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1

OA01.03. Antisecretory and antiulcer activities of eclipta alba Linn.in rats  

PubMed Central

Purpose: Eclipta alba Linn. (Asteraceae) is used traditionally in Indian system of medicine as anti inflammatory, hepatoprotective, hypoglycemic, immunomodulator, in wound healing, and as a potent hair growth promoter. The study was aimed to evaluate the antisecretory and gastroprotective effects of 50% ethanol extract of Eclipta alba. Method: Eclipta alba extract (EAE) at 50, 100 and 200 mg/kg was administered orally, twice daily for 5 days to prevent from, cold restraint stress (CRS), and pylorus ligation (PL) induced ulcers. Antioxidant studies were performed in CRS induced ulcer model. Gastric wall mucus and secretion parameters like volume of gastric juice, acid output and pH were estimated in PL induced ulcer model. Ranitidine (50mg/kg, p.o.) was used as positive control for comparison. Result: A dose dependent and significant (p < 0.05) reduction in lesion index was observed in ulcer-induced rats treated with EAE at various doses when compared with control group in both the models. Gastric wall mucus production was significantly (p < 0.05) elevated in EAE treated rats. Significant attenuation in lipid peroxidation, superoxide dismutase activity was observed, whereas, catalase enzyme levels were elevated in EAE treated groups. Antisecretory activity of EAE was evidenced by significant reduction in gastric volume, acid output and increase in gastric pH when compared to their control values. The findings were further supported by histopathological examination of stomach in both EAE treated and control rats. Conclusion: The results of the present investigation suggest that ethanol extract of Eclipta alba possesses potent antisecretory and gastroprotective activity. The exact mechanism to be evaluated further but in preliminary observation it was thought to be mediated through free radical scavenging activity.

Samaiya, Puneet Kumar; Bhattamisra, Subrat Kumar; Rao, Chandana. V; Vijaykumar, M.; Ojha, Sanjeev Kumar; Eswaran, Bavani M

2012-01-01

2

Antisecretory effect of hydrogen sulfide on gastric acid secretion and the involvement of nitric oxide.  

PubMed

The present study was designed to investigate the effect of H2S on distention-induced gastric acid secretion. Fifty-two rats were randomly assigned to seven experimental groups. The gastric acid secretion was stimulated by gastric distention. Two groups of rats received L-cysteine or saline for 5 days before stimulation of the gastric acid secretion. Two groups of animals also received NaHS or saline just prior to stimulation of the gastric acid secretion. The effect of L-NAME and propargylglycine was also investigated. The mucosal levels of the gene expression of cyclooxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS), and H(+)/K(+)-ATPase ?-subunit were quantified by qPCR and luminal concentrations of NO were determined. NaHS and L-cysteine decreased the gastric acid output in response to distention. The mRNA expression of H(+)/K(+)-ATPase ?-subunit decreased by NaHS and L-cysteine as compared with the control group while gene expression of eNOS and COX-2 was upregulated. The inhibitory effect of NaHS on distention-induced gastric acid secretion was mitigated by pretreatment of L-NAME. These findings suggest the involvement of NO in mediating the antisecretory effect of H2S. PMID:24707486

Mard, Seyyed Ali; Askari, Hasan; Neisi, Niloofar; Veisi, Ali

2014-01-01

3

Antisecretory Effect of Hydrogen Sulfide on Gastric Acid Secretion and the Involvement of Nitric Oxide  

PubMed Central

The present study was designed to investigate the effect of H2S on distention-induced gastric acid secretion. Fifty-two rats were randomly assigned to seven experimental groups. The gastric acid secretion was stimulated by gastric distention. Two groups of rats received L-cysteine or saline for 5 days before stimulation of the gastric acid secretion. Two groups of animals also received NaHS or saline just prior to stimulation of the gastric acid secretion. The effect of L-NAME and propargylglycine was also investigated. The mucosal levels of the gene expression of cyclooxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS), and H+/K+-ATPase ?-subunit were quantified by qPCR and luminal concentrations of NO were determined. NaHS and L-cysteine decreased the gastric acid output in response to distention. The mRNA expression of H+/K+-ATPase ?-subunit decreased by NaHS and L-cysteine as compared with the control group while gene expression of eNOS and COX-2 was upregulated. The inhibitory effect of NaHS on distention-induced gastric acid secretion was mitigated by pretreatment of L-NAME. These findings suggest the involvement of NO in mediating the antisecretory effect of H2S. PMID:24707486

Mard, Seyyed Ali; Askari, Hasan; Neisi, Niloofar; Veisi, Ali

2014-01-01

4

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

PubMed Central

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

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

5

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

PubMed Central

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

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

2013-01-01

6

Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats.  

PubMed

In the present study, the gastroprotective mechanism of Xylocarpus granatum fruit and its active constituents gedunin and photogedunin was investigated. Chloroform fraction (Fr-CHCl(3)) of X. granatum fruit was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats and histamine (HA) induced duodenal ulcer model in guinea pigs. Potential anti-ulcer activity of Fr-CHCl(3) was observed against CRU (58.28%), AS (67.81%), AL (84.38%), PL (65.66%) and HA (61.93%) induced ulcer models. The standard drug omeprazole (10mg/kg, p.o.) showed 68.25% protection against CRU, 57.08% against AS and 69.42% against PL model and 70.79% against HA induced duodenal ulcer. Sucralfate, another standard drug (500 mg/kg, p.o.) showed 62.72% protection in AL induced ulcer model. Fr-CHCl(3) significantly reduced free acidity (51.42%), total acidity (30.76%) and upregulated mucin secretion by 58.37% respectively. Phytochemical investigations of Fr-CHCl(3) yielded gedunin (36%), photogedunin (2%). Further, Fr-CHCl(3) and its compounds gedunin and photogedunin significantly inhibited H(+) K(+)-ATPase activity in vitro with IC(50) of 89.37, 56.86 and 66.54 microg/ml respectively as compared to the IC(50) value of omeprazole (30.24 microg/ml) confirming their anti-secretory activity. Conclusively, Fr-CHCl(3) of Xylocarpus granatum was found to possess anti-ulcerogenic activity which might be due to its anti-secretory activity and subsequent strengthening of the defensive mechanism. This study is the first of its kind to show significant anti-secretory effect of gedunin and photogedunin. Therefore it could act as a potent therapeutic agent against peptic ulcer disease. PMID:19962286

Lakshmi, V; Singh, N; Shrivastva, S; Mishra, S K; Dharmani, P; Mishra, V; Palit, G

2010-07-01

7

Design, synthesis, and preliminary activity evaluation of novel pyrimidine derivatives as Acid pump antagonists.  

PubMed

Acid-related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation. PMID:24995399

Song, Weiguo; Zhang, Xiaopan; Li, Shutao; Xu, Wenfang

2015-03-01

8

A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals.  

PubMed

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. However, several medical needs such as suppression of night-time acid secretion and rapid symptom relief remain unmet. In this study, we investigated the effects of 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel potassium-competitive acid blocker, on acid secretion in rats and dogs under various conditions, in comparison with the PPI lansoprazole [2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl]sulfinyl]-1H-benzimidazole], to characterize the antisecretory action of TAK-438. TAK-438 showed a more potent and longer-lasting inhibitory effect than lansoprazole on the histamine-stimulated gastric acid secretion in rats and dogs. A pharmacokinetic study in rats showed that TAK-438 accumulated and was retained in the gastric tissue for more than 24 h, unlike that in the plasma. TAK-438 showed significant antisecretory activity with or without cimetidine pretreatment, in contrast to lansoprazole, which did not show antisecretory activity after cimetidine pretreatment in rats. TAK-438 increased the pH of the gastric perfusate to 5.7 in an unstimulated condition, and this effect was maintained in the presence of subsequent histamine stimulation. On the other hand, lansoprazole also increased the pH in an unstimulated condition, but this effect diminished after histamine stimulation. These results indicated that TAK-438 exerted a more potent and longer-lasting antisecretory effect than lansoprazole through high accumulation and slow clearance from the gastric tissue. In addition, TAK-438 was unaffected by the gastric secretory state, unlike PPIs. Therefore, TAK-438 can provide a novel mechanism of action to improve the present PPI-based treatment of acid-related diseases. PMID:21411494

Hori, Yasunobu; Matsukawa, Jun; Takeuchi, Toshiyuki; Nishida, Haruyuki; Kajino, Masahiro; Inatomi, Nobuhiro

2011-06-01

9

[Antisecretory therapy as a component of hemostasis in acute gastroduodenal ulcer bleedings].  

PubMed

Results of antisecretory therapy (pyrenzepin, H(2)-blockers, inhibitors of proton pump, octreotid) in 962 patients with acute gastroduodenal ulcer bleedings (AGDUB) were analyzed over 14-years period. Antisecretory treatment in AGDUB has principally different goals and potential depending on risk of bleeding's recurrence and morphological changes in tissue of gastroduodenal ulcer. Antisecretory therapy is the main treatment in high risk of AGDUB recurrence or before urgent surgery. Intravenous infusion of omeprazol has demonstrated the highest clinical efficacy due to maximal inhibition of gastric secretion and absence of negative influences on oxygen regimen in tissue of ulcer. PMID:16091681

Gostishchev, V K; Evseev, M A

2005-01-01

10

Misoprostol: a prostaglandin E1 analog with antisecretory and cytoprotective properties.  

PubMed

Misoprostol, a methylester analog of prostaglandin E1, with antisecretory and cytoprotective properties, has undergone extensive investigation and has received Food and Drug Administration approval for the prevention of nonsteroidal-induced ulceration. The drug represents the first synthetic, orally active prostaglandin evaluated for the treatment of peptic ulcer disease. Clinical studies reveal a trend toward slightly lower healing rates with misoprostol when compared with histamine (H2)-receptor antagonists in the treatment of gastric and duodenal ulcers. In addition, misoprostol was less effective than H2-blockers in reducing ulcer pain, and caused a higher incidence of adverse reactions, particularly diarrhea occurring in up to 13 percent of the patients treated. Several studies have shown misoprostol to be superior to cimetidine and sucralfate in the prevention of alcohol- and drug-induced gastritis. This report summarizes the biopharmaceutics, pharmacokinetics, and clinical efficacy of misoprostol in the treatment of gastric and duodenal ulcers and in the prevention of mucosal injury. PMID:2499129

Jones, J B; Bailey, R T

1989-04-01

11

Evaluation of antiulcer and antisecretory potential of Linum usitatissimum fixed oil and possible mechanism of action.  

PubMed

The aim of the study was to evaluate the antiulcer activity of Linum usitatissimum fixed oil against aspirin-, indomethacin-, ethanol-, reserpine-, serotonin- and stress-induced gastric ulceration in rats and histamine-induced gastric ulceration in guinea pigs. Attempts were also made to evaluate the in vitro anticholinergic and antihistaminic activity and in vivo antisecretary and antiulcer activity of oil following pylorus ligation in rats. L. usitatissimum fixed oil exhibited significant antiulcer activity against different ulcerogens in experimental animal models. The fixed oil significantly inhibited acetylcholine- and histamine-induced contraction of guinea pig and rat ileums, respectively, suggesting its anticholinergic and antihistaminic activity. The oil also exhibited significant inhibitory effect on gastric secretion/total acidity and aspirin-induced gastric ulceration in pylorus-ligated rats. The lipoxygenase inhibitory, histamine antagonistic and antisecretory (anticholinergic) effects of the oil could probably have contributed towards antiulcer activity. L. usitatissimum fixed oil may be considered to be a drug of natural origin which possesses significant antiulcer activity. The present observation is the first experimental data showing antiulcer activity of L. usitatissimum fixed oil. PMID:20405222

Kaithwas, Gaurav; Majumdar, Dipak K

2010-06-01

12

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

PubMed Central

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

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

13

Gastric antiulcerogenic and hypokinetic activities of Terminalia fagifolia Mart. & Zucc. (Combretaceae).  

PubMed

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

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

14

JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.  

PubMed Central

1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity. PMID:7647984

Palacios, B.; Montero, M. J.; Sevilla, M. A.; Román, L. S.

1995-01-01

15

Antisecretory factor suppresses intestinal inflammation and hypersecretion  

Microsoft Academic Search

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 fromClostridium 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

E Johansson; E Jennische; S Lange; I Lönnroth

1997-01-01

16

Activity-guided fractionation to characterize a coffee beverage that effectively down-regulates mechanisms of gastric acid secretion as compared to regular coffee.  

PubMed

In some individuals, the consumption of coffee beverages is related to symptoms of gastric irritation. Hot water steam-treatment of raw coffee beans is hypothesized to reduce the contents of stomach irritating compounds, and products to which this technology is applied are launched as stomach-friendly coffee. However, data on the effect of steam-treated coffee on gastric acid secretion are conflicting and it has not been proven yet as to which coffee components act as pro- or antisecretory stimulants. The work presented here aimed at the characterization of a coffee beverage that effectively down-regulates mechanisms of proton secretion in human gastric cells (HGT-1). At first, a regular coffee beverage was fractionated by using solvents of different polarity: water, ethylacetate, dichloromethane, and pentane. Functional assays on the proton secretory activity (PSA) of these solvent fractions revealed the least pronounced effect for the water fraction, for which quantitative analyses demonstrated the highest distribution of chlorogenic acid (95%), (beta)N-alkanoyl-5-hydroxytryptamides (55%), and N-methylpyridinium (N-MP, >99%) among all fractions. Following experiments demonstrated that HGT-1 cells treated with regular coffee fortified with N-MP at a concentration of about 20 mg/mL N-MP showed a significantly decreased PSA as compared to cells which were exposed to coffee beverages containing higher (32-34 mg/L) or lower (5 mg/L) N-MP concentrations. Results from cellular pathway analyses of transcription (ATF-1 and Akt1) and signaling (cAMP and EGFr) factors and kinases (ERK1/2), and experiments on the gene expression of pro (histamine-HRH2 and acetylcholine-CHRM3)- and anti (somatostatin-SSTR1)-secretory receptors and H(+),K(+)-ATPase verified this antisecretory activity of N-MP in coffee beverages. PMID:20235536

Rubach, Malte; Lang, Roman; Skupin, Carola; Hofmann, Thomas; Somoza, Veronika

2010-04-14

17

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats  

SciTech Connect

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.

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

1987-05-01

18

Gastric activity studies using a magnetic tracer.  

PubMed

A magnetic pulse generator has been set up in order to study gastric activity. Two coils 1.05 m in diameter, arranged in a Helmholtz configuration, were used. The system generated magnetic field pulses higher than 15 mT, of duration 17.3+/-1.2 ms. Measurements were performed in 11 male volunteers, with average age 29.3+/-6.4 years and body mass index 26.0+/-4.8 kg m(-2). Magnetite (Fe3O4) particles with diameters from 75 to 125 microm were used as magnetic tracers, which were mixed in 250 ml of yogurt in concentrations from 2 to 5 g. Signals were registered by using a high speed 3 axis fluxgate digital magnetometer and processed to determine the relaxation of the magnetic tracers by fitting a first-order exponential function to the data, a mean relaxation constant K = 116+/-40 s(-1) was obtained. Also, an average gastric peristaltic frequency was measured; a value of 3.2+/-0.3 cpm was determined. PMID:15535190

Cordova-Fraga, T; Bernal-Alvarado, J J; Gutierrez-Juarez, G; Sosa, M; Vargas-Luna, M

2004-10-01

19

Gastric Electrical Activity and Gastrointestinal Hormones in Dyspeptic Patients  

Microsoft Academic Search

Aims: To explore the patterns of gastric electrical activity, gastric emptying and gastrointestinal hormones in dyspeptic patients and relate them to Helicobacter pylori status. Methods: Twenty-two patients with functional dyspepsia and 29 healthy volunteers underwent cutaneous electrogastrography and dynamic ultrasound before and after a test meal. All dyspeptic patients underwent endoscopy and biopsy; all subjects were examined for the presence

Giuseppe Riezzo; Marisa Chiloiro; Francesco Russo; Caterina Clemente; Giovanni Di Matteo; Vito Guerra; Alfredo Di Leo

2001-01-01

20

Enhanced cellular uptake of antisecretory peptide AF-16 through proteoglycan binding.  

PubMed

Peptide AF-16, which includes the active site of Antisecretory Factor protein, has antisecretory and anti-inflammatory properties, making it a potent drug candidate for treatment of secretory and inflammatory diseases such as diarrhea, inflammatory bowel diseases, and intracranial hypertension. Despite remarkable physiological effects and great pharmaceutical need for drug discovery, very little is yet understood about AF-16 mechanism of action. In order to address interaction mechanisms, we investigated the binding of AF-16 to sulfated glycosaminoglycan, heparin, with focus on the effect of pH and ionic strength, and studied the influence of cell-surface proteoglycans on cellular uptake efficiency. Confocal laser scanning microscopy and flow cytometry experiments on wild type and proteoglycan-deficient Chinese hamster ovary cells reveal an endocytotic nature of AF-16 cellular uptake that is, however, less efficient for the cells lacking cell-surface proteoglycans. Isothermal titration calorimetry provides quantitative thermodynamic data and evidence for that the peptide affinity to heparin increases at lower pH and ionic strength. Experimental data, supported by theoretical modeling, of peptide-glycosaminoglycan interaction indicate that it has a large electrostatic contribution, which will be enhanced in diseases accompanied by decreased pH and ionic strength. These observations show that cell-surface proteoglycans are of general and crucial importance for the antisecretory and anti-inflammatory activities of AF-16. PMID:25289567

Matson Dzebo, Maria; Reymer, Anna; Fant, Kristina; Lincoln, Per; Nordén, Bengt; Rocha, Sandra

2014-10-21

21

The effect of drugs and stimulants on gastric myoelectrical activity  

PubMed Central

Electrogastrography (EGG) is a non-invasive diagnostic method useful for the registration and analysis of gastric myoelectrical activity. Abnormalities within an electrogastrogram were found to correlate with a number of disorders and symptoms, like functional dyspepsia, diabetic gastroparesis and terminal hepatic or renal failure. The EGG is also a valuable diagnostic method enabling the evaluation of the effect of drugs on gastric myoelectrical activity, which can be intentional, as in the case of prokinetics, or can have an adverse character. Our review focuses on drugs with a proven impact on gastric myoelectrical activity and hence on the electrogastrogram. The paper assembles and discusses the results of investigations dealing with changes in the electrogastrograms evoked by various drugs. Moreover, the mechanisms of the influence on the gastric myoelectrical activity of drugs, curative substances and stimulants are presented. PMID:25097708

Kwiecie?, Jaros?aw; Kasicka-Jonderko, Anna; Buschhaus, Magdalena

2014-01-01

22

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

PubMed Central

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

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

2014-01-01

23

Changes in gastric myoelectric activity during space flight  

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

24

Biglycan enhances gastric cancer invasion by activating FAK signaling pathway.  

PubMed

Biglycan (BGN) is an important member of small leucine-rich proteoglycans family, and has been implicated in oncogenesis and development of various human cancer types. Here we report that BGN promotes tumor invasion and metastasis of gastric cancer both in vitro and in vivo. BGN expression is significantly higher in gastric cancer tissues and associated with lymph node metastasis, depth of tumor invasion and TNM stage. BGN enhances gastric cancer cell wound healing, migration and invasion ability as well as the tube formation ability of endothelial cells in vitro. Animal experiments results in vivo are consistent with outcomes in vitro. BGN induces increased phosphorylation of FAK (Tyr576/577, Tyr925 and Tyr397) and Paxillin. These results indicate that BGN is upregulated, and plays an oncogenic role, in gastric cancer metastasis by activating the FAK signaling pathway. PMID:24681892

Hu, Lei; Duan, Yan-Tao; Li, Jian-Fang; Su, Li-Ping; Yan, Min; Zhu, Zheng-Gang; Liu, Bing-Ya; Yang, Qiu-Meng

2014-04-15

25

Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats  

PubMed Central

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

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

2014-01-01

26

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

PubMed Central

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

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

2014-01-01

27

Gastric electrical activity and gastric emptying in term and preterm newborns.  

PubMed

The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28-32 weeks, 11 preterm newborns with a gestational age of 32-36 weeks, and 10 full-term newborns with a gestational age of 36-40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7-92.3) vs. 29.6% (3.7-78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4-87.4), 60.9% (38.1-89.7), 77.8% (66.4-84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T(1/2) was longer in the preterm newborns of 28-32 weeks than preterm newborns of 32-36 weeks and full-term newborns (fasting antral area: 0.96 cm2 (0.6-1.5), 0.63 cm2 (0.4-1.2), 0.55 cm2 (0.1-0.9) respectively, P < 0.05; T(1/2): 83.4 min (76.0-108.5), 70 min (57.5-89.5) and 71.8 min (54.9-81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28-32 weeks compared to full-term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age. PMID:10867619

Riezzo, G; Indrio, F; Montagna, O; Tripaldi, C; Laforgia, N; Chiloiro, M; Mautone, A

2000-06-01

28

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

PubMed Central

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

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

2008-01-01

29

The antisecretory factor: synthesis and intracellular localisation in porcine tissues  

Microsoft Academic Search

The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and

Stefan Lange; Eva Jennische; Ewa Johansson; Ivar Lönnroth

1999-01-01

30

Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.  

PubMed

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

Tradtrantip, Lukmanee; Namkung, Wan; Verkman, A S

2010-01-01

31

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

PubMed Central

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

Tradtrantip, Lukmanee; Namkung, Wan

2010-01-01

32

Environmental noise alters gastric myoelectrical activity: Effect of age  

Microsoft Academic Search

AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in random order, to three auditory stimuli (Hospital noise, conversation babble and traffic noise) after a 20-min baseline. All periods lasted 20 min and were

James S Castle; Jin-Hong Xing; Mark R Warner; Mark A Korsten

2007-01-01

33

Chemotherapy Is More Active against Proximal than Distal Gastric Carcinoma  

Microsoft Academic Search

Objective: Patients with localized proximal gastric carcinoma (PGC) have a poorer outcome than those with distal gastric carcinoma (DGC) following curative resection. However, it remains uncertain whether the location of the primary tumor influences the effect of chemotherapy in advanced gastric carcinoma. Methods: We assessed 270 eligible patients with unresectable, advanced gastric carcinoma who had received first-line chemotherapy between 1989

Katsuhiko Higuchi; Wasaburo Koizumi; Satoshi Tanabe; Katsunori Saigenji; Jaffer A. Ajani

2004-01-01

34

Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress  

PubMed Central

AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury. METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis. RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro. In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro. Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury. PMID:21876619

Singh, Laishram Pradeepkumar; Mishra, Amartya; Saha, Debjit; Swarnakar, Snehasikta

2011-01-01

35

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

PubMed Central

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

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

2015-01-01

36

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

Microsoft Academic Search

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

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

2007-01-01

37

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

Microsoft Academic Search

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

Li Sun; Xu Wang

2003-01-01

38

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

PubMed Central

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

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

2014-01-01

39

Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats  

PubMed Central

The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE2 production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes. PMID:23203107

Luiz-Ferreira, Anderson; Cola, Maira; Barbastefano, Victor; de-Faria, Felipe Meira; de Almeida, Ana Beatriz A.; Farias-Silva, Elisângela; Calvo, Tamara Regina; Hiruma-Lima, Clélia A.; Vilegas, Wagner; Souza-Brito, Alba Regina M.

2012-01-01

40

AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis.  

PubMed

Helicobacter pylori (H pylori), infecting half of the world's population, causes gastritis, duodenal and gastric ulcer, and gastric cancers. AMP-activated protein kinase (AMPK) is a highly conserved regulator of cellular energy and metabolism. Recent studies indicated an important role for AMPK in promoting cell survival. In this study, we discovered that H Pylori induced AMPK activation in transformed (GEC-1 line) and primary human gastric epithelial cells (GECs). Inhibition of H Pylori-stimulated AMPK kinase activity by AMPK inhibitor compound C exacerbated apoptosis in transformed and primary GECs. Meanwhile, downregulation of AMPK expression by targeted shRNAs promoted apoptosis in H pylori-infected GECs. In contrast, A-769662 and resveratrol, two known AMPK activators, or AMPK?1 over-expression, enhanced H Pylori-induced AMPK activation, and inhibited GEC apoptosis. Our data suggested that transforming growth factor-? (TGF-?)-activated kinase 1 (TAK1) could be the upstream kinase for AMPK activation by H pylori. Partial depletion of TAK1 by shRNAs not only inhibited AMPK activation, but also suppressed survival of H pylori-infected GECs. Taken together, these results suggest that TAK1-dependent AMPK activation protects GECs from H pylori-Induced apoptosis. PMID:25229685

Lv, Guoqiang; Zhu, Huanhuan; Zhou, Feng; Lin, Zhou; Lin, Gang; Li, Chenwan

2014-10-10

41

Gastroduodenal motor activity associated with gastric emptying rate in sheep.  

PubMed

1. Gastric emptying rate was calculated from dye dilution and was measured as the net flow over periods of 5 days through an electromagnetic probe inserted into a T-cannula, 5 cm beyond the pylorus in conscious hay-fed sheep. The net aboral flow was related to the motor activity of the antrum and duodenal bulb which was recorded via chronically fixed strain-gauge transducers. Nichrome wire electrodes were also implanted in order to quantify the electrical activity of the musculature associated with the abomasal outflow in sheep sustained on a liquid diet infused at fixed rates. 2. The abomasal outflow occurred as gushes of 2.1-9.2 ml associated with antroduodenal contractions during 90-95% of the recording time. In the sheep eating 0.7 kg/day hay, the daily outflow of chyme was 5.1 l which increased to 7.5 l of less viscous chyme when the sheep was fed 1 kg/day lucerne hay. During gastric infusion of 3.9 and 7.9 l of the liquid diet, the outflow was 5.7 and 8.3 l/day respectively of low-viscosity chyme propelled as gushes of 5.9-6.9 ml during 95% of the recording time. 3. Increasing the viscosity of the liquid diet with guar-gum caused a reduction in both antroduodenal motility and flow. Dilution of the liquid diet with saline doubled the flow as a result of an increase in the amplitude of the antral contractions. Circadian variations in outflow were also related to concomitant variations in antral motility. 4. It is concluded that the minute-to-minute flow rate of chyme through the pylorus could be satisfactorily measured at the duodenal bulb level and related to the motor activity of the antrum and duodenum. The rate of abomasal outflow depended primarily upon the strength of antral contractions, while the viscosity of the chyme also appeared capable of exerting a major influence on the outflow rate. PMID:3171986

Malbert, C H; Ruckebusch, Y

1988-07-01

42

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

PubMed

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

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

2013-01-01

43

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

PubMed Central

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

Shahrokhi, Nader; Keshavarzi, Zakieh; Khaksari, Mohammad

2015-01-01

44

GKN2 contributes to the homeostasis of gastric mucosa by inhibiting GKN1 activity.  

PubMed

Gastrokine 1 (GKN1) plays an important role in maintaining gastric mucosa integrity. Here, we investigated whether gastrokine 2 (GKN2) contributes to the homeostasis of gastric epithelial cells by regulating GKN1 activity. We analyzed cell viability, proliferation, and death in AGS cells transfected with GKN1, GKN2, GKN1 plus GKN2 using MTT, BrdU incorporation, and apoptosis assays, respectively. In addition, the expression levels of the cell cycle- and apoptosis-related proteins, miR-185, DNMT1, and EZH2 were determined. We also compared the expression of GKN1, GKN2, and CagA in 50 non-neoplastic gastric mucosae and measured GKN2 expression in 169 gastric cancers by immunohistochemistry. GKN2 inhibited anti-proliferative and pro-apoptotic activities, miR-185 induction, and anti-epigenetic modifications of GKN1. There was a positive correlation between GKN1 and GKN2 expression (P?=?0.0074), and the expression of GKN1, but not GKN2, was significantly lower in Helicobacter pylori CagA-positive gastric mucosa (P?=?0.0013). Interestingly, ectopic GKN1 expression in AGS cells increased GKN2 mRNA and protein expression in a time-dependent manner (P?=?0.01). Loss of GKN2 expression was detected in 126 (74.6%) of 169 gastric cancers by immunohistochemical staining and was closely associated with GKN1 expression and differentiation of gastric cancer cells (P?=?0.0002 and P?=?0.0114, respectively). Overall, our data demonstrate that in the presence of GKN2, GKN1 loses its ability to decrease cell proliferation, induce apoptosis, and inhibit epigenetic alterations in gastric cancer cells. Thus, we conclude that GKN2 may contribute to the homeostasis of gastric epithelial cells by inhibiting GKN1 activity. PMID:24151046

Kim, Olga; Yoon, Jung Hwan; Choi, Won Suk; Ashktorab, Hassan; Smoot, Duane T; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

2014-06-01

45

Aberrant DNA methylation and tumor suppressive activity of the EBF3 gene in gastric carcinoma.  

PubMed

The early B-cell factors (EBFs) are a group of four highly conserved DNA-binding transcription factors with an atypical zinc-finger and a helix-loop-helix domain. The EBF3 locus on chromosome 10q26.3 is epigenetically silenced or deleted in several types of cancers. In addition, EBF3 activates genes involved in cell cycle arrest and inhibits cell survival. However, inactivation of EBF3 gene expression was not fully studied in gastric carcinoma and the functions of EBF3 that underlie EBF3-regulated tumor suppression have not been identified. In our study, we found that inactivation of the EBF3 gene is frequently accompanied by promoter region hypermethylation in several gastric cancer cell lines and that the gene is reactivated by 5-aza-2'-deoxycytidine (5-aza-dc) and/or trichostatin A (TSA) in all ten gastric cancer cell lines. We performed functional analysis using small interfering RNA or expressional cDNA transfection in gastric cancer cell lines and demonstrate that EBF3 represses gastric cancer cell growth and migration, but activates cell cycle arrest and apoptosis. Promoter methylation of EBF3 was detected in 42/104 (40.4%) gastric cancer tissues but not in normal gastric tissues. Furthermore, promoter methylation of EBF3 was found to be significantly correlated with lymphatic invasion (p = 0.013) and poor survival (p = 0.038) in gastric carcinoma. These results suggest that EBF3 tumor suppressor is epigenetically silenced and that it serves as an independent prognostic marker in gastric carcinoma. PMID:21387304

Kim, Jin; Min, Sun Young; Lee, Hee Eun; Kim, Woo Ho

2012-02-15

46

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

PubMed Central

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

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

2012-01-01

47

Urokinase plasminogen activator receptor on invasive cancer cells: a prognostic factor in distal gastric adenocarcinoma.  

PubMed

Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. uPAR was expressed by neoplastic cells, macrophages, myofibroblasts and neutrophils in both intestinal and diffuse subtypes. No association was demonstrated between the expression of uPAR on cancer cells and histological subtype (p = 0.64) or TNM stage (p = 0.75). Univariate analysis revealed a significant association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor for overall survival in gastric cancer (HR = 2.39; 95% CI: 1.22-4.69; p = 0.011). In consequence, scoring of uPAR-positive cancer cells may be a direct measure for the invasive potential of gastric adenocarcinomas. PMID:21901747

Alpízar-Alpízar, Warner; Christensen, Ib Jarle; Santoni-Rugiu, Eric; Skarstein, Arne; Ovrebo, Kjell; Illemann, Martin; Laerum, Ole Didrik

2012-08-15

48

Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer  

PubMed Central

Background Helicobacter pylori (H. pylori) is the most important gastric carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis through STAT3 activation are largely unknown. We evaluated the effects of H. pylori infection on STAT3 activation and dissected the signalling network of STAT3 in H. pylori- infected gastric carcinogenesis. Methods The expression of phospho-STAT3 (pSTAT3) was evaluated by immunohistochemistry and western blot. Gene expression array and chromatin immunoprecipitation were used to dissect the STAT3 signalling network on H. pylori co-cultured AGS. Results pSTAT3 was significantly higher in H. pylori -positive gastritis than in H. pylori -negative gastritis ( P = 0.003). In addition, 98% of H. pylori positive intestinal metaplasia specimens showed STAT3 activation, whereas pSTAT3 was significantly decreased in all 43 specimens one year after H. pylori eradication ( P < 0.001). Moreover, pSTAT3 was only detected in the H. pylori -infected gastric tissues of mice but not in control mice. We further identified 6 candidates ( BRUNOL4, FGFR1, SHOX2, JAK3, MAPK8, and PDPN ) were directly up-regulated by H. pylori induced STAT3 activation. Conclusion H. pylori infection triggers the activation of STAT3 and de-regulates multitude of tumorigenic genes which may contribute to the initiation and progression of gastric cancer. PMID:25594045

Kang, Wei; Go, Minnie Y.; Tong, Joanna HM.; Ng, Enders KW.; Chiu, Philip WY.; Cheng, Alfred SL.; To, Ka Fai; Sung, Joseph JY.; Yu, Jun

2014-01-01

49

URG11 promotes gastric cancer growth and invasion by activation of ?-catenin signalling pathway  

PubMed Central

Abstract Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate ?-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and metastasis. URG11 was found to be highly expressed in gastric cancer tissues compared with adjacent nontumourous ones by immunohistochemical staining and western blot. Knockdown of URG11 expression by small interfering RNA (siRNA) effectively attenuated the proliferation, anchorage-independent growth, invasiveness and metastatic potential of gastric cancer cells. URG11 inhibition led to decreased expression of ?-catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and ?-catenin was observed in gastric cancer tissues. Transient transfection assays with the ?-catenin promoter showed that it was inhibited by URG11-specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of ?-catenin/TCF and its downstream effector genes, cyclinD1 and membrane type 1 matrix metallopeptidase (MT1-MMP), which are known to be involved in cell proliferation and invasion, respectively. Taken together, our data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of ?-catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer. PMID:19413886

Du, Rui; Xia, Lin; Sun, Shiren; Lian, Zhaorui; Zou, Xue; Gao, Juan; Xie, Huahong; Fan, Rui; Song, Jiugang; Li, Xiaohua; Liu, Jie; Fan, Daiming

2010-01-01

50

Clostridium difficile toxin A induces a specific antisecretory factor which protects against intestinal mucosal damage.  

PubMed Central

Peroral challenge with toxin A from Clostridium difficile induced the formation of antisecretory factor in rats. The animals were given 100 micrograms of the toxin, which was followed by a pronounced diarrhoea and by the appearance of antisecretory factor in the pituitary gland. In electrofocusing, the induced antisecretory factor separated in two peaks (pI 5.4 and 5.0); both fractions showed a lectin-like binding to agarose. The pI 5.4 fraction inhibited cholera toxin as well as toxin A induced fluid secretion, while pI 5.0 inhibited toxin A induced secretion only. Immunohistochemistry showed that an antisecretory factor of pI 5.0 protected the mucosa from the cytotoxic effect of toxin A, but did not affect the binding of toxin A to the intestinal epithelium. Sodium dodecyl-sulphate-polyacrylamide gel electrophoresis of the pI 5.0 protein showed two major fractions to be present, one of molecular weight 60 kDa, the other of 30 kDa, the latter probably being a degradation product of the former. Images Figure 3 PMID:1855687

Torres, J; Jennische, E; Lange, S; Lönnroth, I

1991-01-01

51

Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome  

Microsoft Academic Search

During the last 5 years important advances have occurred in the control of gastric acid hypersecretion in Zollinger-Ellison syndrome (ZES). The increased availability of potent gastric acid antisecretory agents such as histamine H2-receptor antagonists and more recently the H+K+-ATPase inhibitors such as omeprazole and lansoprazole have made it possible to medically control acid secretion in all patients. Increased understanding of

David C. Metz; Joseph R. Pisegna; Vitaly A. Fishbeyn; Richard V. Benya; Robert T. Jensen

1993-01-01

52

Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells  

PubMed Central

The gastric pathogen Helicobacter pylori (H. pylori) is linked to peptic ulcer and gastric cancer, but the relevant pathophysiological mechanisms are unclear. We now report that H. pylori stimulates the expression of plasminogen activator inhibitor (PAI)-1, urokinase plasminogen activator (uPA), and its receptor (uPAR) in gastric epithelial cells and the consequences for epithelial cell proliferation. Real-time PCR of biopsies from gastric corpus, but not antrum, showed significantly increased PAI-1, uPA, and uPAR in H. pylori-positive patients. Transfection of primary human gastric epithelial cells with uPA, PAI-1, or uPAR promoters in luciferase reporter constructs revealed expression of all three in H+/K+ATPase- and vesicular monoamine transporter 2-expressing cells; uPA was also expressed in pepsinogen- and uPAR-containing trefoil peptide-1-expressing cells. In each case expression was increased in response to H. pylori and for uPA, but not PAI-1 or uPAR, required the virulence factor CagE. H. pylori also stimulated soluble and cell surface-bound uPA activity, and both were further increased by PAI-1 knockdown, consistent with PAI-1 inhibition of endogenous uPA. H. pylori stimulated epithelial cell proliferation, which was inhibited by uPA immunoneutralization and uPAR knockdown; exogenous uPA also stimulated proliferation that was further increased after PAI-1 knockdown. The proliferative effects of uPA were inhibited by immunoneutralization of the EGF receptor and of heparin-binding EGF (HB-EGF) by the mutant diphtheria toxin CRM197 and an EGF receptor tyrosine kinase inhibitor. H. pylori induction of uPA therefore leads to epithelial proliferation through activation of HB-EGF and is normally inhibited by concomitant induction of PAI-1; treatments directed at inhibition of uPA may slow the progression to gastric cancer. PMID:18599586

Kenny, Susan; Duval, Cedric; Sammut, Stephen J.; Steele, Islay; Pritchard, D. Mark; Atherton, John C.; Argent, Richard H.; Dimaline, Rod; Dockray, Graham J.; Varro, Andrea

2008-01-01

53

Increased expression of the urokinase plasminogen activator system by Helicobacter pylori in gastric epithelial cells.  

PubMed

The gastric pathogen Helicobacter pylori (H. pylori) is linked to peptic ulcer and gastric cancer, but the relevant pathophysiological mechanisms are unclear. We now report that H. pylori stimulates the expression of plasminogen activator inhibitor (PAI)-1, urokinase plasminogen activator (uPA), and its receptor (uPAR) in gastric epithelial cells and the consequences for epithelial cell proliferation. Real-time PCR of biopsies from gastric corpus, but not antrum, showed significantly increased PAI-1, uPA, and uPAR in H. pylori-positive patients. Transfection of primary human gastric epithelial cells with uPA, PAI-1, or uPAR promoters in luciferase reporter constructs revealed expression of all three in H+/K+ATPase- and vesicular monoamine transporter 2-expressing cells; uPA was also expressed in pepsinogen- and uPAR-containing trefoil peptide-1-expressing cells. In each case expression was increased in response to H. pylori and for uPA, but not PAI-1 or uPAR, required the virulence factor CagE. H. pylori also stimulated soluble and cell surface-bound uPA activity, and both were further increased by PAI-1 knockdown, consistent with PAI-1 inhibition of endogenous uPA. H. pylori stimulated epithelial cell proliferation, which was inhibited by uPA immunoneutralization and uPAR knockdown; exogenous uPA also stimulated proliferation that was further increased after PAI-1 knockdown. The proliferative effects of uPA were inhibited by immunoneutralization of the EGF receptor and of heparin-binding EGF (HB-EGF) by the mutant diphtheria toxin CRM197 and an EGF receptor tyrosine kinase inhibitor. H. pylori induction of uPA therefore leads to epithelial proliferation through activation of HB-EGF and is normally inhibited by concomitant induction of PAI-1; treatments directed at inhibition of uPA may slow the progression to gastric cancer. PMID:18599586

Kenny, Susan; Duval, Cedric; Sammut, Stephen J; Steele, Islay; Pritchard, D Mark; Atherton, John C; Argent, Richard H; Dimaline, Rod; Dockray, Graham J; Varro, Andrea

2008-09-01

54

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

PubMed Central

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

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

2014-01-01

55

Ghrelin increases vagally-mediated gastric activity by central sites of action  

PubMed Central

Background Vagally dependent gastric reflexes are mediated through vagal afferent fibers synapsing upon neurons of the nucleus tractus solitarius (NTS) which, in turn modulate the preganglionic parasympathetic dorsal motor nucleus of the vagus (DMV) neurons within the medullary dorsal vagal complex (DVC). The expression and transport of ghrelin receptors has been documented for the afferent vagus nerve, and functional studies have confirmed that vagal pathways are integral to ghrelin-induced stimulation of gastric motility. However, the central actions of ghrelin within the DVC have not been explored fully. Methods We assessed the responses to ghrelin in fasted rats using: 1) in vivo measurements of gastric tone and motility following IVth ventricle application or unilateral microinjection of ghrelin into the dorsal vagal complex (DVC); and, 2) whole cell recordings from gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV) Results 1) IVth ventricle application or unilateral microinjection of ghrelin into the DVC elicited contractions of the gastric corpus via excitation of a vagal cholinergic efferent pathway; 2) Ghrelin facilitates excitatory, but not inhibitory, presynaptic transmission to DMV neurons. Conclusions Our data indicate that ghrelin acts centrally by activating excitatory synaptic inputs onto DMV neurons, resulting in increased cholinergic drive by way of vagal motor innervation to the stomach. PMID:24261332

Swartz, Emily M.; Browning, Kirsteen N.; Travagli, R. Alberto; Holmes, Gregory M.

2014-01-01

56

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

PubMed Central

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

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

2013-01-01

57

Sensitivity and Specificity of Hypnosis Effects on Gastric Myoelectrical Activity  

PubMed Central

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

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

2013-01-01

58

Systemic activation of K-ras rapidly induces gastric hyperplasia and metaplasia in mice  

PubMed Central

Mouse models with conditional activation of K-ras (K-rasG12D) are used widely to investigate the role of oncogenic K-ras in a tissue-specific manner. However, the effect of ubiquitous activation of K-ras in adult mice has not been well studied. Herein, we report that systemic activation of K-ras in mice leads to rapid changes in gastric cellular homeostasis. Conditional activation of K-ras results in activation of the MAPK pathway and hyperproliferation of squamous epithelium in the forestomach and metaplasia in the glandular stomach. Parietal cells almost completely disappear from the upper part of the stomach adjacent to forestomach of K-ras activated mice. CDX2, a caudal-related homeobox transcription factor normally expressed in the intestine, is upregulated in parts of the stomach, following activation of K-ras in mice. Cyclooxygenase 2 (COX-2), a mediator of inflammation, is also upregulated in parts of the stomach of the K-ras activated mice with concomitant infiltration of hematopoietic cells in the hyperplastic tissue. Moreover, in K-ras activated mice, the expression of putative progenitor cell marker Dcamkl1 is upregulated in the glandular stomach. Expression of CD44, a candidate stomach cancer stem cell marker, is also increased in forestomach and the glandular stomach. These results suggest that cells of the stomach, potentially stem or progenitor cells, are highly susceptible to K-ras activation-induced initiation of gastric precancerous lesions. The histological changes in the K-ras activated mice resemble the pre-neoplastic changes that take place during gastric carcinogenesis in humans. Thus, a mouse model with systemic K-rasG12D activation could be useful for studying the early molecular events leading to gastric carcinogenesis. PMID:21761008

Matkar, Smita S; Durham, Amy; Brice, Angela; Wang, Timothy C; Rustgi, Anil K; Hua, Xianxin

2011-01-01

59

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

PubMed Central

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

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

2014-01-01

60

Anti-cancer activity of DHA on gastric cancer--an in vitro and in vivo study.  

PubMed

Treatment of gastric cancer remains a major challenge, and new anticancer drugs are urgently required. This study investigated whether dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, could inhibit the growth of gastric cancer both in vitro and in vivo. A series of in vitro experiments including MTT, colony-forming, wound healing, invasion, cell cycle, cellular senescence, and apoptosis assays were performed to examine the antiproliferative and antimetastatic effects of DHA on three gastric cancer cell lines, SGC-7901, BGC823, and MGC803. The result showed that the proliferation rate and colony-forming abilities of gastric cancer cells were significantly suppressed by DHA together with significant suppression of the expressions of proliferation markers (PCNA, cyclin E, and cyclin D1), and upregulation of p21 and p27. Moreover, DHA induced cellular senescence, G1 phase cell cycle arrest and hindered the migration and invasion of gastric cancer cells corresponding with downregulation of MMP-9 and MMP-2. Furthermore, DHA significantly induced apoptosis through suppressing Bcl-2 as well as activating caspase-9 and PARP. Treatment of gastric cancer cells with DHA increased miR-15b and miR-16 expression, caused a downregulation of Bcl-2, resulting in apoptosis of gastric cancer cells. In vivo, our data showed that DHA significantly inhibited the growth of SGC7901 cell-transplanted tumors. In summary, we have shown that DHA is able to inhibit the growth and metastasis of human gastric cancer. The modulation of miR-15b and miR-16 mediated the apoptosis effects of DHA in gastric cancer cells. Our work suggested that DHA has significant anticancer effects against gastric cancer both in vivo and in vitro, indicating that it is a promising therapy for human gastric cancer. PMID:23907579

Sun, Haijun; Meng, Xianzhi; Han, Jihua; Zhang, Zhe; Wang, Bing; Bai, Xuedong; Zhang, Xin

2013-12-01

61

Gastroprotective activity of FRG-8813, a novel histamine H2-receptor antagonist, in rats.  

PubMed

FRG-8813 ((+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2- pyridyl]oxy-(Z)-2-butenyl]acetamide) is a novel histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activities. The present study was designed to investigate the property of gastroprotective action. The oral ED50 values for inhibition of mucosal lesions against 1% NH3-, 60% ethanol in 0.15 N HCl-, 100% ethanol-, 0.6 N HCl- and sodium taurocholate in 0.4 N HCl-induced damage were 3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective despite pretreatment with omeprazole, suggesting that the protective effect is independent of its antisecretory activity. It is unlikely that FRG-8813 works as a mild irritant because it showed a gastroprotective effect after intraperitoneal injection, but oral administration itself did not influence the rat gastric mucosa. Although pretreatment with indomethacin or N-ethylmaleimide did not affect the gastroprotection of FRG-8813, chemical deafferentation induced by capsaicin abolished the gastroprotection. Furthermore, prior administration of tetrodotoxin, the calcitonin gene-related peptide (CGRP) antagonist hCGRP or NG-nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither enhanced the susceptibility of the mucosa to damage nor affected the gastroprotective action of short-term treatment. In conclusion, these results suggest that FRG-8813 has gastroprotective activity independently of acid antisecretory activity and that capsaicin-sensitive nerves may be partially or fully involved in the gastroprotective mechanisms of FRG-8813. PMID:7563973

Onodera, S; Shibata, M; Tanaka, M; Inaba, N; Yamaura, T; Ohnishi, H

1995-06-01

62

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

SciTech Connect

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.

Pai, Rama [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States)]. E-mail: rpai@uci.edu; Lin Cal [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States); Tran, Teresa [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States); Tarnawski, Andrzej [Medical Service, Department of Veterans Affairs Medical Center, Long Beach, California, Department of Medicine, University of California, Irvine (United States)]. E-mail: atarnawski@yahoo.com

2005-06-17

63

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

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

64

Antiulcer and in vitro antioxidant activities of Jasminum grandiflorum L.  

PubMed

The study was aimed at evaluating the antiulcer and antioxidant activities of 70% ethanolic axtract of leaves of Jasminum grandiflorum L. (JGLE). The leaves of Jasminum grandiflorum L. (Family: Oleaceae) is used in folk medicine for treating ulcerative stomatitis, skin diseases, ulcers, wounds, corns - a hard or soft hyperkeratosis of the sole of the human foot secondary to friction and pressure (Stedman's Medical Dictionary, 28th ed. Lippincott Williams & Wilkins, Philadelphia. p. 443), etc., Antiulcerogenic activity of JGLE (100 and 200 mg/kg, b.w., orally) was evaluated employing aspirin + pylorus ligation (APL) and alcohol (AL) induced acute gastric ulcer models and ulcer-healing activity using acetic acid-induced (AC) chronic ulcer model in rats. Both the antisecretory and cytoprotection hypothesis were evaluated. The antioxidant activity of JGLE has been assayed by using in vitro methods like 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH) assay, reductive ability, superoxide anion scavenging activity, nitric oxide scavenging activity and total phenolic content, in order to explain the role of antioxidant principles in the antiulcerogenic activity of the extract. There was a significant (P<0.01) dose-dependent decrease in the ulcerative lesion index produced by all the three models in rats as compared to the standard drug famotidine (20 mg/kg, b.w. orally). The reduction in gastric fluid volume, total acidity and an increase in the pH of the gastric fluid in APL rats proved the antisecretory activity of JGLE. Additionally, JGLE completely healed the ulcer within 20 days of treatment in AC model as evidenced by histopathological studies. Like antiulcer activity, the free radical scavenging activities of JGLE depends on concentration and increased with increasing amount of the extract. These results suggest that leaves of Jasminum grandiflorum possess potential antiulcer activity, which may be attributed to its antioxidant mechanism of action. PMID:17125945

Umamaheswari, M; Asokkumar, K; Rathidevi, R; Sivashanmugam, A T; Subhadradevi, V; Ravi, T K

2007-04-01

65

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

PubMed Central

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 in gastric cancer (GC), activated Notch1 has been associated with de-differentiation of lineage-committed stomach cells into stem progenitors and GC progression. However, the specific role of the Notch1 ligand (DLL1) in GC has not yet been elucidated. To assess the role of DLL1 in GC cancer, the expression of Notch1 and its ligands DLL1 and Jagged1, was analyzed in 8 gastric cancer cell lines (KATOIII, SNU601, SNU719, AGS, SNU16, MKN1, MKN45, TMK1). DLL1 expression was absent in KATOIII, SNU601, SNU719 and AGS. The lack of DLL1 expression in these cells was associated with promoter hypermethylation and 5-aza-2’deoxycitidine caused up-regulation of DLL1. The increase in DLL1 expression was associated with activation of Notch1 signalling, with an increase in cleaved Notch1 intracellular domain (NICD) and Hes1, and down-regulation in Hath1. Concordantly, Notch1 signalling was activated with the overexpression of DLL1. Moreover, Notch1 signalling together with DLL1 methylation were evaluated in samples from 52 GC patients and 21 healthy control as well as in INS-GAS mice infected with H. pylori and randomly treated with eradication therapy. In GC patients, we found a correlation between DLL1 and Hes1 expression, while DLL1 methylation and Hath1 expression were associated with the diffuse and mixed type of gastric cancer. Finally, none of the samples from INS-GAS mice infected with H. pylori, a model of intestinal-type gastric tumorigenesis, showed promoter methylation of DLL1. This study shows that Notch1 activity in gastric cancer is controlled by the epigenetic silencing of the ligand DLL1, and that Notch1 inhibition is associated with the diffuse type of gastric cancer. PMID:22249198

Piazzi, Giulia; Fini, Lucia; Selgrad, Michael; Garcia, Melissa; Daoud, Yahya; Wex, Thomas; Malfertheiner, Peter; Gasbarrini, Antonio; Romano, Marco; Meyer, Richard L.; Genta, Robert M.; Fox, James G.; Boland, C. Richard; Bazzoli, Franco; Ricciardiello, Luigi

2011-01-01

66

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

SciTech Connect

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.

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

1986-03-05

67

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

PubMed Central

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

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

2014-01-01

68

Regulation of Gastric Electrical and Mechanical Activity by Cholinesterases in Mice  

PubMed Central

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

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

2015-01-01

69

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

PubMed

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

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

2015-06-01

70

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

PubMed Central

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

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

2011-01-01

71

Interaction of indomethacin and naproxen with gastric surface-active phospholipids: a possible mechanism for the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) ? ? Prof. J. Delattre, personal communication  

Microsoft Academic Search

The possibility that the molecular mechanism underlying the topical gastric irritancy of nonsteroidal anti-inflammatory drugs (NSAIDs) may involve alterations in the surface-active properties of gastric phospholipids was investigated. Indomethacin and naproxen were intragastrically administered to rats and the hydrophobicity of the luminal surface of the stomach wall was assessed by contact angle analysis. Both NSAIDs have the ability to attenuate

Marie-Noëlle Giraud; Claude Motta; Jimmy J. Romero; Gilles Bommelaer; Lenard M. Lichtenberger

1999-01-01

72

Gastric parietal cell secretory membrane contains PKA- and acid-activated Kir2.1 K+ channels.  

PubMed

Our objective was to identify and localize a K+ channel involved in gastric HCl secretion at the parietal cell secretory membrane and to characterize and compare the functional properties of native and recombinant gastric K+ channels. RT-PCR showed that mRNA for Kir2.1 was abundant in rabbit gastric mucosa with lesser amounts of Kir4.1 and Kir7.1, relative to beta-actin. Kir2.1 mRNA was localized to parietal cells of rabbit gastric glands by in situ RT-PCR. Resting and stimulated gastric vesicles contained Kir2.1 by Western blot analysis at approximately 50 kDa as observed with in vitro translation. Immunoconfocal microscopy showed that Kir2.1 was present in parietal cells, where it colocalized with H+ -K+ -ATPase and ClC-2 Cl- channels. Function of native K+ channels in rabbit resting and stimulated gastric mucosal vesicles was studied by reconstitution into planar lipid bilayers. Native gastric K+ channels exhibited a linear current-voltage relationship and a single-channel slope conductance of approximately 11 pS in 400 mM K2SO4. Channel open probability (Po) in stimulated vesicles was high, and that of resting vesicles was low. Reduction of extracellular pH plus PKA treatment increased resting channel Po to approximately 0.5 as measured in stimulated vesicles. Full-length rabbit Kir2.1 was cloned. When stably expressed in Chinese hamster ovary (CHO) cells, it was activated by reduced extracellular pH and forskolin/IBMX with no effects observed in nontransfected CHO cells. Cation selectivity was K+ = Rb+ > Na+ = Cs+ = Li+ = NMDG+. These findings strongly suggest that the Kir2.1 K+ channel may be involved in regulated gastric acid secretion at the parietal cell secretory membrane. PMID:14602583

Malinowska, Danuta H; Sherry, Ann M; Tewari, Kirti P; Cuppoletti, John

2004-03-01

73

Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population  

Microsoft Academic Search

BACKGROUND: Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by ?-radiation. METHODS: To explore this hypothesis, 246

Xianli He; Qing Qiao; Naijian Ge; Jing Nan; Shuqun Shen; Zizhong Wang; Yefa Yang; Guoqiang Bao

2010-01-01

74

Effects of genomic imbalances on telomerase activity in gastric cancer: clues to telomerase regulation.  

PubMed

Telomerase is a specialized cellular reverse transcriptase that adds telomeric repeats (TTAGGG) at the ends of each chromosome. Nearly the complete spectrum of human cancers has been shown to be telomerase positive. The understanding of the telomerase regulation in concert with other genetic alterations in the process of malignant transformation of human cells has important clinical and practical implications. Regulation of telomerase activity (TA) is highly complex, and both putative positive and negative regulators have been reported. However, the mechanisms involved in telomerase regulation are not fully established. Identification of additional telomerase components and associated proteins will certainly contribute to further investigations of the effect of telomerase in telomere elongation, telomere length maintenance, oncogenesis, and functionally new, unidentified cellular functions. In this study our aim was to determine the chromosomal localizations of putative unidentified telomerase activator(s) and/or repressor(s) by high resolution-comparative genomic hybridization (HR-CGH) in highly telomerase expressing gastric tumor samples. For this purpose TAs and genomic imbalances were identified in the same tumor samples and relation between these was evaluated. Genomic changes affecting telomerase activity in 50 gastric tumor samples were investigated by HR-CGH. We have found that genomic imbalances including 1q+, 8p+, 8q+, 10q+, 17p-, and 20p+ are associated with the higher telomerase activity. Our results suggest that 1q24, 8p21-p11.2, 8q21.1-q23, 10q21-qter and 20pter-p11.2 may contain putative telomerase activator(s), whereas the 17p12 region may harbor candidate telomerase suppressor(s). PMID:19725225

Gümü?-Akay, Güvem; Elhan, Atilla Halil; Unal, Ali Ekrem; Demirkazik, Ahmet; Sunguro?lu, Asuman; Tükün, Ajlan

2009-01-01

75

Activation of epidermal growth factor receptor signaling by the prostaglandin E(2) receptor EP4 pathway during gastric tumorigenesis.  

PubMed

Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis through prostaglandin E(2) (PGE(2)) biosynthesis. It has been shown by in vitro studies that PGE(2) signaling transactivates epidermal growth factor receptor (EGFR) through an intracellular mechanism. However, the mechanisms underlying PGE(2)-induced EGFR activation in in vivo tumors are still not fully understood. We previously constructed transgenic mice that develop gastric tumors caused by oncogenic activation and PGE(2) pathway induction. Importantly, expression of EGFR ligands, epiregulin, amphiregulin, heparin-binding EGF-like growth factor, and betacellulin, as well as a disintegrin and metalloproteinases (ADAMs), ADAM8, ADAM9, ADAM10, and ADAM17 were significantly increased in the mouse gastric tumors in a PGE(2) pathway-dependent manner. These ADAMs can activate EGFR by ectodomain shedding of EGFR ligands. Notably, the extensive induction of EGFR ligands and ADAMs was suppressed by inhibition of the PGE(2) receptor EP4. Moreover, EP4 signaling induced expression of amphiregulin and epiregulin in activated macrophages, whereas EP4 pathway was required for basal expression of epiregulin in gastric epithelial cells. In contrast, ADAMs were not induced directly by PGE(2) in these cells, suggesting indirect mechanism possibly through PGE(2)-associated inflammatory responses. These results suggest that PGE(2) signaling through EP4 activates EGFR in gastric tumors through global induction of EGFR ligands and ADAMs in several cell types either by direct or indirect mechanism. Importantly, gastric tumorigenesis of the transgenic mice was significantly suppressed by combination treatment with EGFR and COX-2 inhibitors. Therefore, it is possible that inhibition of both COX-2/PGE(2) and EGFR pathways represents an effective strategy for preventing gastric cancer. PMID:21205091

Oshima, Hiroko; Popivanova, Boryana K; Oguma, Keisuke; Kong, Dan; Ishikawa, Tomo-o; Oshima, Masanobu

2011-04-01

76

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

PubMed

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

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

2015-01-01

77

Activated CD8+ T cells contribute to clearance of gastric Cryptosporidium muris infections.  

PubMed

The role of CD4+ and CD8+ T lymphocytes in the development of a protective immune response against Cryptosporidium muris infection was studied by the reconstitution of severe combined immunodeficient (SCID) mice with well-defined populations of either naive or immune CD8+ or CD4+ T lymphocytes. Adoptive transfer of both naive and immune CD4+ T lymphocyte subpopulations protects SCID mice against cryptosporidiosis. Moreover, a significant biological impact of activated CD8+ T cells against gastric cryptosporidiosis was observed. The significant difference in the course and intensity of the infection in reconstituted SCID mice was found to be dependent on the protective function of both the CD4+ and CD8+ T-cell populations transferred. While SCID mice reconstituted with either immune or naive CD4+ or immune CD8+ T-cell subpopulations resolved the infection within 29, 37 and 51 days post-infection, respectively, those reconstituted with naive CD8+ T cells suffered from chronic infection similar to control SCID mice. Reconstitution with CD4+ T cells resulted in suppression of oocyst excretion and shortening of patent period in comparison with SCID mice reconstituted with CD8+ T cells. Thus, although CD4+ T cells are considered important in protective immunity, our results are the first to demonstrate the involvement of activated CD8+ T lymphocytes in the protection of mice against gastric cryptosporidiosis. PMID:21204850

Kvá?, M; Kodádková, A; Sak, B; Kv?to?ová, D; Jalovecká, M; Rost, M; Salát, J

2011-04-01

78

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

PubMed Central

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

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

2015-01-01

79

Evaluation of the antipeptic ulcer activity of the leaf extract of Plantago lanceolata L. in rodents.  

PubMed

The effect of the leaf extract of Plantago lanceolata L. (Plantaginaceae) on gastric secretion and cytoprotection was evaluated using different models of gastroduodenal ulcer, including acetic acid induced chronic gastric ulcer, indomethacin induced gastric ulcer, cysteamine induced duodenal ulcer and pylorus ligation induced gastric ulcer. The aqueous extract was administered at 200?mg/kg and 400?mg/kg and 140?mg/kg and 280?mg/kg for mice and rats, respectively, and compared with vehicle or the standard, ranitidine (50 or 70?mg/kg) or misopristol (280??g/kg). In addition, activity of the mucilage (172?mg/kg) was also evaluated in acetic acid induced chronic gastric ulcer. Administration was done orally except in pylorus ligation, where the intraduodenal route was used. In all cases, higher doses of the extract provided better protection than lower doses and the mucilage, hinting at a dose-dependent effect. Whilst higher doses of the extract showed a better healing of the ulcer as well as protection in indomethacin and pylorus ligation models, activities of lesser magnitude than ranitidine were noted in the cysteamine model. Together these findings indicate that higher doses used in the present study provided an overall better protection against gastroduodenal ulcers than the standard drugs employed through antisecretory and cytoprotective mechanisms. PMID:21298726

Melese, Endale; Asres, Kaleab; Asad, Mohammed; Engidawork, Ephrem

2011-08-01

80

Comparison and Analysis of Inter-Subject Variability of Simulated Magnetic Activity Generated from Gastric Electrical Activity  

PubMed Central

Electrogastrograms (EGGs) produced from gastric electrical activity (GEA) are used as a non-invasive method to aid in the assessment of a subject’s gastric condition. It has been documented that recordings of the magnetic activity generated from GEA are more reliable. Typically, with magnetic measurements of GEA, only activity perpendicular to the body is recorded. Also, external anatomical landmarks are used to position the magnetic recording devices, SQUIDs, (Superconducting Quantum Interference Devices) over the stomach with no allowance made for body habitus. In the work presented here, GEA and its corresponding magnetic activity are simulated. Using these data, we investigate the effects of using a standard SQUID location as well as a customized SQUID position and the contribution the magnetic component perpendicular to the body makes to the magnetic field. We also explore the effects of the stomach wall thickness on the resultant magnetic fields. The simulated results show that the thicker the wall, the larger the magnitude of the magnetic field holding the same signal patterns. We conclude that most of the magnetic activity arising from GEA occurs in a plane parallel to the anterior body. We also conclude that using a standard SQUID position can be suboptimal. PMID:18330701

Komuro, Rie; Cheng, Leo K.; Pullan, Andrew J.

2014-01-01

81

Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets  

PubMed Central

AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets. METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H+-K+-ATPase mRNA in gastric mucosa. H+-K+-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H+-K+-ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H+-K+-ATPase and somatostatin (SS) as well as the H+-K+-ATPase activity were determined. RESULTS: in vivo, both mRNA expression and activity of H+-K+-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H+-K+-ATPase was affected significantly by weaning. CS increased the mRNA expression of H+-K+-ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H+-K+-ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H+-K+-ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H+-K+-ATPase expression: P=0.03; H+-K+-ATPase activity: P = 0.014) and high concentrations (H+-K+-ATPase expression: P=0.017; H+-K+-ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H+-K+-ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H+-K+-ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells. CONCLUSION: No significant changes are observed in mRNA expression and activity of H+-K+-ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H+-K+-ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H+-K+-ATPase expression and activity in weaning piglets. PMID:16425370

Shi, Zhi-Min; Du, Gai-Mei; Wei, Xi-Hui; Zhang, Lei; Chen, Jie; Zhao, Ru-Qian

2005-01-01

82

Effect of folic acid supplementation on oxidative gastric mucosa damage and acid secretory response in the rat  

PubMed Central

Objective: This study investigated the antioxidative and antisecretory properties of folic acid in the rats’ stomach. Materials and Methods: Male Wistar rats were treated with 2 mg/kg diet of folic acid for 21 days. Gastric ulceration was induced by indomethacin, scored, and assayed to determine the concentration of total protein, mucus, malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) in homogenized samples. Normal saline and Ranitidine treated group served as negative and positive control, respectively. Basal and stimulated acid secretion was measured by continuous perfusion method. Result: Indomethacin caused severe damage to the rats’ stomach with an ulcer index of 4.32 ± 0.13, increase in MDA concentration and reduction in the concentration of protein, mucus, catalase and superoxide dismutase (P < 0.001). Pre-treatment with folic acid prevented the formation of ulcers by 32%, and attenuated the inhibition of mucus by 14%, CAT, 51% and SOD, 150%. Ranitidine afforded 56% prevention in ulcer formation with 67%, 55% and 78% attenuation of the inhibition of mucus, CAT and SOD, respectively, by indomethacin. While indomethacin-induced lipid peroxidation was attenuated by 58% reduction in MDA concentration on pretreatment with folic acid, Ranitidine offered 65% reduction. Basal and stimulated acid secretions were significantly reduced in the treated when compared with control animals. Folic acid produced a 21% reduction in the basal acid output when compared with the control animals (P < 0.05), and 140% reduction in histamine-induced acid response. Conclusion: The results indicate the gastroprotective activity of folic acid due its antioxidative and anti-secretory properties. PMID:22022004

Ajeigbe, K. O.; Olaleye, S. B.; Oladejo, E. O.; Olayanju, A. O.

2011-01-01

83

3,3'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway.  

PubMed

Recent studies have revealed that 3,3-diindolylmethane (DIM) has antitumor effects in both in vivo and in vitro tumor models. However, the biological function of DIM in human gastric cancer cells is unknown. Genetic and biological studies have confirmed the importance of the novel Hippo tumor-suppressor pathway in regulating cell proliferation, apoptosis, organ size and tumorigenesis in mammals. Thus, the purpose of this study was to investigate the cytotoxic effects of DIM in human gastric cancer cells and to elucidate whether DIM induces cell death by activating the Hippo signaling pathway. Two human gastric cancer cell lines (SNU-1 and SNU-484) were used to investigate the DIM response. DIM significantly inhibited the proliferation of human gastric cancer cells in a dose-dependent manner. The percentage of G1 phase cells increased 24 h following DIM treatment. DIM reduced CDK2, CDK4, CDK6 and cyclin D1 protein levels, while increasing p53 protein levels. DIM induced the levels of cleaved poly(ADP-ribose) polymerase, cleaved-caspase-9, and diminished pro-caspase-3 protein production. In addition, DIM increased pLATS1, Mob1, pMob1, pYAP and Ras association domain family 1 (RASSF1) protein levels and reduced Yap protein production levels. DIM stimulated the binding of RASSF1 with the Mst1/2-LATS1-Mob1 complex, promoting an active Hippo signaling pathway and favoring YAP phosphorylation (pYAP) that inactivates cell proliferation. Furthermore, DIM inhibited the growth of human gastric tumors in a xenograft mouse model. These results indicate that DIM suppresses the growth of gastric cancer cells by activating the Hippo signaling pathway. PMID:24008339

Li, Xiu Juan; Park, Eun Sung; Park, Man Hee; Kim, Soo Mi

2013-11-01

84

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

PubMed Central

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

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

2012-01-01

85

MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells  

PubMed Central

HER2 amplification is found in >15% of gastric cancers (GC), and is associated with poor clinical outcome. Lapatinib, a dual HER2 and EGFR tyrosine kinase inhibitor, has shown promising in-vitro results in treating HER2+ cancer cells. However, several studies have shown that activation of alternative receptor tyrosine kinases can mediate resistance to HER-targeted therapy. Here we investigated whether activated MET can confer resistance to lapatinib inhibition of GC cells. A panel of gastric cancer cell lines were treated with lapatinib and we observed that cell proliferation was reduced by 70% and that the degree of HER2 amplification corresponds to sensitivity to lapatinib. Immunoblotting analysis indicated that phosphorylation of HER2, EGFR, MET, AKT and ERK were inhibited by lapatinib and presumably led to cell cycle arrest as observed using flow cytometry. HGF activation of MET receptors rescued cells from lapatinib-induced growth inhibition by re-stimulating the downstream pathways and restoring normal cell cycle progression. This rescue effect could be abrogated by inhibiting MET using PHA-665752 (a highly specific MET inhibitor), or downregulating MET expression with siRNA. No synergy in growth inhibition was observed when cells were treated with a combination of lapatinib and PHA-665752. Repeat studies using insulin-like growth factor 1 and fibroblast growth factor 3 could not uniformly rescue the lapatinib treated GC cells. In conclusion, HGF/MET mediated resistance to lapatinib is a novel mechanism of resistance to HER2-targeted agents in GC cells. Development of inhibitors targeting multiple receptors or common downstream signaling proteins merits further investigation. PMID:22238368

Chen, Chin-Tung; Kim, Hyaehwan; Liska, David; Gao, Sizhi; Christensen, James G.; Weiser, Martin R.

2014-01-01

86

TFF1 activates p53 through down-regulation of miR-504 in gastric cancer.  

PubMed

The expression of TFF1 is frequently down-regulated in human gastric cancer whereas its knockout leads to the development of gastric adenomas and carcinomas in mouse models. The molecular mechanisms underlying the TFF1 tumor suppressor functions remain unclear. In this study, we demonstrate, using colony formation assay and Annexin V staining, that reconstitution of TFF1 expression in gastric cancer cell models suppresses cell growth and promotes cell death. Furthermore, using a tumor xenograft mouse model of gastric cancer, we demonstrated that reconstitution of TFF1 suppresses tumor growth in vivo. The results from PG13-luciferase reporter assay and Western blot analysis indicated that TFF1 promotes the expression and transcription activity of p53 protein. Further analysis using cycloheximide-based protein assay and quantitative real-time PCR data suggested that TFF1 does not interfere with p53 mRNA levels or protein stability. Alternatively, we found that the reconstitution of TFF1 down-regulates miR-504, a negative regulator of p53. Western blot analysis data demonstrated that miR-504 abrogates TFF1-induced p53 protein expression and activity. In conclusion, the in vitro and in vivo data demonstrate, for the first time, a novel mechanism by which the tumor suppressor functions of TFF1 involve activation of p53 through down-regulation of miR-504. PMID:25015107

Soutto, Mohammed; Chen, Zheng; Saleh, Mohamed A; Katsha, Ahmed; Zhu, Shoumin; Zaika, Alexander; Belkhiri, Abbes; El-Rifai, Wael

2014-07-30

87

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

PubMed Central

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

Indrio, Flavia

2013-01-01

88

Inhibition of histone deacetylase activity down-regulates urokinase plasminogen activator and matrix metalloproteinase-9 expression in gastric cancer.  

PubMed

Histone acetylation and deacetylaion play important roles in chromatin remodeling and gene expression. An imbalance of these reactions leads to aberrant behavior of the cells in the cell cycle, which in turn contributes to carcinogenesis. Histone deacetylase (HDAC) inhibitors have been shown to have anti-tumor effects in clinical trials. However, the exact mechanisms by which HDAC inhibitors exert anti-tumor effects and modulate gene expression are not completely understood, and remain a subject of intense investigation. In the current study, we determined whether HDACs regulate urokinase plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and tumor invasion. Using cDNA microarray analysis, we found that hepatocyte growth factor (HGF) induced HDAC5 expression in gastric cancer cell lines, NUGC-3 and MKN-28. TSA, a HDAC inhibitor, decreased HGF-induced HADC-5 expression and also repressed uPA and MMP-9 expression. TSA inhibited cell proliferation in both cell lines. In vitro Matrigel invasion assays showed that the HDAC inhibitor decreased cancer cell invasion. Furthermore, GO6976, a PKC inhibitor, significantly inhibited not only HGF-induced HDAC5 expression but also cell invasion. These results demonstrated that HDACs regulate HGF-induced uPA and MMP-9 expression through a PKC-dependent signal pathway in gastric cancer cells. Our data probably suggest that such activities serve as anti-tumor mechanisms of the HDAC inhibitor. PMID:20559690

Lee, Kyung Hee; Choi, Eun Young; Kim, Min Kyoung; Kim, Kyeong Ok; Jang, Byung Ik; Kim, Se Won; Kim, Sang Woon; Song, Sun Kyo; Kim, Jae-Ryong

2010-10-01

89

Notch4 promotes gastric cancer growth through activation of Wnt1/?-catenin signaling.  

PubMed

Gastric cancer (GC) is one of the most common cancers and lethal malignancies in the world. Discovering novel biomarkers that correlate with GC may provide opportunities to reduce the severity of GC. As one of Notch receptor family members in mammals, Notch4 plays an important role in carcinogenesis of several tumors. However, the precise function and mechanism of Notch4 in GC remain undefined. To address this question, we investigated whether Notch4 could be involved in GC progression. We found that Notch4 was activated by overexpressing exogenous intracellular domain of Notch4 (ICN4), and Notch4 activation promoted GC growth in vitro and in vivo, while Notch4 inhibition using ICN4 siRNA had opposite effects. In addition, Notch4 activation induced expression and activation of Wnt1, ?-catenin and downstream target genes, c-Myc and cyclin D1, in GC cells, while Notch4 inhibition had opposite effects. Moreover, ?-catenin depletion by siRNA attenuated cell proliferation induced by Notch4 activation. Therefore, our results revealed that Notch4 activates Wnt1/?-catenin signaling to regulate GC growth. PMID:25511451

Qian, Cuijuan; Liu, Fuqiang; Ye, Bei; Zhang, Xin; Liang, Yong; Yao, Jun

2015-03-01

90

miR-30b, Down-Regulated in Gastric Cancer, Promotes Apoptosis and Suppresses Tumor Growth by Targeting Plasminogen Activator Inhibitor-1  

PubMed Central

Background Gastric cancer is one of the most common malignant diseases worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with tumor development and progression. Our previous studies have revealed that H. pylori infection was able to induce the altered expression of miR-30b in gastric epithelial cells. However, little is known about the potential role of miR-30b in gastric cancer. Methods We analyzed the expression of miR-30b in gastric cancer cell lines and human gastric cancer tissues. We examined the effect of miR-30b mimics on the apoptosis of gastric cancer cells in vitro by flow cytometry (FCM) and caspase-3/7 activity assays. Nude mouse xenograft model was used to determine whether miR-30b is involved in tumorigenesis of gastric cancer. The target of miR-30b was identified by bioinformatics analysis, luciferase assay and Western blot. Finally, we performed the correlation analysis between miR-30b and its target expression in gastric cancer. Results miR-30b was significantly down-regulated in gastric cancer cells and human gastric cancer tissues. Enforced expression of miR-30b promoted the apoptosis of gastric cancer cells in vitro, and miR-30b could significantly inhibit tumorigenicity of gastric cancer by increasing the apoptosis proportion of cancer cells in vivo. Moreover, plasminogen activator inhibitor-1 (PAI-1) was identified as the potential target of miR-30b, and miR-30b level was inversely correlated with PAI-1 expression in gastric cancer. In addition, silencing of PAI-1 was able to phenocopy the effect of miR-30b overexpression on apoptosis regulation of cancer cells, and overexpression of PAI-1 could suppressed the effect of promoting cell apoptosis by miR-30b, indicating PAI-1 is potentially involved in miR-30b-induced apoptosis on cancer cells. Conclusion miR-30b may function as a novel tumor suppressor gene in gastric cancer by targeting PAI-1 and regulating the apoptosis of cancer cells. miR-30b could serve as a potential biomarker and therapeutic target against gastric cancer. PMID:25170877

Zhu, En-Dong; Li, Na; Li, Bo-Sheng; Li, Wei; Zhang, Wei-Jun; Mao, Xu-Hu; Guo, Gang; Zou, Quan-Ming; Xiao, Bin

2014-01-01

91

STAT3 activation in tumor cell-free lymph nodes predicts a poor prognosis for gastric cancer  

PubMed Central

STAT3 is constitutively activated in many human cancers including gastric cancer and plays crucial roles in modulating cancer cell proliferation, survival, metastasis as well as the microenvironment of pre-metastatic niches. Accumulating evidence has implicated STAT3 as a promising target for cancer therapy and it has been well established that tumor cell metastasized to lymph node is associated with poor prognosis. However, little is known about the relation between STAT3 activation in tumor cell-free lymph nodes and patient clinical outcomes. The objective of the current study was to investigate the role of STAT3 activity in tumor cell-free lymph nodes in tumor progression and prognosis for gastric cancer patients. Immunohistochemical analyses for p-STAT3, Ki-67, CD68 and Bcl-xL were performed in tumor cell-free lymph nodes from 60 gastric cancer patients. Survival analysis was conducted by using the Kaplan-Meier method. Immunohistochemical analyses showed that hyperactivity of STAT3 in tumor cell-free lymph nodes was significantly associated with tumor recurrence, and STAT3 activation pattern coincides with expression Ki-67, CD68, Bcl-xL. Survival analysis revealed that persistent STAT3 activation in uninvolved lymph nodes was positively associated with poor overall survival (P<0.05). These findings suggest that STAT3 activation in tumor-free lymph nodes is involved in the pathogenesis and metastasis of gastric cancer and that elevated STAT3 activity in lymph nodes prior to tumor cell arrival may indicate a poorer prognosis. These clinical studies support our findings in mouse tumor models showing that STAT3 activation is crucial for pre-metastatic niche formation and metastasis. PMID:24696730

Wu, Li-Jun; Li, Hai-Xia; Luo, Xiao-Ting; Lu, Rong-Ze; Ma, Yun-Fang; Wang, Rui; Zhang, Jun; Yang, Dong-Qin; Yu, Hua; Liu, Jie

2014-01-01

92

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

PubMed

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

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

2014-11-01

93

p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line.  

PubMed Central

A protein with an Mr of 145,000 (p145) was detected by antibodies to phosphotyrosine by Western blot (immunoblot) analysis. This protein was phosphorylated on tyrosine in a gastric carcinoma cell line. In cells that were metabolically labeled with 32Pi, this protein was phosphorylated on tyrosine and serine. p145 is a cysteine-rich transmembrane glycoprotein. The extracellular domain could be labeled by 125I under nonpermeating conditions and was cleaved by mild trypsin treatment of intact cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions revealed a shift of p145 mobility to an apparent Mr of 190,000. After immunoprecipitation with phosphotyrosine antibodies, p145 displayed a strong associated protein kinase activity in vitro, becoming phosphorylated on tyrosine. There was no immunological cross-reaction between p145 and known tyrosine kinases. Both in vivo and in vitro tyrosine phosphorylations were unaffected by the addition of known growth factors. However, p145 was rapidly dephosphorylated in vivo when cells were exposed to low pH, a condition that is known to dissociate ligands from their receptors. These data suggest that p145 is associated with a protein tyrosine kinase activity which, in the tumor cell line studied, is activated by an as yet unidentified factor. Images PMID:3211149

Giordano, S; Di Renzo, M F; Ferracini, R; Chiadò-Piat, L; Comoglio, P M

1988-01-01

94

AKT/ERK activation is associated with gastric cancer cell resistance to paclitaxel  

PubMed Central

Paclitaxel (PTX) has shown encouraging activity in the treatment of advanced gastric cancer (GC). However, the fact that more than half of GC patients respond poorly to PTX-based chemotherapies demonstrates the urgent need for biomarkers of PTX sensitivity in GC patients. In the present work, three GC cell lines (BGC-823, HGC-27 and NCI-N87) with different sensitivities to PTX were subjected to DNA microarray analysis. The significantly differentially expressed genes and microRNAs (miRs) were identified and pathway signatures for PTX sensitivity were proposed. Ingenuity Pathway Analysis results showed that the differentially expressed genes were mainly enriched in the ErbB signaling pathway and other pathways. Additionally, the AKT/ERK signaling pathway, which is the pathway downstream of ErbB, was predicted to be active in PTX-resistant GC cell lines. ErbB3 overexpression and AKT/ERK activation in PTX-resistant cell lines were validated, respectively, by quantitative PCR and immunoblotting. Furthermore, 10 miRs were dramatically differently expressed in the three GC cell lines, and a miR-gene network was constructed from these data. Our work uncovered a reliable signature for PTX sensitivity in GC and potential therapeutic targets for GC treatments. PMID:24817940

Wu, Gang; Qin, Xue-Qian; Guo, Jing-Jing; Li, Tian-Yi; Chen, Jin-Hong

2014-01-01

95

NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer  

PubMed Central

The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation. PMID:18827818

Murray, D; Horgan, G; MacMathuna, P; Doran, P

2008-01-01

96

Salovum Egg Yolk Containing Antisecretory Factor As an Adjunct Therapy in Severe Cholera in Adult Males: A Pilot Study  

PubMed Central

Cholera involves stimulation of intestinal secretory process in response to cholera toxin leading to profuse watery diarrhoea that might cause death due to dehydration unless timely rehydration therapy is initiated. Efforts to identify and test potential antisecretory agents are ongoing. Antisecretory factor (AF) is a naturally-occurring protein produced in the human secretory organs, including the intestine, with antisectory properties demonstrated in animal and human models of secretory diarrhoea. Salovum egg yolk powder contains proteins with antisecretory properties in a much higher (500 times) concentration than that of normal hen eggs. This is achieved by feeding hens with specially-processed cereals, capable of inducing proteins with antisecretory properties in the yolk. The aim of the study was to examine the effect of Salovum egg yolk powder containing AF in the treatment of adult cholera patients. In an open, randomized controlled trial (pilot study), 40 adult male patients with severe cholera were studied: 20 received standard treatment (oral rehydration solution, antibiotic, and usual hospital diet) plus Salovum egg yolk powder (study group) and 20 received standard treatment alone (control group). All the patients received tablet doxycycline (300 mg) once immediately after randomization. Written informed consent was obtained from each subject before enrollment. The main outcome measures were stool weight and duration of diarrhoea. The demographic and baseline clinical characteristics of the study patients were comparable between the groups. No significant differences were found in the mean stool weight, g/kg of body-weight during the first 24 hours [study vs control group, mean±standard deviation (SD), 218±119 vs 195±136], second 24 hours (mean±SD, 23±39 vs 22±34), and cumulative up to 72 hours (mean±SD, 245±152 vs 218±169). The duration (hours) of diarrhoea after admission in the hospital was also similar in both the groups (mean±SD, 33±14 vs 32±10). No adverse effect was observed. Salovum egg powder containing AF as an adjunct therapy in the treatment of severe cholera could not demonstrate any beneficial effect. Further studies with higher doses of Salovum egg yolk powder might be considered in future to establish its antisecretory effect. PMID:21957667

Ashraf, Hasan; Olesen, Maryam; Salam, Mohammed A.; Gyr, Niklaus; Meier, Remy

2011-01-01

97

Activation of Infiltrating Cytotoxic T Lymphocytes and Lymphoma Cell Apoptotic Rates in Gastric MALT Lymphomas  

PubMed Central

In this study, we have characterized infiltrating T lymphocytes from 13 low-grade and 17 high-grade primary gastric MALT lymphomas by immunohistochemistry, with particular regard to the presence, activation, and topographic distribution of cytotoxic effectors. Although the prevalence of CD4+ and CD8+ cells was similar in low- and high-grade lymphomas, higher numbers of TIA-1+ cytotoxic effectors were found in this latter group of cases (11.6 versus 7.8%; P = 0.004). Activation of CD8+ cytotoxic T lymphocytes (CTLs) was significantly more pronounced in high- than in low-grade lymphomas, as shown by immunostaining for perforin (8.7 versus 4.0%; P = 0.001) and granzyme-B (GrB) (8.7% versus 3.0%; P < 0.0001). Of note, CD20/GrB double labeling showed that high-grade lymphomas carried a markedly higher content (about ninefold) of activated CTLs relative to the number of CD20+ lymphoma B cells (0.081 ± 0.076 versus 0.009 ± 0.011; P < 0.0001). Moreover, high-grade lymphomas showed significantly increased apoptotic rates compared to low-grade cases (5.3 and 1.1% of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, respectively; P < 0.0001). In the whole series, the percentage of GrB+ cells and the GrB+/CD20+ ratio showed a strong linear correlation with the number of TUNEL-labeled cells. These findings, together with the frequent colocalization of CTLs and TUNEL+ neoplastic cells, suggested that apoptotic death of lymphoma cells may be due at least in part to the killing by cytotoxic effectors. Our results are consistent with the occurrence of host antitumor cell-mediated immune responses in gastric MALT lymphomas. Moreover, the finding of stronger cytotoxic responses in high- than in low-grade cases is of potential usefulness in the design of more effective therapeutic strategies for the management of these disorders. PMID:10487840

Guidoboni, Massimo; Doglioni, Claudio; Laurino, Licia; Boiocchi, Mauro; Dolcetti, Riccardo

1999-01-01

98

Gastric lavage.  

PubMed

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

Lanphear, W F

1986-01-01

99

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

PubMed Central

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

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

2015-01-01

100

Clinical impact of the HGF/MET pathway activation in patients with advanced gastric cancer treated with palliative chemotherapy.  

PubMed

In gastric cancer, available clinical studies focusing on the activated hepatocyte growth factor (HGF)/MET pathway are limited to surgical and often heterogeneous series. MET copy number gain (CNG) and an activating truncation in the HGF promoter (deoxyadenosine tract element, DATE+) were studied in tumors of 95 patients with advanced gastric cancer treated with palliative chemotherapy. Associations with overall survival (OS) and the pattern of metastatic disease were studied. Median OS was 9.7 months in 80 MET CNG <5 copies cases (MET-), and 6.4 months in 15 MET CNG was ?5 copies cases (MET+) (P=0.001). MET+ status confirmed the adverse prognostic effect in the multivariate model. A significantly different distribution of MET+/DATE+ and MET-/DATE- cases was observed between patients with and without peritoneal carcinomatosis (PC). MET+ status confirms its adverse prognostic role in advanced gastric cancer patients. The activated MET/HGF axis seems to be associated with PC. These findings are relevant to the development of anti-MET/HGF compounds. PMID:24663077

Graziano, F; Catalano, V; Lorenzini, P; Giacomini, E; Sarti, D; Fiorentini, G; De Nictolis, M; Magnani, M; Ruzzo, A

2014-10-01

101

IL-1?-stimulated urokinase plasminogen activator expression through NF-?B in gastric cancer after HGF treatment.  

PubMed

The potential of hepatocyte growth factor (HGF) to regulate the expression of urokinase plasminogen activator (uPA) in a gastric cancer cell is not widely acknowledged. To identify the genes associated with the plasminogen activator proteolytic axis by HGF, we used cDNA microarray technology and selected genes upregulated or downregulated in two gastric cell lines (NUGC-3 and MKN-28). First, IL-1? RNA and protein were confirmed to be upregulated. Then, we investigated the effect of IL-1? induced by HGF on the uPA system, facilitating the migration and invasion of cancer cells in the metastatic process. The role for IL-1? in HGF-induced upregulation of uPA was determined by knockdown of IL-1? with IL-1? shRNA and a chromatin immune precipitation assay. The levels of IL-1? and uPA were upregulated in cells treated with HGF in a dose-dependent manner. HGF-induced upregulation of uPA was suppressed by IL-1? knockdown. HGF enhanced the binding activity of NF-?B to the uPA promoter in control cells, but not in the IL-1? shRNA cells. We confirmed the functional role of HGF inactivation of the uPA promoter by a reporter gene assay. Downregulation of IL-1? using IL-1? shRNA also decreased cell proliferation and in vitro cell invasion. IL-1? stimulated uPA expression through ERK and NF-?B in gastric cancer, which may therefore be promising targets for gastric cancer therapy. PMID:24626561

Lee, Kyung Hee; Choi, Eun Young; Koh, Sung Ae; Kim, Min Kyoung; Jang, Byung Ik; Kim, Sang Woon; Kim, Jae-Ryong

2014-05-01

102

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

PubMed

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

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

103

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

PubMed

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

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

2014-01-01

104

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

PubMed Central

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

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

2014-01-01

105

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents.  

PubMed

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound. PMID:21702226

Onasanwo, Samuel A; Singh, Neetu; Olaleye, Samuel B; Palit, Gautam

2011-06-01

106

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

PubMed

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

Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

2014-02-01

107

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

PubMed

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

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

2000-01-01

108

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

PubMed

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

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

2015-04-01

109

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

PubMed Central

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

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

2015-01-01

110

[A decrease in the activity of the nucleolar organizers of the gastric and duodenal mucosal cells in peptic ulcer patients].  

PubMed

Silver plating of nucleoli was used to study the activity of nucleolar organizers (NO) in the cells of one-layer prismatic epithelium of the gastric and duodenal mucosae. The activity of NO was established to be lowered in patients suffering from ulcer disease and in patients with compression stenosis of the celiac trunk, which may point to the impairment of protein synthetic processes in the cells. Factor of ischemia as the most probable cause of the enumerated changes is under discussion. PMID:1692425

Sorin, V F; Morozov, V P; Mamaev, N N; Kudrevatykh, I P; Shchetinin, V N

1990-01-01

111

Effects of Glutamine on Gastrointestinal Motor Activity in Patients following Gastric Surgery  

Microsoft Academic Search

Background  Postoperative ileus (POI) is one of the most common complications of gastrointestinal surgery. The present study was performed\\u000a to evaluate the effects of glutamine administration on POI after gastric surgery in humans.\\u000a \\u000a \\u000a \\u000a \\u000a Subjects and methods  The subjects were 31 patients who underwent partial distal gastrectomy for gastric cancer and who were randomly assigned to\\u000a one of two groups based on postoperative

Erito Mochiki; Tetsuro Ohno; Mitsuhiro Yanai; Yoshitaka Toyomasu; Hiroyuki Andoh; Hiroyuki Kuwano

2011-01-01

112

Gastric dysrhythmias and nausea of pregnancy  

Microsoft Academic Search

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

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

1990-01-01

113

MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis  

PubMed Central

Background: MicroRNA (miRNA, miR)-18a is a member of the miR-17–92 cluster, an important locus that is markedly overexpressed in several cancers and associated with cancer development and progression. However, the mechanism of action of the miR-17–92 cluster and its individual miRNAs are largely unknown. Methods and Results: In this study, we investigated the expression of the miR-17–92 cluster by in situ hybridisation (ISH) assay and copy-number analysis in gastric tissue microarray (TMA) specimens. We determined that miR-18a was present at higher levels than the other five miRNAs in the cluster. In addition, we identified Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3 (PIAS3) as a direct target of miR-18a in gastric cancer. miR-18a level was positively correlated with levels of Survivin, Bcl-xL, and c-Myc, which are downstream transcriptional targets of Signal Transducer and Activator of Transcription 3 (STAT3). STAT3-induced transcription can be negatively regulated by PIAS3; consistent with this, PIAS3 level was negatively correlated with levels of Survivin, Bcl-xL, and c-Myc. Conclusion: Our findings indicate that miR-18a acts as an oncogene and plays a role in gastric adenocarcinogenesis, at least in part by negatively regulating PIAS3 and thereby modulating expression of STAT3 target genes. PMID:23322197

Wu, W; Takanashi, M; Borjigin, N; Ohno, S-i; Fujita, K; Hoshino, S; Osaka, Y; Tsuchida, A; Kuroda, M

2013-01-01

114

Palm vitamin E reduces catecholamines, xanthine oxidase activity and gastric lesions in rats exposed to water-immersion restraint stress  

PubMed Central

Background This study examined the effects of Palm vitamin E (PVE) and ?-tocopherol (?-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO?+?XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Methods Sixty male Sprague–Dawley rats (200-250?g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or ?-TF at 60?mg/kg body weight. After the treatment period of 28?days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO?+?XD activities. Results The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and ?-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and ?-TF treatments reduced these parameters significantly compared to the stressed control. Conclusions Supplementations with either PVE or ?-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities. PMID:22639913

2012-01-01

115

Elevated expression of NEDD9 is associated with metastatic activity in gastric cancer  

PubMed Central

Objective To investigate the protein and mRNA expression of NEDD9 in gastric cancer (GC) tissues, adjacent atypical hyperplasia tissues, and normal gastric mucosa tissues, and analyze its relationship with the pathological features and prognosis of GC. Methods Forty cases of GC tissues, 20 cases of adjacent atypical hyperplasia tissues, and 40 cases of normal gastric mucous tissues were collected. Immunohistochemistry and Western blot were used to examine the expression of NEDD9 protein in various tissues. Situ hybridization and reverse transcription polymerase chain reaction were applied to detect the expression of NEDD9 mRNA in various tissues. The correlation of NEDD9 expression with invasion and metastasis of GC was analyzed. Results The protein expression level of NEDD9 was significantly higher in GC tissues than in adjacent atypical hyperplasia tissues and normal gastric mucous tissues (P<0.05). The protein expression level of NEDD9 was positively related to the invasion depth of carcinoma and tumor lymph node metastasis (P<0.05), but unrelated to age, sex, tumor size, and clinical classification of cancer (P<0.05). The mRNA expression level of NEDD9 was also significantly higher in GC tissues than in adjacent atypical hyperplasia tissues and normal gastric mucous tissues (P<0.05), and positively related with the tumor lymph node metastasis and invasion depth of carcinoma (P<0.05). Conclusion NEDD9 is involved in the occurrence and development of GC, and it may be an important biological marker of GC metastasis and infiltration.

Zhang, Si-sen; Wu, Li-hua; Liu, Qing; Chen, Kui-sheng; Zhang, Xie-fu

2015-01-01

116

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

SciTech Connect

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}.

Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan)] [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)] [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

2010-11-19

117

Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats  

PubMed Central

AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an exper-imental model. METHODS: Male Wistar albino rats were assigned into 4 groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis. RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue. CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity. PMID:16425361

Kanter, Mehmet; Demir, Halit; Karakaya, Cengiz; Ozbek, Hanefi

2005-01-01

118

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

PubMed Central

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

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

2005-01-01

119

Loss of TFF1 is associated with activation of NF-?B–mediated inflammation and gastric neoplasia in mice and humans  

PubMed Central

Trefoil factor 1 (TFF1) is a tumor suppressor gene that encodes a peptide belonging to the trefoil factor family of protease-resistant peptides. Although TFF1 expression is frequently lost in gastric carcinomas, the tumorigenic pathways this affects have not been determined. Here we show that Tff1-knockout mice exhibit age-dependent carcinogenic histological changes in the pyloric antrum of the gastric mucosa, progressing from gastritis to hyperplasia, low-grade dysplasia, high-grade dysplasia, and ultimately malignant adenocarcinoma. The histology and molecular signatures of gastric lesions in the Tff1-knockout mice were consistent with an inflammatory phenotype. In vivo, ex-vivo, and in vitro studies showed that TFF1 expression suppressed TNF-?–mediated NF-?B activation through the TNF receptor 1 (TNFR1)/I?B kinase (IKK) pathway. Consistent with these mouse data, human gastric tissue samples displayed a progressive decrease in TFF1 expression and an increase in NF-?B activation along the multi-step carcinogenesis cascade. Collectively, these results provide evidence that loss of TFF1 leads to activation of IKK complex–regulated NF-?B transcription factors and is an important event in shaping the NF-?B–mediated inflammatory response during the progression to gastric tumorigenesis. PMID:21490402

Soutto, Mohammed; Belkhiri, Abbes; Piazuelo, M. Blanca; Schneider, Barbara G.; Peng, DunFa; Jiang, Aixiang; Washington, M. Kay; Kokoye, Yasin; Crowe, Sheila E.; Zaika, Alexander; Correa, Pelayo; Peek, Richard M.; El-Rifai, Wael

2011-01-01

120

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

PubMed Central

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

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

121

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

PubMed

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

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

2013-01-01

122

Gastric cancer  

Microsoft Academic Search

Gastric cancer is one of the most common cancers and one of the most frequent causes of cancer-related deaths. The incidence, diagnostic studies, and therapeutic options have undergone important changes in the last decades, but the prognosis for gastric cancer patients remains poor, especially in more advanced stages. Surgery is the mainstay of treatment of this disease, even if it

Vincenzo Catalano; Roberto Labianca; Giordano D. Beretta; Gemma Gatta; Filippo de Braud; Eric Van Cutsem

2005-01-01

123

Helicobacter pylori and gastric autoimmunity.  

PubMed

Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry. PMID:15596126

D'Elios, Mario Milco; Bergman, Mathijs P; Amedei, Amedeo; Appelmelk, Ben J; Del Prete, Gianfranco

2004-12-01

124

Helicobacter pylori and gastric autoimmunity  

Microsoft Academic Search

Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry.

Mario Milco D’Elios; Mathijs P. Bergman; Amedeo Amedei; Ben J. Appelmelk; Gianfranco Del Prete

2004-01-01

125

2-Furoyl-LIGRL-NH2, a potent agonist for proteinase-activated receptor-2, as a gastric mucosal cytoprotective agent in mice.  

PubMed

1. Proteinase-activated receptor-2 (PAR(2)), expressed in capsaicin-sensitive sensory neurons, plays a protective role in gastric mucosa. The present study evaluated gastric mucosal cytoprotective effect of 2-furoyl-LIGRL-NH(2), a novel highly potent PAR(2) agonist, in ddY mice and in wild-type and PAR(2)-knockout mice of C57BL/6 background. 2. Gastric mucosal injury was created by oral administration of HCl/ethanol solution in the mice. The native PAR(2)-activating peptide SLIGRL-NH(2), administered intraperitoneally (i.p.) at 0.3-1 micromol kg(-1) in combination with amastatin, an aminopeptidase inhibitor, but not alone, revealed gastric mucosal protection in ddY mice, which was abolished by ablation of capsaicin-sensitive sensory neurons. 3. I.p. administration of 2-furoyl-LIGRL-NH(2) at 0.1 micromol kg(-1), without combined treatment with amastatin, exhibited gastric mucosal cytoprotective activity in ddY mice, the potency being much greater than SLIGRL-NH(2) in combination with amastatin. This effect was also inhibited by capsaicin pretreatment. 4. Oral administration of 2-furoyl-LIGRL-NH(2) at 0.003-0.03 micromol kg(-1) also protected against gastric mucosal lesion in a capsaicin-reversible manner in ddY mice. 5. I.p. 2-furoyl-LIGRL-NH(2) at 0.1-0.3 micromol kg(-1) caused prompt salivation in anesthetized mice, whereas its oral administration at 0.003-1 micromol kg(-1) was incapable of eliciting salivation. 6. In wild-type, but not PAR(2)-knockout, mice of C57BL/6 background, i.p. administration of 2-furoyl-LIGRL-NH(2) caused gastric mucosal protection. 7. Thus, 2-furoyl-LIGRL-NH(2) is considered a potent and orally available gastric mucosal protective agent. Our data also substantiate a role for PAR(2) in gastric mucosal protection and the selective nature of 2-furoyl-LIGRL-NH(2). PMID:15655521

Kawabata, Atsufumi; Oono, Yuko; Yonezawa, Daiki; Hiramatsu, Kaori; Inoi, Naoki; Sekiguchi, Fumiko; Honjo, Masami; Hirofuchi, Michiko; Kanke, Toru; Ishiwata, Hiroyuki

2005-01-01

126

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

SciTech Connect

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.

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

2013-01-11

127

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

PubMed Central

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

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

2014-01-01

128

13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression.  

PubMed

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

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

2014-10-01

129

Gastric carcinogenesis  

PubMed Central

Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700?000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates: at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called “intestinal metaplasia”; phenotypic antralization of fundic units, which is called “spasmolytic polypeptide-expressing metaplasia”; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research. PMID:23066309

Gomceli, Ismail; Demiriz, Baris; Tez, Mesut

2012-01-01

130

Myorelaxant activity of 2- t-butyl-4-methoxyphenol (BHA) in guinea pig gastric fundus  

Microsoft Academic Search

This study investigates the mechanism whereby the antioxidant 2-t-butyl-4-methoxyphenol (BHA) relaxes guinea pig gastric fundus smooth muscle. In circular smooth muscle strips, 10 ?M cyclopiazonic acid, a specific inhibitor of sarcoplasmic reticulum Ca2+-ATPase, induced a prolonged rise in tension which depended on the presence of extracellular Ca2+. BHA (pIC50=5.83), sodium nitroprusside (6.85), isoproterenol (7.69) and nifedipine (8.02), but not 2,6-di-t-butyl-4-methoxyphenol

Fabio Fusi; Massimo Valoti; Georgi V. Petkov; Kiril K. Boev; Gian P. Sgaragli

1998-01-01

131

Evaluation of anti-ulcer activity of Samanea saman (Jacq) merr bark on ethanol and stress induced gastric lesions in albino rats  

PubMed Central

Objective: To evaluate the antiulcer activity of Samanea saman (Jacq) Merr bark on ethanol and stress induced gastric lesions in albino rats. Materials and Methods: Gastric lesions were induced in rats by oral administration of absolute ethanol (5 ml/kg) and stress induced by water immersion. The antiulcer activity of methanolic extract of Samanea saman (Jacq) Merr bark (100 mg/kg, 200 mg/kg, 400 mg/kg) was compared with standard drugs. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity. Result: Samanea saman (Jacq) Merr showed a dose dependent curative ratio compared to ulcer control groups. The extract at 400 mg/kg showed significant anti ulcer activity which is almost equal to that of the standard drug in both models. The volume of acid secretion, total and free acidity was decreased and pH of the gastric juice was increased compared to ulcer control group. Conclusions: The present study indicates that Samanea saman (Jacq) Merr bark extracts have potential anti ulcer activity. PMID:22022006

Arumugam, Suresh; Selvaraj, Senthil Velan; Velayutham, Suresh; Natesan, Senthil Kumar; Palaniswamy, Karthikeyan

2011-01-01

132

Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats.  

PubMed

Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats. Gastric ulcers were induced by intragastric administration of 75% ethanol. Ghrelin alone or in combination with cyclooxygenase inhibitors was administered twice, 1 and 13 hours after ethanol application. Cyclooxygenase-1 (COX-1) inhibitor (SC-560, 10 mg/kg/dose) or COX-2 inhibitor (celecoxib, 10 mg/kg/dose) were given 30 min prior to ghrelin. Twelve or 24 hours after administration of ethanol, rats were anesthetized and experiments were terminated. The study revealed that administration of ethanol induced gastric ulcers in all animals and this effect was accompanied by the reduction in gastric blood flow and mucosal DNA synthesis. Moreover induction of gastric ulcer by ethanol significantly increased mucosal expression of mRNA for COX-2, IL-1? and TNF-?. Treatment with ghrelin significantly accelerated gastric ulcer healing. Therapeutic effect of ghrelin was associated with significant reversion of the ulcer-evoked decrease in mucosal blood flow and DNA synthesis. Ghrelin administration also caused the reduction in mucosal expression of mRNA for IL-1? and TNF-?. Addition of SC-560 slightly reduced the therapeutic effect of ghrelin in the healing of ethanol-induced ulcer and the ulcer area in rats treated SC-560 plus ghrelin was significantly smaller than that observed in rats treated with saline or SC-560 alone. Pretreatment with celecoxib, a COX-2 inhibitor, abolished therapeutic effect of ghrelin. We concluded that treatment with ghrelin increases healing rate of gastric ulcers evoked by ethanol and this effect is related to improvement in mucosal blood flow, an increase in mucosal cell proliferation, and reduction in mucosal expression of proinflammatory cytokines. Ghrelin is able to reverse a deleterious effect of COX-1 inhibitor on healing of ethanol-induced gastric ulcers. Activity of COX-2 is necessary for the therapeutic effect of ghrelin in healing of ethanol-induced gastric ulcers. PMID:24622834

Warzecha, Z; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Ginter, G; Ptak-Belowska, A; Dembinski, A

2014-02-01

133

Destabilized Adhesion in the Gastric Proliferative Zone and c-Src Kinase Activation Mark the Development of Early Diffuse Gastric Cancer  

Microsoft Academic Search

The initial development of diffuse gastric cancer (DGC) is poorly understood. The study of E-cadherin (CDH1) germ line mutation carriers predisposed to DGC provides a rare opportunity to elucidate the genetic and biological events surrounding disease initiation. Samples from various stages of hereditary and sporadic DGC were investigated to determine general mecha- nisms underlying early DGC development. Paraffin-embedded tissues from

Bostjan Humar; Ryuji Fukuzawa; Vanessa Blair; Anita Dunbier; Helen More; Amanda Charlton; Han Kwang Yang; Anthony E. Reeve; Iain Martin; Parry Guilford

2007-01-01

134

Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi.  

PubMed

Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50 values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+ I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of 1 is due to the inhibition of gastric H+, K(+)-ATPase. PMID:1982146

Murakami, S; Kijima, H; Isobe, Y; Muramatsu, M; Aihara, H; Otomo, S; Baba, K; Kozawa, M

1990-10-01

135

A PVP-extract fungal protein of Omphalia lapideacens and its antitumor activity on human gastric tumors and normal cells.  

PubMed

Omphalia lapidescens is an important medicinal fungus as well as traditional Chinese medicine used for disease treatment. It is mainly used as a vermifuge for anthelmintic therapy, but it has not been hitherto reported to possess antitumor activity. In this study, a purified bioactive protein in O. lapidescens (pPeOp) was obtained using polyvinylpyrrolidone (PVP) followed by gel filtration chromatography. To evaluate the in vitro antitumor activity of pPeOp in human gastric tumor cells (MC-4 and SGC-7901) and normal cells (MC-1), MTT assay and FCM assay were used and the morphological changes, cell viability, cell death rate and cell apoptosis rate of MC-4, SGC-7901 and MC-1 cells were estimated. The results showed that pPeOp could significantly reduce the cell viability of MC-4 and SGC-7901 cells in a concentration-dependent manner, with IC50 values of 236.05 and 156.28 µg/ml, respectively. The morphological observation also indicated a similar result. In FCM assays, a significant increase of cell death rate and cell apoptosis rate of the tumor cells were observed, indicating probable necrosis-inducing effects and/or apoptosis-inducing effects of pPeOp. Importantly, there was no significant effect of pPeOp on MC-1 cells in each assay, showing that pPeOp has no adverse effects on the normal cells. In conclusion, pPeOp is a newly discovered bioactive protein in O. lapidescens and this is the first report on antitumor activity of such a fungal protein. This may provide a meaningful basis for developing a new protein drug for treatment against cancer, especially gastric cancer. PMID:21894437

Chen, Yi-Tao; Lu, Qun-Ying; Lin, Mei-Ai; Cheng, Dong-Qing; Ding, Zhi-Shan; Shan, Le-Tian

2011-12-01

136

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

PubMed

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

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

2014-05-01

137

Gastric culture  

MedlinePLUS

... test or procedure preparation (3 to 6 years) School age test or procedure preparation (6 to 12 ... immune system. The final results of the gastric culture test may take several weeks. Your health care ...

138

Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.  

PubMed

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels. PMID:18237473

Areche, Carlos; Theoduloz, Cristina; Yáñez, Tania; Souza-Brito, Alba R M; Barbastefano, Víctor; de Paula, Débora; Ferreira, Anderson L; Schmeda-Hirschmann, Guillermo; Rodríguez, Jaime A

2008-02-01

139

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

PubMed

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

Cha, Boram; Lim, Joo Weon; Kim, Hyeyoung

2015-05-01

140

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

PubMed Central

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

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

2014-01-01

141

Gastric cancer: basic aspects.  

PubMed

Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation (GSK3?, CD133, DSC2, P-Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE-HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy. PMID:21896084

Resende, Carlos; Thiel, Alexandra; Machado, José C; Ristimäki, Ari

2011-09-01

142

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

PubMed

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

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

2011-12-01

143

DACT2 is frequently methylated in human gastric cancer and methylation of DACT2 activated Wnt signaling  

PubMed Central

Dapper, Dishevelled-associated antagonist of ?-catenin (DACT), is a key regulator of Wnt signaling pathway. The purpose of this study is to explore the epigenetic changes and the function ofDACT2 in human gastric cancer (GC). Eight human gastric cancer cell lines, 167 cases of primary gastric cancer and 8 cases of normal gastric mucosa were involved in this study. In addition, methylation Specific PCR (MSP), semi-quantitative RT-PCR, colony formation assay, flow cytometry assay, siRNA, immunofluorescence techniques and xenograft mice models were employed. The results indicate that DACT2 is frequently methylated in human primary gastric cancer (55.7%), and that methylation of DACT2 is associated with lost or reduction in its expression (X2 test, P<0.01). We found that DACT2 expression was regulated by promoter region hypermethylation. Methylation of DACT2 is associated with tumor differentiation, invasion and intravascular cancerous emboli (X2 test, P<0.05, P<0.05 and P<0.05). In gastric cancer patients treated with 5-FU and cisplatin, the five-year survival rates are higher in DACT2 methylated cases. DACT2 inhibits cell proliferation, migration and invasion in gastric cancer cells and suppresses gastric cancer xenografts in mice. Restoration of DACT2 expression inhibits both canonical and noncanonical WNT signaling in SGC7901 cells. Restoration of DACT2 expression sensitized gastric cancer cells to paclitaxel and 5-FU. In conclusion, DACT2 is frequently methylated in human gastric cancer and DACT2 expression is silenced by promoter region hypermethylation. DACT2 suppressed gastric cancer proliferation, invasion and metastasis by inhibiting Wnt signaling both in vitro and in vivo. PMID:25520862

Yu, Yuanzi; Yan, Wenji; Liu, Xuefeng; Jia, Yan; Cao, Baoping; Yu, Yingyan; Lv, Youyong; Brock, Malcolm V; Herman, Jame G; Licchesi, Julien; Yang, Yunsheng; Guo, Mingzhou

2014-01-01

144

Gastric inhibitory polypeptide and gastric acid secretion in pregnant rats.  

PubMed

The effects of pregnancy on the basal and pentagastrin-stimulated gastric acid secretion and the level of plasma gastric inhibitory polypeptide (GIP) in rats were studied on pentobarbital-anaesthetized non-pregnant rats and rats in the 1st, 2nd, or 3rd week of gestation. Acid output was determined by titration of the gastric perfusate. Basal secretion was collected for 45 min before a 30 min infusion of pentagastrin (8 micrograms/ml/300 g body weight). Concentration of plasma GIP was measured by a radioimmunoassay (RIA). The immunoreactivity of GIP-like substance in the extract of the rat placenta collected from the rat at day 21 of gestation was examined by RIA. The biological activity of GIP-like substance in the rat placenta extract was tested by the reduction of pentagastrin-stimulated gastric acid secretion in male rats. The basal level of gastric secretion was higher in late pregnancy as compared with the non-pregnant rats. Pentagastrin induced a greater increase of gastric acid secretion in early but not late pregnant rats as compared with the non-pregnant animals. The basal and post-pentagastrin level of plasma GIP was higher in rats in late pregnancy. Both immunoreactivity and biological activity of GIP exist in the rat placenta extract. These results suggest that the normalization of gastric acid secretion in late pregnant rats is at least in part due to the production of GIP-like substance from placenta. PMID:7716131

Chen, T S; Yeh, G H; Pu, H F; Doong, M L; Lu, C C; Liu, S R; Young, T K; Ho, L T; Chang, F Y; Wang, P S

1995-01-01

145

Properties and synthesis of 2-{2-fluoro (or bromo)-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic acid: nonsteroidal anti-inflammatory drugs with low membrane permeabilizing and gastric lesion-producing activities.  

PubMed

We previously proposed that membrane permeabilization activity of NSAIDs is involved in NSAID-induced gastric lesions. We here synthesized derivatives of loxoprofen that have lower membrane permeabilization activity than other NSAIDs. Compared to loxoprofen, the derivatives 10a and 10b have lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that 10a and 10b are likely to be therapeutically beneficial as safer NSAIDs. PMID:20954731

Yamakawa, Naoki; Suemasu, Shintaro; Matoyama, Masaaki; Kimoto, Ayumi; Takeda, Miho; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Katsu, Takashi; Okamoto, Yoshinari; Otsuka, Masami; Mizushima, Tohru

2010-11-11

146

Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA  

PubMed Central

The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20?mg/kg) or tocotrienol (60?mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA. PMID:23970937

Kamisah, Yusof; Chua, Kien Hui; Qodriyah, Hj Mohd Saad

2013-01-01

147

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

PubMed

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

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

2014-01-01

148

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

PubMed Central

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

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

2014-01-01

149

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

PubMed

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

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

2015-04-01

150

Neuroimaging of Gastric Distension and Gastric Bypass Surgery  

PubMed Central

Several neuroimaging studies are presented, which derived from prior work on gastric distension. Using a nonsurgical approach, we inserted gastric balloons into rats, which led to a marked decrease in food intake that normalized at 8 weeks. Body weight, however, remained below controls, which encouraged pursuit of studies in humans. A gastric balloon was inserted in obese and lean subjects, and filled through a tube that led behind the subject with water to 0, 200, 400, 600, 800 mL, on different days prior to ingestion of a liquid meal. As gastric volume increased, intake decreased by about 40%. Stomach capacity was then investigated using a gastric balloon, by assessing subjective (maximal tolerance) and objective measures (gastric compliance). Obese individuals had a much larger stomach capacity than lean by both measures. Next, in a 2-month study, an indwelling gastric balloon was inflated to 400 mL for 1 month and deflated for 1 month in counterbalanced order. Body weight was reduced during the month when the balloon was inflated within the 2nd and 3rd week. The subsequent study involved fMRI in response to gastric distension of 0, 250, and 500 mL while the subject was in a scanner. Ratings of fullness, but not discomfort, increased at 500 mL. Amygdala and insula activation were associated with gastric distension. The amygdala, as part of the limbic system, is involved in emotion and reward, and the insula in interoception. The right amygdala activation was inversely related to BMI, consistent with greater gastric capacity ata higher BMI. The next fMRI study in obese and lean subjects used visual and auditory stimuli of high energy dense (ED) and low ED foods. Increased activation was observed in the midbrain, putamen, posterior cingulate gyrus, hippocampus, and superior temporal gyrus in the obese vs. lean group in response to high vs. low ED food cues. Several of these areas lie within the mesolimbic reward pathway, and greater activation to high ED foods in the obese, suggests they have increased reward-driven eating behavior. Lastly, an fMRI study using the same stimuli was conducted pre and post gastric bypass surgery. There were postsurgical reductions in neural activity in mesolimbic areas including the prefrontal cortex, to a greater degree for high ED than low ED cues, reflecting more normalized responses. Through the use of various methodologies, the stomach’s influence on food intake, sensations of fullness, and brain activation is described with suggestions for future research. PMID:23932915

Geliebter, Allan

2013-01-01

151

Evaluation of antisecretory drug therapy of zollinger-ellison syndrome (ZES) using 24-hour pH monitoring  

Microsoft Academic Search

Clinical and endoscopic findings were compared with 24-hr pH profiles in 8 patients with Zollinger-Ellison syndrome (ZES), who were being treated, during consecutive periods, with doses of cimetidine or ranitidine. There was a positive correlation between the effect on gastric pH and the outcome of treatment, with ranitidine proving to be more effective. The reduction of gastric acidity was correlated

T. Vallot; M. Mignon; R. Mazure; S. Bonfils

1983-01-01

152

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

PubMed Central

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

2013-01-01

153

Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NF?B signaling pathway in gastric cancer cells  

PubMed Central

Background Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Results Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-?B in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-?B-DNA-binding activity. Conclusions Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-?B may explain a new role of resistin in the link of obesity and gastric cancer. PMID:24929539

2014-01-01

154

Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric oxide synthase and gastric mucosal inflammatory reaction to Helicobacter pylori lipopolysaccharide  

Microsoft Academic Search

Infection with Helicobacter pylori is recognized as a primary factor in the etiology of gastric disease and its early pathogenic effects are manifested by up-regulation in proinflammatory cytokine release, enhancement in nitric oxide generation, and amplification of apoptotic events. We applied the animal model of H. pylori -induced gastritis to study the effect of a specific inhibitor of p38 mitogen-activated

B. L. Slomiany; A. Slomiany

2000-01-01

155

Gastroprotective activity and mechanism of novel dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration.  

PubMed

Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P<0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P<0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-? and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa. PMID:22178775

Salga, Muhammad Saleh; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Abdelwahab, Siddig Ibrahim

2012-01-25

156

Antiproliferative activity of fucoidan was associated with the induction of apoptosis and autophagy in AGS human gastric cancer cells.  

PubMed

Fucoidan, a sulfated polysaccharide purified from brown algae, possesses a variety of pharmacologic effects, including antiinflammatory, antioxidant, and anticancer properties; however, the underlying action mechanisms are not completely understood. This study investigated the possible mechanisms through which fucoidan exerts its antiproliferative action in cultured AGS human gastric adenocarcinoma cells. We found that fucoidan effectively inhibits the growth of AGS cells by inducing autophagy, as well as apoptosis. Apoptosis by fucoidan treatment was associated with the downregulation of antiapoptotic Bcl-2 and Bcl-xL expression, loss of mitochondrial membrane potential, activation of caspases, and concomitant degradation of poly-(ADP-ribose) polymerase protein. In addition, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in fucoidan-treated AGS cells. Furthermore, markers of autophagy, namely, the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Overall, the present data suggest that fucoidan induces apoptotic and autophagic cell death, and both apoptotic and autophagic mechanisms contribute to the fucoidan-induced AGS cell death. PMID:21535865

Park, Hyun Soo; Kim, Gi-Young; Nam, Taek-Jeong; Deuk Kim, Nam; Hyun Choi, Yung

2011-04-01

157

Multiple simultaneous gastric carcinomas.  

PubMed Central

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations. PMID:9413949

Wittekind, C.; Klimpfinger, M.; Hermanek, P.; Tannapfel, A.

1997-01-01

158

Gastric Carcinoids  

PubMed Central

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

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

2005-01-01

159

Expression of ST3GAL4 Leads to SLex Expression and Induces c-Met Activation and an Invasive Phenotype in Gastric Carcinoma Cells  

PubMed Central

Sialyl-Lewis X (SLex) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferases (STs). In this study we determined the capacity of ST3GAL3 and ST3GAL4 sialyltransferases to synthesize the SLex antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLex overexpression in cancer cell behavior both in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. The activation of tyrosine kinase receptors and their downstream molecular targets was also addressed. Our results showed that the expression of ST3GAL4 in MKN45 gastric cancer cells leads to the synthesis of SLex antigens and to an increased invasive phenotype both in vitro and in the in vivo CAM model. Analysis of phosphorylation of tyrosine kinase receptors showed a specific increase in c-Met activation. The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and Src proteins and activation of Cdc42, Rac1 and RhoA GTPases. Inhibition of c-Met and Src activation abolished the observed increased cell invasive phenotype. In conclusion, the expression of ST3GAL4 leads to SLex antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, in association with Src, FAK and Cdc42, Rac1 and RhoA GTPases activation. PMID:23799130

Gomes, Catarina; Osório, Hugo; Pinto, Marta Teixeira; Campos, Diana; Oliveira, Maria José; Reis, Celso A.

2013-01-01

160

Expression of Telomerase-associated Genes: Reflection of Telomerase Activity in Gastric Cancer?  

Microsoft Academic Search

.   Telomerase activation is a characteristic of immortalized tumor cells but not of normal cells. Telomerase activity has been\\u000a detected in approximately 85% of malignant tumors, and assaying for telomerase activity is thought to be useful for diagnosing\\u000a cancer. Three telomerase-associated molecules [human telomerase RNA component (hTR), telomerase-associated protein (TEP1),\\u000a and human telomerase reverse transcriptase (hTERT)] have been cloned. We

Hidekazu Kameshima; Atsuhito Yagihashi; Tomomi Yajima; Daisuke Kobayashi; Koichi Hirata; Naoki Watanabe

2001-01-01

161

Peroxisome proliferator-activated receptor ? upregulates galectin-9 and predicts prognosis in intestinal-type gastric cancer.  

PubMed

The importance of PPAR? (peroxisome proliferator-activated receptor ?) in gastric cancer (GC) is unclear. We investigated the role of PPAR? in GC cell lines and an animal model, and its prognostic significance of PPAR? in GC patients. We controlled PPAR? and galectin-9 expression by using siRNAs and lentiviral constructs. Interaction between PPAR? and galectin-9 was evaluated using luciferase and chromatin immunoprecipitation assays. PPAR? expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPAR? was accompanied by increased galectin-9. Enhanced PPAR? or galectin-9 expression increased E-cadherin expression; decreased expression of N-cadherin, fibronectin, snail, twist and slug and reduced cell invasion and migration. PPAR? bound to the galectin-9 promoter region. Galectin-9 activity increased in PPAR?-overexpressing cells but decreased in PPAR? siRNA-treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPAR?-overexpressing GC cells. PPAR? was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal-type GC, those with PPAR?-positive tumors had lower overall and cancer-specific mortalities than those with PPAR?-negative tumors. PPAR? expression was an independent prognostic factor for overall and GC-specific mortality in patients with intestinal-type GC (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.81). PPAR? inhibits cell invasion, migration and epithelial-mesenchymal transition through upregulation of galectin-9 in vitro and in vivo. PMID:24976296

Cho, Soo-Jeong; Kook, Myeong-Cherl; Lee, Jun Ho; Shin, Ji-Young; Park, JuRi; Bae, Young-Ki; Choi, Il Ju; Ryu, Keun Won; Kim, Young-Woo

2015-02-15

162

Enzymatic sulfation of gastric mucous glycoprotein in rat--changes in glycoprotein sulfotransferase activity with stress and anti-ulcer agent, sofalcone  

SciTech Connect

Enzymatic sulfation of mucous glycoprotein (GP) was studied in gastric mucosa of rat. After rat stomach was incubated with (/sup 35/S)-sulfate, incorporation of radioactivity into gastric mucosal APS (adenosine 5'-phosphosulfate), PAPS (3'-phosphoadenosine 5'-phosphosulfate) and endogenous GPs could be detected. The degree of sulfation of endogenous GPs was highest in the macromolecular GP (peak I) and lowest in the low molecular GP (peak III). By using a crude preparation of GP sulfotransferase from rat gastric mucosa, the transfer of (/sup 35/S)-sulfate from (/sup 35/S)-PAPS into macromolecular mucous GP was determined as being the activity of sulfotransferase. The activity of GP sulfotransferase was mainly distributed in the microsomal fraction, and was proportional to the incubation time, substrate (mucous GP) concentration and (/sup 35/S)-PAPS concentration. The enzyme activity was significantly higher in the corpus than that in the antral mucosa. The activity of GP sulfotransferase was significantly decreased at 6 h and was significantly increased at 12 h after the stress load, compared with that of the non-stressed condition. Anti-ulcer agent, sofalcone, increased the GP sulfotransferase activity under the stressed condition. On the other hand, cimetidine showed a significant inhibitory effect under the same condition. Changes in the GP sulfotransferase activity with stress and anti-ulcer agents were consistent with those in the incorporation of (/sup 35/S)-sulfate into macromolecular mucous GP. These results suggest the importance of GP sulfotransferase as a key enzyme regulating the sulfation of mucous GP.

Murakami, S.; Muramatsu, M.; Aihara, H.; Honda, A.; Mori, Y.

1987-07-01

163

Acid secretion and gastric surgery.  

PubMed

It was long believed that there were major differences in the pathophysiology between the three major categories of peptic ulcers. The unifying feature was that all peptic ulcers occurred in a mucosal compartment exposed to acid-pepsin secretions. All ulcers tended to heal more rapidly when acid secretion was more readily neutralized or inhibited. Decreased local resistance was considered to be present in primarily acute and chronic gastric ulcer. Surgery for peptic ulcer intended to reduce acid secretion, which also resulted in a diminished pepsin enzyme activity. The corresponding reduction could be accomplished either by gastric resection, different vagotomies or a combination of resections and vagotomies. Most of the procedures were basically abandoned at the time of introduction of modern medical therapeutic strategies. For duodenal ulcer and prepyloric ulcer diseases, various vagotomies were generally recommended or combined with antrectomy. Partial gastrectomy or antrectomy with gastroduodenostomy was the standard procedure for treatment of type 1 gastric ulcer. The great caveat associated with surgical procedures for elective treatment of uncomplicated peptic ulcer disease is confined to operative mortality, postoperative morbidity, and late postoperative metabolic sequelae. The only remaining indication today of remedial gastric surgery for peptic ulcer disease is when there is a defined risk for gastric cancer in an unhealed gastric ulcer and very seldom in a case with recurrent or therapy-resistant peripyloric ulcer. PMID:22095015

Lundell, Lars

2011-01-01

164

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

E-print Network

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 ...

Piazzi, Giulia

165

Calcium carbonate breath test for non-invasive estimation of gastric acid secretion.  

PubMed

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO?) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO?), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO? breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO? breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO? concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO? breath test values well reflected the fasting intragastric acidity. The ¹³CO? concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO? breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO? breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO? breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human. PMID:24670370

Shinkai, Hirohiko; Iijima, Katsunori; Koike, Tomoyuki; Nakagawa, Kenichiro; Maejima, Ryuhei; Endo, Hiroyuki; Ara, Nobuyuki; Asano, Naoki; Imatani, Akira; Ohara, Shuichi; Shimosegawa, Tooru

2014-01-01

166

Gastric anti-ulcer and cytoprotective effect of selenium in rats  

SciTech Connect

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.

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

1988-01-01

167

Presynaptic BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of noradrenaline release from the rat gastric sympathetic nerves.  

PubMed

Previously, we reported that prostanoid TP receptor mediates the inhibition of electrically evoked noradrenaline release from gastric sympathetic nerves in rats. Prostanoid TP receptor has been shown to activate phospholipase C (PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-triphosphate (IP(3)) and diacylglycerol; IP(3) triggers the release of Ca(2+) from intracellular stores and diacylglycerol activates protein kinase C. In the present study, therefore, we examined whether these PLC-mediated mechanisms are involved in the TP receptor-mediated inhibition of gastric noradrenaline release using an isolated, vascularly perfused rat stomach. U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy PGF(2alpha)) (a prostanoid TP receptor agonist)-induced inhibition of noradrenaline release from the stomach was reduced by U-73122 [1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]-amino]hexyl]-1H-pyrrole-2,5-dine] (a PLC inhibitor) and ET-18-OCH(3) (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine) (a phosphatidylinositol-specific PLC inhibitor), respectively. 2-APB (2-aminoethyldiphenyl borate) (a putative IP(3) receptor antagonist) also abolished the U-46619-induced inhibition of noradrenaline release, but Ro 31-8220 [2-{1-[3-(amidinothio)propyl]-1H-indol-3-yl}-3-(1-methylindol-3-yl)-maleimide] (a protein kinase C inhibitor) had no effect. Furthermore, a small dose of tetraethylammonium and charybdotoxin [blockers of BK type Ca(2+)-activated K(+) channel] abolished the U-46619-induced inhibition, but apamin (a blocker of SK-type Ca(2+)-activated K(+) channel) had no effect. These results suggest that BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of electrically evoked noradrenaline release from the gastric sympathetic nerve terminals in rats. PMID:19961846

Nakamura, Kumiko; Yokotani, Kunihiko

2010-03-10

168

?-Lipoic Acid Inhibits Helicobacter pylori-Induced Oncogene Expression and Hyperproliferation by Suppressing the Activation of NADPH Oxidase in Gastric Epithelial Cells  

PubMed Central

Hyperproliferation and oncogene expression are observed in the mucosa of Helicobacter pylori- (H. pylori-) infected patients with gastritis or adenocarcinoma. Expression of oncogenes such as ?-catenin and c-myc is related to oxidative stress. ?-Lipoic acid (?-LA), a naturally occurring thiol compound, acts as an antioxidant and has an anticancer effect. The aim of this study is to investigate the effect of ?-LA on H. pylori-induced hyperproliferation and oncogene expression in gastric epithelial AGS cells by determining cell proliferation (viable cell numbers, thymidine incorporation), levels of reactive oxygen species (ROS), NADPH oxidase activation (enzyme activity, subcellular levels of NADPH oxidase subunits), activation of redox-sensitive transcription factors (NF-?B, AP-1), expression of oncogenes (?-catenin, c-myc), and nuclear localization of ?-catenin. Furthermore, we examined whether NADPH oxidase mediates oncogene expression and hyperproliferation in H. pylori-infected AGS cells using treatment of diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase. As a result, ?-LA inhibited the activation of NADPH oxidase and, thus, reduced ROS production, resulting in inhibition on activation of NF-?B and AP-1, induction of oncogenes, nuclear translocation of ?-catenin, and hyperproliferation in H. pylori-infected AGS cells. DPI inhibited H. pylori-induced activation of NF-?B and AP-1, oncogene expression and hyperproliferation by reducing ROS levels in AGS cells. In conclusion, we propose that inhibiting NADPH oxidase by ?-LA could prevent oncogene expression and hyperproliferation occurring in H. pylori-infected gastric epithelial cells. PMID:25210229

Byun, Eunyoung; Lim, Joo Weon; Kim, Jung Mogg; Kim, Hyeyoung

2014-01-01

169

Effects of cisapride on ulcer formation and gastric secretion in rats: comparison with ranitidine and omeprazol.  

PubMed

1. The antiulcerogenic effects of cisapride, a potent benzamide-stimulating gastrointestinal motility agent, were studied on cold-resistant and pylorus-ligated gastric ulcers. Acidity, composition of gastric secretion, and quantitative and qualitative changes on mucus glycoprotein content were also determined. These effects were compared with those of ranitidine (50 mg/kg) and omeprazol (10 mg/kg). 2. Oral cisapride (10-100 mg/kg) dose-relatedly and significantly (P < 0.01, P < 0.05) decreased the severity of the lesions induced by cold-resistant stress. In stressed rats, cisapride increased the amount of mucus secretion and markedly enhanced the glycoprotein content. Morphometric evaluation of mucus secretion revealed a significant increase in both the PAS area (neutral glycoproteins) and Alcian blue area (sulfated glycoproteins). 3. In 4 h pyloric-ligated animals, cisapride (10-100 mg/kg) showed a significant reduction in the number and severity of ulcers (P < 0.01) and histamine concentration (P < 0.01, P < 0.001). In addition, at the highest doses (50-100 mg/kg), cisapride produced a significant decreases in acidity; however, it did not alter the gastric volume secretion or pepsin concentrations. 4. These results suggest that cisapride shows antiulcerogenic effects which could possibly be explained through antisecretory and cytoprotective mechanisms involving an enhancement of cuality and production of gastric mucus. PMID:9304418

Alarcón de la Lastra, C; Martin, M J; La Casa, M; López, A; Motilva, V

1996-12-01

170

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

PubMed Central

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

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

171

Influence of Activity Levels and Energy Intake on Percent Excess Weight Loss After Roux-en-Y Gastric Bypass  

Microsoft Academic Search

Background  Gastric bypass is a successful medical intervention for weight loss for obesity. Weight loss is substantial after this surgery.\\u000a Predictors of the most successful weight loss are not yet fully known. The purpose of this study was to define variables that\\u000a improve percent excess weight loss (%EWL) in this post-surgical population.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  All patients who underwent the Roux-en-Y gastric bypass (RYGB)

Steven Forbush; Leah Nof; John Echternach; Cheryl Hill; Jacquie Rainey

172

Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-?B activation in gastric tissues of diabetic gastroparesis rats  

PubMed Central

Background Diabetes mellitus is associated with many kinds of complications. Recent studies have shown that oxidative stress and inflammatory reactions have critical roles in the pathogenesis of diabetic gastroparesis. Curcumin is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on diabetic gastric motility in a Sprague Dawley rat model of type 1 diabetes mellitus. Methods Male SD rats were divided into a control group, a control group receiving curcumin, a diabetic group, and a diabetic group receiving curcumin. Diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin (150 mg/kg) was given intragastrically for 6 weeks, and blood glucose levels and body weights were measured. Stomachs were excised for analysis of gastric emptying rates, and levels of oxidative stress. NF-?B, I-?B, and stem cell factor (SCF)/c-kit protein levels were assessed by western blot analysis, while the apoptosis of interstitial cells of Cajal (ICCs) was assessed by TUNEL staining. Results Curcumin-treated diabetic rats showed significantly improved gastric emptying rates [(59.4 ± 7.5)%] compared with diabetic rats [(44.3 ± 5.7)%], as well as decreased levels of MDA [21.4 ± 1.8 (nmol/mg) vs 27.9 ± 2.1 (nmol/mg)], and increased SOD activity [126.2 ± 8.8 (units/mg) vs 107.9 ± 7.5 (units/mg)]. On the other hand, the gastric emptying level in the control group was not significantly different from that in the control group receiving curcumin treatment. In addition, curcumin-treated diabetic rats showed significantly increased levels of SCF/c-kit protein in stomach tissues, inhibited I-?B degradation and NF-?B activation, and reduced ICC apoptosis index [(26.2 ± 4.1)% vs (47.5 ± 6.2)%], compared with the diabetic group. Conclusion Curcumin treatment improved gastric emptying by blocking the production of oxidative stress, abolishing NF-?B signal transduction and enhancing expression of SCF/c-kit in rats with diabetic gastroparesis. PMID:23448582

2013-01-01

173

Hunger Control and Regular Physical Activity Facilitate Weight Loss After Laparoscopic Adjustable Gastric Banding  

Microsoft Academic Search

Background Bariatric surgery facilitates substantial and durable weight loss; however, outcomes vary. In addition to physiological and technical factors, weight loss efficacy is dependent on modification of behavior to maintain a long-term change in energy balance. This study aimed to assess the extent and nature of change in energy intake and physical activity and identify factors associated with per- centage

Susan L. Colles; John B. Dixon; Paul E. O'Brien

2007-01-01

174

Expression of Telomerase Activity, Human Telomerase RNA, and Telomerase Reverse Transcriptase in Gastric Adenocarcinomas  

Microsoft Academic Search

Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosome ends to compensate for sequence loss during DNA replication. It has been detected in 85–90% of all primary human cancers, implicating that the telomerase seems to be reactivated in tumors and that such activity may play a role in the tumorigenic process. The purpose of this study

Jinyoung Yoo; Sonya Y Park; Seok Jin Kang; Byung Kee Kim; Sang In Shim; Chang Suk Kang

2003-01-01

175

Acidic Digestion in a Teleost: Postprandial and Circadian Pattern of Gastric pH, Pepsin Activity, and Pepsinogen and Proton Pump mRNAs Expression  

PubMed Central

Two different modes for regulation of stomach acid secretion have been described in vertebrates. Some species exhibit a continuous acid secretion maintaining a low gastric pH during fasting. Others, as some teleosts, maintain a neutral gastric pH during fasting while the hydrochloric acid is released only after the ingestion of a meal. Those different patterns seem to be closely related to specific feeding habits. However, our recent observations suggest that this acidification pattern could be modified by changes in daily feeding frequency and time schedule. The aim of this study was to advance in understanding the regulation mechanisms of stomach digestion and pattern of acid secretion in teleost fish. We have examined the postprandial pattern of gastric pH, pepsin activity, and mRNA expression for pepsinogen and proton pump in white seabream juveniles maintained under a light/dark 12/12 hours cycle and receiving only one morning meal. The pepsin activity was analyzed according to the standard protocol buffering at pH 2 and using the actual pH measured in the stomach. The results show how the enzyme precursor is permanently available while the hydrochloric acid, which activates the zymogen fraction, is secreted just after the ingestion of food. Results also reveal that analytical protocol at pH 2 notably overestimates true pepsin activity in fish stomach. The expression of the mRNA encoding pepsinogen and proton pump exhibited almost parallel patterns, with notable increases during the darkness period and sharp decreases just before the morning meal. These results indicate that white seabream uses the resting hours for recovering the mRNA stock that will be quickly used during the feeding process. Our data clearly shows that both daily illumination pattern and feeding time are involved at different level in the regulation of the secretion of digestive juices. PMID:22448266

Yúfera, Manuel; Moyano, Francisco J.; Astola, Antonio; Pousão-Ferreira, Pedro; Martínez-Rodríguez, Gonzalo

2012-01-01

176

Hunger Control and Regular Physical Activity Facilitate Weight Loss After Laparoscopic Adjustable Gastric Banding  

Microsoft Academic Search

Background  Bariatric surgery facilitates substantial and durable weight loss; however, outcomes vary. In addition to physiological and\\u000a technical factors, weight loss efficacy is dependent on modification of behavior to maintain a long-term change in energy\\u000a balance. This study aimed to assess the extent and nature of change in energy intake and physical activity and identify factors\\u000a associated with percentage weight loss

Susan L. Colles; John B. Dixon; Paul E. O’Brien

2008-01-01

177

Angiotensin-I-converting enzyme inhibitory activities of gastric and pancreatic proteinase digests of whey proteins  

Microsoft Academic Search

Enzymatic hydrolysates of bovine ?-lactoglobulin (?-Lg), ?-lactalbumin (?-La) and whey protein concentrate (WPC) were analysed for their angiotensin-I-converting enzyme (ACE) inhibitory activity. The unhydrolysed substrates gave very low ACE inhibitory indices, i.e. < 10%. Hydrolysis of the whey proteins by pepsin, trypsin, chymotrypsin and the commercially available enzyme preparations, Corolase PP and PTN 3.0S, resulted in high ACE inhibition indices,

Margaret M. Mullally; Hans Meisel; Richard J. FitzGerald

1997-01-01

178

Orally active fumagillin analogues: transformations of a reactive warhead in the gastric environment.  

PubMed

Semisynthetic analogues of fumagillin, 1, inhibit methionine aminopeptidase-2 (MetAP2) and have entered the clinic for the treatment of cancer. An optimized fumagillin analogue, 3 (PPI-2458), was found to be orally active, despite containing a spiroepoxide function that formed a covalent linkage to the target protein. In aqueous acid, 3 underwent ring-opening addition of water and HCl, leading to four products, 4-7, which were characterized in detail. The chlorohydrin, but not the diol, products inhibited MetAP2 under weakly basic conditions, suggesting reversion to epoxide as a step in the mechanism. In agreement, chlorohydrin 6 was shown to revert rapidly to 3 in rat plasma. In an ex vivo assay, rats treated with purified acid degradants demonstrated inhibition of MetAP2 that correlated with the biochemical activity of the compounds. Taken together, the results indicate that degradation of the parent compound was compensated by the formation of active equivalents leading to a pharmacologically useful level of MetAP2 inhibition. PMID:24900682

Arico-Muendel, Christopher C; Blanchette, Heather; Benjamin, Dennis R; Caiazzo, Teresa M; Centrella, Paolo A; DeLorey, Jennifer; Doyle, Elisabeth G; Johnson, Steven R; Labenski, Matthew T; Morgan, Barry A; O'Donovan, Gary; Sarjeant, Amy A; Skinner, Steven; Thompson, Charles D; Griffin, Sarah T; Westlin, William; White, Kerry F

2013-04-11

179

Isorhamnetin Inhibits Proliferation and Invasion and Induces Apoptosis through the Modulation of Peroxisome Proliferator-activated Receptor ? Activation Pathway in Gastric Cancer*  

PubMed Central

Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3?-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor ? (PPAR-?) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-? inhibitor. We found that IH increased PPAR-? activity and modulated the expression of PPAR-? regulated genes in GC cells. Also, the increase in PPAR-? activity was reversed in the presence of PPAR-?-specific inhibitor and a mutated PPAR-? dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-?. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-? that are reported to be critical for its activity and could competitively bind to PPAR-?. IH significantly increased the expression of PPAR-? in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-? activation pathway in GC. PMID:22992727

Ramachandran, Lalitha; Manu, Kanjoormana Aryan; Shanmugam, Muthu K.; Li, Feng; Siveen, Kodappully Sivaraman; Vali, Shireen; Kapoor, Shweta; Abbasi, Taher; Surana, Rohit; Smoot, Duane T.; Ashktorab, Hassan; Tan, Patrick; Ahn, Kwang Seok; Yap, Chun Wei; Kumar, Alan Prem; Sethi, Gautam

2012-01-01

180

Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor ? activation pathway in gastric cancer.  

PubMed

Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate due to GC, chemoresistance remains as one of the major causes for poor prognosis and high recurrence rate. In this study, we investigated the potential effects of isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin on the peroxisome proliferator-activated receptor ? (PPAR-?) signaling cascade using proteomics technology platform, GC cell lines, and xenograft mice model. We observed that IH exerted a strong antiproliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of GC cells, which could be reversed in the presence of PPAR-? inhibitor. We found that IH increased PPAR-? activity and modulated the expression of PPAR-? regulated genes in GC cells. Also, the increase in PPAR-? activity was reversed in the presence of PPAR-?-specific inhibitor and a mutated PPAR-? dominant negative plasmid, supporting our hypothesis that IH can act as a ligand of PPAR-?. Using molecular docking analysis, we demonstrate that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-? that are reported to be critical for its activity and could competitively bind to PPAR-?. IH significantly increased the expression of PPAR-? in tumor tissues obtained from xenograft model of GC. Overall, our findings clearly indicate that antitumor effects of IH may be mediated through modulation of the PPAR-? activation pathway in GC. PMID:22992727

Ramachandran, Lalitha; Manu, Kanjoormana Aryan; Shanmugam, Muthu K; Li, Feng; Siveen, Kodappully Sivaraman; Vali, Shireen; Kapoor, Shweta; Abbasi, Taher; Surana, Rohit; Smoot, Duane T; Ashktorab, Hassan; Tan, Patrick; Ahn, Kwang Seok; Yap, Chun Wei; Kumar, Alan Prem; Sethi, Gautam

2012-11-01

181

Correlation between the activities and the oligomeric forms of pig gastric H/K-ATPase.  

PubMed

Membrane-bound H/K-ATPase was solubilized by octaethylene glycol dodecyl ether (C(12)E(8)) or n-octyl glucoside (nOG). H/K-ATPase activity and the distribution of protomeric and oligomeric components were evaluated by high-performance gel chromatography (HPGC) and by single-molecule detection using total internal reflection fluorescence microscopy (TIRFM). As evidenced by HPGC of the C(12)E(8)-solubilized enzyme, the distribution of oligomers was 12% higher oligomeric, 44% diprotomeric, and 44% protomeric species, although solubilization by C(12)E(8) reduced the H/K-ATPase activity to 1.8% of that of the membrane-bound enzyme. The electron microscopic images of the C(12)E(8)-solubilized enzyme showed the presence of protomers and a combination of two and more protomers. While the nOG-solubilized H/K-ATPase retained the same turnover number and 71% of the specific activity as that of the membrane-bound enzyme, 56% higher oligomeric, 34% diprotomeric, and 10% protomeric species were detected. TIRFM analysis of solubilized fluorescein 5'-isothiocyanate (FITC)-modified H/K-ATPase at Lys-518 of the alpha-chain showed a quantized photobleaching of the FITC fluorescence intensity. For the C(12)E(8)-solubilized FITC-enzyme, the fraction of each of the initial relative fluorescence intensity units of 4, 2, and 1 was, respectively, 5%, 44% and 51%. In the case of the nOG-solubilized FITC-enzyme, each fraction of 4 and 2 units was, respectively, 54% and 46% with no detectable 1 unit fraction. This represents the first direct observation of H/K-ATPase in aqueous solution. The correlation between the enzymatic activities and distribution of oligomeric forms of H/K-ATPase by HPGC and the observation of a single molecule of H/K-ATPase and others suggests that the tetraprotomeric form of H/K-ATPase molecules represents the functional species in the membrane. PMID:14690423

Abe, Kazuhiro; Kaya, Shunji; Hayashi, Yutaro; Imagawa, Toshiaki; Kikumoto, Mahito; Oiwa, Kazuhiro; Katoh, Tsuyoshi; Yazawa, Michio; Taniguchi, Kazuya

2003-12-30

182

Predicted vs. Actual Resting Energy Expenditure and Activity Coefficients: Post-Gastric Bypass, Lean and Obese Women  

PubMed Central

Total Energy Expenditure (TEE) and energy requirements are commonly estimated from equations predicting Resting Energy Expenditure (REE) multiplied by a Physical Activity (PA) coefficient that accounts for both PA energy expenditure and the thermogenic effect of food. PA coefficients based on PA self-reports are a potential source of error that has not been evaluated. Therefore, in this study we compared: 1) the Harris-Benedict (HB), Mifflin-St. Jeor (MSJ), and the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) REE equations with REE measured (REE-m) with indirect calorimetry; 2) PA coefficients determined with PA self-reports vs. objectively assessed PA; and 3) TEE estimates in post-Gastric Bypass (GB = 13), lean (LE = 7), and obese (OB = 12) women. REE was measured in the morning after an overnight fast with participants resting supine for 30 min. Self-reported PA was evaluated with a questionnaire and objectively measured with accelerometers worn for 5-7 days. Nutritional intake was evaluated with a food frequency questionnaire. Anthropometry included DEXA, and abdominal CT scans. Eligible GB had surgery ? 12 months before the study, and had ? 10 kg of body weight loss. All participants were 18-45 years of age, able to engage in ambulatory activities, and not taking part in exercise training programs. One-way ANOVA was used to detect differences in REE and TEE. Accuracy of REE prediction equations were determined by cases within 10% of REE-m, and agreement analyses. REE predictions were not different than REE-m, but agreements were better with HB and MSJ, particularly in the GB and LE groups. Discrepancies in the PA coefficients determined with self-report vs. objectively assessed PA resulted in TEE overestimates (approximately 200-300 Kcal/day) using HB and MSJ equations. FAO/WHO/UNU overestimated TEE in all groups regardless of the PA assessment method (approximately 300-900 kcal/day). These results suggest that: 1) HB and MSJ equations are good predictors of REE among GB and LE, but not among OB women, 2) PA coefficients used to estimate TEE must be determined with objective PA assessment, and 3) TEE estimates using PA coefficients with the FAO/WHO/UNU equation must be used with caution.

Ramirez-Marrero, Farah A.; Edens, Kim L.; Joyner, Michael J.; Curry, Timothy B.

2015-01-01

183

Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells.  

PubMed

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC50) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 ?g/mL of VCR, the respective IC50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs. PMID:24213508

Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

2012-01-01

184

Chrysin inhibits cell invasion by inhibition of Recepteur d'origine Nantais via suppressing early growth response-1 and NF-?B transcription factor activities in gastric cancer cells.  

PubMed

Cell invasion is one of crucial reasons for cancer metastasis and malignancy. Recepteur d'origine Nantais (RON) has been reported to play an important role in the cancer cell invasion process. High accumulation and activation of RON has been implicated in gastric adenocarcinoma AGS cells. Chrysin is a naturally occurring phytochemical, a type of flavonoid, which has been reported to suppress tumor metastasis. However, the effects of chrysin on RON expression in gastric cancer are not well studied. In the present study, we examined whether chrysin affects RON expression in gastric cancer, and if so, its underlying mechanism. We examined the effect of chrysin on RON expression and activity, via RT-PCR, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin significantly inhibited endogenous and inducible RON expression in a dose-dependent manner. After demonstrating that Egr-1 and NF-?B are the critically required transcription factors for RON expression, we discovered that chrysin suppressed Egr-1 and NF-?B transcription factor activities. Additionally, the phorbol-12-myristate-13-acetate- (PMA) induced cell invasion was partially abrogated by chrysin and an RON antibody. Our results suggest that chrysin has anticancer effects at least by suppressing RON expression through blocking Egr-1 and NF-?B in gastric cancer AGS cells. PMID:25625479

Xia, Yong; Lian, Sen; Khoi, Pham Ngoc; Yoon, Hyun Joong; Han, Jae Young; Chay, Kee Oh; Kim, Kyung Keun; Jung, Young Do

2015-04-01

185

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

PubMed Central

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

2012-01-01

186

Antiulcer activity of cod liver oil in rats  

PubMed Central

Objective: Cod liver oil is used widely as a dietary supplement. The present study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and 1 g/kg, p.o.) on gastric and duodenal ulcers. Materials and Methods: The study was carried out on different gastric ulcer models such as acetic acid induced chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100 µg/kg, p.o.) were used as standard drugs. Results: Both doses of cod liver oil showed gastric ulcer healing effect in acetic acid induced chronic gastric ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced ulcer. Cod liver oil also produced a significant reduction in the development of stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose (0.5 g/kg, p.o.). Conclusion: Cod liver oil increases healing of gastric ulcers and prevents the development of experimentally induced gastric and duodenal ulcers in rats. PMID:20040959

Khare, Salaj; Asad, Mohammed; Dhamanigi, Sunil S.; Prasad, V. Satya

2008-01-01

187

HGF triggers activation of the COX2 gene in rat gastric epithelial cells: action mediated through the ERK2 signaling pathway  

Microsoft Academic Search

Although it is established that growth factors and prostaglandins function in the mainte- nance of gastric mucosal integrity and in the healing of gastric mucosal injury and ulceration, the regula- tory relationship between growth factors and prosta- glandins in the gastric mucosa is not well character- ized. Therefore, we investigated whether hepatocyte growth factor (HGF) affects expression of COX-2 (the

MICHAEL K. JONES; EIJI SASAKI; FRED HALTER; RAMA PAI; TOSHIKAZU NAKAMURA; TETSUO ARAKAWA; TETSUO KUROKI; ANDRZEJ S. TARNAWSKI

188

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

PubMed

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

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

2013-09-01

189

A comparative pharmacological investigation of three samples of 'Guduchi ghrita' for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats.  

PubMed

This study was undertaken to investigate the impact of formulation factors and adjuvants on the expression of biological activity of Tinospora cordifolia (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita, prepared using plain ghee (clarified butter) obtained from three different sources was studied in albino rats and compared with expressed juice of stem of Guduchi. The test preparations were evaluated against forced-swimming induced hypothermia, gastric ulceration and changes in the hematological parameters. The test drug given in the form of 'ghrita' produced better effect in comparison to the expressed juice. Among the three 'ghrita' preparations evaluated, only the 'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of stress hypothermia and gastric ulceration. The other two preparations 'Nanded Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a marginal effect. In hematological parameters 'Guduchi' juice produced better reversal of the stress-induced changes in comparison to the test 'ghrita' preparations. The present study provides evidence highlighting the importance of formulation factors for the expression of biological activity. PMID:20814518

Savrikar, Shriram S; Dole, Vilas; Ravishankar, B; Shukla, Vinay J

2010-04-01

190

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NF?B signaling pathway  

PubMed Central

Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NF?B signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NF?B signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NF?B signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC. PMID:23298905

Wang, Jin; Kang, Wei-Ming; Yu, Jian-Chun; Liu, Yu-Qin; Meng, Qing-Bin; Cao, Zhan-Jiang

2013-01-01

191

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NF?B signaling pathway.  

PubMed

Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NF?B signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NF?B signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NF?B signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC. PMID:23298905

Wang, Jin; Kang, Wei-Ming; Yu, Jian-Chun; Liu, Yu-Qin; Meng, Qing-Bin; Cao, Zhan-Jiang

2013-03-01

192

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

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

2013-01-01

193

Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats  

SciTech Connect

Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.

Poulsen, S.S.; Raaberg, L.; Therkelsen, K.; Skov Olsen, P.; Kirkegaard, P.

1986-07-01

194

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

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

Mat Jais, Abdul Manan; Afreen, Adiba

2013-01-01

195

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer.  

PubMed

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects. PMID:24009139

Yoshida, Takeichi; Kato, Jun; Inoue, Izumi; Yoshimura, Noriko; Deguchi, Hisanobu; Mukoubayashi, Chizu; Oka, Masashi; Watanabe, Mika; Enomoto, Shotaro; Niwa, Toru; Maekita, Takao; Iguchi, Mikitaka; Tamai, Hideyuki; Utsunomiya, Hirotoshi; Yamamichi, Nobutake; Fujishiro, Mitsuhiro; Iwane, Masataka; Takeshita, Tatsuya; Ushijima, Toshikazu; Ichinose, Masao

2014-03-15

196

Epigenetic silencing of DACH1 induces the invasion and metastasis of gastric cancer by activating TGF-? signalling  

PubMed Central

Gastric cancer (GC) is the fourth most common malignancy in males and the fifth most common malignancy in females worldwide. DACH1 is frequently methylated in hepatic and colorectal cancer. To further understand the regulation and mechanism of DACH1 in GC, eight GC cell lines, eight cases of normal gastric mucosa, 98 cases of primary GC and 50 cases of adjacent non-tumour tissues were examined. Methylation-specific PCR, western blot, transwell assay and xenograft mice were used in this study. Loss of DACH1 expression correlated with promoter region methylation in GC cells, and re-expression was induced by 5-Aza-2?-deoxyazacytidine. DACH1 is methylated in 63.3% (62/98) of primary GC and 38% (19/50) of adjacent non-tumour tissues, while no methylation was found in normal gastric mucosa. Methylation of DACH1 correlated with reduced expression of DACH1 (P < 0.01), late tumour stage (stage III/IV) (P < 0.01) and lymph node metastasis (P < 0.05). DACH1 expression inhibited epithelial–mesenchymal transition and metastasis by inhibiting transforming growth factor (TGF)-? signalling and suppressed GC cell proliferation through inducing G2/M phase arrest. The tumour size is smaller in DACH1-expressed BGC823 cell xenograft mice than in unexpressed group (P < 0.01). Restoration of DACH1 expression also sensitized GC cells to docetaxel. These studies suggest that DACH1 is frequently methylated in human GC and expression of DACH1 was controlled by promoter region methylation. DACH1 suppresses GC proliferation, invasion and metastasis by inhibiting TGF-? signalling pathways both in vitro and in vivo. Epigenetic silencing DACH1 may induce GC cells' resistance to docetaxel. PMID:24912879

Yan, Wenji; Wu, Kongming; Herman, James G; Brock, Malcolm V; Zhou, Yusen; Lu, Youyong; Zhang, Zhiqian; Yang, Yunsheng; Guo, Mingzhou

2014-01-01

197

Gastric sarcoidosis: rare presentation of a rare disease.  

PubMed

Gastrointestinal sarcoidosis is a rare form of extrapulmonary sarcoidosis. Most of the cases are represented by gastric involvement. We describe a patient with previous systemic sarcoidosis who presented with non-specific abdominal complaints. The workup showed the unusual combination of isolated active gastric sarcoidosis and quiescent activity of the disease elsewhere. We briefly review the clinical, diagnostic and therapeutic aspects of gastric sarcoidosis. We hope to increase awareness about this rare disease. PMID:25435277

Vanderhulst, J

2015-02-01

198

Regulation of MMP-2 expression and activity by ?-1,3- N -acetylglucosaminyltransferase-8 in AGS gastric cancer cells  

Microsoft Academic Search

?-1,3-N-acetylglucosaminyltransferase-8(?3Gn-T8) catalyzes the transfer of GlcNAc to the non-reducing terminus of the Gal?1-4GlcNAc\\u000a of tetraantennary N-glycan in vitro. It has been reported to be involved in malignant tumors, but a comprehensive understanding of how the glycolsyltransferase\\u000a correlates with the invasive potential of human gastric cancer is not currently available. Therefore, we investigated the\\u000a ability and possible mechanism involved with ?3Gn-T8

Li Shen; Zhenhua Liu; Youbin Tu; Lan Xu; Xiaoya Sun; Shiliang Wu

2011-01-01

199

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)

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.

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

1991-01-01

200

Targeting receptor tyrosine kinases in gastric cancer  

PubMed Central

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

Morishita, Asahiro; Gong, Jian; Masaki, Tsutomu

2014-01-01

201

Effect of an intraduodenal injection of fat on the activities of the adrenal efferent sympathetic nerve and the gastric efferent parasympathetic nerve in urethane-anesthetized rats.  

PubMed

Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane-anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, epsilon-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs-the degradation products of fats-in the intestinal lumen. PMID:20362017

Matsumura, Shigenobu; Eguchi, Ai; Kitabayashi, Nobuhide; Tanida, Mamoru; Shen, Jiao; Horii, Yuko; Nagai, Katsuya; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

2010-07-01

202

Primary Gastric Malignant Melanoma Mimicking Adenocarcinoma  

PubMed Central

We report a case of primary gastric malignant melanoma that was diagnosed after curative resection but initially misdiagnosed as adenocarcinoma. A 68-year-old woman was referred to our department for surgery for gastric adenocarcinoma presenting as a polypoid lesion with central ulceration located in the upper body of the stomach. The preoperative diagnosis was confirmed by endoscopic biopsy. We performed laparoscopic total gastrectomy, and the final pathologic evaluation led to the diagnosis of primary gastric malignant melanoma without a primary lesion detected in the body. To the best of our knowledge, primary gastric malignant melanoma is extremely rare, and this is the first case reported in our country. According to the literature, it has aggressive biologic activity compared with adenocarcinoma, and curative resection is the only promising treatment strategy. In our case, the patient received an early diagnosis and underwent curative gastrectomy with radical lymphadenectomy, and no recurrence was noted for about two years. PMID:25580362

Cho, Jun-Min; Lee, Chang Min; Jang, You-Jin; Park, Sung-Soo; Park, Seong-Heum; Kim, Seung-Joo; Mok, Young-Jae; Kim, Chong-Suk; Lee, Ju-Han

2014-01-01

203

Synthesis and biological evaluation of derivatives of 2-{2-fluoro-4-[(2-oxocyclopentyl)methyl]phenyl}propanoic acid: nonsteroidal anti-inflammatory drugs with low gastric ulcerogenic activity.  

PubMed

We previously reported that 2-fluoroloxoprofen has lower gastric ulcerogenic activity than loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID) without selectivity for COX-2. We synthesized derivatives of 2-fluoroloxoprofen and studied their properties. Compared to 2-fluoroloxoprofen, one derivative, 11a, exhibited higher anti-inflammatory activity and an equivalent ulcerogenic effect. These results suggest that 11a could be therapeutically beneficial for use as an NSAID. PMID:22404396

Yamakawa, Naoki; Suemasu, Shintaro; Okamoto, Yoshinari; Tanaka, Ken-Ichiro; Ishihara, Tomoaki; Asano, Teita; Miyata, Keishi; Otsuka, Masami; Mizushima, Tohru

2012-06-14

204

Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations  

PubMed Central

Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

2012-01-01

205

A Novel Functional TagSNP Rs7560488 in the DNMT3A1 Promoter Is Associated with Susceptibility to Gastric Cancer by Modulating Promoter Activity  

PubMed Central

DNA-methyltransferase (DNMT)-3A which contains DNMT3A1 and DNMT3A2 isoforms have been suggested to play a crucial role in carcinogenesis and showed aberrant expression in most cancers. Accumulated evidences also indicated that single nucleotide polymorphisms (SNP) in DNMT genes were associated with susceptibility to different tumors. We hypothesized that genetic variants in DNMT3A1 promoter region are associated with gastric cancer risk. We selected the tagSNPs from the HapMap database for the Chinese and genotyped in a case-control study to evaluate the association with gastric cancer (GC) in a Chinese population. We identified that the functional tagSNP rs7560488 T>C associated with a significantly increased risk of GC. In vitro functional analysis by luciferase reporter assay and EMSA indicated that the tagSNP rs7560488 T>C substantially altered transcriptional activity of DNMT3A1 gene via influencing the binding of some transcriptional factors, although a definite transcriptional factor remains to be established. Compared with TT homozygotes, subjects who were TC heterozygotes and CC homozygotes exhibited a reduced expression of DNMT3A1. Furthermore, stratified analysis showed that individuals who harbor TC or CC genotypes less than 60 years old were more susceptible to GC. Our results suggest that the genetic variations in the DNMT3A1 promoter contribute to the susceptibility to GC and also provide an insight that tagSNP rs7560488 T>C may be a promising biomarker for predicting GC genetic susceptibility and a valuable information in GC pathogenesis. PMID:24667323

Gong, Pihai; Qiao, Fengchang; Wang, Ling; Cui, He; Sui, Xinyuan; Gao, Jifan; Fan, Hong

2014-01-01

206

Comparative study of the antitumor activity of Nab-paclitaxel and intraperitoneal solvent-based paclitaxel regarding peritoneal metastasis in gastric cancer.  

PubMed

Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has been shown to be a promising treatment strategy for peritoneal metastasis. The present study focused on the comparative evaluation of the therapeutic efficacy of nanoparticle albumin-bound PTX (Nab-PTX) and i.p. administration of the conventional solvent-based PTX (Sb-PTX). We also investigated the difference in antitumor activity depending on the route of administration in the Nab-PTX treatment. Nab-PTX was administered i.p. or intravenously (i.v.) and Sb-PTX was administered i.p. at equitoxic and equal doses to nude mice bearing gastric cancer OCUM-2MD3 cell subcutaneous and peritoneal xenografts. Therapeutic efficacy of Sb-PTX and Nab-PTX was evaluated as inhibition of tumor growth using a peritoneal metastatic model with subcutaneous xenografts. The survival rate was also investigated using mouse peritoneal models. For assessment of subcutaneous tumors, the change in tumor volume was measured, and for assessment of peritoneal tumors, the weight of ascitic fluid and the total peritoneal tumor burden were measured for each individual mouse. At equitoxic doses, treatment with Nab-PTX resulted in a greater reduction in the size of subcutaneous tumors and the weight of ascites and peritoneal burden as compared with i.p. Sb-PTX (p<0.05). Treatment with i.p. and i.v. Nab-PTX also achieved greater survival benefit than i.p. Sb-PTX (p<0.05). In contrast, there was no significant difference in the degree of tumor reduction and the survival time between both drugs at equal doses. With regard to the route of administration, the antitumor efficacy of Nab-PTX after i.v. administration was equivalent to the efficacy after i.p. administration. These results suggest that i.v. Nab-PTX may be another encouraging treatment option that can target peritoneal dissemination in gastric cancer. PMID:24859429

Kinoshita, Jun; Fushida, Sachio; Tsukada, Tomoya; Oyama, Katsunobu; Watanabe, Toshihumi; Shoji, Masatoshi; Okamoto, Koichi; Nakanuma, Shinichi; Sakai, Seisho; Makino, Isamu; Furukawa, Hiroyuki; Hayashi, Hironori; Nakamura, Keishi; Inokuchi, Masahumi; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Ninomiya, Itasu; Fujimura, Takashi; Masakazu, Yashiro; Hirakawa, Kosei; Ohta, Tetsuo

2014-07-01

207

Pioglitazone induced gastric acid secretion.  

PubMed

PPARgamma agonists, such as pioglitazone, are widely used in the treatment of diabetes and several further disorders. They enhance transcription of the serum and glucocorticoid inducible kinase SGK1, which could in turn enhance gastric acid secretion by stimulating KCNQ1 K+ channels. The present study explored whether pioglitazone upregulates SGK1 protein expression in gastric glands and thus modifies gastric acid secretion. Food containing the PPARgamma agonist pioglitazone (approximately 25 mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1-/-, n=11) and their wild-type littermates (sgk1+/+, n=11). Western blotting was employed to analyze SGK1 expression, BCECF-fluorescence to determine acid secretion in isolated gastric glands and immunohistochemistry to elucidate KCNQ1 and H+/K+-ATPase protein abundance in the parietal cell membrane. Pioglitazone significantly increased SGK1 expression. Cytosolic pH and cellular buffer capacity were not significantly different between sgk1+/+ and sgk1-/- mice and not significantly modified in either genotype by pioglitazone. Without pioglitazone treatment, Na+-independent pH-recovery following an ammonium pulse (DeltapH/min) reflecting H+/K+-ATPase activity was again similar in sgk1+/+ and sgk1-/- mice. Pioglitazone significantly increased DeltapH/min (approximately 3 fold) in sgk1+/+ but not in sgk1-/- mice. H+/K+-ATPase inhibitor omeprazole (100 microM) abolished DeltapH/min in both genotypes irrespective of pioglitazone treatment. Increase in local K+ concentrations to 35 mM (replacing Na+/NMDG) significantly increased DeltapH/min and abrogated the differences between genotypes. KCNQ1 and H+/K+-ATPase protein abundance in the parietal cell membrane was enhanced by pioglitazone treatment in sgk1+/+ but not in sgk1-/- mice. In conclusion, pioglitazone increases gastric acid secretion, an effect at least partially due to stimulation of SGK1 expression and SGK1-dependent upregulation of KCNQ1. PMID:19710534

Rotte, Anand; Mack, Andreas F; Bhandaru, Madhuri; Kempe, Daniela S; Beier, Norbert; Scholz, Wolfgang; Dicks, Edith; Pötzsch, Sven; Kuhl, Dietmar; Lang, Florian

2009-01-01

208

Update on gastric varices  

PubMed Central

Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding remains a serious complication of portal hypertension, with a high associated mortality. In this review we provide an update on the aetiology, classification and management of gastric varices, including acute bleeding, prevention of rebleeding and primary prophylaxis. We describe the optimum management strategies for gastric varices including drug, endoscopic and radiological therapies, focusing on recent published evidence. PMID:24891929

Triantafyllou, Maria; Stanley, Adrian J

2014-01-01

209

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

PubMed

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

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

2015-02-01

210

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

PubMed Central

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

2014-01-01

211

Treatment Option Overview (Gastric Cancer)  

MedlinePLUS

... are different types of treatment for patients with gastric cancer. Different types of treatments are available for patients with gastric cancer . Some treatments are standard (the currently used ...

212

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

PubMed Central

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

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

2015-01-01

213

Human Primary Gastric Dendritic Cells Induce a Th1 Response to H. pylori  

PubMed Central

Adaptive CD4 T-cell responses are important in the pathogenesis of chronic Helicobacter pylori gastritis. However, the gastric antigen-presenting cells that induce these responses have not yet been identified. Here we show that dendritic cells (DCs) are present in the gastric mucosa of healthy subjects but are more prevalent and more activated in the gastric mucosa of H. pylori -infected subjects. H. pylori induced gastric DCs isolated from noninfected subjects to express increased levels of CD11c, CD86 and CD83, and to secrete proinflammatory cytokines, particularly interleukin (IL)-6 and IL-8. Importantly, gastric DCs pulsed with live H. pylori, but not control DCs, mediated T-cell secretion of interferon-?. The ability of H. pylori to induce gastric DC maturation and stimulate gastric DC activation of Th1 cells implicates gastric DCs as initiators of the immune response to H. pylori. PMID:20237463

Bimczok, D; Clements, RH; Waites, KB; Novak, L; Eckhoff, DE; Mannon, PJ; Smith, PD; Smythies, LE

2013-01-01

214

Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease.  

PubMed Central

Gastro-oesophageal reflux disease is a common condition with a complex pathophysiology. Despite the spectrum of abnormalities, gastric acid has a central role in mucosal damage, and the mainstay of medical treatment is suppression of gastric acid secretion. The results of antisecretory treatment as assessed by endoscopic healing are reviewed. H2 receptor antagonists give more rapid symptom relief than placebo and can produce endoscopic improvement in 31-88% of cases depending on the severity of oesophagitis. Complete healing, however, is seen only in 27-45% of patients and these have mainly grades I-II disease. Improved healing rates can be obtained by increasing the degree of acid suppression or the length of treatment. The addition of a prokinetic agent may be beneficial. Omeprazole heals 67-92% of patients overall and although most successful in the lower grades of oesophagitis, can also heal 48-62% of patients with grade IV disease. The degree and rate of healing seem to be related to the reduction in oesophageal acid exposure and thus may correlate with the degree and duration of acid suppression over 24 hours obtained by the various treatments. The underlying pathophysiology is unchanged, however, and long term treatment may be needed to maintain remission. PMID:1346769

Bell, N J; Hunt, R H

1992-01-01

215

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

PubMed Central

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

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

2015-01-01

216

Gastric lipase secretion in children with gastritis.  

PubMed

Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis. PMID:23899880

Tomasik, Przemyslaw J; W?drychowicz, Andrzej; Rogatko, Iwona; Zaj?c, Andrzej; Fyderek, Krzysztof; Sztefko, Krystyna

2013-08-01

217

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

PubMed Central

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

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

2015-01-01

218

First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying  

Microsoft Academic Search

Background—Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol.Aims—To study the effect of modulation of GE on FPM of ethanol in the stomach and liver.Methods—Sixteen volunteers

C M Oneta; U A Simanowski; M Martinez; A Allali-Hassani; X Parés; N Homann; C Conradt; R Waldherr; W Fiehn; C Coutelle; H K Seitz

1998-01-01

219

Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity  

Microsoft Academic Search

Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells that recognize both H+, K+-adenosine triphosphatase and H. pylori antigens. We characterized the submolecular specificity of such gastric T cells and identified cross-reactive epitopes

A. Amedei; M. P. Bergman; B. J. Appelmelk; A. Azzurri; M. Benagiano; C. Tamburini; R. van der Zee; J. L. Telford; C. M. J. E. Vandenbroucke-Grauls; M. M. D'Elios; G. Del Prete

2003-01-01

220

Treatment of gastric cancer  

PubMed Central

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

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

221

Gastric Necrosis due to Acute Massive Gastric Dilatation  

PubMed Central

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

222

Activation of PAX3-MET pathways due to miR-206 loss promotes gastric cancer metastasis.  

PubMed

MicroRNAs (miRNAs) are thought to have an important role in tumor metastasis by regulating diverse cellular pathways. Here, we describe the function and regulation network of miR-206 in gastric cancer (GC) metastasis. MiR-206 expression was downregulated in GC cells especially in high metastatic potential cells and was also significantly decreased in metastatic lesions compared with their corresponding primary tumor samples. Both gain- and loss-of-function studies confirmed that miR-206 significantly suppressed GC cell invasion and metastasis both in vitro and in vivo. Mechanistically, paired box gene 3 (PAX3) was identified as a functional target of miR-206 in GC cells. MiR-206 inhibited GC metastasis by negatively regulating expression of PAX3. In addition, PAX3 expression was markedly higher in GC tissues than in adjacent non-cancerous tissues. GC patients with positive PAX3 expression had shorter overall survival times. Transwell assays and in vivo metastasis assays demonstrated that overexpression of PAX3 significantly promoted the invasiveness and pulmonary metastasis of GC cells. On the other hand, downregulation of PAX3 markedly reduced cell metastatic potential. Mechanistic investigations indicated that prometastasis function of PAX3 was mediated by upregulating downstream target MET. Moreover, we found that levels of PAX3 and MET were positively correlated in matched human GC specimens, and their coexpression was associated with poor prognoses. In conclusion, our results reveal that miR-206-PAX3-MET signaling is critical to GC metastasis. Targeting the pathway described here may open new therapeutic prospects to restrict the metastatic potential of GC. PMID:25653235

Zhang, Lin; Xia, Limin; Zhao, Lina; Chen, Zhangqian; Shang, Xin; Xin, Jing; Liu, Muhan; Guo, Xuegang; Wu, Kaichun; Pan, Yanglin; Fan, Daiming

2015-03-01

223

Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP  

Microsoft Academic Search

Aims\\/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (cAMP) production was assessed in Chinese hamster lung fibroblast

F. P. M. O'Harte; V. A. Gault; J. C. Parker; P. Harriott; M. H. Mooney; C. J. Bailey; P. R. Flatt

2002-01-01

224

IL-1?-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9  

PubMed Central

Background Interleukin-1? (IL-1?) has been implicated in the progression of gastric adenocarcinoma (GA); however, the molecular mechanisms of action of IL-1? in GA are poorly characterized. P38 and JNK are the major MAPK family members that regulate IL-1? signaling pathways. Here, we investigated the role of both p38 and JNK in IL-1?-induced GA cell migration, invasion and metastatic potential. Methods The effects of IL-1?-induced p38 and JNK activation in GA cells were determined using in vitro Transwell migration and invasion assays of MKN-45 and AGS cells, or an in vivo metastasis assay in nude mice. The IL-1?-induced p38 signaling pathway was further characterized in GA cells. Activation of the IL-1?/p38 signaling pathway was also assessed in human primary GA tissues by immunohistochemistry. Results IL-1?-induced activation of p38 increased GA cell migration and invasion in vitro and promoted the metastatic potential of GA cells in vivo; these effects were attenuated by p38 siRNA or the p38 inhibitor SB202190. MMP2 or MMP9 siRNAs and the MMP2/9 inhibitor BiPS also inhibited IL-1?-induced GA cell migration and invasion in vitro. IL-1?-induced p38 activation significantly increased MMP2 and MMP9 mRNA and protein expression and activity. Luciferase reporter assays demonstrated that the activator protein-1 (AP-1) and the AP-1 binding sites of the MMP9 promoter (?670/MMP9) were activated by IL-1?-induced p38 activation. Phospho-p38 was significantly upregulated in human GA tissues (compared to matched non-neoplastic tissues), and significantly associated with lymph node metastasis, and invasion beyond the serosa. Expression of phospho-p38 significantly correlated with IL-1?, MMP2, MMP9, and c-fos expression in both human GA tissues and GA cell metastases in the lungs of nude mice. IL-1? was also capable of activating JNK in GA cells, but activation of JNK was not associated with GA cell migration and invasion. Therefore, IL-1?-induced the migration and invasion in GA cells were regulated by p38, but not by JNK. Conclusions IL-1?-induced p38 activation and the IL-1?/p38/AP-1(c-fos)/MMP2 & MMP9 pathway play an important role in metastasis in GA; this pathway may provide a novel therapeutic target for GA. PMID:24479681

2014-01-01

225

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

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.

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

2008-12-01

226

Protective effects of steroid saponins from Paris polyphylla var. yunnanensis on ethanol- or indomethacin-induced gastric mucosal lesions in rats: structural requirement for activity and mode of action.  

PubMed

The methanolic extract from the rhizomes of Paris polyphylla SM. var. yunnanensis (FR.) H-M. was found to potently inhibit ethanol-induced gastric lesions in rats. Through bioassay-guided separation, four known spirostanol-type steroid saponins, pennogenin 3-O-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-arabinofuranosyl(1-->4)]-beta-D-glucopyranoside (1), pennogenin 3-O-alpha-L-rhamnopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-glucopyranoside (2), diosgenin 3-O-alpha-L-rhamnopyranosyl(1-->2)-[alpha-L-arabinofuranosyl(1-->4)]-beta-D-glucopyranoside (3), and diosgenin 3-O-alpha-L-rhamnopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D-glucopyranoside (4), and a new furostanol-type steroid saponin, parisaponin I (5), together with two known furostanol-type steroid saponins, trigofoenoside A (6) and protogracillin (7), were isolated from the active fraction. Compounds 1-4 (1.25-10 mg/kg, po) strongly inhibited gastric lesions induced by ethanol and indomethacin. With regard to structural requirement of steroid saponins, the 3-O-glycoside moiety and spirostanol structure were found to be essential for the activity and the 17-hydroxyl group in the aglycon part enhanced the protective effects against ethanol-induced gastric lesions. The protective effects of 1 and 3 against ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin and N-ethylmaleimide. Compounds 1 and 3 weakly inhibited acid secretions in pylorus-ligated rats. These findings suggested that endogenous prostaglandins and sulfhydryl compounds were involved in the protective activity. PMID:12643921

Matsuda, Hisashi; Pongpiriyadacha, Yutana; Morikawa, Toshio; Kishi, Akinobu; Kataoka, Shinya; Yoshikawa, Masayuki

2003-03-24

227

Gastric conduit perforation.  

PubMed

As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized. PMID:25133156

Patil, Nilesh; Kaushal, Arvind; Jain, Amit; Saluja, Sundeep Singh; Mishra, Pramod Kumar

2014-08-16

228

Gastric conduit perforation  

PubMed Central

As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized. PMID:25133156

Patil, Nilesh; Kaushal, Arvind; Jain, Amit; Saluja, Sundeep Singh; Mishra, Pramod Kumar

2014-01-01

229

Signal transducer and activator of transcription 3 signaling upregulates fascin via nuclear factor-?B in gastric cancer: Implications in cell invasion and migration.  

PubMed

Fascin protein plays important roles in tumor metastasis and is prognostically relevant to human gastric cancer (GC). However, its role in the development and progression of GC has not been comprehensively investigated. In the present study, results revealed that upregulation of fascin by interleukin-6 promotes GC cell migration and invasion in a signal transducer and activator of transcription 3 (STAT3)-dependent manner in MKN45 cells. Furthermore, STAT3 directly regulated fascin expression and nuclear factor-?B (NF-?B) bound to the fascin promoter in a STAT3-dependent and Notch-independent manner. Therefore, results demonstrate that STAT3 and NF-?B are required for upregulation of fascin and for cell migration and invasion in MKN45 cells. Effects of the treatments on cell signaling were detected by qPCR, western blot analysis and chromatin immunoprecipitation (ChIP) assay. Cell migration and invasion were analyzed using in vitro scratch wound healing assay, transwell and Matrigel assays, and xenograft model. In addition, the STAT3-NF-?B-fascin signaling axis is identified as a therapeutic target for blocking GC cell invasion and migration. PMID:24527098

Yao, Jun; Qian, Cui-Juan; Ye, Bei; Zhao, Zhi-Qiang; Wei, Jie; Liang, Yong; Zhang, Xin

2014-03-01

230

MicroRNA-183 inhibits gastric cancer proliferation and invasion via directly targeting Bmi-1  

PubMed Central

The aberrant expression of microRNA-183 (miRNA/miR-183) has been found to be involved in numerous tumor types. However, the role of miR-183 in gastric cancer pathology is unclear and requires investigation. In the present study, the miR-183 expression levels of gastric cancer cell lines and tissues obtained from gastric cancer patients were measured by reverse transcription quantitative polymerase chain reaction analysis. The effect of miR-183 on gastric cancer cell proliferation and invasion was evaluated using MTT, colony formation and Transwell assays. The target of miR-183 was identified and confirmed using a luciferase activity assay. The results revealed that miR-183 was significantly downregulated in gastric cancer cells compared with GES-1 normal gastric epithelial cells. In addition, miR-183 was reduced in gastric cancer tissues compared with adjacent normal tissues. The ectopic expression of miR-183 significantly inhibited gastric cancer cell proliferation, colony formation and invasion. Bmi-1 was also confirmed as a downstream target of miR-183 in the gastric cancer cells by western blot analysis and luciferase activity assays. In conclusion, miR-183 is downregulated in gastric cancer cells and tissues, and inhibits gastric cancer cell proliferation and invasion by targeting Bmi-1. Therefore, targeting miR-183 may be a potential therapeutic strategy in gastric cancer patients. PMID:25295122

XU, LANG; LI, YUHONG; YAN, DAN; HE, JUN; LIU, DAN

2014-01-01

231

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

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.

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

2013-01-01

232

APC sensitive gastric acid secretion.  

PubMed

Adenomatous polyposis coli (APC) is a tumor suppressor gene inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying a loss-of-function mutation in the apc gene (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC fosters degradation of beta-catenin, which in turn upregulates the serum- and glucocorticoid-inducible kinase SGK1. SGK1 stimulates KCNQ1, which is required for luminal K+ recycling and thus for gastric acid secretion. BCECF-fluorescence was utilized to determine gastric acid secretion in isolated gastric glands from apc(Min/+) mice and their wild type littermates (apc(+/+)). Western blotting was employed to analyse beta-catenin and SGK1 expression and immunohistochemistry to determine KCNQ1 protein abundance. beta-catenin and SGK1 expression were enhanced in apc(Min/+) mice. Cytosolic pH was similar in apc(Min/+) mice and apc(+/+) mice. Na+-independent pH recovery following an ammonium pulse (DeltapH/min), which reflects H+/K+ ATPase activity, was, however, significantly faster in apc(Min/+) mice than in apc(+/+)mice. In both genotypes DeltapH/min was abolished in the presence of H+/K+ ATPase inhibitor omeprazole (100 microM). Treatment of apc(Min/+) and apc(+/+)mice with 5 microM forskolin 15 minutes prior to the experiment or increase in local K+-concentrations to 35 mM (replacing Na+/NMDG) significantly increased DeltapH/min and abrogated the differences between genotypes. The increase of DeltapH/min in apc(Min/+)mice required SGK1, as it was abolished by additional knockout of SGK1 (apc(Min/+)/sgk1(-/-)). In conclusion, basal gastric acid secretion is significantly enhanced in apc(Min/+)mice, pointing to a role of APC in the regulation of gastric acid secretion. The effect of APC requires H+/K+ ATPase activity and is at least partially due to SGK1-dependent upregulation of KCNQ1. PMID:19255508

Rotte, Anand; Bhandaru, Madhuri; Föller, Michael; Biswas, Raja; Mack, Andreas F; Friedrich, Björn; Rexhepaj, Rexhep; Nasir, Omaima; Ackermann, Teresa F; Boini, Krishna M; Kunzelmann, Karl; Behrens, Jürgen; Lang, Florian

2009-01-01

233

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

PubMed

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

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

234

Treatment Options by Stage (Gastric Cancer)  

MedlinePLUS

... available from the NCI Web site . Stage I Gastric Cancer Treatment of stage I gastric cancer may ... available from the NCI Web site . Stage II Gastric Cancer Treatment of stage II gastric cancer may ...

235

Localization of gastric peroxidase and its inhibition by mercaptomethylimidazole, an inducer of gastric acid secretion.  

PubMed Central

Mercaptomethylimidazole (MMI) is a potent inducer of gastric acid secretion which is associated with significant inhibition of peroxidase activity of rat gastric mucosa in vivo. A time-dependent increase in acid secretion correlates well with time-dependent decrease in the peroxidase activity. In a chamber experiment in vitro using isolated gastric mucosa, MMI stimulates acid secretion, showing an almost linear response up to 600 microM. The time-dependent increase in acid secretion is also correlated with time-dependent inhibition of the peroxidase activity. This effect is not mediated through oxidation of MMI by flavin-containing mono-oxygenase, which is absent from gastric mucosa. The peroxidase has been localized mainly in parietal cells isolated and purified from gastric mucosa by controlled digestion with collagenase followed by Percoll-density-gradient centrifugation. Peroxidase activity was further localized in the outer membrane of the purified mitochondria of the parietal cell by some membrane-impermeant reagents, indicating outward orientation of the enzyme. MMI can inhibit the peroxidase activity of both the parietal cell and its mitochondria in a concentration-dependent manner. The possible involvement of the parietal-cell peroxidase-H2O2 system in MMI-induced acid secretion may be suggested. PMID:1318028

Bandyopadhyay, U; Bhattacharyya, D K; Chatterjee, R; Banerjee, R K

1992-01-01

236

Occupation and gastric cancer  

PubMed Central

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

Raj, A; Mayberry, J; Podas, T

2003-01-01

237

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

PubMed

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

Gomathy, G; Venkatesan, D; Palani, S

2014-12-01

238

In Oesophageal Squamous Cells Exposed to Acidic Bile Salt Medium, Omeprazole Inhibits IL-8 Expression through Effects on Nuclear Factor-?B and Activator Protein-1  

PubMed Central

Objective Oesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPIs) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts. Design Human primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-?B and AP-1 subunits to the IL-8 promoter was assessed by ChIP assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system. Results Acidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-?B and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-?B subunit) and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration. Conclusions In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-?B and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognized PPI effects might contribute to the healing of reflux oesophagitis. PMID:24048734

Huo, Xiaofang; Zhang, Xi; Yu, Chunhua; Zhang, Qiuyang; Cheng, Edaire; Wang, David H.; Pham, Thai H.; Spechler, Stuart J.; Souza, Rhonda F.

2013-01-01

239

Capsaicin and Gastric Ulcers  

Microsoft Academic Search

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

M. N. Satyanarayana

2006-01-01

240

Gastric cáncer: Overview.  

PubMed

Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer. PMID:24892619

Piazuelo, M Blanca; Correa, Pelayo

2013-07-01

241

Gastric cáncer: Overview  

PubMed Central

Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidence in some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases being diagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is a complex and multifactorial process involving a number of etiological factors and multiple genetic and epigenetic alterations. Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and in a small percentage of patients, a familial genetic component. More than 95% of stomach cancer cases are adenocarcinomas, which are classified into two major histologic types: intestinal and diffuse. Intestinal type adenocarcinoma is preceded by a sequence of gastric lesions known as Correa´s cascade and is the histologic type associated with the global decrease in gastric cancer rates. Diffuse type adenocarcinomas have a more aggressive behavior and worse prognosis than those of the intestinal type. According to the anatomical location, adenocarcinomas are classified as proximal (originating in the cardia) and distal (originating in the body and antrum). This classification seems to recognize two different clinical entities. Surgical resection of the tumor at an early stage is the only effective treatment method. Therefore, the identification and surveillance of patients at risk may play a significant role in survival rates. Anti-Helicobacter pylori therapy has been shown to be an effective measure in the prevention of gastric cancer. PMID:24892619

Correa, Pelayo

2013-01-01

242

Role of Notch signaling pathway in gastric cancer pathogenesis  

PubMed Central

Notch signaling pathway is activated dynamically during evolution playing significant role in cell fate determination and differentiation. It has been known that alterations of this pathway may lead to human malignancies, including gastric cancer. Despite a decline in the overall incidence, this disease still remains an important global health problem. Therefore, a better understanding of the molecular alterations underlying gastric cancer may contribute to the development of rationally designed molecular targeted therapies. It has been reported that Notch1 receptor could become a prognostic marker of gastric cancer and novel target for gastric cancer therapy. Among the novel and targeted approaches for the treatment of gastric cancer is also the process of Notch receptors regulation by specific microRNA. ?-secretase inhibitors are also taken into consideration. PMID:23788953

Miela?czyk, ?ukasz; Michalski, Marek; Malinowski, ?ukasz; Kowalczyk-Ziomek, Gra?yna; Helewski, Krzysztof; Harabin-S?owi?ska, Marzena; Wojnicz, Romuald

2013-01-01

243

A review on gastric leptin: the exocrine secretion of a gastric hormone  

PubMed Central

A major advance in the understanding of the regulation of food intake has been the discovery of the adipokine leptin a hormone secreted by the adipose tissue. After crossing the blood-brain barrier, leptin reaches its main site of action at the level of the hypothalamic cells where it plays fundamental roles in the control of appetite and in the regulation of energy expenditure. At first considered as a hormone specific to the white adipose tissue, it was rapidly found to be expressed by other tissues. Among these, the gastric mucosa has been demonstrated to secrete large amounts of leptin. Secretion of leptin by the gastric chief cells was found to be an exocrine secretion. Leptin is secreted towards the gastric lumen into the gastric juice. We found that while secretion of leptin by the white adipose tissue is constitutive, secretion by the gastric cells is a regulated one responding very rapidly to secretory stimuli such as food intake. Exocrine-secreted leptin survives the hydrolytic conditions of the gastric juice by forming a complex with its soluble receptor. This soluble receptor is synthesized by the gastric cells and the leptin-leptin receptor complex gets formed at the level of the gastric chief cell secretory granules before being released into the gastric lumen. The leptin-leptin receptor upon resisting the hydrolytic conditions of the gastric juice is channelled, to the duodenum. Transmembrane leptin receptors expressed at the luminal membrane of the duodenal enterocytes interact with the luminal leptin. Leptin is actively transcytosed by the duodenal enterocytes. From the apical membrane it is transferred to the Golgi apparatus where it binds again its soluble receptor. The newly formed leptin-leptin receptor complex is then secreted baso-laterally into the intestinal mucosa to reach the blood capillaries and circulation thus reaching the hypothalamus where its action regulates food intake. Exocrine-secreted gastric leptin participates in the short term regulation of food intake independently from that secreted by the adipose tissue. Adipose tissue leptin on the other hand, regulates in the long term energy storage. Both tissues work in tandem to ensure management of food intake and energy expenditure. PMID:22536547

Cammisotto, Philippe

2012-01-01

244

A review on gastric leptin: the exocrine secretion of a gastric hormone.  

PubMed

A major advance in the understanding of the regulation of food intake has been the discovery of the adipokine leptin a hormone secreted by the adipose tissue. After crossing the blood-brain barrier, leptin reaches its main site of action at the level of the hypothalamic cells where it plays fundamental roles in the control of appetite and in the regulation of energy expenditure. At first considered as a hormone specific to the white adipose tissue, it was rapidly found to be expressed by other tissues. Among these, the gastric mucosa has been demonstrated to secrete large amounts of leptin. Secretion of leptin by the gastric chief cells was found to be an exocrine secretion. Leptin is secreted towards the gastric lumen into the gastric juice. We found that while secretion of leptin by the white adipose tissue is constitutive, secretion by the gastric cells is a regulated one responding very rapidly to secretory stimuli such as food intake. Exocrine-secreted leptin survives the hydrolytic conditions of the gastric juice by forming a complex with its soluble receptor. This soluble receptor is synthesized by the gastric cells and the leptin-leptin receptor complex gets formed at the level of the gastric chief cell secretory granules before being released into the gastric lumen. The leptin-leptin receptor upon resisting the hydrolytic conditions of the gastric juice is channelled, to the duodenum. Transmembrane leptin receptors expressed at the luminal membrane of the duodenal enterocytes interact with the luminal leptin. Leptin is actively transcytosed by the duodenal enterocytes. From the apical membrane it is transferred to the Golgi apparatus where it binds again its soluble receptor. The newly formed leptin-leptin receptor complex is then secreted baso-laterally into the intestinal mucosa to reach the blood capillaries and circulation thus reaching the hypothalamus where its action regulates food intake. Exocrine-secreted gastric leptin participates in the short term regulation of food intake independently from that secreted by the adipose tissue. Adipose tissue leptin on the other hand, regulates in the long term energy storage. Both tissues work in tandem to ensure management of food intake and energy expenditure. PMID:22536547

Cammisotto, Philippe; Bendayan, Moise

2012-03-01

245

Osteogenesis Imperfecta, Pseudoachalasia, and Gastric Cancer  

PubMed Central

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

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

2015-01-01

246

Endoscopic treatment for early gastric cancer  

PubMed Central

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

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

2014-01-01

247

GASTRIC REFLUX IN MECHANICALLY VENTILATED GASTRIC FED ICU PATIENTS  

E-print Network

Background: Reflux of gastric contents in gastric fed patients is a contributor to pulmonary aspiration. Aspiration events are reported in approximately 50-75% of patients with endotracheal tubes. Aspiration of oral and ...

Schallom, Marilyn

2013-08-31

248

Glutathione and GSH-dependent enzymes in the human gastric mucosa  

Microsoft Academic Search

Summary The ?-glutamyl-transferase activity, the total glutathione content, the GSH-peroxidase activity, and the GSH S-transferase activity using an aryl substrate were estimated in the S9 fraction of gastric biopsy specimens taken from patients with normal stomach morphology (n=24), acute gastritis (n=15), chronic-atrophic gastritis (n=10), gastric ulcer (n=9), and carcinoma of the stomach (n=12). The total glutathione content of normal gastric

R. Hoppenkamps; E. Thies; M. Younes; C.-P. Siegers

1984-01-01

249

A Method for Estimation of Urease Activity in Gastric Mucosa Biopsy Specimens and Helicobacter pylori Cell Suspensions  

Microsoft Academic Search

A method for measuring urease activity in biopsy specimens and Helicobacter pylori cultures from these specimens is proposed. The method is based on measurement (with a portable pH-meter) of the rate of pH changes in a reaction mixture consisting of buffer, substrate (urea), and biopsy specimen or bacterial cells. This method revealed that urease activity of biopsy specimens correlated with

N. O. Vartanova; V. G. Arzumanyan; I. A. Basnak'yan; K. G. Kaverina; T. A. Chulok

2002-01-01

250

History of minimally invasive surgery for gastric cancer in Korea.  

PubMed

Laparoscopic gastrectomy was begun in 1995 in Korea. But, there was 4 years gap to reactivate in 1999. High incidence of gastric cancer and increasing proportion of early cancer through national screening program along with huge effort and enthusiasm of laparoscopic gastric surgeon, and active academic exchange with Japanese doctors contributed development of laparoscopic gastrectomy in Korea. Study group activity of Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) group and Collaborative Action for Gastric Cancer (COACT) group were paramount to evoke large scale multicenter clinical study and various well performed clinical studies. This review encompasses mainly international publications about this area so far in Korea. PMID:22500259

Kim, Young-Woo; Yoon, Hong Man; Eom, Bang Wool; Park, Ji Yeon

2012-03-01

251

New spiral bacterium in gastric mucosa  

Microsoft Academic Search

A new spiral bacterium, distinct from Campylobacter pylori, was found in the gastric mucosa of six patients with gastrointestinal symptoms. All patients had chronic active type B gastritis and four had oesophagitis. Culture and microscopy for C pylori infection was negative. These unculturable spiral organisms were probably an incidental finding in patients presenting for upper gastrointestinal endoscopy, but it is

C A McNulty; J C Dent; A Curry; J S Uff; G A Ford; M W Gear; S P Wilkinson

1989-01-01

252

Gastric cancer and trastuzumab: first biologic therapy in gastric cancer  

PubMed Central

Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer. PMID:23450234

Gunturu, Krishna S.; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.

2013-01-01

253

The Role of Gastrokine 1 in Gastric Cancer  

PubMed Central

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

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

2014-01-01

254

Gastric Electrical Stimulation  

PubMed Central

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

2006-01-01

255

Gastric emphysema secondary to laparoscopic gastric band erosion  

PubMed Central

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

Su, Michael Z.; Munro, William S.

2014-01-01

256

Do We Need Gastric Acid?  

Microsoft Academic Search

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

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

2008-01-01

257

Epigenetic alterations in gastric carcinogenesis  

Microsoft Academic Search

Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss

In-Seon CHOI; Tsung-Teh WU

2005-01-01

258

Gastric cancer is associated with NOS2 -954G\\/C polymorphism and environmental factors in a Brazilian population  

Microsoft Academic Search

BACKGROUND: Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from Helicobacter pylori infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (NOS2), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of NOS2

Yvana C Jorge; Marcia C Duarte; Ana E Silva

2010-01-01

259

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

Microsoft Academic Search

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

Ellen J. Beswick; Victor E. Reyes

2008-01-01

260

Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors  

PubMed Central

We evaluated the effects of two laboratory stressors (speech preparation and isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and the extent to which autonomic responses to these stressors and somatization predict reports of motion sickness during exposure to a rotating optokinetic drum. Both stressors prompted a decrease in preejection period (PEP) and respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced decreases in RSA and higher somatization scores predicted increased reports of motion sickness during drum rotation. These results demonstrate that laboratory stressors concurrently affect gastric myoelectrical activity and autonomic control of the heart, and that stressor-induced decreases in RSA and higher levels of somatization predict motion sickness susceptibility. PMID:11446577

GIANAROS, PETER J.; QUIGLEY, KAREN S.; MORDKOFF, J. TOBY; STERN, ROBERT M.

2010-01-01

261

Gastric metabolism of ethanol in Syrian golden hamster.  

PubMed

First-pass metabolism (FPM) of orally ingested alcohol has been attributed to gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we sought a species lacking this enzyme. We found that Syrian golden hamsters have negligible gastric ADH yet alcohol FPM (265 +/- 25 mg ethanol/kg) was comparable to that of rats (251 +/- 31 mg/kg). To determine whether hamster gastric mucosal cells metabolize sufficient alcohol to account for this FPM, primary cultures were established, and these cells metabolized 1.99 +/- 0.84 mumol ethanol/10(6) cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa (870 +/- 93 units/g tissue) was eightfold higher than in rat gastric mucosa (111 +/- 9 units/g tissue; P < 0.0001). FPM in hamsters treated with 3-aminotriazole was reduced from 242 +/- 24 to 130 +/- 22 mg/kg (P < 0.05) but was not reduced in rats. The results imply that catalase participates in gastric alcohol metabolism of hamsters. PMID:8536535

Batra, S C; Haber, P S; Mirmiran-Yazdy, F S; Korsten, M A; Gentry, R T; Lieber, C S

1995-12-01

262

Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells  

SciTech Connect

Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M-BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.

Yasuda, Hiroshi [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan)]. E-mail: hiroshi-yasuda@showa-university-fujigaoka.gr.jp; Hirata, Shuko [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan); Inoue, Kazuaki [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan); Mashima, Hirosato [Department of Gastroenterology, University of Tokyo, Tokyo (Japan); Ohnishi, Hirohide [Department of Gastroenterology, Jichi Medical School, Tochigi 329-0498 (Japan); Yoshiba, Makoto [Division of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Yokohama 227-8501 (Japan)

2007-03-02

263

Mouse Models of Gastric Carcinogenesis  

PubMed Central

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

Yu, Sungsook; Yang, Mijeong

2014-01-01

264

Performance of microbial phytases for gastric inositol phosphate degradation.  

PubMed

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

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

2015-01-28

265

of Gastric Submucosal Tumor  

E-print Network

Purpose: Laparoscopic wedge resection of gastric submucosal tumor may be difficult in case of the endophytic mass or the mass located unreachable area such as cardia, and intragastric approach can be useful. We would present the experiences of the intragastric wedge resection. Materials and Methods: There were 7 patients diagnosed as gastric submucosal tumor and underwent the intragastric wedge resection at Surgery, Chungnam National University Hospital. We reviewed medical record. Results: There were 3 male and 4 female. Mean age was 65 years-old (57~73). Mean body mass index was 26.28 kg/m 2 (21.28~35.30). Location of lesions was 4 cardia, 2 fundus and 1 midbody, respectively. Mean operation time was 83.6 minutes (70~105). All patients were healed without any complication. Mean postoperative hospital stay was 5.4 days (4~6). Mean size was 2.7 cm (2.3~3.8). Pathologic finding was 5 gastrointestinal stromal tumor and 2 leiomyoma. Conclusions: The single incision intragastric wedge resection of gastric submucosal tumor is feasible and acceptable, especially in mass of gastric upper part. Key Words: Laparoscopy; Surgical procedures, minimally invasive; Gastrointestinal stromal tumors; Gastrectomy; Stomach neoplasms

266

Primary gastric Hodgkin's lymphoma  

Microsoft Academic Search

BACKGROUND: Primary Hodgkin's disease of the stomach is an extremely rare entity. Nearly all cases of primary gastric lymphoma are of the non-Hodgkin's variety. Diagnoses in such cases are difficult due to considerable histological similarities between the 2 disease entities. CASE PRESENTATION: We report the case of a 77 year old lady with a 1 year history of weight loss

Fahad S Hossain; Yashwant Koak; Farrukh H Khan

2007-01-01

267

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

SciTech Connect

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

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

2006-07-07

268

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

PubMed

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

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

2015-04-01

269

Gastroprotective Activity of Violacein Isolated from Chromobacterium violaceum on Indomethacin-Induced Gastric Lesions in Rats: Investigation of Potential Mechanisms of Action  

PubMed Central

Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K+ATP channels, and ?2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K+ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability. PMID:25162059

Antonisamy, Paulrayer; Kannan, Ponnusamy; Aravinthan, Adithan; Duraipandiyan, Veeramuthu; Valan Arasu, Mariadhas; Ignacimuthu, Savarimuthu; Abdullah Al-Dhabi, Naif; Kim, Jong-Hoon

2014-01-01

270

Molecular Mimicry between Helicobacter pylori Antigens and H+,K+–Adenosine Triphosphatase in Human Gastric Autoimmunity  

PubMed Central

Autoimmune gastritis and Helicobacter pylori–associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+–adenosine triphosphatase as autoantigen. Here, we report that H. pylori–infected patients with gastric autoimmunity harbor in vivo–activated gastric CD4+ T cells that recognize both H+,K+–adenosine triphosphatase and H. pylori antigens. We characterized the submolecular specificity of such gastric T cells and identified cross-reactive epitopes from nine H. pylori proteins. Cross-reactive H. pylori peptides induced T cell proliferation and expression of T helper type 1 functions. We suggest that in genetically susceptible individuals, H. pylori infection can activate cross-reactive gastric T cells leading to gastric autoimmunity via molecular mimicry. PMID:14568977

Amedei, Amedeo; Bergman, Mathijs P.; Appelmelk, Ben J.; Azzurri, Annalisa; Benagiano, Marisa; Tamburini, Carlo; van der Zee, Ruurd; Telford, John L.; Vandenbroucke-Grauls, Christina M.J.E.; D'Elios, Mario M.; Del Prete, Gianfranco

2003-01-01

271

Molecular mimicry between Helicobacter pylori antigens and H+, K+ --adenosine triphosphatase in human gastric autoimmunity.  

PubMed

Autoimmune gastritis and Helicobacter pylori-associated gastric atrophy develop through similar mechanisms involving the proton pump H+,K+-adenosine triphosphatase as autoantigen. Here, we report that H. pylori-infected patients with gastric autoimmunity harbor in vivo-activated gastric CD4+ T cells that recognize both H+, K+-adenosine triphosphatase and H. pylori antigens. We characterized the submolecular specificity of such gastric T cells and identified cross-reactive epitopes from nine H. pylori proteins. Cross-reactive H. pylori peptides induced T cell proliferation and expression of T helper type 1 functions. We suggest that in genetically susceptible individuals, H. pylori infection can activate cross-reactive gastric T cells leading to gastric autoimmunity via molecular mimicry. PMID:14568977

Amedei, Amedeo; Bergman, Mathijs P; Appelmelk, Ben J; Azzurri, Annalisa; Benagiano, Marisa; Tamburini, Carlo; van der Zee, Ruurd; Telford, John L; Vandenbroucke-Grauls, Christina M J E; D'Elios, Mario M; Del Prete, Gianfranco

2003-10-20

272

Molecular specificity and functional properties of autoreactive T-cell response in human gastric autoimmunity.  

PubMed

Human autoimmune gastritis (AIG) is a chronic inflammatory disorder of the gastric corpus. We have defined the antigen repertoire and the functional properties of in vivo activated CD4+ T cells derived from the gastric mucosa of patients with AIG. A remarkable proportion of the CD4+ T cell clones proliferated in response to H+,K+-ATPase. Six epitopes identified in the alpha chain, and 5 in the beta chain, of gastric K+,K+-ATPase were recognized by autoreactive gastric T cell clones. The majority of the autoreactive T cell clones secreted IFN-gamma and showed a T helper 1 (Th1) profile. All clones produced TNF-alpha,provided help for B cell immunoglobulin production, expressed perforin-mediated cytotoxicity, and most induced Fas-Fas ligand-mediated apoptosis. Data suggest that activation of gastric H+,K+-ATPase-specific Th1 T cells is crucial in the pathogenesis of human gastric autoimmunity and atrophy. PMID:15763992

D'Elios, Mario M; Amedei, Amedeo; Azzurri, Annalisa; Benagiano, Marisa; Del Prete, Gianfranco; Bergman, Mathijs P; Vandenbroucke-Grauls, Christina M; Appelmelk, Ben J

2005-01-01

273

[Surgical treatment of gastric carcinoma].  

PubMed

The gastric cancer is the most common cancer in Korea. The only treatment modality showing improved survival for gastric cancer is curative surgical resection, which comprises the resection of stomach, proper lymphadenectomy, and reconstruction. However, specific surgical procedures should be decided according to the location of the cancer, advancement of the tumor, and patients condition. Surgical treatment for gastric cancer has been developed toward two directions that are minimal invasive surgery for early gastric cancer and multi-disciplinary approach for advanced gastric cancer. Laparoscopic surgery for early gastric cancer has been accepted for minimally invasive surgery. Moreover, the advancement of diagnostic tools to assess biological aggressiveness of the tumor enables physicians to perform endoscopic resection or minimized resection for early gastric cancer. Recently, surgeons try to extend the application of laparoscopic gastric resection and D2 lymphadenectomy to advanced gastric cancer. However, technical and oncological evidences based on clinical trials should be filed up before adopting it as a standard therapy. In case of advanced gastric cancer, in addition to radical surgery, various treatment modalities including chemotherapy, radiation, and molecular target therapy also have been applied in many clinical trials. However, it should be stressed that a prerequisite for precise evaluation of the efficacy of these combined treatment modalities would be the standardization of surgical procedure. PMID:19696536

Hur, Hoon; Park, Cho Hyun

2009-08-01

274

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

Microsoft Academic Search

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

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

2004-01-01

275

Gastric inhibitory polypeptide and gastric acid secretion in pregnant rats  

Microsoft Academic Search

The effects of pregnancy on the basal and pentagastrin-stimulated gastric acid secretion and the level of plasma gastric inhibitory polypeptide (GIP) in rats were studied on pentobarbital-anaesthetized non pregnant rats and rats in the 1st, 2nd, or 3rd week of gestation. Acid output was determined by titration of the gastric perfusate. Basal secretion was collected for 45 min before a

T.-S. Chen; G.-H. Yeh; H.-F. Pu; M.-L. Doong; C.-C. Lu; S.-R. Liu; T.-K. Young; L.-T. Ho; F.-Y. Chang; P. S. Wanga

1995-01-01

276

[Multidisciplinary therapy for gastric cancer with liver metastasis].  

PubMed

Gastric cancer with liver metastasis (GCLM) is the leading cause of death in patients with advanced gastric cancer. Multiple metastasis was common in GCLM and usually complicated with lesions outside the liver, especially peritoneal metastasis. Most of liver metastasis lesions could not be resected radically. Currently, main treatments for GCLM included radical operation, palliative resection of gastric cancer, ablation of metastatic lesions, intervention and systemic chemotherapy. Based on the current progress in the treatment for GCLM and our clinical experience, the general status of patients, the type of gastric cancer and the degree of liver metastasis should be analyzed, and a cooperative multidisciplinary team (MDT) should be applied to conduct and to choose active and suitable comprehensive treatment for GCLM patients based on individualized therapy principle. PMID:24577759

Chen, Lin; Xi, Hongqing; Shen, Weisong

2014-02-01

277

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

PubMed

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

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

2014-01-01

278

Gastric bezoars: treatment and prevention.  

PubMed

Gastric bezoars may occur in the normal stomach as a result of ingestion of various objects which do not pass through the pylorus. Most gastric bezoars occur as a complication of previous gastric surgery in which there is a loss of normal pyloric function, hypoperistalsis, and low gastric acidity. They may also occur as a complication of cimetidine therapy. Symptoms include epigastric fullness, regurgitation, nausea and vomiting, and epigastric pain. A simple treatment utilizing an ordinary Teledyne Water Pik jet stream through a gastroscope is described to break up a large phytobezoar. This method is probably the treatment of choice and should be used more widely. PMID:6720657

Rider, J A; Foresti-Lorente, R F; Garrido, J; Puletti, E J; Rider, D L; King, A H; Bradley, S P

1984-05-01

279

Lifestyle and gastric function.  

PubMed

The stomach has a range of functions, including chemical digestion and mechanical breakdown of food, temporary storage of bulk intake, and regulation of the passage of nutrients into the duodenum. Further gastric functions are the nonspecific defense against microbes entering the gastrointestinal tract, preparation of ions as well as liberation of protein-bound cobalamin and production of intrinsic factor for uptake further along the tract, and finally limited absorption of water, alcohol, and some fat-soluble food components including some drugs. These functions are influenced by various lifestyle factors, such as smoking and alcohol intake with interference by Helicobacter pylori colonization. This paper focuses on the interaction between lifestyle and gastric function. PMID:24732183

Kuipers, Ernst J

2014-01-01

280

Gastric cancer review  

PubMed Central

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

Carcas, Lauren Peirce

2014-01-01

281

Laparoscopic Adjustable Gastric Banding  

Microsoft Academic Search

. We introduced open adjustable silicone gastric banding (ASGB) for treatment of morbid obesity in our institution\\u000a in 1991. It was done in a prospective study comparing ASGB with vertical banded gastroplasty (VBG) with regard to weight loss.\\u000a After 200 cases of open ASGB and 210 VBG procedures and the encouraging weight loss results, we started laparoscopic placement\\u000a of the

Mitiku Belachew; Marc Legrand; Vernon Vincent; Michel Lismonde; Nicole Le Docte; Veronique Deschamps

1998-01-01

282

Tricholithobezoar Causing Gastric Perforation  

PubMed Central

A bezoar is an intraluminal mass formed by the accumulation of undigested material in the gastrointestinal tract. Trichobezoar is a rare condition seen almost exclusively in young women with trichotillomania and trichotillophagia. When not recognized, the trichobezoar continues to grow, which increases the risk of severe complications such as gastric ulceration and even perforation. Formation of a gallstone within the trichobezoar (tricholithobezoar) is an event that has not yet been described. We report the case of a 22-year-old woman admitted to the emergency room with signals and symptoms of an epigastric mass and perforative acute abdomen. Radiological study revealed bilateral pneumoperitoneum. Personal history revealed depressive syndrome, trichotillomania and trichophagia. With a diagnosis of visceral perforation, an urgent exploratory laparotomy was performed. This confirmed the diagnosis of gastric perforation due to a large trichobezoar with the formation of a gastrolith that was removed by anterior gastrotomy. Biochemical study of the gastric stone revealed that it was composed of bile salts. There were no complications. The patient was discharged on the 5th postoperative day and was referred for psychiatric treatment. PMID:22379468

Santos Valenciano, Juliana; Nonose, Ronaldo; Bragattini Cruz, Rodrigo; Tiemi Sato, Daniela; Monteiro Fernandes, FelipeCappellette; Fabrício Nascimento, Enzo; Real Martinez, Carlos Augusto

2012-01-01

283

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

PubMed Central

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

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

2014-01-01

284

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

PubMed

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

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

2015-01-01

285

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

PubMed Central

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

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

2015-01-01

286

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

PubMed Central

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

2014-01-01

287

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

NASA Technical Reports Server (NTRS)

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.

Zabrodin, O. N.

1980-01-01

288

Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric cancer  

PubMed Central

Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin. PMID:25780510

Kim, Min Ji; Hong, Ji Hyung; Park, Eun Su; Byun, Jae Ho

2015-01-01

289

Gastric metastasis from primary lung adenocarcinoma mimicking primary gastric cancer.  

PubMed

Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin. PMID:25780510

Kim, Min Ji; Hong, Ji Hyung; Park, Eun Su; Byun, Jae Ho

2015-03-15

290

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

PubMed Central

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

2014-01-01

291

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

NASA Astrophysics Data System (ADS)

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.

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

292

Transcytosis of gastric leptin through the rat duodenal mucosa.  

PubMed

Leptin is secreted into the gastric juice by epithelial Chief cells and reaches the duodenum in a biologically intact active form. We assessed the possibility that this gastric leptin crosses the intestinal mucosa by transcytosis through enterocytes to reach blood circulation. Endogenous gastric leptin secretion was triggered by cholinergic stimulation. In another set of experiments, recombinant leptin was inserted in vivo into the duodenal lumen. Plasma levels of leptin were assessed by enzyme immunoassay and Western blot, and duodenal tissue was processed for immunocytochemistry. We first observed that leptin was found inside duodenal enterocytes from fed rats but not inside those from fasted ones. Stimulation of gastric secretion by a cholinergic agent led to rapid increases in plasma leptin levels (202 +/- 39%) except when the pylorus was clamped. Insertion of recombinant leptin into the duodenal lumen raised plasma leptin concentrations (558 +/- 34%) quite rapidly, whereas carrier solution without leptin had no effect. The use of FITC-tagged leptin reinforced these results. Light and electron microscopy revealed the cellular compartments involved in its transcytosis, namely, the enterocyte microvilli, the endocytotic vesicles, the Golgi complex, and the basolateral interdigitations. Leptin was also present in the lamina propria, in capillary endothelial cell plasmalemmal vesicles, and in capillary lumina. These results demonstrate that gastric exocrine leptin is internalized by duodenal enterocytes and delivered to the lamina propria and blood circulation. It may thus be able to play important paracrine and endocrine functions for the control of gastric emptying and nutrient absorption. PMID:17673543

Cammisotto, Philippe G; Gingras, Diane; Bendayan, Moïse

2007-10-01

293

INCREASE IN GASTRIC ACID-INDUCED AFFERENT INPUT TO THE BRAINSTEM IN MICE WITH GASTRITIS  

PubMed Central

Acid challenge of the gastric mucosa is signalled to the brainstem. This study examined whether mild gastritis due to dextrane sulfate sodium (DSS) or iodoacetamide (IAA) enhances gastric acid-evoked input to the brainstem and whether this effect is related to gastric myeloperoxidase activity, gastric histology, gastric volume retention or cyclooxygenase stimulation. The stomach of conscious mice was challenged with NaCl (0.15 M) or HCl (0.15 and 0.25 M) administered via gastric gavage. Two hours later, activation of neurons in the nucleus tractus solitarii (NTS) was visualized by c-Fos immunocytochemistry. Gastritis was induced by DSS (molecular weight 8,000; 5 %) or IAA (0.1 %) added to the drinking water for 7 days. Relative to NaCl, intragastric HCl increased the number of c-Fos protein-expressing cells in the NTS. Pretreatment with DSS or IAA for 1 week did not alter the c-Fos response to NaCl but significantly enhanced the response to HCl by 54 and 74 %, respectively. Either pretreatment elevated gastric myeloperoxidase activity and induced histological injury of the mucosal surface. In addition, DSS caused dilatation of the gastric glands and damage to the parietal cells. HCl-induced gastric volume retention was not altered by IAA but attenuated by DSS pretreatment. Indomethacin (5 mg/kg) failed to significantly alter HCl-evoked expression of c-Fos in the NTS of control, DSS-pretreated and IAA-pretreated mice. We conclude that the gastritis-evoked increase in the gastric acid-evoked c-Fos expression in the NTS is related to disruption of the gastric mucosal barrier, mucosal inflammation, mucosal acid influx and enhanced activation of the afferent stomach – NTS axis. PMID:17303342

Holzer, Peter; Wultsch, Thomas; Edelsbrunner, Martin; Mitrovic, Martina; Shahbazian, Anaid; Painsipp, Evelin; Bock, Elisabeth; Pabst, Maria Anna

2015-01-01

294

Mouse Models of Gastric Cancer  

PubMed Central

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

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

2013-01-01

295

Epigenetic mechanisms in gastric cancer.  

PubMed

Cancer is considered one of the major health issues worldwide, and gastric cancer accounted for 8% of total cases and 10% of total deaths in 2008. Gastric cancer is considered an age-related disease, and the total number of newly diagnosed cases has been increasing as a result of the higher life expectancy. Therefore, the basic mechanisms underlying gastric tumorigenesis is worth investigation. This review provides an overview of the epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling complex and miRNA, involved in gastric cancer. As the studies in gastric cancer continue, the mapping of an epigenome code is not far for this disease. In conclusion, an epigenetic therapy might appear in the not too distant future. PMID:22690664

Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Burbano, Rommel Rodriguez; Smith, Marilia Arruda Cardoso

2012-06-01

296

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

PubMed

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

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

2014-12-01

297

Gastric band migration following laparoscopic adjustable gastric banding (LAGB): two cases of endoscopic management using a gastric band cutter.  

PubMed

Laparoscopic adjustable gastric banding (LAGB) is one of the most frequently used minimally invasive and reversible procedures for the treatment of morbid obesity. Migration of the gastric band into the gastric lumen is a rare late complication of LAGB. Previous attempts at endoscopic removal of migrated bands have included the use of endoscopic scissors, laser ablation and argon plasma coagulation (APC). We report two cases of successful endoscopic management of gastric band migration using a gastric band cutter. PMID:23256012

Rogalski, Pawel; Hady, Hady Razak; Baniukiewicz, Andrzej; D?browski, Andrzej; Kaminski, Fabian; Dadan, Jacek

2012-06-01

298

Aurora Kinase A Promotes Inflammation and Tumorigenesis in Mice and Human Gastric Neoplasia  

PubMed Central

Background & Aims Chronic inflammation contributes to the pathogenesis of gastric tumorigenesis. The Aurora kinase A gene (AURKA) is frequently amplified and overexpressed in gastrointestinal cancers. We investigated the roles of AURKA in inflammation and gastric tumorigenesis. Methods We used quantitative real-time reverse transcription PCR, immunofluorescence, immunohistochemistry, luciferase reporter, immunoblot, co-immunoprecipitation, and in vitro kinase assays to analyze AGS and MKN28 gastric cancer cells. We also analyzed Tff1?/? mice, growth of tumor xenografts, and human tissues. Results We correlated increased expression of AURKA with increased levels of tumor necrosis factor-? and inflammation in the gastric mucosa of Tff1?/? mice (r = 0.62; P=.0001). MLN8237, an investigational small-molecule selective inhibitor of AURKA, reduced nuclear staining of NF?Bp65 in human gastric cancer samples and mouse epithelial cells, suppressed NF?B reporter activity, and reduced the expression of NF?B target genes that regulate inflammation and cell survival. Inhibition of AURKA also reduced growth of xenograft tumors from human gastric cancer cells in mice and reversed the development of gastric tumors in Tff1?/? mice. AURKA was found to regulate NF?B activity by binding directly and phosphorylating I?B? in cells. Premalignant and malignant lesions from the gastric mucuosa of patients had increased levels of AURKA protein and nuclear NF?B, compared with healthy gastric tissue. Conclusions In analyses of gastric cancer cell lines, human tissue samples, and mouse models, we found AURKA to be upregulated during chronic inflammation to promote activation of NF?B and tumorigenesis. AURKA inhibitors might be developed as therapeutic agents for gastric cancer. PMID:23993973

Katsha, Ahmed; Soutto, Mohammed; Sehdev, Vikas; Peng, Dunfa; Washington, M. Kay; Piazuelo, M. Blanca; Tantawy, Mohammed N.; Manning, H. Charles; Lu, Pengcheng; Shyr, Yu; Ecsedy, Jeffrey; Belkhiri, Abbes; El-Rifai, Wael

2013-01-01

299

Diosmin Protects against Ethanol-Induced Gastric Injury in Rats: Novel Anti-Ulcer Actions  

PubMed Central

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

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

2015-01-01

300

Pediatric Gastric Teratoma  

PubMed Central

Neoplasms from germ cell origin are a heterogeneous group of tumors rarely seen in the pediatric population, teratoma is the most frequent among them. They can occur in either gonadal or extragonadal locations. Extragonadal teratoma arising from abdominal viscera is very unusual. There are less than a hundred reported cases of gastric teratoma in the worldwide literature. Since the occurrence of this pathology in the pediatric age group is quite rare, we describe a case of a teratoma located in the lesser curvature of the stomach in an infant with an emphasis in radiologic-pathologic correlation. PMID:22470691

Valenzuela-Ramos, Marco Cesar; Mendizábal-Méndez, Ana Luisa; Ríos-Contreras, Carlos Alberto; Rodríguez-Montes, Claudia Esther

2010-01-01

301

Low direct cytotoxicity of loxoprofen on gastric mucosal cells.  

PubMed

Pro-drugs of non-steroidal anti-inflammatory drugs (NSAIDs), such as loxoprofen are widely used for clinical purposes because they are not so harmful to the gastrointestinal mucosa. We recently showed that NSAIDs such as indomethacin and celecoxib have direct cytotoxicity (ability to induce necrosis and apoptosis in gastric mucosal cells) due to their membrane permeabilizing activities, which is involved in NSAID-induced gastric lesions. We show here that under conditions where indomethacin and celecoxib clearly induce necrosis and apoptosis, loxoprofen and its active metabolite loxoprofen-OH, do not have such effects in primary culture of guinea pig gastric mucosal cells. Loxoprofen and loxoprofen-OH induced apoptosis more effectively in cultured human gastric cancer cells than in the primary culture. Loxoprofen and loxoprofen-OH exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We thus consider that the low direct cytotoxicity of loxoprofen observed in vitro is involved in its relative safety on production of gastric lesions in clinical situation. PMID:20190399

Yamakawa, Naoki; Suemasu, Shintaro; Kimoto, Ayumi; Arai, Yasuhiro; Ishihara, Tomoaki; Yokomizo, Kazumi; Okamoto, Yoshinari; Otsuka, Masami; Tanaka, Ken-Ichiro; Mizushima, Tohru

2010-01-01

302

The Use of Lentinan for Treating Gastric Cancer  

PubMed Central

Natural compounds containing fungal ?-glucans have been used to improve general health for thousands of years in China and Japan. Lentinan, the backbone of ?-(1, 3)-glucan with ?-(1, 6) branches, is one of the active ingredients purified from Shiitake mushrooms and has been approved as a biological response modifier for the treatment of gastric cancer in Japan. Despite recent advances in chemotherapeutic agents, unresectable or recurrent gastric cancer remains an incurable disease, with survival rates being far from satisfactory. Recent clinical studies have shown that chemo-immunotherapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemotherapy alone. In addition, trastuzumab, an antibody against HER2/neu growth factor receptor, has been used for the treatment of gastric cancer in combination with cytotoxic chemotherapeutic agents. Lentinan may exert a synergistic action with anti-cancer monoclonal antibodies to activate complement systems through the mechanism of antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. Because a better understanding of its biological activities should enable us to use lentinan more efficiently in the treatment of gastric cancer, immunological effects provided by ?-glucans, a possible mode of action of lentinan, and its clinical application including future potential uses are discussed in the present review. PMID:23092289

Ina, Kenji; Kataoka, Takae; Ando, Takafumi

2013-01-01

303

Photodynamic therapy of gastric cancer  

NASA Astrophysics Data System (ADS)

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

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

1996-01-01

304

Comprehensive molecular characterization of gastric adenocarcinoma  

PubMed Central

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

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

305

Comprehensive molecular characterization of gastric adenocarcinoma.  

PubMed

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

2014-09-11

306

Micrometastasis in gastric cancer.  

PubMed

Circulating tumor cells (CTCs) are a crucial contributor and indicator for cancer metastasis. The presence of CTCs and other two forms of occult disease including circulating tumor microembolus (CTMs) as well as disseminated tumor cells (DTCs) as a sign for micrometastasis has been associated with adverse survival of both localized and metastatic cancers. However, their assignments in micrometastasis are still not well understood. This mini-review is aimed to provide an overview of the biological features and the clinical impact of CTCs, DTCs and CTM in gastric cancer (GC), and to summarize the technical limitations of detection methods in addition to the significance of distinct migration modes in epithelial-mesenchymal transition (EMT) and gastric micrometastasis. Although there are controversies over current CTC identification strategies, both single and collective migration modes as indispensable parts of micrometastasis are influential participants in GC progression, diagnosis and prognosis. CTCs, CTM and DTCs are not separated forms of the occult disease; however available techniques fail to detect all subsets of them. Therefore, micrometastatic detection should be combined with conventional pathological examinations in order to make more accurate predictions of tumor outcomes. Novel markers further defining the features of CTC subsets are warranted. PMID:23624301

Zhang, Zhen-yu; Ge, Hai-yan

2013-08-01

307

Sonic Hedgehog Pathway Contributes to Gastric Cancer Cell Growth and Proliferation  

PubMed Central

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

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

2014-01-01

308

Human gastric juice contains chitinase that can degrade chitin.  

PubMed

Chitin digestion by humans has generally been questioned or denied. Only recently chitinases have been found in several human tissues and their role has been associated with defense against parasite infections and to some allergic conditions. In this pilot study we tested the gastric juices of 25 Italian subjects on the artificial substrates 4-methylumbelliferyl-beta-D-N,N',diacetylchitobiose or/and fluorescein isothiocyanate (FITC) chitin to demonstrate the presence of a chitinase activity. Since this chitinase activity was demonstrated at acidic pH, it is currently referred to acidic mammalian chitinase (AMCase). AMCase activity was present in gastric juices of twenty of 25 Italian patients in a range of activity from 0.21 to 36.27 nmol/ml/h and from 8,881 to 1,254,782 fluorescence emission (CPS), according to the used methods. In the remaining five of 25 gastric juices, AMCase activity was almost absent in both assay methods. An allosamidine inhibition test and the measurement at different pH values confirmed that this activity was characteristic of AMCase. The absence of activity in 20% of the gastric juices may be a consequence of virtual absence of chitinous food in the Western diet. PMID:17587796

Paoletti, Maurizio G; Norberto, Lorenzo; Damini, Roberta; Musumeci, Salvatore

2007-01-01

309

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

PubMed Central

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

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

2014-01-01

310

Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide.  

PubMed

Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-? and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-? and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-? and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress. PMID:21640099

Luo, Xiu-Ju; Li, Nian-Sheng; Zhang, Yi-Shuai; Liu, Bin; Yang, Zhi-Chun; Li, Yuan-Jian; Dong, Xin-Rong; Peng, Jun

2011-09-01

311

Delayed gastric emptying after pancreatoduodenectomy.  

PubMed

With pylorus-preserving pancreatoduodenectomy (PPPD) the goal is to reduce long-term morbidities such as gastric dumping, marginal ulceration or bile-reflux gastritis. Compared with te classical Whipple procedure, PPPD is affected by an equal postoperative morbidity but is known to induce delayed gastric emptying (DGE). It is difficult to evaluate the true incidence of DGE after PPPD (from 5 to 50% according to the literature). Early and low doses of erythromycin in the postoperative period could prevent the onset of DGE and the administration of cisapride 15 mg/day improves gastric emptying up to 6 months after PPPD. PMID:12914377

Closset, J; Gelin, M

2003-06-01

312

Analysis of gastric emptying data  

SciTech Connect

How should gastric emptying data be summarized to allow comparisons between males or between groups of subjects within a study, and to facilitate comparisons of results from study to study. We review standardization issues for reporting gastric emptying data, discuss criteria for choosing a method of analysis, review methods which have been used to describe gastric emptying data, recommend trial of the power exponential curve, and illustrate its use in the analysis and interpretation of data from several studies involving different types of meals and different types of subjects. We show why nonlinear curves should be fit using nonlinear least squares.

Elashoff, J.D.; Reedy, T.J.; Meyer, J.H.

1982-12-01

313

Characterization of sonic hedgehog inhibition in gastric carcinoma cells  

PubMed Central

Aberrant activation of the sonic hedgehog (Shh) signaling pathway plays an important role in gastric cancer. The exact mechanisms defining how the Shh pathway promotes tumorigenesis or regulates its downstream targets remains elusive. In the present study, the effects of inhibiting the Shh signaling pathway in gastric cancer AGS cells was examined. It was identified that the Shh antagonist, cyclopamine, inhibited cancer proliferation, migration and invasion in a dose- and time-dependent manner. Additionally, it was revealed that several key targets that are activated by the Shh signaling pathway, Gli1 and CXCR4, were downregulated at an RNA and protein level by cyclopamine. The results from the present study may be of benefit in facilitating the development of novel therapeutic strategies to treat gastric cancer in human patients. PMID:24765141

BAI, RUXUE; ZHAO, HONGCHUAN; ZHANG, XIANG; DU, SHIYU

2014-01-01

314

Gastric decontamination--a view for the millennium.  

PubMed Central

The management of acute poisoning remains an important part of accident and emergency (A&E) care. Three gastric decontamination procedures have been widely used: gastric lavage, ipecac, and activated charcoal. Their role has recently been reviewed and position statements developed by working groups of the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. These have important implications for A&E, as they indicate that activated charcoal is now the agent of choice for most poisons, but than in most situations it is probably only effective if given within an hour of overdose. Ipecac is effectively obsolete and gastric lavage has a narrow range of indications, principally for potentially serious amounts of agents not adsorbed by charcoal. Protocols for care of overdose patients should be modified accordingly. PMID:10191436

Bateman, D N

1999-01-01

315

Gastric autoimmunity: the role of Helicobacter pylori and molecular mimicry.  

PubMed

Pathogens can induce autoreactive T cells to initiate autoimmune disease by several mechanisms. Pathogen-induced inflammation results in the enhanced presentation of self antigens, which causes the expansion of the activated autoreactive T cells that are required for disease onset. Alternatively, a pathogen might express antigens with epitopes that are structurally similar to epitopes of autoantigens, resulting in a mechanism of molecular mimicry. This is the case for Helicobacter pylori-associated human autoimmune gastritis, in which the activated CD4+ Th1 cells that infiltrate the gastric mucosa cross-recognize the epitopes of self gastric parietal cell H(+)K(+)-ATPase and of various H. pylori proteins. Therefore, in genetically susceptible individuals, H. pylori infection can start or worsen gastric autoimmunity, leading to atrophic gastritis. PMID:15242679

D'Elios, Mario M; Appelmelk, Ben J; Amedei, Amedeo; Bergman, Mathijs P; Del Prete, Gianfranco

2004-07-01

316

An acid transporting enzyme in human gastric mucosa.  

PubMed Central

Isolation of a microsomal fraction from human gastric mucosa followed by density gradient centrifugation yielded a vesicular membrane preparation free of mitochondrial markers, containing a K+-activated, ouabain-insensitive ATPase with an activity of 20.7 mumol P1 released/mg protein per h. Sodium dodecyl sulfate gel electrophoresis showed that the human gastric membrane vesicles contained a major polypeptide of 110,000 daltons, which accounted for approximately or equal to 30% of the total protein stained and was phosphorylated by [gamma-32P]ATP and dephosphorylated in the presence of K+. Electron microscopy revealed the presence of vesicles with an average size of 0.13 micrometer in diameter. Addition of 0.65 microM ATP to this vesicular preparation resulted in the uptake of 17 nmol H+/mg protein which was dependent on the presence of K+. The gradient was dissipated by a combination of valinomycin and protonophore after consumption of the ATP. Incubation of fixed human fundic sections or human gastric biopsy with monospecific hog gastric membrane antibody followed by fluorescein-conjugated goat anti-rabbit gamma-globulin, showed fluorescent staining in the middle portion of the gastric glands. These data indicate that human stomach contains a H+ transport ATPase with characteristics similar to those established for lower species. Images PMID:156736

Saccomani, G; Chang, H H; Mihas, A A; Crago, S; Sachs, G

1979-01-01

317

RNA interference targeting raptor inhibits proliferation of gastric cancer cells  

SciTech Connect

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.

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

2011-06-10

318

Diffuse type gastric carcinoma presenting as giant gastric folds: lessons learned from six miss diagnosed cases.  

PubMed

Hyperplastic gastropathy is a rare condition characterized by giant gastric folds. There are numerous causes of giant gastric folds included benign diseases (Menetrier's disease, pseudolymphoma and lymphocytic gastritis) and malignant diseases (gastric carcinoma, lymphoma and Zollinger-Ellison syndrome). Six gastric carcinoma presenting as giant gastric folds were described. Lessons learned from six miss diagnosed cases and how to improve the accuracy of diagnosis were elucidated. Moreover, we propose a hypothesis that in diffuse type gastric carcinoma gastric cancer, which manifested with thickness of gastric folds, there must be some media which is released by cancer cells to stimulate superficial mucosa layer benign cells proliferation, instead of malignant cells infiltrating directly. PMID:22651965

Mei, Mei; Jingmei, Ni; Zongming, Chen; Mei, Jin; Leimin, Sun

2012-10-01

319

Serological assessment of gastric mucosal atrophy in gastric cancer  

PubMed Central

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

2012-01-01

320

Protective Effect of Liriodendrin Isolated from Kalopanax pictus against Gastric Injury  

PubMed Central

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

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

321

Gastric emptying following Colles' fracture.  

PubMed Central

There are few complications associated with intravenous regional anaesthesia but convulsions with loss of consciousness induced by local anaesthetic toxicity may result in pulmonary aspiration. In many hospitals, patients are fasted prior to the procedure although such a delay would be of little value if gastric emptying was inhibited following painful injury. Utilizing the kinetics of paracetamol absorption, we investigated the rate of gastric emptying in patients sustaining a Colles' fracture within the previous 4 h. Post-manipulation control values were obtained at their first out-patient attendance. There was no statistically significant difference in the rate of gastric emptying. Since gastric emptying is not delayed by a recent Colles' fracture, the simple precaution of fasting patients prior to intravenous regional anaesthesia should reduce the risk of pulmonary aspiration. PMID:1930499

Steedman, D J; Payne, M R; McClure, J H; Prescott, L F

1991-01-01

322

Gastric tissue biopsy and culture  

MedlinePLUS

Abnormal results may be due to: Gastric cancer Gastritis, when the lining of the stomach becomes inflamed ... Saunders; 2010:chap 40. Lee EL, Feldman M. Gastritis and gastropathies. In: Feldman M, Friedman LS, Brandt ...

323

General Information about Gastric Cancer  

MedlinePLUS

... attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is a type of targeted therapy used in the treatment of gastric cancer. Monoclonal antibody therapy uses antibodies made in the laboratory from a ...

324

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

SciTech Connect

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.

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

2013-10-04

325

[Ocular metastasis heralding gastric adenocarcinoma].  

PubMed

Ocular metastasis is a rare presenting feature of gastric adenocarcinoma. We report a 48-year-old woman who presented with a decrease in visual acuity of the right eye leading to the discovery of an ocular metastasis. Diagnostic work-up identified a gastric adenocarcinoma with pulmonary metastases. She received four cycles of chemotherapy combining epirubicin, cisplatin and fluorouracil. The patient died 6 months after the diagnosis of respiratory failure. PMID:20554090

Chekrine, T; Tawfiq, N; Bouchbika, Z; Benchakroun, N; Jouhadi, H; Sahraoui, S; Benider, A

2010-10-01

326

Gastric perforation after cardiopulmonary resuscitation.  

PubMed

Gastric rupture is a rare complication after cardiopulmonary resuscitation (CPR). In most cases, incorrect management of airways during CPR is the main cause. Therefore, a medical emergency becomes a surgical emergency also. We present a case of gastric perforation in a middle-aged patient after CPR performed by his family. He eventually presented with bloody vomitus and a tympanic abdomen. When faced with a patient with abdominal signs post-CPR, surgical complications of CPR should be considered. PMID:22867822

Jalali, Sayed Mahdi; Emami-Razavi, Hassan; Mansouri, Asieh

2012-11-01

327

Gastric emptying in young pigs  

PubMed Central

1. Gastric emptying in young pigs has been studied by using a serial test meal procedure. 2. Phenol red was used as a reference substance. In acute experiments the recovery of phenol red from the stomach with the pylorus occluded was 94·8 ± 2·2 (S.E.)% of that introduced. 3. Gastric emptying was examined in seven fasted conscious pigs provided with a chronic gastric cannula. After emptying the stomach 500 ml. of a liquid meal containing 20 g citrus pectin, 35·0 g sucrose and 100 mg phenol red made up to 1 l. was introduced. After 5-60 min the meal was withdrawn, the volume of meal that had left the stomach was assessed from the recovery of phenol red and the secretion of gastric juice was calculated from the dilution of phenol red and the rate of emptying. After an initial very rapid outflow, the rate of emptying fell with time, as did the rate of secretion. 4. In three pigs 200, 400, 600 or 800 ml. meal was introduced into the stomach and the stomach was emptied 20 min later. The rate of gastric emptying varied directly with the volume of meal introduced. 5. Atropine sulphate, 0·5 mg/kg body weight, injected I.M. 30 min before the test, greatly inhibited gastric emptying and secretion. PMID:4754870

Ochia, B. A.

1973-01-01

328

Gene methylation in gastric cancer.  

PubMed

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

Qu, Yiping; Dang, Siwen; Hou, Peng

2013-09-23

329

Environmental and lifestyle risk factors of gastric cancer.  

PubMed

Effective prevention and early diagnostic strategies are the most important public health interventions in gastric cancer, which remains a common malignancy worldwide. Preventive strategies require identification and understanding of environmental risk factors that lead to carcinogenesis. Helicobacter pylori (H. pylori) is the primary carcinogen as this ancient bacterium has a complex ability to interact with its human host. Smoking and salt are strong independent risk factors for gastric cancer whereas alcohol is only a risk when it is heavily consumed. Red meat and high fat increase the risk of gastric cancer however fresh fruits, vegetables (allium family) and certain micronutrients (selenium, vitamin C) reduce the risk, with evidence lacking for fish, coffee and tea. Foods that inhibit H. pylori viability, colonization and infection may reduce cancer risk. Obesity is increasingly recognized as a contributory factor in gastric cardia carcinogenesis. Therefore, modest daily physical activities can be protective against cancer. Foundry workers are at risk for developing gastric cancer with dust iron being an important cause. Other risk factors include Epstein-Barr virus (EBV), possibly JC virus and radiation but the effects of these are likely to remain small. PMID:23725070

Lee, Yeong Yeh; Derakhshan, Mohammad H

2013-06-01

330

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

PubMed

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

Gallier, Sophie; Singh, Harjinder

2012-05-01

331

Enhanced expression of long noncoding RNA CARLo-5 is associated with the development of gastric cancer  

PubMed Central

The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are vital for understanding the molecular biology and progression of cancer. The CARLo-5, a newly identified long non-coding RNA, was found to be upregulated in colon cancer. However, little is known about its role in gastric cancer. In the present study, a great upregulation of CARLo-5 was observed in gastric cancer compared to paired adjacent normal tissues. Knockdown of CARLo-5 in gastric cancer cell lines significantly inhibited the cell proliferation via inducing G0/G1 cell-cycle arrest and apoptosis. Furthermore, ERK/MAPK pathway was found to be inactivated in the gastric cells after CARLo-5 knockdown. These results indicated that CARLo-5 might serve as a pro-oncogenic lncRNA that promotes proliferation of gastric cancer and activates the ERK/MAPK pathway. PMID:25674211

Zhang, Yan; Ma, Mingzhe; Liu, Weiyong; Ding, Wenping; Yu, Honggang

2014-01-01

332

Bisdemethoxycurcumin attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction  

PubMed Central

Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin. In this study, a human gastric adenocarcinoma xenograft model was generated in vivo using nude mice and BDMC was observed to suppress the growth and activity of tumors, in addition to improving the physical and mental capacity of the mice. An increased number of apoptotic cells, decreased ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein and increased caspase-3 expression was also observed following treatment with BDMC, indicating that BDMC may promote apoptosis in tumors via mitochondrial modulation. The growth of SGC 7901 gastric cancer cells was inhibited and arrested at G1 phase. Specific indicators of mitochondrial dysfunction, a reduction in adenosine triphosphate generation, the inner mitochondrial membrane potential, augmentation of reactive oxygen species production and cytochrome c were also detected in the mitochondria following treatment with BDMC. These results indicate that BDMC attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction. PMID:25435973

LUO, CHANGJIANG; DU, ZHIXING; WEI, XING; CHEN, GANG; FU, ZHONGXUE

2015-01-01

333

Gastric lipase: localization of the enzyme in the stomach  

SciTech Connect

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.

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

1986-03-05

334

Spiral bacteria in the human stomach: the gastric helicobacters.  

PubMed Central

During the past decade, Helicobacter pylori has become recognized as one of the most common human pathogens, colonizing the gastric mucosa of almost all persons exposed to poor hygienic conditions from childhood. It also is often found, albeit with a lower frequency, in groups of high socioeconomic status. H. pylori causes chronic active gastritis and is a major factor in the pathogenesis of duodenal ulcers and, to a lesser extent, gastric ulcers. In addition, the presence of this bacterium is now recognized as a risk factor for gastric adenocarcinoma and lymphoma. Nevertheless, most infections appear without clinical consequences. In this second decade of intensive research, it is important to understand why H. pylori is sometimes a dangerous pathogen, and to determine how it can be eradicated in those at highest risk for severe disease. PMID:8903168

Dubois, A.

1995-01-01

335

Bisdemethoxycurcumin attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction.  

PubMed

Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin. In this study, a human gastric adenocarcinoma xenograft model was generated in vivo using nude mice and BDMC was observed to suppress the growth and activity of tumors, in addition to improving the physical and mental capacity of the mice. An increased number of apoptotic cells, decreased ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein and increased caspase-3 expression was also observed following treatment with BDMC, indicating that BDMC may promote apoptosis in tumors via mitochondrial modulation. The growth of SGC 7901 gastric cancer cells was inhibited and arrested at G1 phase. Specific indicators of mitochondrial dysfunction, a reduction in adenosine triphosphate generation, the inner mitochondrial membrane potential, augmentation of reactive oxygen species production and cytochrome c were also detected in the mitochondria following treatment with BDMC. These results indicate that BDMC attenuates gastric adenocarcinoma growth by inducing mitochondrial dysfunction. PMID:25435973

Luo, Changjiang; DU, Zhixing; Wei, Xing; Chen, Gang; Fu, Zhongxue

2015-01-01

336

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

PubMed

Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population and are largely due to chronic Helicobacter pylori infection. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis, 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. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling 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 signalling 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 signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease. PMID:25363776

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

2014-12-18

337

Detection of Synchronous Gastric Schwannoma on FDG PET/CT Aided by Discordant Metabolic Response.  

PubMed

This is a case of an unsuspected synchronous gastric schwannoma demonstrating increased F-FDG accumulation on PET/CT in a 65-year-old female patient diagnosed with non-Hodgkin lymphoma on the basis of different metabolic activity to other sites of disease at staging and discordant metabolic response to therapy. The gastric schwannoma was confirmed by histopathology and immunohistochemistry after surgical resection. This case adds to the limited literature on FDG-avid gastric schwannoma and highlights the importance of investigating differential metabolic activity and response on serial PET/CT imaging. PMID:25706785

Yap, June; Huang, Yi-Tung Tom; Lin, Michael

2015-05-01

338

Effects of Ulmi Pumilae Cortex on AGS Gastric Cancer Cells  

PubMed Central

Objective: Ulmi Pumilae Cortex(UPC) is a deciduous tree with uneven pinnate leaves and is classified as a subfamily of Ulmuceae and contains many pharmacologically active constituents. The aim of this study was to investigate the effects of UPC on the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell lines. Methods: The AGS cells were treated with varying concentrations of UPC. Analyses of the sub G1, caspase-3 activity, and mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Furthermore, to identify the role of the transient receptor potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels. Results: The addition of UPC to a culture medium inhibited AGS cell growth and survival. Experimental results showed that the sub G1, caspase-3 activity, and mitochondrial depolarization were increased. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated UPC-induced cell death. Conclusion: These findings indicate that UPC inhibits the growth and survival of gastric cancer cells due to a blockade of the TRPM7 channel activity. Therefore, UPC is a potential drug for treatment of gastric cancer, and TRPM7 channels may play an important role in survival in cases of gastric cancer.

Lim, Bora; Lee, Hee Jung; Kim, Min Chul; Kim, Byung Joo

2013-01-01

339

RhoA Mutations Identified in Diffuse Gastric Cancer  

PubMed Central

The diffuse-type histologic variant of gastric cancer is characterized by highly invasive growth patterns and lack of cellular cohesion. Two recent studies have identified highly recurrent mutations of the gene encoding the small GTPase RhoA and suggest that RhoA activity may have a tumor suppressive role in this disease. PMID:25026207

Zhou, Jin; Hayakawa, Yoku; Wang, Timothy C.; Bass, Adam J.

2014-01-01

340

Absence of ras gene mutations in early gastric carcinomas  

Microsoft Academic Search

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

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

1995-01-01

341

Function and subsets of dendritic cells and natural killer cells were decreased in gastric cancer  

PubMed Central

Dendritic cells (DCs) and natural killer (NK) cells initiate specific immune responses against tumor cells. The aim of the present study was to determine the cytotoxicity and the subsets of the DC and NK cells and the cytokines level of DC and NK cells from cancer tissue and peripheral blood in the gastric cancer patients. Cytotoxicity of DC and NK was determined using the Cytotox non-radioactive assay. The cytotoxic activity of DC or NK isolated from cancer tissue and peripheral blood was attenuated in gastric cancer patients. CD11c, CD80, CD83, CD16, CD57 and CD69 were decreased in the cancer tissue and peripheral blood in the gastric cancer patients. CD86, CCR7 and CD59 were no significance in the cancer tissue and peripheral blood from gastric cancer patients. Tumor necrosis factor (TNF)-?, interleukin (IL)-2, T-bet and IL-15R? levels were decreased in DC and NK from the gastric cancer tissue and peripheral blood in the gastric cancer patients. IL-15 and IL-15R? level were no significance in DC and NK in the gastric cancer tissue and peripheral blood in the gastric cancer patients. These results indicate that the cytotoxic activity and subsets and cytokines of DC and NK cells in the cancer tissue and peripheral blood in the gastric cancer patients were decreased. The decrease of subsets content and cytokines of DC and NK may contribute to a decrease in the function of DC and NK in the tissue and peripheral blood in the gastric cancer patients. PMID:25550889

Chen, Jianping; Yang, Jing; Jiang, Jingting; Zhuang, Yun; He, Wei

2014-01-01

342

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

PubMed Central

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

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

343

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

PubMed

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

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

2014-05-01

344

Risks of Stomach (Gastric) Cancer Screening  

MedlinePLUS

... NCI Publications Español Stomach (Gastric) Cancer Screening (PDQ®) Risks of Stomach (Gastric) Cancer Screening Key Points for ... by the screening test itself. Screening tests have risks. Decisions about screening tests can be difficult. Not ...

345

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

PubMed Central

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

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

2014-01-01

346

Dietary free amino acids and the gastric phase of digestion.  

PubMed

In the stomach, pre-absorptive perception of food constituents is of particular importance in maintaining secretion and motility that matches the quantity and quality of nutrients. Products of food protein hydrolysis, free amino acids and short peptides, are the most potent chemical stimulants of the gastric phase of digestion. They are recognized by a variety of extracellular receptors belonging to the G-protein-coupled receptor superfamily, which are expressed by gastric mucosal exocrine and endocrine cells. Enteroendocrine G and D cells are likely the first level of integration of amino-acid-induced signals influencing a balance of endocrine activation and inhibition of gastric functions. This review focuses mainly on the physiological significance of dietary L-glutamate (Glu) in control of the gastric phase of digestion. The Glu signaling system in the stomach is linked to activation of the vagal afferents. In contrast to other natural amino acids, luminal Glu activates a paracrine cascade led by nitric oxide and followed by serotonin (5-HT), interacting in turn with 5- HT3 receptors on the afferent endings in the sub-mucosal layer. Glu, the only amino acid regularly ingested in a free form, enhances secretory and gastroprokinetic responses to protein- and amino-acid-rich diets but has no effect when applied alone or with carbohydrates. Possible mechanisms are discussed. PMID:23886390

Zolotarev, Vasiliy A

2014-01-01

347

Chestnut extract induces apoptosis in AGS human gastric cancer cells  

PubMed Central

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

Lee, Hyun Sook; Kim, Eun Ji

2011-01-01

348

Gastric adenocarcinoma associated with isolated granulomatous gastritis  

Microsoft Academic Search

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

Christopher Newton; Lucien Nochomovitz; Jonathan M. Sackier

1998-01-01

349

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

PubMed

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

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

2012-12-15

350

Helicobacter pylori secreted peptidyl prolyl cis, trans-isomerase drives Th17 inflammation in gastric adenocarcinoma.  

PubMed

Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer. PMID:23054412

Amedei, Amedeo; Munari, Fabio; Bella, Chiara Della; Niccolai, Elena; Benagiano, Marisa; Bencini, Lapo; Cianchi, Fabio; Farsi, Marco; Emmi, Giacomo; Zanotti, Giuseppe; de Bernard, Marina; Kundu, Manikuntala; D'Elios, Mario Milco

2014-04-01

351

Role of epithelial-mesenchymal transition in gastric cancer initiation and progression  

PubMed Central

Gastric cancer is one of the most common malignant tumors worldwide. Due to its intricate initiation and progression mechanisms, early detection and effective treatment of gastric cancer are difficult to achieve. The epithelial-mesenchymal transition (EMT) is characterized as a fundamental process that is critical for embryonic development, wound healing and fibrotic disease. Recent evidence has established that aberrant EMT activation in the human stomach is closely associated with gastric carcinogenesis and tumor progression. EMT activation endows gastric epithelial cells with increased characteristics of mesenchymal cells and reduces their epithelial features. Moreover, mesenchymal cells tend to dedifferentiate and acquire stem cell or tumorigenic phenotypes such as invasion, metastasis and apoptosis resistance as well as drug resistance during EMT progression. There are a number of molecules that indicate the stage of EMT (e.g., E-cadherin, an epithelial cell biomarker); therefore, certain transcriptional proteins, especially E-cadherin transcriptional repressors, may participate in the regulation of EMT. In addition, EMT regulation may be associated with certain epigenetic mechanisms. The aforementioned molecules can be used as early diagnostic markers for gastric cancer, and EMT regulation can provide potential targets for gastric cancer therapy. Here, we review the role of these aspects of EMT in gastric cancer initiation and development. PMID:24833870

Peng, Zhao; Wang, Chen-Xiao; Fang, Er-Hu; Wang, Guo-Bin; Tong, Qiang

2014-01-01

352

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

PubMed

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

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

2014-01-01

353

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

PubMed Central

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

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

2014-01-01

354

Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.  

PubMed

Curcumin is known to possess anti?inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+?ATPase activity, the mechanism underlying the curcumin?induced inhibition of the transcription of the H+, K+?ATPase ? subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+?ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress?induced gastric ulcers was produced, in which the anti?ulcer effects of curcumin were examined. Curcumin?induced inhibition of the H+, K+?ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress?induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+?ATPase promoter and in the expression of the gastric H+,K+?ATPase ? subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+?ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+?ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease. PMID:25405899

He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

2015-03-01

355

Quercetin protects gastric epithelial cell from oxidative damage in vitro and in vivo.  

PubMed

Epithelial injury caused by reactive oxygen species (ROS) including H2O2 plays a critical role in the pathogenesis of gastric disorders. Therefore, pharmacological intervention targeting reactive oxygen species elimination has highly clinical values in therapy of gastric diseases. Although quercetin has been found to possess gastroprotective activity, whether it has a protective activity againress related injury to gastric epithelial cells remains unknown. The aim of the study is herein to investigate a possible protective effect of quercetin against oxidative stress in vitro and vivo. Human gastric epithelial GES-1 cells were pretreated with quercetin and then challenged with H2O2. In vivo reactive oxygen species production in acute gastric mocosa injury was assessed using a chemiluminescent probe L-012 (8-amino-5-chloro-7-phenylpyrido [3,4-d]pyridazine-1,4-(2H,3H)dione) after quercetin was administered to mice. In GES-1 cells, pretreatment of quercetin can significantly diminish H2O2-induced cell viability loss; decrease intracellular reactive oxygen species and Ca(2+) influx; restore H2O2-induced ??m dissipation. It also upregulates peroxisome proliferator-activated receptor-? coactivator (PGC-1?) expression under the state of oxidative stress, and the downstream cell apoptosis significantly decreased. In vivo, chemiluminescence imaging shows that quercetin attenuates reactive oxygen species production and gastric damages in acute gastric mucosal injury. We first reported the evidence that quercetin can protect gastric epithelial GES-1 cells from oxidative damage and ameliorate reactive oxygen species production during acute gastric mucosal injury in mice. This might be ascribed to its inhibition of oxidative stress, regulation of mitochondrial dysfunction, initiation of antioxidant defense and inhibition of apoptosis. PMID:25701726

Hu, Xin-Ting; Ding, Chen; Zhou, Nan; Xu, Chen

2015-05-01

356

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

PubMed

The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-?) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-?B in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-?B signalling pathway. PMID:24300194

Li, Wei-Feng; Hao, Ding-Jun; Fan, Ting; Huang, Hui-Min; Yao, Huan; Niu, Xiao-Feng

2014-02-01

357

Prickly Pear Cactus (Opuntia ficus indica var. saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats  

PubMed Central

Abstract The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6?h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague–Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800–1600?mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-? and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production. PMID:23062184

Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha

2012-01-01

358

Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.  

PubMed

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6?h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600?mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-? and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production. PMID:23062184

Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

2012-11-01

359

Pediatric gastric cancer presenting with massive ascites  

PubMed Central

Gastric adenocarcinoma is quite rare in children and as a result very little experience has been reported on with regards to clinical presentation, treatment and outcome. We describe the case of a 16-year-old boy presenting with abdominal fullness and poor appetite for 7 d. Sonography showed massive ascites and computed tomography imaging revealed the presence of gastric mucosa thickness with omentum caking. The diagnosis of gastric adenocarcinoma was biopsy-proven endoscopically. Despite gastric adenocarcinoma being quite rare in the pediatric patient population, we should not overlook the possibility of gastric adenocarcinoma when a child presents with distended abdomen and massive ascites. PMID:25805952

Lin, Chien-Heng; Lin, Wei-Ching; Lai, I-Hsiu; Wu, Shu-Fen; Wu, Kang-Hsi; Chen, An-Chyi

2015-01-01

360

Combination chemotherapy with irinotecan and cisplatin in pretreated patients with unresectable or recurrent gastric cancer  

Microsoft Academic Search

Background  The combination of irinotecan (CPT-11) and cisplatin (CDDP) is an active regimen for metastatic gastric cancer in the first-line\\u000a setting. The objective of this retrospective study was to clarify its efficacy and safety in patients with prior chemotherapy\\u000a for advanced or recurrent gastric cancer.\\u000a \\u000a \\u000a \\u000a Methods  Patients in the study fulfilled the following selection criteria: (1) histologically proven gastric cancer with metastatic

Shinya Ueda; Shuichi Hironaka; Narikazu Boku; Akira Fukutomi; Takayuki Yoshino; Yusuke Onozawa

2006-01-01

361

Human ribosomal protein S13 promotes gastric cancer growth through down-regulating p27Kip1  

PubMed Central

Abstract Our previous works revealed that human ribosomal protein S13 (RPS13) was up-regulated in multidrug-resistant gastric cancer cells and overexpression of RPS13 could protect gastric cancer cells from drug-induced apoptosis. The present study was designed to explore the role of RPS13 in tumorigenesis and development of gastric cancer. The expression of RPS13 in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemical staining and Western blot analysis. It was found RPS13 was expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa. RPS13 was then genetically overexpressed in gastric cancer cells or knocked down by RNA interference. It was demonstrated that up-regulation of RPS13 accelerated the growth, enhanced in vitro colony forming and soft agar cologenic ability and promoted in vivo tumour formation potential of gastric cancer cells. Meanwhile, down-regulation of RPS13 in gastric cancer cells resulted in complete opposite effects. Moreover, overexpression of RPS13 could promote G1 to S phase transition whereas knocking down of RPS13 led to G1 arrest of gastric cancer cells. It was further demonstrated that RPS13 down-regulated p27kip1 expression and CDK2 kinase activity but did not change the expression of cyclin D, cyclin E, CDK2, CDK4 and p16INK4A. Taken together, these data indicate that RPS13 could promote the growth and cell cycle progression of gastric cancer cells at least through inhibiting p27kip1 expression. PMID:19912438

Guo, Xueyan; Shi, Yongquan; Gou, Yawen; Li, Jipeng; Han, Shuang; Zhang, Yanqi; Huo, Jianhua; Ning, Xiaoxuan; Sun, Li; Chen, Yu; Sun, Shiren; Fan, Daiming

2011-01-01

362

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

PubMed

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

Amirshahrokhi, Keyvan; Khalili, Ali-Reza

2015-01-01

363

Promoter methylation of tumor-related genes in gastric carcinogenesis.  

PubMed

Aberrant promoter methylation and subsequent silencing of cancer-related genes has been recognized as an important pathway involved in gastric carcinogenesis. In fact, several factors are believed to contribute to its induction in gastric epithelia, including aging, diet, chronic inflammation and infection of Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV). However, the underling mechanisms are not completely identified, despite the belief that increased expression or activity of DNA methyltransferases (DNMTs), or decreased demethylation activity may contribute to the excessive methylation. A great number of genes with promoter methylation have been observed in gastric cancer (GC), among which p16INK4A (p16), Mut L homologue 1 (MLH1), Epithelial-cadherin (E-cadherin), Runt-related transcription factor 3 (RUNX3), adenomatous polyposis coli (APC), O(6)-methylguanine-DNA methyltransferase (MGMT), Ras association domain family 1A (RASSF1A) and Death-associated protein kinase (DAPK) have been extensively studied. Unlike the distinct methylation characterization in single genes, methylation analysis of multiple genes may provide more information in risk prediction, early detection, prognosis assessment and chemotherapy choice for GC. Specifically, particular monitoring and screening should be performed on those over 45 years old, with precancerous gastric disease or infection of H. pylori or EBV. As an alternative to tumor tissues, methylation detection in patient sera or gastric washes may also be used in risk prediction and early detection. However, what still poses a great challenge as well as a puzzle is the determination of the very genes that should be used in methylation analysis. Because epigenetic alterations are normally reversible, drugs or chemical compounds with demethylating activity, such as 5-aza-2'-deoxycytidine (5-aza-dC) could be used in the treatment of patients with multiple gene methylation. In view of the adverse effects of 5-aza-dC, DNMT-targeted strategy has been proposed and may prove to be more effective than demethylating agents. PMID:22936446

Zhao, Chenghai; Bu, Xianmin

2012-10-01

364

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

PubMed Central

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

Tavares, Raquel; Pathak, Sushil Kumar

2015-01-01

365

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

PubMed Central

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

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

2010-01-01