication or inefficacy in cancer prevention with eradication alone. Still its linkage to gastric cancer is incontestable. Since the multiple combination of bacterial factors, environmental insults, and the host immune response that drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer is intervened, simple eradication deemed the feasibility of cancer prevention. Therefore, our group open strong hypothesis that non-microbial, dietary approach might be the alternate, for which several interventions of nutritional components can highlight rejuvenation of chronic atrophic gastritis as well as amelioration of H. pylori-associated procarcinogenic inflammation. In this review article, the experience and outcome regarding nutritional application to rejuvenate gastric atrophy will be introduced, using Korean red ginseng, garlic extracts, cancer preventive Korea kimchi, n-3 polyunsaturated fatty acids (PUFA), special form of licorice, and probiotics. The detailed influence of dietary intervention and bacterial eradication therapy on disease progression and reversibility of premalignant lesions are discussed. PMID:26207250

  1. Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells.

    PubMed

    Wu, Jie; Tan, Zhujun; Chen, Jian; Dong, Cheng

    2015-01-01

    Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects of CVB-D on gastric cancer cells and the underlying mechanisms of action. CVB-D reduced cell viability and colony formation ability of MGC-803 and MKN28 cells in a time- and concentration-dependent manner. Flow cytometry showed that cell cycle of CVB-D treated cells was arrested at the S-phase. CVB-D also induced apoptosis in MGC-803 and MKN28 cells, especially early stage apoptosis. Furthermore, mitochondria membrane potential (??m) was reduced and apoptosis-related proteins, cleaved Caspase-3 and Bax/Bcl-2, were up-regulated in CVB-D-treated MGC-803 and MKN28 cells. Taken together, our studies found that CVB-D plays important roles in inhibition of gastric tumorigenesis via arresting cell cycle and inducing mitochondria-mediated apoptosis, suggesting the potential application of CVB-D in gastric cancer therapy. PMID:26610442

  2. Dietary, non-microbial intervention to prevent Helicobacter pylori-associated gastric diseases

    PubMed Central

    Han, Young-Min; Park, Jong-Min; Jeong, Migyeong; Yoo, Jun-Hwan; Kim, Won-Hee; Shin, Seok-Pyo; Ko, Weon-Jin

    2015-01-01

    Since the discovery of Helicobacter pylori (H. pylori) infection as the major cause of gastroduodenal disorders including acute and chronic gastritis, gastroduodenal ulcer, chronic atrophic gastritis, and gastric cancer almost three decades ago, the possibility of preventing these clinical diseases through eradicating H. pylori has been the focus of active research, but soon debate in the scientific community, though eradication opens the feasibility of cancer prevention and the removal of bacteria significantly prevents development or recurrence of peptic ulcer diseases and some clinical diseases, was proposed due to uncertainty in either achievement of complete eradication or inefficacy in cancer prevention with eradication alone. Still its linkage to gastric cancer is incontestable. Since the multiple combination of bacterial factors, environmental insults, and the host immune response that drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer is intervened, simple eradication deemed the feasibility of cancer prevention. Therefore, our group open strong hypothesis that non-microbial, dietary approach might be the alternate, for which several interventions of nutritional components can highlight rejuvenation of chronic atrophic gastritis as well as amelioration of H. pylori-associated procarcinogenic inflammation. In this review article, the experience and outcome regarding nutritional application to rejuvenate gastric atrophy will be introduced, using Korean red ginseng, garlic extracts, cancer preventive Korea kimchi, n-3 polyunsaturated fatty acids (PUFA), special form of licorice, and probiotics. The detailed influence of dietary intervention and bacterial eradication therapy on disease progression and reversibility of premalignant lesions are discussed. PMID:26207250

  3. Helicobacter pylori infection following partial gastrectomy for gastric cancer

    PubMed Central

    Park, Sanghoon; Chun, Hoon Jai

    2014-01-01

    Gastric remnants are an inevitable consequence of partial gastrectomy following resection for gastric cancer. The presence of gastric stumps is itself a risk factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori) infection is also a well-known characteristic of gastric carcinogenesis. H. pylori colonization in the remnant stomach therefore draws special interest from clinicians in terms of stomach cancer development and pathogenesis; however, the H. pylori-infected gastric remnant is quite different from the intact organ in several aspects and researchers have expressed conflicting opinions with respect to its role in pathogenesis. For instance, H. pylori infection of the gastric stump produced controversial results in several recent studies. The prevalence of H. pylori infection in the gastric stump has varied among recent reports. Gastritis developing in the remnant stomach presents with a unique pattern of inflammation that is different from the pattern seen in ordinary gastritis of the intact organ. Bile refluxate also has a significant influence on the colonization of the stomach stump, with several studies reporting mixed results as well. In contrast, the elimination of H. pylori from the gastric stump has shown a dramatic impact on eradication rate. H. pylori elimination is recognized to be important for cancer prevention and considerable agreement of opinion is seen among researchers. To overcome the current discrepancies in the literature regarding the role of H. pylori in the gastric stump, further research is required. PMID:24659869

  4. [Studies on the muscarine receptors in rat gastric smooth muscle].

    PubMed

    Ujiie, H; Hongo, M; Satake, K; Okuno, Y; Goto, Y; Lin, Y F

    1988-01-01

    It has been reported that the two types of muscarinic receptors, "M1" and "M2", exist in the opossum lower esophageal sphincter. The presence of these muscarinic receptor subtypes had been confirmed with the discovery of the M1 selective antagonist, pirenzepine. But little is known about muscarinic receptor subtypes in gastric smooth muscle. The aim of this study was to identify the muscarinic receptor subtypes on the gastric smooth muscle responsible for the contraction of rat gastric muscle strip. Also, we examined the mechanism of the action of aclatonium napadisilate on rat gastric smooth muscle in vitro. The stimulation of M2 receptor caused the contraction of the gastric smooth muscle. McN-A-343, selective M1 agonist, caused weak contraction of the gastric smooth muscle, and this response was not affected by the selective M1 antagonist, pirenzepine. Aclatonium napadisilate stimulated M2 receptor and caused the gastric smooth muscle contraction. We conclude that the contraction of the gastric smooth muscle is caused by the stimulation of the M2 receptor and this reaction was not affected by tetrodotoxin, suggesting the M2 receptor is located directly on the gastric smooth muscle. The weak contraction of the gastric smooth muscle caused by McN-A-343 was not affected by the selective M1 antagonist, pirenzepine, suggesting that McN-A-343 may not be a pure M1 selective agonist. The action of aclatonium napadisilate is supposed to stimulate the M2 receptor. PMID:3386085

  5. A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium

    PubMed Central

    Adriaenssens, Alice; Lam, Brian Yee Hong; Billing, Lawrence; Skeffington, Katie; Sewing, Sabine

    2015-01-01

    The stomach epithelium contains a myriad of enteroendocrine cells that modulate a range of physiological functions, including postprandial secretion of regulatory peptides, gastric motility, and nutrient absorption. Somatostatin (SST)-producing D-cells are present in the oxyntic and pyloric regions of the stomach, and provide a tonic inhibitory tone that regulates activity of neighboring enteroendocrine cells and gastric acid secretion. Cellular mechanisms underlying the effects of regulatory factors on gastric D-cells are poorly defined due to problems in identifying primary D-cells, and uncertainty remains about which stimuli influence D-cells directly. In this study, we introduce a transgenic mouse line, SST-Cre, which upon crossing with Cre reporter strains, facilitates the identification and purification of gastric D-cells, or cell-specific expression of genetically encoded calcium indicators. Populations of D-cells from the gastric antrum and corpus were isolated and analyzed by RNA sequencing and quantitative RT-PCR. The expression of hormones, hormone receptors, neurotransmitter receptors, and nutrient receptors was quantified. Pyy, Gipr, Chrm4, Calcrl, Taar1, and Casr were identified as genes that are highly enriched in D-cells compared with SST-negative cells. Hormone secretion assays performed in mixed gastric epithelial cultures confirmed that SST secretion is regulated by incretin hormones, cholecystokinin, acetylcholine, vasoactive intestinal polypeptide, calcitonin gene-related polypeptide, oligopetides, and trace amines. Cholecystokinin and oligopeptides elicited increases in intracellular calcium in single-cell imaging experiments performed using cultured D-cells. Our data provide the first transcriptomic analysis and functional characterization of gastric D-cells, and identify regulatory pathways that underlie the direct detection of stimuli by this cell type. PMID:26241122

  6. A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium.

    PubMed

    Adriaenssens, Alice; Lam, Brian Yee Hong; Billing, Lawrence; Skeffington, Katie; Sewing, Sabine; Reimann, Frank; Gribble, Fiona

    2015-11-01

    The stomach epithelium contains a myriad of enteroendocrine cells that modulate a range of physiological functions, including postprandial secretion of regulatory peptides, gastric motility, and nutrient absorption. Somatostatin (SST)-producing D-cells are present in the oxyntic and pyloric regions of the stomach, and provide a tonic inhibitory tone that regulates activity of neighboring enteroendocrine cells and gastric acid secretion. Cellular mechanisms underlying the effects of regulatory factors on gastric D-cells are poorly defined due to problems in identifying primary D-cells, and uncertainty remains about which stimuli influence D-cells directly. In this study, we introduce a transgenic mouse line, SST-Cre, which upon crossing with Cre reporter strains, facilitates the identification and purification of gastric D-cells, or cell-specific expression of genetically encoded calcium indicators. Populations of D-cells from the gastric antrum and corpus were isolated and analyzed by RNA sequencing and quantitative RT-PCR. The expression of hormones, hormone receptors, neurotransmitter receptors, and nutrient receptors was quantified. Pyy, Gipr, Chrm4, Calcrl, Taar1, and Casr were identified as genes that are highly enriched in D-cells compared with SST-negative cells. Hormone secretion assays performed in mixed gastric epithelial cultures confirmed that SST secretion is regulated by incretin hormones, cholecystokinin, acetylcholine, vasoactive intestinal polypeptide, calcitonin gene-related polypeptide, oligopetides, and trace amines. Cholecystokinin and oligopeptides elicited increases in intracellular calcium in single-cell imaging experiments performed using cultured D-cells. Our data provide the first transcriptomic analysis and functional characterization of gastric D-cells, and identify regulatory pathways that underlie the direct detection of stimuli by this cell type. PMID:26241122

  7. Aqueous extracts of Fructus Ligustri Lucide induce gastric carcinoma cell apoptosis and G2/M cycle arrest

    PubMed Central

    Zhang, Ru; Li, Ying-Xue; Wang, Li-Sheng; Song, Yang; Huang, Qing-Juan; Zhang, Ding-Guo

    2015-01-01

    Objective: Previous studies have shown that Fructus Ligustri Lucide (FLL) can be used to anti-cancer. However, the mechanism by which FLL mediate this effect is unclear. In the present study, aqueous extracts of FLL induced cell apoptosis in human gastric carcinoma cell was investigated. Methods: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining and hoechst 33342 staining. The protein expression of cell cycle regulators and tumor suppressors were analyzed by western blotting. Results: Treatment of human gastric carcinoma cells with FLL induced cell death in a dose- and time-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that the proportion of the early and terminal phase of apoptosis cells had gained after FLL treatment as compared to untreated group. Moreover, human gastric carcinoma cells were exposed to the aqueous extracts of FLL for 48 h, which resulted in an accumulation of cells in G2/M phase. Apoptotic bodies were clearly observed in human gastric carcinoma that had been treated with FLL for 48 h and then stained with Hochest 33342. Treatment of gastric carcinoma cells with increasing doses of FLL and increasing durations significantly increased the protein expression of Bax and Caspase3, decreased the anti-apoptotic Bcl-2 level. The expression of CDC2 and cdc25C were downregulated upon FLL treatment in human gastric carcinoma. In contrast, p53 and p21 were obviously upregulated by FLL treatment in a concentration-dependent manner. Conclusions: These results confirmed that FLL could induce apoptosis in human gastric carcinoma, the underlying molecular mechanisms, at least partially, through activation p21/p53 and suppression CDC2/cdc25C signaling in vitro. PMID:26550140

  8. Effects of kramecyne on LPS induced chronic inflammation and gastric ulcers.

    PubMed

    Alonso-Castro, Angel Josabad; Pérez-Ramos, Julia; Sánchez-Mendoza, Ernesto; Pérez-González, Cuauhtemoc; Pérez-Gutiérrez, Salud

    201