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1

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

PubMed

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

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

2012-04-01

2

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

3

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats.  

PubMed

In the present investigation, an ethanol extract of celery [Apium graveolens L. (Apiaceae/Umbelliferae)], at doses of 250 and 500 mg/kg body weight, was evaluated for antigastric ulcer activity using various experimental gastric ulcer models in rats. Ulcers were induced by indomethacin, cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) and cold restraint stress. Gastric secretory studies were undertaken by using pylorus ligation (Shay rat model). In addition to gastric wall mucus (GWM), non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in gastric tissues after 80% ethanol treatment. Pretreatment of celery extract produced dose-dependent reduction in all experimentally induced gastric lesions. Ethanol (80%) decreased the levels of GWM, NP-SH and increase in MDA concentration in gastric tissue. Celery extract showed the ability to significantly replenish the ethanol-induced depleted levels of GWM and gastric mucosal NP-SH. The gastric mucosal MDA level was also significantly lowered in extract pretreated rats. The celery extract showed stomach protection against the models used for ulcerogenesis. Results were further confirmed by using histopathological assessment. The phytochemical screening showed the presence of various chemical constituents such as flavonoids, tannins, volatile oils, alkaloids, sterols and/or triterpenes. Acute toxicity test revealed no deleterious or toxic symptoms or mortality over a period of 14 days. However, the LD(50) was found to be 7.55 g/kg, and showed a large margin of safety. The results suggest that Apium graveolens extract significantly protects the gastric mucosa and suppresses the basal gastric secretion in rats, possibly through its antioxidant potential. PMID:20645778

Al-Howiriny, Tawfeq; Alsheikh, Abdulmalik; Alqasoumi, Saleh; Al-Yahya, Mohammed; ElTahir, Kamal; Rafatullah, Syed

2010-07-01

4

Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea  

PubMed Central

Aim: The roots of the plant Aconitum heterophyllum (EAH) are traditionally used for curing hysteria, throat infection, dyspepsia, abdominal pain, diabetes, and diarrhea. Therefore, the present study was undertaken to determine the mechanism involved in the anti-diarrheal activity of roots of A. heterophyllum. Materials and Methods: Ant-diarrheal activity of ethanol extract at 50, 100, and 200 mg/kg p.o. was evaluated using fecal excretion and castor oil-induced diarrhea models, while optimized dose, that is, 100 mg/kg p.o. was further subjected to small intestinal transit, intestinal fluids accumulation, PGE2-induced enteropooling and gastric emptying test. To elucidate the probable mechanism, various biochemical parameters and Na+, K+ concentration in intestinal fluids were also determined. Further, antibacterial activity of extract along with its standardization using aconitine as a marker with the help of HPLC was carried out. Results: The results depicted a significant (P < 0.05) reduction in normal fecal output at 100 and 200 mg/kg p.o. of extract after 5th and 7th h of treatment. Castor oil-induced diarrhea model demonstrated a ceiling effect at 100 mg/kg p.o. with a protection of 60.185% from diarrhea. EAH at 100 mg/kg p.o. also showed significant activity in small intestinal transit, fluid accumulation, and PGE2-induced enteropooling models, which also restored the altered biochemical parameters and prevented Na+ and K+ loss. The extract with 0.0833% w/w of aconitine depicted a potential antibacterial activity of extract against microbes implicated in diarrhea. Conclusion: The study concluded antisecretory and antimotility effect of A. heterophyllum, which mediates through nitric oxide path way. PMID:24550590

Prasad, Satyendra K.; Jain, Divya; Patel, Dinesh K.; Sahu, Alakh N.; Hemalatha, Siva

2014-01-01

5

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

Microsoft Academic Search

TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be\\u000a studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.8–8 nmol\\/rat)\\u000a or peripheral (48–240 nmol\\/kg, intraperitoneally) TLQP-21 administration on gastric acid secretion in pylorus-ligated rats.\\u000a The mechanisms involved in such activity were also examined.

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

6

Mastication suppresses initial gastric emptying by modulating gastric activity.  

PubMed

Because various mastication-related factors influence gastric activity, the functional relationship between mastication and gastric function has not been fully elucidated. To investigate the influence of mastication on gastric emptying and motility, we conducted a randomized trial to compare the effects of mastication on gastric emptying and gastric myoelectrical activity under conditions that excluded the influences of food comminution, taste, and olfaction. A (13)C-acetate breath test with electrogastrography and electrocardiography was performed in 14 healthy men who ingested a test meal with or without chewing gum. Autonomic nerve activity was evaluated by fluctuation analysis of heart rate. Gastric emptying was significantly delayed in the 'ingestion with mastication' group. Gastric myoelectrical activity was significantly suppressed during mastication and increased gradually in the post-mastication phase. A decrease in the high-frequency power of heart rate variability was observed coincidentally with gastric myoelectrical activity suppression. These findings suggest that initial gastric emptying is suppressed by mastication, and that the suppression is caused by mastication-induced inhibition of gastric activity (UMIN Clinical Trial Registration no. UMIN000005351). PMID:22205636

Ohmure, H; Takada, H; Nagayama, K; Sakiyama, T; Tsubouchi, H; Miyawaki, S

2012-03-01

7

Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy  

Microsoft Academic Search

BACKGROUNDThe incidence of early gastric cancer has not increased despite better access to endoscopic facilities for general practitioners. Many patients receive a course of symptomatic treatment while waiting for gastroscopy.AIMSTo ascertain the effect of antisecretory therapy on the diagnostic process and findings for patients with upper gastrointestinal cancer.METHODSA consecutive case study survey of the primary care records of 133 patients

M G Bramble; Z Suvakovic; A P S Hungin

2000-01-01

8

A model of abnormal gastric electrical activity  

Microsoft Academic Search

A mathematical model of abnormal gastric electrical activity is presented and used to investigate the accuracy of surface EGGs in the detection of gastric electrical abnormalities. The results show that current surface electrode configurations, cannot detect abnormalities that are not widespread. Substantial improvements can be obtained by using electrode arrays. Surface maps of the slow waves and the signal-to-noise ratio

B. O. Familoni; T. L. Abell; R. Praturu; S. Katragadda; P. Sabourin

1989-01-01

9

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

PubMed

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

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

2012-12-01

10

Comparison of Gastric Electrical Activity and Gastric Emptying in Healthy and Dyspeptic Children  

Microsoft Academic Search

To assess and compare gastric electrical activity and gastric emptying recorded from dyspeptic and healthy children, cutaneous electrogastrography and ultrasound examination of the gastric emptying were simultaneously performed in 52 children with nonulcer dyspepsia and 114 healthy children. Symptoms were scored from 0 (none) to 6 (severe). A higher percentage of tachygastria, a higher instability of gastric power, and a

Giuseppe Riezzo; Marisa Chiloiro; Vito Guerra; Osvaldo Borrelli; Gennaro Salvia; Salvatore Cucchiara

2000-01-01

11

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

PubMed Central

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

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

2013-01-01

12

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats.  

PubMed

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats. PMID:17825442

Tümer, Cemil; Oflazo?lu, Hüda Diken; Obay, Basra Deniz; Kelle, Mustafa; Ta?demir, Ezel

2008-02-01

13

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

14

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

15

Sympathetic nervous control of gastric motility and interaction with vagal activity.  

PubMed

Gastro-gastric reflexes controlling gastric motility were studied in anaesthetized cats. Distensions and contractions of the gastric wall elicited two different inhibitory responses: 1) A spinal adrenergic reflex inhibiting cholinergic neurons in the gastric wall leading to suppression of rhythmic gastric contractions and increasing gastric reservoir capacity. 2) A vago-vagal reflex involving non-adrenergic vagal fibres to the stomach. This latter storage reflex seems to be of major importance for gastric reservoir capacity. It is concluded that stimulation of gastric mechanoreceptors activates sympathetic adrenergic reflexes which together with simultaneously activated vagal inhibitory reflexes can influence gastric contractions and reservoir capacity. PMID:6588475

Abrahamsson, H; Glise, H

1984-01-01

16

Activation-Induced Cytidine Deaminase Expression in Gastric Cancer  

Microsoft Academic Search

Helicobacter pylori increases the risk of gastric cancer development and triggers aberrant expression of activation-induced cytidine deaminase (AID). The goal of the present study was to investigate whether AID expression is involved in the development or progression of gastric cancer and the nuclear expression of p53 protein in cancer cells. We examined the expression pattern of the AID and p53

Chang Jae Kim; Jae Hwi Song; Yong Gu Cho; Zhang Cao; Su Young Kim; Suk Woo Nam; Jung Young Lee; Won Sang Park

2007-01-01

17

Gastric-mucous membrane protection activity of coptisine derivatives.  

PubMed

Coptisine and 8-oxocoptisine were isolated as principles of the gastric-mucous membrane protection from Coptidis rhizoma. The two compounds showed stronger activity than cimetidine and sucralfate. We prepared several derivatives having a partial structure of coptisine from commercially available starting materials. The compounds obtained were tested for gastric-mucous membrane protective activity and a correlation between activity and structure was studied. Our results suggest that the partial charge of the catechol skeleton is related to activity. PMID:11725963

Hirano, H; Osawa, E; Yamaoka, Y; Yokoi, T

2001-11-01

18

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

PubMed

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

19

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

20

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

PubMed

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

21

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

22

Gastric cytoprotection: a critical appraisal of the concept, methodology, implications, mechanisms and future research prospects  

Microsoft Academic Search

Gastric cytoprotection is the property of certain substances, particularly prostaglandins, when used in non-antisecretory doses, to protect the gastric mucosa from becoming inflammed and necrotic on being exposed to noxious agents. An association between alterations in endogenous prostaglandins and gastric mucosal damage induced by a number of drugs has also been observed. The process of adaptive cytoprotection in which mild

Narayan S. Parmar; Mohammad Tariq; A. M. Ageel

1987-01-01

23

Gastric myoelectrical activity as an index of emotional arousal  

Microsoft Academic Search

Autonomic nervous system parameters such as electrodermal activity, heart rate, and facial EMG have been utilized extensively as measures of emotional arousal. One measure that has rarely been employed in this setting is gastric myoelectrical activity, despite the fact that “gut feelings” have an obvious and even profound role in everyday emotional life. It has been shown that the gastrointestinal

E. P. M. Vianna; D. Tranel

2006-01-01

24

Myoelectrical activity of the Billroth II gastric remnant.  

PubMed Central

This study was undertaken to investigate the extent to which gastric electrical control activity and phasic contractile activity are preserved after Billroth II resection and to assess the relation between these activities and postprandial symptoms in patients who have undergone Billroth II resection. Thirty three patients were studied after Billroth II resection without vagotomy. Gastric electrical activity was recorded from surface electrodes and intraluminal pressure was recorded simultaneously. The electrogastrographic signals were analysed by Running Spectrum Analysis. In addition, three dogs with a Billroth II stomach and implanted serosal electrodes were studied. Phasic gastric pressure waves were observed in most patients. Electrogastrographic signals recorded from 82% of the Billroth II patients contained a mean (SD) peak at 3.1 (0.2) cycles per minute (cpm). Fasting and postprandial frequencies correlated significantly (p less than 0.02) with the score for nausea and vomiting. In 61% of the patients, the electrogastrographic signal contained a stable component with a frequency of 10.5 (0.6) cpm that was not caused by respiration. We suggest that this activity is of intestinal origin. In all three dogs studied, retrograde conduction of jejunal electrical control activity (16 cpm) into the distal part of the gastric remnant was observed. In the Billroth II patients, the presence of a 10 cpm component correlated negatively with symptoms. Images Figure 2 PMID:2210466

Schaap, H M; Smout, A J; Akkermans, L M

1990-01-01

25

Gastric emptying and myoelectrical activity in children with nonulcer dyspepsia  

Microsoft Academic Search

We examined the effect of oral cisapride on gastric emptying time and myoelectrical activity using real-time ultrasonography and cutaneous electrogastrography in 10 children with nonulcer dyspepsia. A clear dominant frequency close to 3 cpm was present both at baseline and after eight weeks of cisapride. After cisapride, nine children had an increase in the normal slow wave percentage and the

Giuseppe Riezzo; Salvatore Cucchiara; Marisa Chiloiro; Raffaele Minella; Vito Guerra; Italo Giorgio

1995-01-01

26

Chymotrypsin-like activity of proteasomes and total calpain activity in gastric and colorectal cancer.  

PubMed

Chymotrypsin-like activity of proteasomes and total calpain activity were studied in patients with stage T2-4N0-3M0 gastric cancer and stage T2-4N0-2M0-1 colorectal cancer. Activities of proteasomes and calpains in gastric and colorectal cancer tissues were higher than in the corresponding normal tissues. Changes in activities of proteasomes and calpains were mutually related. The appearance of lymphogenic metastases in gastric cancer was associated with the increase in calpain activity. The progress of colorectal cancer and development of lymphogenic and hematogenic metastases were associated with elevated chymotrypsin-like activity of proteasomes. PMID:25342484

Ivanova, E V; Kondakova, I V; Spirina, L V; Afanas'ev, S G; Avgustinovich, A V; Cheremisina, O V

2014-10-01

27

Biomagnetic Techniques for Assessing Gastric and Small Bowel Electrical Activity  

NASA Astrophysics Data System (ADS)

Recent advances in electrophysiology of the gastrointestinal tract have emphasized the need for methods of noninvasive assessment of gastric and small intestinal electrical activity (GEA and IEA). While the cutaneous electrogastrogram (EGG) may reveal the frequency dynamics of gastric electrical activity, other parameters important for characterizing the propagating electrical activity are not available from EGG recordings. Recent studies on the electroenterogram (EENG) are promising, but low-conductivity abdominal layers have complicated the identification of small intestinal electrical rhythms in cutaneous recordings. The magnetogastrogram (MGG) and magnetoenterogram (MENG) are able to characterize gastric and intestinal electrical activity noninvasively in terms of its frequency, power and characteristics of its propagation. Superconducting QUantum Interference Device (SQUID) magnetometers are used to detect the minute magnetic fields associated with electrical activity of the gastrointestinal syncytium formed by interstitial cells of Cajal and smooth muscle networks. Changes in GEA and IEA that occur in response to disease or abnormal conditions are reflected in MGG and MENG signals. Magnetic methods for assessing the electrical activity of the stomach and small bowel thus show great clinical promise.

Bradshaw, L. Alan

2004-09-01

28

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

Microsoft Academic Search

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

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

1998-01-01

29

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

PubMed

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

2014-12-01

30

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

31

Effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal ulcers in rats.  

PubMed

We studied the effects of TU-199, a novel H+, K(+)-ATPase inhibitor, on gastric acid secretion and gastroduodenal lesions in rats in comparison with those of omeprazole. TU-199 inhibited hog gastric H+, K(+)-ATPase activity and its potency was almost equal to that of omeprazole (IC50 = 6.2 and 4.2 microM, respectively). In vivo, TU-199 inhibited basal gastric acid secretion in pylorus-ligated rats in a dose-dependent manner (ED50 = 4.2 mg/kg p.o.). In gastric fistula rats. TU-199 (2.5 and 5 mg/kg i.d.) also inhibited gastric acid secretion stimulated by histamine, carbachol or tetragastrin. Furthermore, TU-199 prevented the formation of water-immersion restraint stress-, pylorus ligation- and indomethacin-induced gastric lesions, and mepirizole-induced duodenal ulcer in rats. These antisecretory and antiulcer effects of TU-199 were 2-4 times more potent than those of omeprazole. The results demonstrate that TU-199 potently inhibits the acid secretion and formation of ulcers in various experimental rat models via an inhibition of H+, K(+)-ATPase. These findings suggest that TU-199 may have a beneficial effect against peptic ulcer disease in humans. PMID:10327392

Uchiyama, K; Wakatsuki, D; Kakinoki, B; Takeuchi, Y; Araki, T; Morinaka, Y

1999-03-01

32

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, Elisangela; Calvo, Tamara Regina; Hiruma-Lima, Clelia A.; Vilegas, Wagner; Souza-Brito, Alba Regina M.

2012-01-01

33

Do gastric contents modify antidotal efficacy of oral activated charcoal?  

PubMed Central

The effect of food on the antidotal efficacy of activated charcoal was studied in six healthy volunteers, who ingested aspirin 1000 mg, mexiletine 200 mg and tolfenamic acid 400 mg in a randomized cross-over study. Activated charcoal 25 g, suspended in water, was administered 5 min or 60 min after the drugs were taken on an empty stomach or after a standard meal. The serum concentrations and the cumulative excretion into urine of the drugs were followed for 48 h. When the drugs were taken on an empty stomach, activated charcoal given 5 min or 60 min afterwards reduced the bioavailability of the drugs by 75-98% or 10-60%, respectively. Food moderately weakened the effect of activated charcoal administered 5 min after the drugs, but when the charcoal was given 1 h later the effect was still practically the same, the reduction of absorption varying in both cases in the range of 45-85%. Thus the efficacy of charcoal given 60 min after the drugs was better after a standard meal than on an empty stomach. Presence of food in the stomach of patients with drug overdosage modifies the efficacy of activated charcoal and gives it more time to adsorb drugs in the gastrointestinal canal, possibly by slowing gastric emptying rate. PMID:6508975

Olkkola, K T; Neuvonen, P J

1984-01-01

34

Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer.  

PubMed

We have shown earlier that Neem (Azadirachta indica) bark aqueous extract has potent antisecretory and antiulcer effects in animal models and has no significant adverse effect (Bandyopadhyay et al., Life Sciences, 71, 2845-2865, 2002). The objective of the present study was to investigate whether Neem bark extract had similar antisecretory and antiulcer effects in human subjects. For this purpose, a group of patients suffering from acid-related problems and gastroduodenal ulcers were orally treated with the aqueous extract of Neem bark. The lyophilised powder of the extract when administered for 10 days at the dose of 30 mg twice daily caused a significant (p < 0.002) decrease (77%) in gastric acid secretion. The volume of gastric secretion and its pepsin activity were also inhibited by 63% and 50%, respectively. Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained close to the control values. The bark extract when taken at the dose of 30-60 mg twice daily for 10 weeks almost completely healed the duodenal ulcers monitored by barium meal X-ray or by endoscopy. One case of esophageal ulcer (gastroesophageal reflux disease) and one case of gastric ulcer also healed completely when treated at the dose of 30 mg twice daily for 6 weeks. The levels of various blood parameters for organ toxicity after Neem treatment at the doses mentioned above remained more or less close to the normal values suggesting no significant adverse effects. Neem bark extract thus has therapeutic potential for controlling gastric hypersecretion and gastroesophageal and gastroduodenal ulcers. PMID:15454339

Bandyopadhyay, Uday; Biswas, Kaushik; Sengupta, Arnab; Moitra, Puspa; Dutta, Prodip; Sarkar, Dipankar; Debnath, Pratip; Ganguly, Chayan K; Banerjee, Ranajit K

2004-10-29

35

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

36

Afferent signalling of gastric acid challenge.  

PubMed

Gastric acid is a factor in the pain associated with peptic ulcer and other acid-related disorders including functional dyspepsia, given that antisecretory treatment is a mainstay in the treatment of upper abdominal pain. However, the molecular sensors, afferent pathways and central processing systems of gastric chemonociception are little known. This article reviews emerging evidence that vagal afferent pathways play a pivotal role in gastric chemonociception. Exposure of the rat gastric mucosa to backdiffusing concentrations of luminal acid is signalled to the brainstem, but not spinal cord, as visualized by functional neuroanatomy based on the rapid expression of c-fos. This observation is complemented by the finding that the visceromotor response to gastric acid challenge is suppressed by vagotomy, but not splanchnectomy. The gastric acid-induced expression of c-fos in the brainstem is reduced by inhibition of gastric acid secretion and enhanced by pentagastrin-evoked stimulation of gastric acid secretion. These data indicate that endogenous acid modulates the sensory gain of acid-sensitive vagal afferents. Further consistent with a role of these neurons in gastric nociception is the finding that exposure to proinflammatory cytokines and the induction of experimental gastritis or gastric ulceration sensitizes vagal afferent pathways to gastric acid. Taken together, these observations are of relevance to the understanding and treatment of gastric hyperalgesia and dyspeptic pain. PMID:15075448

Holzer, P

2003-12-01

37

Verbascoside isolated from Tectona grandis mediates gastric protection in rats via inhibiting proton pump activity  

Microsoft Academic Search

Evidences have suggested that Tectona grandis (TG) attenuates gastric mucosal injury; however its mechanism has not yet been established. The aim of present study was to evaluate the gastroprotective mechanism of ethanolic extract of TG (E-EtOH), butanolic fraction (Fr-Bu) and to identify its active constituents. Anti-ulcer activities were evaluated against cold restraint (CRU) and pyloric ligation (PL) induced gastric ulcer

Neetu Singh; Nivedita Shukla; Pratibha Singh; Rolee Sharma; S. M. Rajendran; Rakesh Maurya; Gautam Palit

2010-01-01

38

Gastric pharmacological activities of tripotassium dicitrato bismuthate in rats and dogs.  

PubMed

The effects of tripotassium dicitrato bismuthate (TDB) on gastric acid, pepsin and mucoprotein secretion in rats and on hydrochloric-peptic secretion and plasma gastrin levels in dogs were investigated. In Shay rats, TDB did not affect acid secretion but significantly lowered pepsin concentration and increased the amount of bound mucoproteins. In addition, gastric mucosal lesions were significantly prevented by the drug. In dogs, chronically fitted with both gastric fistulae and Heidenhain pouches, acid secretion and plasma gastrin levels stimulated by a meat meal were unaffected by TDB, while pepsin concentration and pepsin output were significantly decreased. On the basis of these results, the antiulcer activity of TDB appears to be ascribed to the protection of the gastric mucosa through an increase in mucoprotein synthesis and a decrease of pepsin activity. PMID:3937162

Soldani, G; Del Tacca, M; Bernardini, C; Polloni, A; Martinotti, E; Malandrino, S; Borsa, M; Tonon, G C

1985-11-01

39

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

PubMed Central

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

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

2014-01-01

40

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

PubMed Central

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

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

2013-01-01

41

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

PubMed Central

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

Jung, Joohee; Choi, Jae Sue

2014-01-01

42

Peroxisome proliferator-activated receptor-? is essential in the pathogenesis of gastric carcinoma  

PubMed Central

AIM: To investigate whether peroxisome proliferator-activated receptor ? (PPAR-?) is expressed in human gastric carcinoma and whether PPAR-? is a potential target for gastric carcinoma therapy. METHODS: PPAR-? protein in gastric carcinoma was examined by immunohistochemistry. In the gastric carcinoma cell line MGC803, PPAR-?, survivin, Skp2 and p27 protein and mRNA were examined by Western blotting and real-time reverse transcription-polymerase chain reaction, respectively; proliferation was examined by MTT; apoptosis was examined by chromatin staining with Hoechst 33342 and fluorescence activated cell sorting (FACS). and cell cycle was examined by FACS; the knockdown of PPAR-? was done by RNA interference. RESULTS: A high level of expression of PPAR-? was observed in human gastric carcinoma and in a human gastric carcinoma cell line MGC803. The PPAR-? agonist 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2) inhibited growth, and induced apoptosis and G1/G0 cell cycle arrest in MGC803 cells in a concentration-dependent and time-dependent manner. The effect of 15d-PGJ2 on MGC803 cells was not reversed by the selective and irreversible antagonist GW9662 for PPAR-?. Furthermore, survivin and Skp2 expression were decreased, whereas p27 expression was enhanced following 15d-PGJ2 treatment in a dose-dependent manner in MGC803 cells. Interestingly, we also found that small interfering RNA for PPAR-? inhibited growth and induced apoptosis in MGC803 cells. The inhibition of PPAR-? function may be a potentially important and novel modality for treatment and prevention of gastric carcinoma. CONCLUSION: A PPAR-? agonist inhibited growth of human gastric carcinoma MGC803 cells by inducing apoptosis and G1/G0 cell cycle arrest with the involvement of survivin, Skp2 and p27 and not via PPAR-?. PMID:19701967

Ma, Xiu-Mei; Yu, Hong; Huai, Na

2009-01-01

43

In vitro antioxidative activity of yellow tea and its in vivo preventive effect on gastric injury  

PubMed Central

Yellow tea is a traditional Chinese drink widely used in Asia. The aim of this study was to determine the antioxidant activity of yellow tea and its preventive effect on gastric injury. The antioxidant effects were determined by measuring the 1,1-diphenyl-2-picryhydrazyl (DPPH) free radical- and hydroxyl radical-scavenging activity. The yellow tea extract demonstrated high antioxidant activity in the assays of DPPH and hydroxyl radical-scavenging activity. Additionally, an animal model was used to investigate the preventive effect of yellow tea on gastric injury. High concentrations of yellow tea reduced the levels of the serum pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-? to a greater extent than low concentrations. The extent of the gastric injury was significantly reduced by yellow tea, which demonstrated its anti-inflammatory properties. Yellow tea demonstrated the strongest inhibitory effect (74.6%) against gastric injury when administered at a dose of 1,000 mg/kg by gavage. These results suggest that yellow tea possesses good antioxidant activity and a preventive effect on gastric injury in vivo. PMID:24137202

WANG, QIANG; ZHAO, XIN; QIAN, YU; WANG, RUI

2013-01-01

44

Effects of gastric distension and infusion of umami and bitter taste stimuli on vagal afferent activity.  

PubMed

Until recently, sensory nerve pathways from the stomach to the brain were thought to detect distension and play little role in nutritional signaling. Newer data have challenged this view, including reports on the presence of taste receptors in the gastrointestinal lumen and the stimulation of multi-unit vagal afferent activity by glutamate infusions into the stomach. However, assessing these chemosensory effects is difficult because gastric infusions typically evoke a distension-related vagal afferent response. In the current study, we recorded gastric vagal afferent activity in the rat to investigate the possibility that umami (glutamate, 150 mM) and bitter (denatonium, 10 mM) responses could be dissociated from distension responses by adjusting the infusion rate and opening or closing the drainage port in the stomach. Slow infusions of saline (5 ml over 2 min, open port) produced no significant effects on vagal activity. Using the same infusion rate, glutamate or denatonium solutions produced little or no effects on vagal afferent activity. In an attempt to reproduce a prior report that showed distention and glutamate responses, we produced a distension response by closing the exit port. Under this condition, response to the infusion of glutamate or denatonium was similar to saline. In summary, we found little or no effect of gastric infusion of glutamate or denatonium on gastric vagal afferent activity that could be distinguished from distension responses. The current results suggest that sensitivity to umami or bitter stimuli is not a common property of gastric vagal afferent fibers. PMID:21925651

Horn, Charles C; Murat, Chloé; Rosazza, Matthew; Still, Liz

2011-10-24

45

Reactive oxygen species activity and lipid peroxidation inHelicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication  

Microsoft Academic Search

Background—Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species.Aims—To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric

I M Drake; N P Mapstone; C J Schorah; K L M White; D M Chalmers; M F Dixon; A T R Axon

1998-01-01

46

AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion.  

PubMed

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-beta-D: -riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion. PMID:19621238

Sidani, Shafik; Kopic, Sascha; Socrates, Thenral; Kirchhoff, Philipp; Föller, Michael; Murek, Michael; Capasso, Anna; Geibel, John P

2009-11-01

47

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

48

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

PubMed

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

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

2014-12-01

49

Expression of HLA-DR and urokinase-type plasminogen activator in stage IV gastric cancer  

Microsoft Academic Search

:  \\u000a \\u000a Background.\\u000a Some patients with stage IV gastric cancer have a long survival. Host immune response and proteolytic activity in the primary\\u000a tumor may be associated with outcome in these patients. The purpose of this study was to assess prognostic factors in patients\\u000a with stage IV far advanced gastric cancer.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Methods.\\u000a Findings in 26 patients who underwent resection of stage

Satoshi Murata; Yutaka Eguchi; Nobukuni Terata; Tohru Tani; Masashi Kodama

1998-01-01

50

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

51

The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2.  

PubMed

Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progression of gastric cancer. Herein, we sought to address whether Notch1 signal pathway is involved in the control of progression in gastric cancer. We found that expression of Notch ligand Jagged1 was correlated with aggressiveness of human gastric cancer. Patients with Jagged1 expression in gastric cancer tissues had a poor survival rate compared with those without Jagged1 expression. The Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promoted the colony-forming ability and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. Migration and invasion abilities of SC-M1 cells were enhanced by N1IC. Furthermore, N1IC and C promoter-binding factor 1 (CBF1) bound to cyclooxygenase-2 (COX-2) promoter and elevated COX-2 expression in SC-M1 cells through a CBF1-dependent manner. The colony-forming, migration, and invasion abilities enhanced by N1IC were suppressed in SC-M1 cells after treatment with the COX-2 inhibitor NS-398 or knockdown of COX-2. These cellular processes inhibited by Notch1 knockdown were restored by prostaglandin E(2) or exogenous COX-2. Taken together, these results suggest that activation of Notch1 signal pathway promotes progression of gastric cancer, at least in part through COX-2. PMID:19491270

Yeh, Tien-Shun; Wu, Chew-Wun; Hsu, Kai-Wen; Liao, Wan-Jung; Yang, Min-Chieh; Li, Anna Fen-Yau; Wang, An-Ming; Kuo, Min-Liang; Chi, Chin-Wen

2009-06-15

52

Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells.  

PubMed

Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and we recently showed that lipid raft-regulated epidermal growth factor receptor (EGFR) activation antagonized TRAIL-induced apoptosis. However, it is not clear whether caveolin-1, an essential structural constituent of lipid rafts, regulates lipid raft-mediated EGFR activation. We report here that TRAIL induced the translocation of EGFR into lipid rafts and its activation in gastric cancer SGC-7901 and MGC-803 cells. Simultaneously, caveolin-1 was also activated. Knockdown of caveolin-1 partially prevented EGFR activation and increased TRAIL sensitivity. Moreover, TRAIL promoted the translocation of Src into lipid rafts and its activation, as well as the interaction of Src with both EGFR and caveolin-1. A Src inhibitor prevented these interactions and the activation of caveolin-1 and EGFR, and thus enhanced TRAIL-induced apoptosis. These data suggest that Src activates EGFR through the interaction of both Src-EGFR and Src-caveolin-1, and then antagonizes TRAIL-induced apoptosis in gastric cancer cells. PMID:24840271

Xu, Ling; Qu, Xiujuan; Li, Heming; Li, Ce; Liu, Jing; Zheng, Huachuan; Liu, Yunpeng

2014-07-01

53

CDX2 can be regulated through the signalling pathways activated by IL-6 in gastric cells.  

PubMed

The inflammatory infiltrate of the gastric mucosa associated with Helicobacter pylori infection increases the presence of the pro-inflammatory cytokine IL-6 that activates both the SHP-2/ERK/MAPK and the JAK/STAT signalling pathways. Furthermore, the ectopic expression of CDX2 is detected in pre-neoplasic lesions associated with decreased levels of SOX2, and we found that in gastric adenocarcinomas their expression is inversely correlated. To determine the role of IL-6 in the regulation of CDX2, MKN45 that constitutively expresses p-STAT3, and NUGC-4 gastric cancer cell lines were treated with IL-6, which induced the CDX2 up-regulation and SOX2 down-regulation. ChIP assays determined that in IL-6-treated cells, c-JUN and p-STAT3 bound to CDX2 promoter in MKN45 cells whereas in NUGC-4 cells, p-STAT3 binds to and c-JUN releases from the CDX2 promoter. Specific inhibition of STAT3 and ERK1/2 phosphorylation through AG490 and U0126, respectively, and STAT3 down-regulation using shRNA verified that the SHP-2/ERK/MAPK pathway regulates the expression of CDX2 in basal conditions, and the CDX2 up-regulation by IL-6 is through the JAK/STAT pathway in NUGC-4 cells whereas in MKN45 cells both pathways contribute to the CDX2 up-regulation. In conclusion, the signalling pathways activated by IL-6 have a crucial role in the regulation of CDX2 that is a key factor in the process of gastric carcinogenesis, suggesting that the inflammatory infiltrate in the gastric mucosa is relevant in this process and a potential target for new therapeutic approaches. PMID:24953186

Cobler, Lara; Pera, Manuel; Garrido, Marta; Iglesias, Mar; de Bolós, Carme

2014-09-01

54

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

55

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

56

Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role  

Microsoft Academic Search

The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant

Mario Plebani; Làszlo Herszènyi; Paolo Carraro; Massimo De Paoli; Giovanni Roveroni; Romilda Cardin; Zsolt Tulassay; Remo Naccarato; Fabio Farinati

1997-01-01

57

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

PubMed

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

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

2014-07-01

58

Mutagenic Activation of Environmental Carcinogens by Microsomes of Gastric Mucosa with Intestinal Metaplasia1  

Microsoft Academic Search

Coexpression of cytochrome P450 monooxygenases (CYPs) and reduc- tase was found in human gastric mucosa with intestinal metaplasia. Im- munohistochemistry showed reactivity to P450 reductase in metaplastic epithelial cells and in pyloric gland cells in glands showing intestinal metaplasia. These cells exhibit NADPH-diaphorase activity. Reverse tran- scription-PCR analysis and Western blotting showed that CYP1A1 and CYP1A2 were expressed in specimens

Masayuki Tatemichi; Sachiyo Nomura; Tsutomu Ogura; Hideko Sone; Hiroshi Nagata; Hiroyasu Esumi

59

Activation of P21-activated protein kinase 2 is an independent prognostic predictor for patients with gastric cancer  

PubMed Central

Objective p21-activated kinase (PAK) 2, as a member of the PAK family kinases, is involved in a number of hallmark processes including cell proliferation, survival, mitosis, apoptosis, motility and angiogenesis. However, the clinical significance of the activation of PAK2 in human gastric cancer has not been fully elucidated. The aim of this study was to investigate whether PAK2 expression and its phosphorylation status are correlated with tumor progression and prognosis in gastric cancer. Methods Expression patterns and subcellular localizations of PAK2 and Ser20-phosphorylated PAK2 (pSer20PAK2) in 82 gastric cancer patients were detected by immunohistochemistry. Results Both PAK2 and pSer20PAK2 immunostainings were localized in the cytoplasm of tumor cells of gastric cancer tissues. Compared with the normal gastric mucosa, the expression levels of PAK2 and pSer20PAK2 proteins were both significantly increased (both P?gastric cancer. Conclusion Our data suggest for the first time that PAK2 activation may be associated with advanced tumor progression and poor prognosis of gastric cancer. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1236344107120406. PMID:24621074

2014-01-01

60

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

PubMed

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

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

2014-03-01

61

Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications.  

PubMed

Portal hypertensive (PHT) gastropathy is a frequent, serious complication of liver cirrhosis. PHT gastric mucosa has numerous abnormalities such as reduced mucosal potential differences, reduced surface oxygenation, and increased susceptibility to injury caused by alcohol, aspirin, and other noxious factors. Because such mucosal injury is initially mediated by oxygen free radicals, and because mitogen-activated protein (MAP) kinase (ERK2) protects against cellular stress and induces cell proliferation, we postulated that oxidative stress-induced ERK2 activation is defective in PHT gastric mucosa. Here we show that in PHT gastric mucosa, ERK2 activation by oxidative stress is impaired. This impairment is mediated by overexpression of MAP kinase phosphatase-1 (MKP-1), which results from the underlying and continual oxidative state associated with portal hypertension, and is ameliorated by inhibiting MKP-1. Furthermore, we found that supplementing vitamin E, a free radical scavenger, reduces the oxidative state in PHT gastric mucosa, normalizes MKP-1 expression, and thereby reverses impairment of oxidative stress-induced ERK2 activation. Finally, we show that orally administered vitamin E completely reverses the increased susceptibility of PHT gastric mucosa to alcohol injury. Our findings point to a new molecular and mechanistic basis for PHT gastropathy and provide a new therapeutic modality for protection of PHT gastric mucosa. PMID:11679970

Kawanaka, H; Tomikawa, M; Jones, M K; Szabo, I L; Pai, R; Baatar, D; Tsugawa, K; Sugimachi, K; Sarfeh, I J; Tarnawski, A S

2001-11-01

62

Effect of Meal Size and Test Duration on Gastric Emptying and Gastric Myoelectrical Activity as Determined with Simultaneous [13C]Octanoate Breath Test and Electrogastrography in Normal Subjects Using a Muffin Meal  

Microsoft Academic Search

Our purpose was to determine the effect of meal size on gastric emptying (GE) as measured by octanoate breath test (OBT), to determine the effect of the duration of breath collections on assessment of GE by OBT, and to determine the effect of meal size on gastric myoelectrical activity as measured by electrogastrography (EGG). Fourteen normal subjects underwent two modified

Sutep Gonlachanvit; William D. Chey; Keith J. Goodman; Henry P. Parkman

2001-01-01

63

Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation  

Microsoft Academic Search

The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is

J W Konturek; A Dembinski; R Stoll; W Domschke; S J Konturek

1994-01-01

64

Expression of peroxisome proliferator-activated receptor (PPAR)? in gastric cancer and inhibitory effects of PPAR? agonists  

PubMed Central

Peroxisome proliferator-activated receptor (PPAR) ? is expressed in human colon cancer, prostate cancer and breast cancer cells, and PPAR? activation induces growth inhibition in these cells. PPAR? expression in human gastric cancer cells, however, has not been fully investigated. We report the PPAR? expression in human gastric cancer, and the effect of PPAR? ligands on proliferation of gastric carcinoma cell lines. Immunohistochemistry was used to demonstrate the presence of PPAR? protein in surgically resected specimens from well differentiated, moderately differentiated and poorly differentiated adenocarcinoma. We used reverse transcription-polymerase chain reaction and Northern and Western blot analyses to demonstrate PPAR? expression in four human gastric cancer cell lines. PPAR? agonists (troglitazone and 15-deoxy-?12,14-prostaglandin J2) showed dose-dependent inhibitory effects on the proliferation of the gastric cancer cells, and their effect was augmented by the simultaneous addition of 9-cis retinoic acid, a ligand of RXR?. Flow cytometry demonstrated G1 cell cycle arrest and a significant increase of annexin V-positive cells after treatment with troglitazone. These results suggest that induction of apoptosis together with G1 cell cycle arrest may be one of the mechanisms of the antiproliferative effect of PPAR? activation in human gastric cancer cells. © 2000 Cancer ResearchCampaign PMID:11044367

Sato, H; Ishihara, S; Kawashima, K; Moriyama, N; Suetsugu, H; Kazumori, H; Okuyama, T; Rumi, M A K; Fukuda, R; Nagasue, N; Kinoshita, Y

2000-01-01

65

Convective washout reduces the antidiarrheal efficacy of enterocyte surface-targeted antisecretory drugs  

PubMed Central

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

Jin, Byung-Ju; Thiagarajah, Jay R.

2013-01-01

66

Psychosocial and physical activity changes after gastric restrictive procedures for morbid obesity.  

PubMed

Gastric restrictive procedures for morbid obesity are frequently performed to reduce problems arising from the physical limitations and social isolation of massive obesity. Numerous reports have described changes in weight after gastric restrictive operations, yet few studies have documented changes in the secondary effects of obesity. This report deals with changes in psychosocial status and physical activity occurring in 240 patients who remained in the study 3 years after surgery. These patients were members of a group of 310 patients who were entered into a prospective randomized trial to assess the relative benefits of three forms of gastric restrictive procedure. Prior to operation, and at yearly intervals after operation, the physical activities and psychosocial status of each patient was assessed by a standardized semi-structured interview. At the time of the three-year interview the median weight loss for these patients was 29.5 kg which represents 53% of excess weight lost. This weight loss was associated with a marked reduction in the amount of food eaten. There was a significant increase in the number of patients smoking more than 20 cigarettes a day and a mild increase in alcohol intake. There were significant improvements in the level of self-image and state of happiness. The social lives and sex lives of the majority of patients were improved and a significantly greater number of patients reported being in a stable emotional relationship at 3 years after operation than did so pre-operatively. There was a marked increase in the number of patients in full-time or part-time employment from 38% prior to surgery to 60% at 3 years after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2206119

Hawke, A; O'Brien, P; Watts, J M; Hall, J; Dunstan, R E; Walsh, J F; Slavotinek, A H; Elmslie, R G

1990-10-01

67

Sensory Deprivation on Visceral Activity I. The Effect of Visual Deprivation on Canine Gastric Secretion  

Microsoft Academic Search

In 13 dogs with gastric cannulas, a range for gastric acid output and pepsin concentration was established. The vision of each dog was then compromised. A marked inhibition of the gastric secretory output occurred in all dogs over a 4-month period.

H. Schapiro; L. D. Wruble; L G. Britt; T. A. Bell

68

A Newly Identified Extrinsic Input Triggers a Distinct Gastric Mill Rhythm via Activation of Modulatory Projection Neurons  

PubMed Central

Neuronal network flexibility enables animals to respond appropriately to changes in their internal and external states. We are using the isolated crab stomatogastric nervous system to determine how extrinsic inputs contribute to network flexibility. The stomatogastric system includes the well-characterized gastric mill (chewing) and pyloric (filtering of chewed food) motor circuits in the stomatogastric ganglion. Projection neurons with somata in the commissural ganglia (CoGs) regulate these rhythms. Previous work characterized a unique gastric mill rhythm that occurred spontaneously in some preparations, but whose origin remained undetermined. This rhythm includes a distinct protractor phase activity pattern, during which all active gastric mill circuit and projection neurons fire in a pyloric rhythm-timed activity pattern instead of the tonic firing pattern exhibited by these neurons during previously studied gastric mill rhythms. Here we identify a new extrinsic input, the post-oesophageal commissure (POC) neurons, relatively brief stimulation (30 sec) of which triggers a long-lasting (tens of minutes) activation of this novel gastric mill rhythm at least in part via its lasting activation of CoG projection neurons, including the previously identified MCN1 and CPN2. Immunocytochemical and electrophysiological data suggest that the POC neurons excite MCN1 and CPN2 by release of the neuropeptide Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). These data further suggest that the CoG arborization of the POC neurons comprises the previously identified anterior commissural organ (ACO), a CabTRP Ia-containing neurohemal organ. This endocrine pathway thus appears to also have paracrine actions that include activation of a novel and lasting gastric mill rhythm. PMID:18310125

Blitz, Dawn M.; White, Rachel S.; Saideman, Shari R.; Cook, Aaron; Christie, Andrew E.; Nadim, Farzan; Nusbaum, Michael P.

2008-01-01

69

Differential Role of ERK and p38 on NF-?B Activation in Helicobacter pylori-Infected Gastric Epithelial Cells  

PubMed Central

Gastric cancer, as well as inflammation, caused by Helicobacter pylori, activates the production of chemokines by activation of redox-sensitive transcription factor NF-?B in gastric epithelial cells. Mitogen-activated protein kinases including extracellular signal-regulated kinase (ERK) and p38 kinase (p38) are activated by Helicobacter pylori, which may regulate NF-?B activation in the infected cells. However the mechanisms how ERK and p38 induce NF-?B activation have not been investigated. Present study aims to investigate the role of ERK and p38 on the activation of NF-?B in Helicobacter pylori-infected AGS cells. Western blot analysis was performed for determining the levels of I?B, p105, p50 and p65 in gastric epithelial cells infected with Helicobacter pylori and treated with ERK inhibitor U0126 and p38 inhibitor SB203580. Helicobacter pylori induced the degradation of I?B? and upregulation of p105, p50 and p65 in the infected cells. U0126 inhibited the degradation of I?B? while SB203580 suppressed expression of p105, p50 and p65 in Helicobacter pylori-infected cells. ERK and p38 differentially activate NF-?B; ERK induces degradation of I?B? while p38 upregulates the expression of p50 and p65, subunits of NF-?B in Helicobacter pylori-infected gastric epithelial AGS cells. PMID:25337564

Seo, Ji Hye; Lim, Joo Weon; Kim, Hyeyoung

2013-01-01

70

Aqueous extract from taxus baccata inhibits adenosine deaminase activity significantly in cancerous and noncancerous human gastric and colon tissues  

PubMed Central

Objective: To investigate possible effects of aqueous taxus baccata extract on adenosine deaminase (ADA) activity in cancerous and noncancerous human tissues and to clarify mechanism(s) of its anticancer potential. Materials and Methods: Cancerous and noncancerous human gastric and colon tissues were used in the study. The extracts were prepared in distilled water. Before and after treatment with the extracts, ADA activities in the tissue homogenates were measured. Results: ADA activity was found to be higher in gastric tissue compared with colon tissue, but no differences were found between ADA activities of cancerous and noncancerous tissues for both as well. In the plant extract studies, it was found that taxus extract significantly inhibited ADA activity both in cancerous and noncancerous gastric and colon tissues. Conclusion: Our results suggest that aqueous extract from taxus baccata inhibits ADA activities in both gastric and colon tissues significantly. It is suggested that in addition to other proposed mechanisms, accumulated adenosine due to the inhibition of ADA enzyme might also play part in the anticancer properties of taxus species. PMID:24991094

Durak, Zahide Esra; Büber, Süleyman; Devrim, Erdinç; Kocao?lu, Hilmi; Durak, ?lker

2014-01-01

71

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

Microsoft Academic Search

Background and AimFree 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

José M. Alvarez-Suarez; Dragana Dekanski; Slavica Ristic; Nevena V. Radonjic; Natasa D. Petronijevic; Francesca Giampieri; Paola Astolfi; Ana M. González-Paramás; Celestino Santos-Buelga; Sara Tulipani; José L. Quiles; Bruno Mezzetti; Maurizio Battino; Irina V. Lebedeva

2011-01-01

72

Protective Effect of Amtolmetin Guacyl versus Placebo Diclofenac and Misoprostol in Healthy Volunteers Evaluated as Gastric Electrical Activity in Alcohol-Induced Stomach Damage  

Microsoft Academic Search

Amtolmetin guacyl (AMG) is a nonsteroidal antiinflammatory drug (NSAID) of high therapeutic activity and free of damaging effects on the gastrointestinal tract. Since acute ulcer and nausea have been found to be associated with gastric dysrhythmias, cutaneous electrogastrography and ultrasonographic study of the gastric emptying time were performed simultaneously in 24 healthy volunteers before and for 180 min after a

G. Riezzo; M. Chiloiro; S. Montanaro

2001-01-01

73

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

Microsoft Academic Search

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

Mozaffari K; Kavosh Boulevard; Supa Boulevard

74

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

75

Electrogastrography in adults and children: the strength, pitfalls, and clinical significance of the cutaneous recording of the gastric electrical activity.  

PubMed

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 (13)C-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

Riezzo, Giuseppe; Russo, Francesco; Indrio, Flavia

2013-01-01

76

Active neovascularization and possible vascular-centric development of gastric and periscapular elastofibromas.  

PubMed

An elastofibroma is a benign and rare fibrous lesion that most commonly occurs in the periscapular region. A gastrointestinal elastofibroma is extremely rare. In the present study, six cases of elastofibromas including a case in the stomach were evaluated. The gastric case revealed widely distributed lesions in the submucosal layer with perivascular fibrotic lesions (PVFLs) and some PVFLs were distributed to the skip lesions of elastofibroma. These PVFLs were also observed in all five periscapular cases and invariably contained elastic fibers which showed various degree of maturation. CD34-positive stromal cells were observed not only in elastofibromas but also in PVFLs in each case. These findings suggested the possibility of the PVFLs were the primary lesions of elastofibroma and their vascular-centric development. The percentage of the CD105-positive vessels in elastofibroma group was significantly higher than in the control group. This result indicates active neovascularization in elastofibromas. PMID:19132384

Kai, Keita; Kusano, Kenichiro; Sakai, Masashi; Tabuchi, Masanobu; Yunotani, Seiji; Miyazaki, Kohji; Tokunaga, Osamu

2009-02-01

77

Gastrin stimulates expression of plasminogen activator inhibitor-1 in gastric epithelial cells.  

PubMed

Plasminogen activator inhibitor (PAI)-1 is associated with cancer progression, fibrosis and thrombosis. It is expressed in the stomach but the mechanisms controlling its expression there, and its biological role, are uncertain. We sought to define the role of gastrin in regulating PAI-1 expression and to determine the relevance for gastrin-stimulated cell migration and invasion. In gastric biopsies from subjects with elevated plasma gastrin, the abundances of PAI-1, urokinase plasminogen activator (uPA), and uPA receptor (uPAR) mRNAs measured by quantitative PCR were increased compared with subjects with plasma concentrations in the reference range. In patients with hypergastrinemia due to autoimmune chronic atrophic gastritis, there was increased abundance of PAI-1, uPA, and uPAR mRNAs that was reduced by octreotide or antrectomy. Immunohistochemistry revealed localization of PAI-1 to parietal cells and enterochromaffin-like cells in micronodular neuroendocrine tumors in hypergastrinemic subjects. Transcriptional mechanisms were studied by using a PAI-1-luciferase promoter-reporter construct transfected into AGS-G(R) cells. There was time- and concentration-dependent increase of PAI-1-luciferase expression in response to gastrin that was reversed by inhibitors of the PKC and MAPK pathways. In Boyden chamber assays, recombinant PAI-1 inhibited gastrin-stimulated AGS-G(R) cell migration and invasion, and small interfering RNA treatment increased responses to gastrin. We conclude that elevated plasma gastrin concentrations are associated with increased expression of gastric PAI-1, which may act to restrain gastrin-stimulated cell migration and invasion. PMID:21193525

Nørsett, Kristin G; Steele, Islay; Duval, Cedric; Sammut, Stephen J; Murugesan, Senthil V M; Kenny, Susan; Rainbow, Lucille; Dimaline, Rod; Dockray, Graham J; Pritchard, D Mark; Varro, Andrea

2011-09-01

78

Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed gastric emptying in a canine model of diabetic gastroparesis.  

PubMed

1. The aim of the present study was to evaluate the effects of mitemcinal (GM-611), an orally active motilin receptor agonist, on delayed gastric emptying in a canine model of diabetic gastroparesis and to compare these effects with those of cisapride. 2. Moderate hyperglycaemia was induced by a single intravenous injection of a mixture of streptozotocin (30 mg/kg) and alloxan (50 mg/kg). Dogs that maintained moderate hyperglycaemia (fasting plasma glucose 200-300 mg/dL) without insulin treatment were selected and gastric emptying in these dogs was determined by the paracetamol method. 3. One year after the onset of diabetes, there was no difference in the gastric emptying of normal and diabetic dogs. However, after 5 years, the diabetic dogs showed delayed gastric emptying. The motor nerve conduction velocity of the tibial nerve was significantly lower in diabetic dogs compared with normal dogs at both time points. 4. Histopathological examination at the end of the study showed that there were fewer nerve fibres in both dorsal vagal and tibial nerves of diabetic dogs compared with normal dogs. The onset of delayed gastric emptying is thought to have occurred gradually, in parallel with abnormal autonomic nerve function induced by the long period of moderate hyperglycaemia. 5. Oral administration of mitemcinal (0.125, 0.25 or 0.5 mg/kg) dose-dependently accelerated delayed gastric emptying, significant at 0.5 mg/kg, in diabetic dogs, whereas cisapride (1, 3 or 10 mg/kg) had no significant effect. These results add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis. PMID:18346169

Onoma, Mitsu; Ozaki, Ken-ichi; Yogo, Kenji; Monnai, Makoto; Muramatsu, Hiroyasu; Kamei, Kenshi; Kawabe, Yoshiki; Hayashi, Shuji; Shiga, Toshihiko; Matsuo, Saori; Suzuki, Masami; Itoh, Zen; Omura, Satoshi; Takanashi, Hisanori

2008-07-01

79

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

PubMed Central

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

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

2012-01-01

80

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

PubMed

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

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

2012-05-01

81

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; OGrady, Gregory; Du, Peng; Cheng, Leo K

2014-11-01

82

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

83

Influence of Peroxisome Proliferator-activated Receptor (PPAR)? Plo12Ala Polymorphism as a Shared Risk Marker for Both Gastric Cancer and Impaired Fasting Glucose (IFG) in Japanese  

Microsoft Academic Search

Activation of peroxisome proliferator-activated receptor ? (PPAR?) has been shown to inhibit the proliferation of gastric\\u000a cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes\\u000a and colorectal cancer. We investigated the influence of PPAR? gene Plo12Ala polymorphism on the risk of gastric cancer and\\u000a on the severity of Helicobacter

Tomomitsu Tahara; Tomiyasu Arisawa; Tomoyuki Shibata; Masakatsu Nakamura; Fangyu Wang; Naoko Maruyama; Yoshio Kamiya; Masahiko Nakamura; Hiroshi Fujita; Mitsuo Nagasaka; Masami Iwata; Kazuya Takahama; Makoto Watanabe; Ichiro Hirata; Hiroshi Nakano

2008-01-01

84

Denervation suppresses gastric tumorigenesis.  

PubMed

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor-mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

Zhao, Chun-Mei; Hayakawa, Yoku; Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B; Andersen, Gøran T; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A; Renz, Bernhard W; Sandvik, Arne K; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D; Kaneko, Kazuhiro; Fox, James G; Wang, Timothy C; Chen, Duan

2014-08-20

85

Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives.  

PubMed

A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2-pyrazoline derivatives were synthesized by carrying a nitrate ester group or an oxime group onto the prepared pyrazoline derivatives through different spacers. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced rat paw edema and compared to a well-known NSAID, indomethacin as a reference drug. The ability of the prepared compounds to induce gastric toxicity was also evaluated. Most of the prepared compounds showed significant anti-inflammatory activity at the injected dose (100mg/kg) but they were safer than indomethacin in regard to gastric toxicity. The incorporation of the NO-donating group into the parent pyrazoline derivatives caused a non-significant reduction in the anti-inflammatory activity while a marked decrease in gastric ulcerations induced by their parent pyrazolines was observed. PMID:18722034

Shoman, Mai E; Abdel-Aziz, Mohamed; Aly, Omar M; Farag, Hassan H; Morsy, Mohamed A

2009-07-01

86

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

87

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

88

Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer.  

PubMed

Matrix metalloproteinases (MMPs) are suggested to play a critical role in extracellular matrix degradation and remodeling during inflammation and wound healing processes. However, the role of MMPs in indomethacin-induced gastric ulcer and its healing process are not clearly understood. This study is aimed at determining the regulation of MMP-9 and -2 activities in indomethacin-induced acute gastric ulceration and healing. Indomethacin-ulcerated stomach extracts exhibit significant up-regulation of pro-MMP-9 (92 kDa) activity and moderate reduction of MMP-2 activity, which strongly correlate with indomethacin dose and severity of ulcer. The anti-inflammatory and antioxidant properties of curcumin, an active component of turmeric, suggest that curcumin may exert antiulcer activity through scavenging reactive oxygen species, by regulating MMP activity, or both. To test these possibilities, the effect of curcumin in indomethacin-induced gastric ulcer is examined by biochemical and histological methods. The results show that curcumin exhibits potent antiulcer activity in acute ulcer in rat model by preventing glutathione depletion, lipid peroxidation, and protein oxidation. Denudation of epithelial cells during damage of gastric lumen is reversed by curcumin through re-epithelialization. Furthermore, both oral and intraperitoneal administration of curcumin blocks gastric ulceration in a dose-dependent manner. It accelerates the healing process and protects gastric ulcer through attenuation of MMP-9 activity and amelioration of MMP-2 activity. Omeprazole, an established antiulcer drug does not inhibit MMP-9 while protecting indomethacin-induced gastric ulcer. We conclude that antiulcer activity of curcumin is primarily attributed to MMP-9 inhibition, one of the major path-ways of ulcer healing. PMID:15615723

Swarnakar, Snehasikta; Ganguly, Krishnendu; Kundu, Parag; Banerjee, Aditi; Maity, Pallab; Sharma, Anamika V

2005-03-11

89

Effects of cimetidine on adenylate cyclase activity of guinea pig gastric mucosa stimulated by histamine, sodium fluoride and 5'-guanylylimidodiphosphate.  

PubMed

Cimetidine, a recently developed histamine H2-receptor blocking agent has been shown to be a potent inhibitor of histamine-stimulated gastric acid secretion in rat, cat, dog and man. To study the mode of action of cimetidine the modification of stimulatory effects of histamine, sodium flouride and 5'-guanylylimidodiphosphate by cimetidine on the adenylate cyclase activity of guinea pig gastric mucosa was studied. The effect of cimetidine was also compared to that of metiamide, an older histamine H2-receptor antagonist. The effect of cimetidine was qualitatively similar to that of metiamide, i.e. a selective blockade of histamine H2-receptors. Quantitatively cimetidine was about 10-fold more potent than metiamide. PMID:13313

Anttila, P; Westermann, E

1976-08-01

90

Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.  

PubMed

The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively. PMID:17023542

Wang, Gene-Jack; Yang, Julia; Volkow, Nora D; Telang, Frank; Ma, Yeming; Zhu, Wei; Wong, Christopher T; Tomasi, Dardo; Thanos, Panayotis K; Fowler, Joanna S

2006-10-17

91

Heterogeneity in the Activity of Mexican Helicobacter pylori Strains in Gastric Epithelial Cells and Its Association with Diversity in the cagA Gene  

Microsoft Academic Search

Received 12 December 2006\\/Returned for modification 2 February 2007\\/Accepted 9 April 2007 Helicobacter pylori CagA is translocated into gastric epithelial cells by a type IV secretion system and interacts with the Src homology 2 phosphatase, altering cell morphology. Multiple EPIYA motifs in CagA are associated with increased activity in cells and with gastric cancer. The aim of this work was

Adriana Reyes-Leon; John C. Atherton; Richard H. Argent; J. L. Puente; J. Torres

2007-01-01

92

Constitutive activation of glycogen synthase kinase-3? correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer  

Microsoft Academic Search

BACKGROUND: Aberrant regulation of glycogen synthase kinase-3? (GSK-3?) has been implicated in several human cancers; however, it has not been reported in the gastric cancer tissues to date. The present study was performed to determine the expression status of active form of GSK-3? phosphorylated at Tyr216 (pGSK-3?) and its relationship with other tumor-associated proteins in human gastric cancers. METHODS: Immunohistochemistry

Yu Jin Cho; Ji Hun Kim; Jiyeon Yoon; Sung Jin Cho; Young San Ko; Jong-Wan Park; Hye Seung Lee; Hee Eun Lee; Woo Ho Kim; Byung Lan Lee

2010-01-01

93

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

94

Effects of the 5-HT3 receptor antagonist ICS 205-930 on fat-delayed gastric emptying and antral motor activity.  

PubMed Central

1. The selective 5-HT3 receptor antagonist, ICS 205-930 (Sandoz), has been reported to have potent effects on gastric smooth muscle in vivo and to enhance gastric emptying in animals and in man. 2. This study investigated the effects of ICS 205-930 on fat-delayed gastric emptying of a semisolid meal and antral motor activity in humans. 3. Twelve healthy men participated in each of three studies in which 10 or 20 mg of ICS 205-930 or placebo were infused i.v. in a random double-blind fashion. Gastric emptying and antral motor activity were studied scintigraphically. 4. Gastric emptying was not altered after 10 mg but slower after 20 mg of ICS 205-930 than after placebo. Emptying after 20 mg of ICS 205-930 was significantly slower than after 10 mg of ICS 205-930. 5. Antral contraction amplitude was slightly lower after 20 mg of ICS 205-930 than after placebo, whereas the effects of 10 mg ICS 205-930 did not differ from those of placebo. 6. The results suggest that the investigated doses of ICS 205-930 have only slight effects on gastric motor activity of healthy young men, with 20 mg reducing the rate of emptying. PMID:2390431

Stacher, G; Bergmann, H; Schneider, C; Steiner-Mittelbach, G; Gaupmann, G; Steinringer, H; Abatzi, T A; Stacher-Janotta, G

1990-01-01

95

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

Microsoft Academic Search

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

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

2009-01-01

96

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

97

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

98

PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.  

PubMed

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling. PMID:24276243

Yun, S M; Yoon, K; Lee, S; Kim, E; Kong, S-H; Choe, J; Kang, J M; Han, T-S; Kim, P; Choi, Y; Jho, S; Yoo, H; Bhak, J; Yang, H-K; Kim, S-J

2014-11-13

99

Alterations of Hormonally Active Fibroblast Growth Factors after Roux-en-Y Gastric Bypass Surgery  

Microsoft Academic Search

Thirty-five morbidly obese patients underwent Roux-en-Y gastric bypass surgery (RYGB). In addition to weight loss, these patients showed significant improvement of insulin resistance and a reduction of hepatic fat content. Three months after surgery, the serum bile salts were slightly but significantly elevated, and the levels of the endocrine-acting fibroblast growth factor 19 (FGF19) and FGF21 were increased. FGF19 and

Peter L. M. Jansen; Jochem van Werven; Edo Aarts; Frits Berends; Ignace Janssen; Jaap Stoker; Frank G. Schaap

2011-01-01

100

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

101

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

PubMed

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

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

2014-04-01

102

JWA suppresses tumor angiogenesis via Sp1-activated matrix metalloproteinase-2 and its prognostic significance in human gastric cancer.  

PubMed

JWA, a multifunctional microtubule-binding protein, plays an important role in regulating tumor metastasis via inhibition of matrix metalloproteinase-2 (MMP-2). Recent investigations suggest that MMP-2 is an angiogenesis-associated molecule. In this study, we provide novel evidence that JWA inhibits tumor angiogenesis in gastric cancer (GC). In two independent retrospective GC cohorts, we found that the expression of JWA was downregulated and that of MMP-2 was upregulated in GC tissues compared with the same in normal gastric mucosa. For patients treated with surgery alone, a strong and independent negative prognostic value was shown for low JWA and high MMP-2 expressions separately, which was even stronger when combined (hazard ratio = 7.75, P < 0.001, in the training cohort; hazard ratio = 2.31, P < 0.001, in the validation cohort). Moreover, we found that loss of JWA expression was strongly correlated with increased GC angiogenesis. In vitro, JWA inhibited MMP-2 at both messenger RNA and protein levels by modulating Sp1 activity. Knockdown of endogenous JWA resulted in enhanced human umbilical vein endothelial cell tube formation and MMP-2 expression. Furthermore, JWA was found to inhibit Sp1 activity via an ubiquitin-proteasome-dependent mechanism and to downregulate the expression of the proangiogenic MMP-2. Our findings imply that JWA and MMP-2 may serve as promising prognostic markers in resectable GC, with JWA as a useful biomarker of angiogenesis in GC and a potential therapeutic target by MMP-2 modulation. PMID:24072772

Chen, Yansu; Huang, Yefei; Huang, Yulin; Xia, Xiaowei; Zhang, Jianbing; Zhou, Yan; Tan, Yongfei; He, Song; Qiang, Fulin; Li, Aiping; Re, Oluf Dimitri; Li, Gang; Zhou, Jianwei

2014-02-01

103

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

PubMed Central

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

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

2013-01-01

104

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

105

[In vitro evaluation of mucolytic activities of some expectorants using porcine gastric mucin].  

PubMed

The measurement of viscoelasticity of airway secretions (sputum) has been very difficult, because the secretions, mainly consisting of high molecular weight glycoproteins, are heterogeneous and non-Newtonian viscous fluid. In the present study, a new in vitro method was devised for evaluating the effects of mucolytic expectorants, using porcine gastric mucin as a mucous fluid. Twenty percent porcine gastric mucin solution was prepared by dissolving it in tris-HCl buffer solution. The mucolytics tested were incubated with the mucin solution at pH 7.0 and 37 degrees C for 30 min. The viscoelasticity of mucous fluid was determined by the glass plate method and rheometer method. The two cysteine-mucolytics, acetylcysteine (10(-3)-10(-1) M) and ethylcysteine++ (10(-3)-10(-1) M) showed a marked viscoelasticity-lowering effect with either method. On the other hand, another cysteine-mucolytic, carbocysteine had no mucolytic effect at pH 7.0, but showed its effect at pH 6.0. A protease-mucolytic, alpha-chymotrypsin (0.1-10 mg/ml), remarkably lowered the viscoelasticity of mucin fluid with either method. Bromhexine (3 X 10(-4)-3 X 10(-3) M) had no mucolytic effect even at the range of pH 6-8. From the above findings, it is indicated that distinct evaluation of the mucolytic actions of expectorants is feasible using porcine gastric mucin. The glass plate method has many advantages over the rheometer method in terms of required sample volume, measurement time, inexpensive, and so on. PMID:2468589

Misawa, M; Imamura, N

1988-10-01

106

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

107

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

2014-01-01

108

Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat.  

PubMed

The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents. PMID:19453518

Bucinskaite, V; Tolessa, T; Pedersen, J; Rydqvist, B; Zerihun, L; Holst, J J; Hellström, P M

2009-09-01

109

RECK inhibits stemness gene expression and tumorigenicity of gastric cancer cells by suppressing ADAM-mediated Notch1 activation.  

PubMed

The Reversion-inducing Cysteine-rich Protein with Kazal Motifs (RECK) gene encodes a membrane-anchored glycoprotein that exhibits strong inhibitory activity against various matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase 10 (ADAM10). RECK functions as a tumor suppressor by inhibiting migration, invasion, and angiogenesis. However, whether RECK can modulate the stem-like phenotypes of cancer cells is not known. In this study, we demonstrate that RECK is down-regulated in gastric cancer cells and is further reduced in CD133-positive cancer stem-like cells. Ectopic expression of RECK induces down-regulation of the expression of stemness genes including Sox2, Oct4, and Nanog and the cancer stem cell marker CD133. Treatment of DAPT (a ?-secretase inhibitor) or TAPI-2 (a hydroxamate-based inhibitor of MMPs, tumor necrosis factor ? converting enzyme and ADAM17) reduces Notch1 shedding and activation which results in attenuation of stemness genes and CD133. Our data show that ADAM10 and ADAM17 are co-pulled down by RECK suggesting a physical interaction between RECK and ADAMs on cell surface. In addition, RECK suppresses sphere formation and sphere size of CD133-positive gastric cancer cells. Overexpression of Notch intracellular domain (NICD) or ADAM17 effectively reverse the inhibitory effect of RECK in CD133-positive cells. More importantly, RECK reduces tumorigenic activity of CD133-positive cells in vivo. Conversely, knockdown of RECK in non-tumorigenic GI2 cells increases stemness and CD133 expression and sphere forming ability. Collectively, these results indicate that RECK represses stemness gene expression and stem-like properties by inhibiting ADAM-mediated Notch1 shedding and activation. PMID:23881612

Hong, Kun-Jing; Wu, Deng-Chyang; Cheng, Kuang-Hung; Chen, Li-Tzong; Hung, Wen-Chun

2014-02-01

110

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

111

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

112

Galectin-3 Facilitates Cell Motility in Gastric Cancer by Up-Regulating Protease-Activated Receptor-1(PAR-1) and Matrix Metalloproteinase-1(MMP-1)  

PubMed Central

Background Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1(PAR-1) and matrix metalloproteinase-1(MMP-1) PAR-1 thereby promoting gastric cancer metastasis. Methodology/Principal Findings We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a) galectin-3 silencing decreases the expression of PAR-1. b) galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c) galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d) galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e) Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f) Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. Conclusions/Significance Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis. PMID:21966428

Kim, Seok-Jun; Shin, Ji-Young; Lee, Kang-Duck; Bae, Young-Ki; Choi, Il-Ju; Park, Seok Hee; Chun, Kyung-Hee

2011-01-01

113

Gastric Banding  

MedlinePLUS

... received gastric banding have reported the following benefits: Weight-loss Decreased waist and hip circumference Improvements in obesity-related conditions, like diabetes, hypertension, and sleep apnea Improvements in general health Improvements in quality ...

114

Gastric culture  

MedlinePLUS

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

115

Piperine inhibits IL-1?-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells.  

PubMed

Piperine, a kind of natural alkaloid found in peppers, has been reported to exhibit anti-oxidative and anti-tumor activities, both in vitro and in vivo. Interleukin-6 (IL-6) is an important cytokine that activates the signal transduction, promotes tumor cell metastasis, and induces malignancy, including in gastric cancer. However, the effects of piperine on IL-6 expression in gastric cancer cells have not yet been well defined. In this study, we investigated the effects of piperine on the IL-6 expression, and examined the underlying signaling pathways via RT-PCR, promoter studies and Western blotting in human gastric cancer TMK-1 cells. Our results showed that piperine inhibited interleukin-1? (IL-1?)-induced IL-6 expression in a dose-dependent manner. In addition, piperine also inhibited IL-6 promoter activity. Experiments with mitogen-activated protein kinase (MAPK) inhibitors and dominant negative mutant p38 MAPK indicated that p38 MAPK was essential for IL-6 expression in the TMK-1 cells. Additionally, signal transducer and activator of transcription 3 (STAT3) was also involved in the IL-1?-induced IL-6 expression in gastric cancer cells. Piperine inhibited IL-1?-induced p38 MAPK and STAT3 activation and, in turn, blocked the IL-1?-induced IL-6 expression. Furthermore, gastric cancer cells pretreated with IL-1? showed markedly enhanced invasiveness, which was partially abrogated by treatment with IL-6 siRNA, piperine, and inhibitors of p38 MAPK and STAT3. These results suggest that piperine may exert at least part of its anti-cancer effect by controlling IL-6 expression through the suppression of p38 MAPK and STAT3. PMID:25234193

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

2015-01-01

116

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

117

Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase-4 activity in obese patients with type 2 diabetes  

PubMed Central

The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass (GBP) surgery is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10-kg equivalent weight loss by GBP (n = 16) or by caloric restriction (CR, n = 14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p = 0.01), but not after CR. The increased peak glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretin concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined. PMID:21210936

Alam, M. L.; Van der Schueren, B. J.; Ahren, B.; Wang, G. C.; Swerdlow, N. J.; Arias, S.; Bose, M.; Gorroochurn, P.; Teixeira, J.; McGinty, J.; Laferrere, B.

2013-01-01

118

Studies on activity of various extracts of Mentha arvensis Linn against drug induced gastric ulcer in mammals  

PubMed Central

AIM: To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid, ethanol and pylorus ligated ulcer models in rats and mice. METHODS: Various crude extracts of petroleum ether, chloroform, or aqueous at a dose of 2 g/kg po did not produce any signs or symptoms of toxicity in treated animals. In the pyloric ligation model oral administration of different extracts such as petroleum ether, chloroform and aqueous at 375 mg/kg po, standard drug ranitidine 60 mg/kg po and control group 1% Tween 80, 5 mL/kg po to separate groups of Wister rats of either sex (n = 6) was performed. Total acidity, ulcer number, scoring, incidence, area, and ulcer index were assessed. RESULTS: There was a decrease in gastric secretion and ulcer index among the treated groups i.e. petroleum ether (53.4%), chloroform (59.2%), aqueous (67.0%) and in standard drug (68.7%) when compared to the negative control. In the 0.6 mol/L HCl induced ulcer model in rats (n = 6) there was a reduction in ulcerative score in animals receiving petroleum ether (50.5%), chloroform (57.4%), aqueous (67.5%) and standard. drug (71.2%) when compared to the negative control. In the case of the 90% ethanol-induced ulceration model (n = 6) in mice, there was a decrease in ulcer score in test groups of petroleum ether (53.11%), chloroform (62.9%), aqueous (65.4%) and standard drug ranitidine (69.7%) when compared to the negative control. It was found that pre-treatment with various extracts of Mentha arvensis Linn in three rat/mice ulcer models ie ibuprofen plus pyloric ligation, 0.6 mol/L HCl and 90% ethanol produced significant action against acid secretion (49.3 ± 0.49 vs 12.0 ± 0.57, P < 0.001). Pre-treatment with various extracts of Mentha arvensis Linn showed highly -significant activity against gastric ulcers (37.1 ± 0.87 vs 12.0 ± 0.57, P < 0.001). CONCLUSION: Various extracts of Mentha arvensis Linn. 375 mg/kg body weight clearly shows a protective effect against acid secretion and gastric ulcers in ibuprofen plus pyloric ligation, 0.6 mol/L HCl induced and 90% ethanol-induced ulcer models. PMID:21160779

Londonkar, Ramesh L; Poddar, Pramod V

2009-01-01

119

The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance.  

PubMed

Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan-Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC. PMID:24844205

Tapia, Oscar; Riquelme, Ismael; Leal, Pamela; Sandoval, Alejandra; Aedo, Susana; Weber, Helga; Letelier, Pablo; Bellolio, Enrique; Villaseca, Miguel; Garcia, Patricia; Roa, Juan Carlos

2014-07-01

120

Effect of methanolic extract of Terminalia arjuna against Helicobacter pylori 26695 lipopolysaccharide-induced gastric ulcer in rats.  

PubMed

Helicobacter pylori lipopolysaccharide (HP-LPS) is a potent virulence factor in the causation of gastric ulcer and gastritis. H. pylori-induced gastric pathology is prevalent throughout the world. Herbal medicines are attracting attention because of their traditional values, popularity and belief, as well as for their advantages such as less toxicity, affordability and medicinal value. The present study aimed to evaluate the anti-ulcer effect of a methanolic extract of Terminalia arjuna (TA) against HP-LPS-induced gastric damage in rats. Ulcers were induced with HP-LPS (50 mug per animal) administered orally daily for 3 days. The efficacy of TA on gastric secretory parameters such as volume of gastric juice, pH, free and total acidity, pepsin concentration, and the cytoprotective parameters such as protein-bound carbohydrate complexes in gastric juice and gastric mucosa was assessed. The protective effect of TA was also confirmed by histopathological examination of gastric mucosa. HP-LPS-induced alterations in gastric secretory parameters were altered favourably in rats treated with TA, suggesting that TA has an anti-secretory role. Furthermore, HP-LPS-induced impairments in gastric defence factors were also prevented by treatment with TA. These results suggest that the severe cellular damage and pathological changes caused by HP-LPS are mitigated by TA; these effects are comparable with those of sucralfate. The anti-ulcer effect of TA may reflect its ability to combat factors that damage the gastric mucosa, and to protect the mucosal defensive factors. PMID:18380924

Devi, Rethinam Sundaresan; Kist, Manfred; Vani, Ganapathy; Devi, Chennam Srinivasulu Shyamala

2008-04-01

121

Anti-ulcerogenic activity of the methanol root bark extract of Cochlospermum planchonii (Hook f).  

PubMed

Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria traditional medicine for treatment of different ailments including ulcers. The anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii was evaluated using different [ethanol, acetylsalicylic acid (aspirin), cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg body weight using cimetidine (100 mg/kg) as a standard reference drug. The different doses of the extract and the reference drug significantly (p < 0.01) decreased all the ulcer parameters in a dose dependent manner in all the models used. The total number of ulcers were significantly (p < 0.05) decreased. The ulcer index was significantly (p < 0.004) reduced by the extract. Similarly, the percentage ulcer preventive index was also increased from 0% in the negative control up to 93.2% at the dose of 1000 mg/kg, while the percentage ulcer severity was dose dependently reduced by the extract. Furthermore, the extract significantly (p < 0.02) decreased free gastric HCl and total gastric acid. In conclusion, Cochlospermum planchonii methanolic root bark extract showed significant antiulcer activity in this study which may be as a result of its cytoprotective, antioxidant or antisecretory properties. PMID:24311856

Ezeja, Maxwell I; Anaga, Aruh O

2013-01-01

122

The activation of proteinase-activated receptor-1 (PAR1) promotes gastric cancer cell alteration of cellular morphology related to cell motility and invasion.  

PubMed

Cell motility proceeds by cycles of edge protrusion, adhesion and retraction. Whether these functions are coordinated by biochemical or biomechanical processes is unknown. Tumor invasion and metastasis is directly related to cell motility. We showed that stimulation of proteinase-activated receptor-1 (PAR1) can trigger an array of responses that would promote tumor cell growth and invasion. Thus, we examined aspects of PAR1 activation related to cell morphological change that might contribute to cell motility. We established a PAR1 stably transfected MKN45 gastric cancer cell line (MKN45/PAR1). We examined morphological changes, Rho family activation and overexpression of cytoskeletal protein in cells exposed to PAR1 agonists (?-thrombin and TFLLR-NH2). MKN45/PAR1 grows with an elongated and polarized morphology, extending pseudopodia at the leading edge. However, in the presence of PAR1 antagonist, MKN45/PAR1 did not show any changes in cell shape upon addition of either ?-thrombin or TFLLR-NH2. Activated PAR1 induced RhoA and Rac1 phosphorylation, and subsequent overexpression of myosin IIA and filamin B which are stress fiber components that were identified by PMF analysis of peptide mass data obtained by MALDI-TOF/MS measurement. Upon stimulation of MKN45/PAR1 for 24 h with either ?-thrombin or TFLLR-NH2, the distribution of both myosin IIA and filamin B proteins shifted to being distributed throughout the cytoplasm to the membrane, with more intense luminescence signals than in the absence of stimulation. These results demonstrate that PAR1 activation induces cell morphological change associated with cell motility via Rho family activation and cytoskeletal protein overexpression, and has a critical role in gastric cancer cell invasion and metastasis. PMID:23242308

Fujimoto, Daisuke; Hirono, Yasuo; Goi, Takanori; Katayama, Kanji; Matsukawa, Shigeru; Yamaguchi, Akio

2013-02-01

123

[Gastric bezoar].  

PubMed

Bezoar consist of the accumulation of different substances in the digestive tract. We present the clinical case of a girl with gastric trichobezoar discovered in a postoperatory follow-up to an appendicectomy. Ultra-sound images and oesophagus-gastric transit are fundamental points in the diagnosis. Endoscopy was useful in confirming the diagnosis and in ruling out associated ulcus, frequent in these patients. Surgical treatment is the choice in big bezoar but laser, prokinetics and enzymatic dissolutions have also been used. Theses patients should undergo psychological control. PMID:11480198

Correa Antúnez, M I; Serrano Calle, A; Pimentel Leo, J J; Sanjuan Rodríguez, S

2001-04-01

124

Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury.  

PubMed

Oral administration to fasted rats of either absolute ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, 25% sodium chloride, or boiling water produced extensive necrosis of the gastric mucosa. Pretreatment with several prostaglandins of the A, E, or F type, either orally or subcutaneously, prevented such necrosis, and the effect was dose-dependent. This property of prostaglandins is called "cytoprotection." The protective effect against oral administration of absolute ethanol was already maximal 1 min after PGE2 given orally, and 15-30 min after PGE2 given subcutaneously. Cytoprotection by prostaglandins is unrelated to the inhibition of gastric acid secretion since, (a) it is maximal at doses that have no effect on gastric secretion, and (b) anti-secretory compounds (cimetidine, methscopolamine bromide) and antacids are not cytoprotective. Although the mechanism of gastric cytoprotection is unknown, prostaglandins appear to increase the resistance of gastric mucosal cells to the necrotizing effect of strong irritants. These results suggest that certain prostaglandins, by a mechanism other than the inhibition of gastric acid secretion, maintain the cellular integrity of the gastric mucosa, and might be beneficial in the treatment of a variety of diseases in which gastric mucosal injury is present. PMID:456839

Robert, A; Nezamis, J E; Lancaster, C; Hanchar, A J

1979-09-01

125

Tumor-Activated TCR??+ T Cells from Gastric Cancer Patients Induce the Antitumor Immune Response of TCR??+ T Cells via Their Antigen-Presenting Cell-Like Effects  

PubMed Central

Human ?? T cells display the principal characteristics of professional antigen-presenting cells (APCs), in addition to playing a vital role in immunity through cytokine secretion and their cytotoxic activity. However, it is not clear whether ?? T cells perform APC-like functions under pathological conditions. In this study, we showed that, in contrast to peripheral-derived ?? T cells directly isolated from PBMCs of gastric cancer patients, tumor-activated ?? T cells not only killed tumor cells efficiently but also strongly induced primary CD4+ and CD8+???? T cells proliferation and differentiation. More importantly, they abrogated the immunosuppression induced by CD4+CD25+ Treg cells and induced the cytotoxic function of CD8+???? T cells from patients with gastric cancer. In conclusion, tumor-activated ?? T cells can induce adaptive immune responses through their APC-like functions, and these cells may be a potentially useful tool in the development of tumor vaccines and immunotherapy. PMID:24741609

Mao, Chaoming; Mou, Xiao; Zhou, Yuepeng; Yuan, Guoyue; Xu, Chengcheng; Liu, Hongli; Zheng, Tingting; Tong, Jia; Chen, Deyu

2014-01-01

126

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

PubMed

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

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

2014-10-01

127

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

PubMed

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

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

2013-07-01

128

[MALIGNANT GASTRIC LEIOMYOBLASTOMA: CASE REPORT  

PubMed

The gastric leiomyoblastoma is a benign neoplasia -extremely uncommon and potentially malignant-, which arises from the muscular layer of the stomach. We present the case of a 21 year old male patient with this disease, who suddenly had intraperitoneal hemorrhage. He underwent an exploratory operation and the surgical findings showed an ulcerated and bleeding nodular tumor, located on the anterior wall and minor curvature of the gastric antrum, ulcerated and with active bleeding. A distal subtotal gastrectomy was performed, as well as a Billroth II-type gastroenteroanastomosis from the Hoffmeister-Finsterer variety. The anatomopathologic report was, "malignant gastric leiomyoblastoma". We discuss the clinical features and therapeutical options used. PMID:12219107

Díaz Plasencia, Juan; Tantaleán, Enrique; Guzmán, Rafael; Pomatanta Plasencia, Jorge; Grados Méndez, Johnny; Vilela, Carlos

1997-01-01

129

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

130

Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice  

PubMed Central

AIM: To investigate the apoptosis of implanted primary gastric cancer cells in nude mice induced by resveratrol and the relation between this apoptosis and expression of bcl-2 and bax. METHODS: A transplanted tumor model was established by injecting human primary gastric cancer cells into subcutaneous tissue of nude mice. Resveratrol (500 mg/kg, 1000 mg/kg and 1500 mg/kg) was directly injected beside tumor body 6 times at an interval of 2 d. Then changes of tumor volume were measured continuously and tumor inhibition rate of each group was calculated. We observed the morphologic alterations by electron microscope, measured the apoptotic rate by TUNEL staining method, detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistoch-emical staining and PT-PCR. RESULTS: Resveratrol could significantly inhibit carcinoma growth when it was injected near the carcinoma. An inhibitory effect was observed in all therapeutic groups and the inhibition rate of resveratrol at the dose of 500 mg/kg, 1000 mg/kg and 1500 mg/kg was 10.58%, 29.68% and 39.14%, respectively. Resveratrol induced implanted tumor cells to undergo apoptosis with apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation. The inhibition rate of 0.2 mL of normal saline solution, 1 500 mg/kg DMSO, 500 mg/kg resveratrol, 1000 mg/kg resveratrol, and 1500 mg/kg resveratrol was 13.68±0.37%, 13.8±0.43%, 48.7±1.07%, 56.44±1.39% and 67±0.96%, respectively. The positive rate of bcl-2 protein of each group was 29.48±0.51%, 27.56±1.40%, 11.86±0.97%, 5.7±0.84% and 3.92±0.85%, respectively by immunohistochemical staining. The positive rate of bax protein of each group was 19.34±0.35%, 20.88±0.91%, 40.02±1.20%, 45.72±0.88% and 52.3±1.54%, respectively by immunohistochemical staining. The density of bcl-2 mRNA in 0.2 mL normal saline solution, 1500 mg/kg DMSO, 500 mg/kg resveratrol, 1000 mg/kg resveratrol, and 1500 mg/kg resveratrol decreased progressively and the density of bax mRNA in 0.2 mL normal saline solution, 1500 mg/kg DMSO, 500 mg/kg resveratrol, 1000 mg/kg resveratrol, and 1500 mg/kg increased progressively with elongation of time by RT-PCR. CONCLUSION: Resveratrol is able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated by down-regulating apoptosis-regulated gene bcl-2 and up-regulating the expression of apoptosis-regulated gene bax. PMID:15633232

Zhou, Hai-Bo; Chen, Juan-Juan; Wang, Wen-Xia; Cai, Jian-Ting; Du, Qin

2005-01-01

131

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

132

Antibacterial activity of sucralfate versus aluminum chloride in simulated gastric fluid  

Microsoft Academic Search

Studies have previously demonstrated that sucralfate possesses intrinsic antibacterial activity. This study was designed to indirectly assess whether aluminum is the active antibacterial component of sucralfate and to further evaluate factors that may influence this agent's antibacterial activity. Utilizing an in vitro model, the antibacterial activity of sucralfate, an equivalent quantity of aluminum in the form of aluminum chloride, and

L. Welage; P. Carver; K. Welch

1994-01-01

133

Central somatostatin receptor 1 activation reverses acute stress-related alterations of gastric and colonic motor function in mice  

PubMed Central

Background Corticotropin-releasing factor (CRF) signaling induced by stress is well established to delay gastric emptying (GE) and stimulate colonic functions. The somatostatin receptor (sst1-5) agonist, ODT8-SST acts in the brain to inhibit stress-induced adrenocorticotropic hormone and epinephrine secretion. We investigated whether ODT8-SST acts in the brain to influence stress-related alterations of gastric and colonic motor function and sst receptor subtype(s) involved. Methods Peptides were injected intracerebroventricularly (i.c.v.) under short isoflurane anesthesia and GE, fecal pellet output (FPO) and distal colonic motility monitored in conscious mice. Key results The stress of anesthesia/vehicle i.c.v. injection reduced GE by 67% and increased defecation by 99% compared to non-injected controls. Both responses were abolished by ODT8-SST (1?g=0.75nmol) or sst1 agonist (3?g=1.95nmol). The sst1 agonist also prevented the abdominal surgery-induced delayed GE. Octreotide (sst2>sst5>sst3) and the sst2 or sst4 agonists (1?g=0.78 or 0.70nmol, respectively) injected i.c.v. did not influence FPO while i.c.v. somatostatin-28 mimicked ODT8-SST’s effect. The ODT8-SST-induced increased food intake was inhibited by i.c.v. sst2 antagonist while the reduced FPO was unchanged. ODT8-SST i.c.v. reduced distal colonic motility in semi-restrained mice compared with vehicle and blocked water avoidance- and i.c.v. CRF (0.5?g=0.09 nmol)-induced stimulated FPO while a similar colonic secretomotor response to i.p. 5-hydroxytryptophane (10mg/kg=36.4?mol/kg) was unaltered. Conclusions & Inferences ODT8-SST counteracts stress/i.c.v. CRF-related stimulation of colonic motor function and delayed GE which can be reproduced mainly by activation of sst1 receptors. These data opens new insight to brain somatostatinergic signaling pathways interfering with brain circuitries involved in gut motor responses to acute stress. PMID:21564422

STENGEL, A.; GOEBEL-STENGEL, M.; WANG, L.; LARAUCHE, M.; RIVIER, J.; TACHE, Y.

2013-01-01

134

Type II cGMP?dependent protein kinase inhibits RhoA activation in gastric cancer cells.  

PubMed

Small GTPase RhoA is a key signaling component regulating cell migration and stress fiber formation. Previous studies have shown that RhoA activity is regulated by protein kinases, such as cAMP?dependent protein kinase (PKA) and type I cGMP?dependent protein kinase (PKGI), which phosphorylate the protein. This study was designed to investigate the effect of type II cGMP?dependent protein kinase (PKGII) on RhoA activity. Cells of the human gastric cancer line AGS were infected with adenoviral constructs bearing the PKGII cDNA in order to increase its endogenous expression, and were treated with 8?pCPT?cGMP to activate the PKGII enzyme. A transwell assay was performed to measure the migratory activity of the treated cells, and immunofluorescent microscopy was used to observe the formation of stress fibers. The phosphorylation of RhoA was detected by western blotting, and the activity of RhoA was measured by a pull?down assay. Co?immunoprecipitation (co?IP) was performed to detect binding of PKGII to RhoA. Glutathione S?transferase (GST)?fused fragments of RhoA and PKGII were expressed in Escherichia coli and used to investigate the domains required for the binding. The results showed that lysophosphatidic acid (LPA) treatment increased the migration and the formation of stress fibers in AGS cells and that this effect was RhoA?dependent. An increase in PKGII activity, not only inhibited LPA?induced migration and stress fiber formation, but also suppressed LPA?induced activation of RhoA. PKGII caused serine 188 (Ser188) phosphorylation of RhoA, but not the phosphorylation of the mutant RhoA Ser188A, and therefore had no inhibitory effect on the activity of the mutant protein. Co?IP results showed that there is direct binding of PKGII to RhoA. The GST pull?down assay showed that the fragment containing RhoA amino acid residues 1?44 and the N?terminal fragment of PKGII containing amino acid residues 1?176 are required for the binding between the two proteins. These results suggested that PKGII inhibits RhoA activity by binding to this small GTPase and causing phosphorylation at its Ser188 site. PMID:24549567

Wang, Ying; Chen, Yongchang; Li, Yueying; Lan, Ting; Qian, Hai

2014-04-01

135

Detection of ouabain-insensitive H(+)-transporting, K(+)-stimulated p-nitrophenylphosphatase activity in rat gastric glands by cerium-based cytochemistry.  

PubMed

We employed a modification of our previously reported cerium-based cytochemical method for ouabain-sensitive, K-dependent p-nitrophenylphosphatase (Na-K ATPase) activity to detect ouabain-insensitive, K-stimulated p-nitrophenylphosphatase (K-pNPPase) activity in rat gastric glands. Biochemically, the enzyme activity of gastric glands incubated in a medium containing 50 mM Tricine buffer (pH 7.5), 50 mM KCl, 10 mM MgCl2, 2 mM CeCl3, 2 mM p-nitrophenylphosphate (pNPP), 2.5 mM levamisole, 10 mM ouabain, and 0.00015% Triton X-100, was optimal at pH 7.5-8.0 and decreased above pH 8.5. The amount of p-nitrophenol after incubation increased linearly in proportion to the amount of tissue in the medium. The enzyme activity was inhibited by omeprazole, sodium flouride (NaF), N-ethylmaleimide (NEM), and dicyclohexylcarbodiimide (DCCD). Heat-treated specimens had no enzyme activity. The enzyme activity increased with addition of K ions up to the concentration of 50 mM, and became constant above 50 mM. Cytochemically, the parietal cells of the gastric glands reacted positively for ouabain-insensitive K-pNPPase activity. Intense reaction was observed at the microvilli of the luminal surface and the intracellular canaliculi. The tubulovesicular system showed weak enzyme activity. The reaction products were found as fine, granular, electron-dense deposits in the cytoplasm just beneath the plasma membrane. The ouabain-insensitive K-pNPPase activity detected in this study appears, therefore, to be associated with that of H-transporting, K-stimulated adenosine triphosphatase (H-K ATPase). PMID:2174937

Kobayashi, T; Seguchi, H

1990-12-01

136

Non-coding RNAs and gastric cancer  

PubMed Central

Non-coding RNAs (ncRNAs) play key roles in development, proliferation, differentiation and apoptosis. Altered ncRNA expression is associated with gastric cancer occurrence, invasion, and metastasis. Moreover, aberrant expression of microRNAs (miRNAs) is significantly related to gastric cancer tumor stage, size, differentiation and metastasis. MiRNAs interrupt cellular signaling pathways, inhibit the activity of tumor suppressor genes, and affect the cell cycle in gastric cancer cells. Some miRNAs, including miR-21, miR-106a and miR-421, could be potential markers for the diagnosis of gastric cancer. Long non-coding RNAs (lncRNAs), a new research hotspot among cancer-associated ncRNAs, play important roles in epigenetic, transcriptional and post-transcriptional regulation. Several gastric cancer-associated lncRNAs, such as CCAT1, GACAT1, H19, and SUMO1P3, have been explored. In addition, Piwi-interacting RNAs, another type of small ncRNA that is recognized by gastroenterologists, are involved in gastric carcinogenesis, and piR-651/823 represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice. Small interfering RNAs also function in post-transcriptional regulation in gastric cancer and might be useful in gastric cancer treatment. PMID:24833871

Li, Pei-Fei; Chen, Sheng-Can; Xia, Tian; Jiang, Xiao-Ming; Shao, Yong-Fu; Xiao, Bing-Xiu; Guo, Jun-Ming

2014-01-01

137

Anti-gastric adenocarcinoma activity of 2-Methoxy-1,4-naphthoquinone, an anti-Helicobacter pylori compound from Impatiens balsamina L.  

PubMed

2-Methoxy-1,4-naphthoquinone (MeONQ) from Impatiens balsamina L. exhibited strong anti-H. pylori activity in our previous study. In this study, we investigated the cytotoxicity of MeONQ against gastric adenocarcinoma (MKN45 cell line) and propose the relevant mechanisms. MeONQ resulted in serious necrosis via superoxide anion catastrophe when the treatment doses were higher than 50?M, whereas apoptosis occurred at low treatment doses (25-50?M) through the caspase-dependent apoptosis pathway. Necrosis is the dominant mode of cell death. MeONQ exhibited high ability to induce gastric adenocarcinoma necrosis, showing good potential as a candidate agent for H. pylori infection related disease therapy. PMID:22516543

Wang, Yuan-Chuen; Lin, Yi-Han

2012-12-01

138

Macrophage Inhibitory Cytokine1 Induces the Invasiveness of Gastric Cancer Cells by Up-Regulating the Urokinase-type Plasminogen Activator System1  

Microsoft Academic Search

In our search for genes associated with gastric cancer progression, we identified macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor superfamily, as an overexpressed gene in gastric tumor tissues. Expression analysis of MIC-1 in gastric tumor tissues revealed a specific expression in gastric cancer cells, and this expression level was well correlated with invasive potential in various

Dong Hoon Lee; Young Yang; Soon Jung Lee; Kun-Yong Kim; Tae Hyeon Koo; Kyu Sang Song; Young Ho Lee; Yung-Jin Kim; Jung Joon Lee; Inpyo Choi; Jeong-Hyung Lee

2003-01-01

139

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

140

Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells.  

PubMed

Sialyl-Lewis X (SLe(x)) 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 SLe(x) antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLe(x) 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 SLe(x) 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 SLe(x) 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

141

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; Osorio, Hugo; Pinto, Marta Teixeira; Campos, Diana; Oliveira, Maria Jose; Reis, Celso A.

2013-01-01

142

Relative efficacies of gastric proton-pump inhibitors on a milligram basis: desired and undesired SH reactions. Impact of chirality.  

PubMed

Gastric proton-pump inhibitors (PPIs) are prodrugs. Their acid activation at pH 1.0 inside the canaliculus of a parietal cell should be fast relative to their serum elimination rate. Actually, all PPIs display chemical activation half-lives at pH 1.0 of a few minutes at the most, while being eliminated from serum with a half-life of about 1 h. This is the main reason they show similar antisecretory efficacies on a milligram basis. It is in line with about 5% to 15% higher healing rates in GERD, DU and GU when 40 mg is compared to 20 mg of either omeprazole or pantoprazole. The comparably large biological variation between patient samples explains why some studies show statistically significant differences between the two doses, while others do not. However, it would matter to the individual patient if s/he was the one additionally healed by a 40 mg dose within a defined treatment period. Chemical activation of PPI prodrugs is unwanted in weakly acidic tissue compartments such as lysosomes or secretory granules. However, the ratio of the serum elimination half-life (availability at the target) to the chemical activation half-life at a critical pH 5.0 is reversed only with pantoprazole. when compared to pH 1.0 (i.e. the ratio is < 1 at pH 5.0 and > 1.0 at pH 1.0). This is the basis of the high pH selectivity of pantoprazole. In contrast, rabeprazole is activated at pH 5.0 almost as quickly as it is at pH 1.0 and much faster than it is eliminated from serum. This unwanted reactivity of rabeprazole at pH 5.0 does not contribute to the antisecretory action at pH 1.0 and results in poor pH selectivity. Omeprazole and lansoprazole lie in between, as they are activated, at pH 5.0, about as quickly as they are eliminated from serum. The above activation rates refer to room temperature. At 37 degrees C. the activation rates of all PPIs further increase, by about the same factor of between 3 and 4. This renders their differential pH selectivities even more critical for drug safety. Biological consequences have been reported in the literature. It has been claimed that a dose of 40 mg of the S-enantiomer of omeprazole (esomeprazole) results in 10%-15% higher healing rates in GERD patients, compared to 20 mg omeprazole racemate. The same difference is found when the two doses of omeprazole racemate are compared to each other. This is not surprising, as the chiral PPI prodrug is converted by acid into an achiral cyclic sulfenamide which only then reacts with the proton pump. There is therefore no pharmacodynamic argument in favour of any single enantiomer formulation of any PPI. Moreover, potential pharmacokinetic differences between the enantiomers seem to be of little if any importance in the patient. PMID:11768559

Kromer, W

2001-01-01

143

[Gastric emptying in the aged. Effect of clebopride].  

PubMed

Fifteen patients considered as "geronts" (average 70 years) have been performed Radiology, Endoscopy and Gastric Biopsies, with differents degrees of chronic gastritis as only gastric pathology, and 8 "healthy adults" (controls) were assessed on the T1/2 of gastric evacuation, with a solid meal marked with DPTA Tc 99 and measurement of isotopic activity in Gamma Camera before and after administration of a therapeutic dose of Clebopride. In the basal trial it was found that geronts gastric emptying is delayed more than controls (112 and 89 minutes). The activity of Clebopride revealed a significant decrease in both groups, being more important in geronts. This findings suggests the clinic usefulness in different pathological situations, where its useful to accelerate the time of gastric evacuation (gastric esofagic reflux, gastric ulcer) and in the geront with dispeptic symptoms and chronic gastritis related to age, as the only gastric pathology. PMID:6524269

Schraier, M; Guinsburg, R; Valguarnera, J; Rosenfeld, L

1984-01-01

144

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

145

Effect of gastric dysrhythmias on postcibal motor activity of the stomach  

Microsoft Academic Search

The effect of electrical dysrhythmias on the mechanical activity of the fed stomach was investigated in 5 conscious dogs implanted with Ag-AgCl electrodes and strain gauge force transducers. Each dog was fed 1 can of ALPO® and electromechanical activities of the stomach were recorded for the next 120 min. The results show that intraarterial boluses of met-enkephalin (75 µg\\/kg), PGE2

Chung H. Kim; Alan R. Zinsmeister; Juan-R. Malagelada

1988-01-01

146

Gastric afferents to the paraventricular nucleus in the rat  

Microsoft Academic Search

Extracellular recordings were made from vasopressin (AVP) and oxytocin (OXT)-secreting cells in the paraventricular nucleus (PVN) of the hypothalamus in rats anesthetized with urethane-chloralose to determine the effects of electrical stimulation of vagal gastric nerves and gastric distension on their activity. Electrical stimulation of gastric branches of the vagus nerves inhibited 5 and excited 10 of 32 phasically firing neurosecretory

Y. Ueta; H. Kannan; H. Yamashita

1991-01-01

147

Lamb Gastric Lipase and Proteases in Cheese Manufacture  

Microsoft Academic Search

The value of lipase and proteases from lamb gastric tissues in cheese flavor devel- opment was demonstrated independently of lamb pregastric esterase and calf rennet activities. Parmesan, Romauo, Cheddar cheese, and directly acidified Pizza curd were improved in body breakdown and fla- vor development when treated with lamb gastric extract. The best cheese flavor re- sulted when both gastric and

R. V. Chaudhari; G. H. Richardson

1971-01-01

148

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

SciTech Connect

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

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

1985-08-01

149

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

SciTech Connect

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

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

1985-08-01

150

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

Yufera, Manuel; Moyano, Francisco J.; Astola, Antonio; Pousao-Ferreira, Pedro; Martinez-Rodriguez, Gonzalo

2012-01-01

151

Orally Active Fumagillin Analogues: Transformations of a Reactive Warhead in the Gastric Environment  

PubMed Central

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

2013-01-01

152

Evolution of Gastric Electrical Features and Gastric Emptying in Children with Duchenne and Becker Muscular Dystrophy  

Microsoft Academic Search

OBJECTIVES:Although muscular dystrophy (MD) affects primarily striated muscles, smooth muscle cells of the gastrointestinal tract may also be involved. We recorded gastric electrical activity and gastric emptying time (GET) in children with MD at initial presentation and at 3-yr follow-up in order to detect gastric motor abnormalities and study their evolution along the clinical course.METHODS:Twenty children with MD (median age:

Osvaldo Borrelli; Gennaro Salvia; Valentina Mancini; Lucio Santoro; Francesca Tagliente; Erminia Francesca Romeo; Salvatore Cucchiara

2005-01-01

153

Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett’s-like metaplasia  

PubMed Central

Summary Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1? phenocopies human pathology with evolution of esophagitis, Barrett’s-like metaplasia and EAC. Histopathology and gene signatures resembled closely human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1 and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5+ gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1?-IL-6 signaling cascade and Dll1-dependent Notch signaling. PMID:22264787

Quante, Michael; Bhagat, Govind; Abrams, Julian; Marache, Frederic; Good, Pamela; Lee, Michele D.; Lee, Yoomi; Friedman, Richard; Asfaha, Samuel; Dubeykovskaya, Zinaida; Mahmood, Umar; Figueiredo, Jose-Luiz; Kitajewski, Jan; Shawber, Carrie; Lightdale, Charles; Rustgi, Anil K.; Wang, Timothy C.

2011-01-01

154

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

155

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

156

Preventive activity of pyrrolizidine alkaloids from Seneciobrasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats.  

PubMed

The alkaloid extract of Senecio brasiliensis inflorescences contain a mixture of the pyrrolizidine alkaloids (PA) senecionine, integerrimine, retrorsine, usaramine and seneciphylline. We evaluated this PA mixture on preventive antiulcerogenic effects on standard rodent models of induced gastric and duodenal ulcers. In the HCl/ethanol, indomethacin-bethanechol and hypothermic-restraint-induced gastric ulcer, the lesion was significantly inhibited by PA (p.o.) (p < 0.001). In the pylorus-ligature, PA (i.d.), significantly increased the gastric juice content and the pH values and decreased the acid output. In the cysteamine induced duodenal ulcers, PA (p.o.) showed significant inhibition (p < 0.001) of the duodenal lesions when compared to the respective control. The levels of the somatostatin hormone in the blood samples of animals pre-treated with the PA (12.5 mg/kg) and the free mucus and prostaglandin synthesis also increased (p < 0.001) after administration of PA extract (p.o.). The results suggested that the PA extract from Senecio brasiliensis inflorescences presents a significant anti-ulcer effect in the selected ulcer models. The mechanism involved with the action of the PA extract is the cytoprotection. Additional studies are in progress to determine other possible mechanisms involved with effect of the PA as anti-ulcer agents. PMID:15507358

Toma, Walber; Trigo, José Roberto; de Paula, Ana Cláudia Bensuaski; Brito, Alba Regina Monteiro Souza

2004-12-01

157

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

158

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 Central

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.

2010-01-01

159

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

PubMed

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

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

2014-01-15

160

Laparoscopic gastric banding  

MedlinePLUS

Lap-Band; LAGB; Laparoscopic adjustable gastric banding; Bariatric surgery - laparoscopic gastric banding ... J, Welch G, Zagarins S, Kuhn J, Romanelli J. Bariatric surgery for the treatment of morbid obesity: a meta- ...

161

Treatment of gastric carcinoids  

Microsoft Academic Search

Opinion statement  Gastric carcinoid tumors are uncommon, but their percentage among all gastric malignancies has increased to 1.8%. Although\\u000a they are most often discovered incidentally during endoscopy, gastric carcinoids can present with abdominal pain, bleeding,\\u000a or symptoms related to the secretion of bioactive substances, most commonly histamine. Gastric carcinoids originate from the\\u000a foregut and are derived from histamine-containing enterochromaffin-like (ECL) cells.

Wei Hou; Mitchell L. Schubert

2007-01-01

162

The relationship between technetium 99m pertechnetate gastric scanning and gastric contents.  

PubMed

In order to elucidate the gastric handling of 99Tcm, we performed scintiscanning under basal and stimulated conditions while simultaneously monitoring gastric outputs of water and sodium, hydrogen and 99Tcm pertechnetate ions in six healthy fasting volunteers. Our results showed that gastric scintiscanning correlated well with gastric luminal 99Tcm activity (r = 0.99). However, clearance of 99Tcm from plasma into the gastric lumen showed only a poor correlation with hydrogen ion output (r = 0.68) and no correlation with sodium output. Explanation of these results on a cellular basis can be achieved by assuming a two-component mechanism for 99Tcm secretion, with both the parietal cells (H+ ion secretory) and non-parietal cells (Na+ ion secretory) contributing to 99Tcm gastric output. The relative contribution of each cell type to total 99Tcm secretion is dependent on the degree of gastric stimulation, with non-parietal 99Tcm secretion dominating in the basal state and parietal 99Tcm secretion dominating in the stimulated state. It is concluded therefore, that gastric scintiscanning with 99Tcm pertechnetate should stand only as an empirical test of gastric function and not as a means of measuring acid output. PMID:6313111

O'Connor, M K; O'Connell, R; Keane, F B; Byrne, P J; Hennessy, T P

1983-11-01

163

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

164

Gastric cancer.  

PubMed Central

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

McCulloch, P.

1996-01-01

165

Gastric bypass surgery - discharge  

MedlinePLUS

Bariatric surgery - gastric bypass - discharge; Roux-en-Y gastric bypass - discharge; Gastric bypass- Roux-en-Y - discharge ... Leslie D, Kellogg TA, Ikramuddin S. Bariatric surgery primer for the ... Med Clin North Am . 2007;91:353-381. Mechanick JI, Kushner RF, ...

166

Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats.  

PubMed

This study examines the anti-ulcerogenic activity of a chloroform extract of Tanacetum vulgare and purified parthenolide, the major sesquiterpene lactone found in the extract. Gastric ulcers induced by oral administration of absolute ethanol to rats were reduced dose-dependently by oral pretreatment of animals with the chloroform extract (2.5-80 mg kg(-1)) or parthenolide (5-40 mg kg(-1)). When administered 30 min before challenge with the alcohol the protection ranged between 34 and 100% for the extract and 27 and 100% for parthenolide. When the products were administered orally 24 h before treatment with ethanol, 40 mg kg(-1) of the extract and of the lactone reduced the mean ulcer index from 4.8+/-0.3 for control animals to 1.4+/-0.2 and 0.5+/-0.1, respectively. The products also prevented alcohol-induced reduction of the number of sulphydryl groups within the gastric mucosa (50.6+/-2.3 microg (mgprotein)(-1) for normal animals compared with 17.7+/-3.0 microg (mg protein)(-1) for alcohol-treated animals). Administration of the extract (80 mg kg(-1)) or parthenolide (40 mg kg(-1)) 24 h before ethanol treatment restored the numbers of mucosal -SH groups to values near those found for normal animals. These results suggest that the products assayed, in particular parthenolide, might find therapeutic application, although further work is required to establish their profit/risk ratio. PMID:10217322

Tournier, H; Schinella, G; de Balsa, E M; Buschiazzo, H; Mañez, S; Mordujovich de Buschiazzo, P

1999-02-01

167

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

168

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

169

Gastric function measurements in drug development  

PubMed Central

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy. PMID:12895188

Pohle, Thorsten; Domschke, Wolfram

2003-01-01

170

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

PubMed

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

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

2014-12-01

171

Apoptosis induction by glycoprotein isolated from Laminaria japonica is associated with down-regulation of telomerase activity and prostaglandin E2 synthesis in AGS human gastric cancer cells.  

PubMed

Glycoprotein isolated from Laminaria japonica (LJGP) is known to exhibit significant cytotoxic activity against human cancer cells; however, the mechanisms of its cytoxicity are poorly understood. In this study, we investigated further possible mechanisms by which LJGP exerts its anti-cancer action in cultured human gastric carcinoma AGS cells. LJGP treatment of AGS cells resulted in inhibition of growth and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay, fluorescence microscopy, and flow cytometry analysis. The increase in apoptosis was associated with up-regulation of pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bcl-2 and IAP family members, and activation of caspase-3 and -9. LJGP treatment markedly down-regulated the activity of telomerase and expression of human telomerase reverse transcriptase, a main determinant of telomerase enzymatic activity, with inhibition of Sp1 and c-Myc expression in a concentration-dependent manner. Furthermore, LJGP treatment also caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. These results provide important new insights into the possible molecular mechanisms of the anti-cancer activity of LJGP. PMID:21132266

Han, Min Ho; Kim, Gi Young; Moon, Sung-Kwon; Kim, Wun-Jae; Nam, Taek-Jeong; Choi, Yung Hyun

2011-02-01

172

Influence of experimental hypokinesia on gastric secretory function  

NASA Technical Reports Server (NTRS)

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

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

1980-01-01

173

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

174

HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer.  

PubMed

The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant progression in various types of cancer, but the mechanism underlying gastric carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a subset of human gastric cancer cells. HDAC6 knockdown caused the significant inhibition of gastric cancer cell growth without affecting the transition of cell cycles or the processing of cell death. We demonstrate that an increase in epidermal growth factor receptor (EGFR) signaling through decreased EGFR degradation was mediated by HDAC6 in gastric carcinogenesis. These results establish a molecular mechanism responsible for oncogenic HDAC6, explaining how EGFR signaling induced by the growth factor is sustained during the malignant progression of gastric cancer. PMID:25111897

Park, Se Jin; Kim, Jeong Kyu; Bae, Hyun Jin; Eun, Jung Woo; Shen, Qingyu; Kim, Hyung Seok; Shin, Woo Chan; Yang, Hee Doo; Lee, Eun Kyung; You, Jueng Soo; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo

2014-11-01

175

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

176

Vection-induced gastric dysrhythmias and motion sickness  

NASA Technical Reports Server (NTRS)

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

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

1986-01-01

177

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

178

Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer  

Microsoft Academic Search

Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial.

S-H Lee; W K Kang; H Y Kim; J H Kim; S I Lee; J O Park; K Kim; C W Jung; Y S Park; Y-H Im; M H Lee

2004-01-01

179

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

Microsoft Academic Search

Enzymatic sulfation of mucous glycoprotein (GP) was studied in gastric mucosa of rat. After rat stomach was incubated with (³⁵S)-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

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

1987-01-01

180

Small molecule R1498 as a well-tolerated and orally active kinase inhibitor for hepatocellular carcinoma and gastric cancer treatment via targeting angiogenesis and mitosis pathways.  

PubMed

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

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

2013-01-01

181

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

NASA Astrophysics Data System (ADS)

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

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

2006-09-01

182

Human lysosomal acid lipase/cholesteryl ester hydrolase and human gastric lipase: identification of the catalytically active serine, aspartic acid, and histidine residues.  

PubMed

Human lysosomal acid lipase/cholesteryl ester hydrolase (HLAL), human gastric lipase (HGL), and rat lingual lipase (RLL) constitute a family of mammalian lipases characterized by an acidic pH optimum. HGL and RLL are secreted by the chief cells of the stomach and by the serous von Ebner's glands of the tongue, respectively, and hydrolyze dietary longchain triglycerides in the gastrointestinal tract. HLAL, in contrast, catalyzes the intralysosomal degradation of both triglycerides and cholesteryl esters in virtually all cells except erythrocytes. All three enzymes are proposed to be serine esterases with a catalytic Ser-Asp-His triad similar to other lipases, despite their sensitivity towards sulfhydryl modifying reagents. To investigate the role of conserved serine, aspartic acid, and histidine residues in HLAL and HGL, we constructed 24 mutant lipases with single amino acid substitutions using the site-directed mutagenesis approach. Our combined data strongly support the conclusion that Ser153, Asp324, and His355 are components of the catalytic triad of HLAL and HGL. Structural integrity of the conserved His-Gly dipeptide of lipases also appears to be important for neutral lipid hydrolysis, as replacement of His65 by glutamine abolished HLAL and HGL enzymic activity. Substitution of HLAL residues Asp93, Asp130, and Asp328 with glycine, in contrast, had a more pronounced impact on cholesteryl oleate hydrolysis than on triglyceride hydrolysis. These results provide new insights into the structural basis of HLAL and HGL function. PMID:9186907

Lohse, P; Chahrokh-Zadeh, S; Lohse, P; Seidel, D

1997-05-01

183

RNA interference targeting raptor inhibits proliferation of gastric cancer cells.  

PubMed

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(0)/G(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(3) and p21(Waf1), which stabilizes cyclin D/cdk4 complex for G(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. PMID:21396933

Wu, William Ka Kei; Lee, Chung Wa; Cho, Chi Hin; Chan, Francis Ka Leung; Yu, Jun; Sung, Joseph Jao Yiu

2011-06-10

184

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

185

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

186

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

187

Overexpression of CD133 enhances chemoresistance to 5-fluorouracil by activating the PI3K/Akt/p70S6K pathway in gastric cancer cells.  

PubMed

CD133 has been reported to be associated with chemoresistance in various cancer cells. The efficacy of 5-fluorouracil (5-FU), an important chemotherapeutic agent for advanced gastric cancer (GC), is limited by 5-FU resistance. Hence, the present study investigated the function of CD133 in 5-FU resistance in human GC cells. We isolated CD133+ GC cells by immunomagnetic cell sorting and CD133 expression was modulated by transfection of CD133 gene or CD133 small interfering ribonucleic acid. To assess the 5-FU cytotoxicity, Cell Counting Kit-8 was used. Expression of CD133, P-glycoprotein (P-gp), B-cell lymphoma 2 (Bcl?2), Bcl-2-associated X protein (Bax), phospho-Akt (p-Akt) and phospho-p70S6 kinase (p-p70S6K) were analyzed by western blotting. CD133, P-gp, Bcl-2 and Bax messenger ribonucleic acids were evaluated using semi-quantitative reverse transcriptase-polymerase chain reaction. Cell apoptosis was assessed by Hoechst 33258 staining. CD133+ cells were more resistant to 5-FU than CD133- cells, and showed higher expression of P-gp and Bcl-2 with lower expression of Bax. Furthermore, CD133 silencing enhanced 5-FU cytotoxicity and apoptotic characteristics, whereas CD133 overexpression increased 5-FU resistance. CD133 silencing and activation directly decreased and increased the expression of P-gp, Bcl?2, p-Akt and p-p70S6K, respectively. Notably, Akt inhibition by LY294002 restored the 5-FU cytotoxicity suppressed by CD133 overexpression, while Akt activation by epidermal growth factor reversed the 5-FU cytotoxicity enhanced by CD133 silencing. Therefore, CD133 may inhibit 5-FU-induced apoptosis by regulating the expression of P-gp and Bcl-2 family mediated by phosphoinositide 3-kinase/Akt/p70S6K pathway in GC cells. PMID:25230779

Zhu, Youlong; Yu, Jiwei; Wang, Shoulian; Lu, Ruiqi; Wu, Jugang; Jiang, Bojian

2014-12-01

188

Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.  

PubMed

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion. PMID:1387856

Suzuki, T; Tsukamoto, Y; Goto, H; Hase, S; Arisawa, T; Asai, J

1992-01-01

189

The intestinal phase of gastric secretion.  

PubMed Central

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

Kester, R. C.

1975-01-01

190

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

Mielanczyk, Lukasz; Michalski, Marek; Malinowski, Lukasz; Kowalczyk-Ziomek, Grazyna; Helewski, Krzysztof; Harabin-Slowinska, Marzena; Wojnicz, Romuald

2013-01-01

191

Helicobacter pylori and interleukin-8 in gastric cancer  

PubMed Central

Helicobacter pylori (H. pylori) is a major etiological factor in the development of gastric cancer. Large-scale epidemiological studies have confirmed the strong association between H. pylori infection and both cancer development and progression. Interleukin-8 (IL-8) is overexpressed in gastric mucosa exposed to H. pylori. The expression of IL-8 directly correlates with a poor prognosis in gastric cancer. IL-8 is multifunctional. In addition to its potent chemotactic activity, it can induce proliferation and migration of cancer cells. In this review, we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer. The relationship between IL-8 and H. pylori is discussed. We also summarize the current therapeutics against IL-8 in gastric cancer. PMID:24363509

Lee, Ko Eun; Khoi, Pham Ngoc; Xia, Yong; Park, Jung Sun; Joo, Young Eun; Kim, Kyung Keun; Choi, Seok Yong; Jung, Young Do

2013-01-01

192

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

193

DNA and histone methylation in gastric carcinogenesis  

PubMed Central

Epigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. PMID:23482412

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

2013-01-01

194

Elevated risk for gastric adenocarcinoma can be predicted from histomorphology.  

PubMed

The number of patients with gastric cancer has more than doubled since 1985 in developing countries. Thus, the questions of whether it can be predicted from gastritis morphology, who is at risk and who has a lower risk of developing gastric carcinoma are raised. H pylori-infection leads to erosions, ulcerations, carcinoma, mucosa associated lymphoid tissue (MALT)-lymphoma and extragastric diseases only in some individuals. The frequency of ulcerations among H pylori-infected individuals is estimated to be 13%, gastric cancer about 1% and MALT lymphoma around 0.1%. In the literature a multistep model from chronic active H pylori-infection through multifocal atrophy, intestinal metaplasia, dysplasia (intraepithelial neoplasia) and carcinoma has been described. But this model cannot be applied to all routine cases. Since risk factors such as metaplasia and atrophy are paracancerous rather than precancerous conditions, this raises the question whether there is a better morphological marker. Differences in topography, grade and activity of Helicobacter gastritis in the antrum and corpus might be good markers for identifying those who are at risk of developing gastric cancer. It is known that the so-called corpus dominant H pylori gastritis is found more frequently among individuals with early and advanced gastric cancer and within high risk populations. This is valid both for first-degree relatives of gastric cancer patients and for patients with gastric adenoma and hyperplastic polyps. In conclusion, corpus-dominant H pylori gastritis is significantly more common in patients with advanced and early gastric cancer, first-degree relatives of patients with gastric cancer, patients with gastric adenoma and gastric hyperplastic polyps. Therefore, all these patients are at risk of developing gastric cancer. Next, the question of who is at risk of developing corpus-dominant gastritis is raised. It appears that patients with a low acid output more frequently develop gastric cancer. Eradication therapy is never performed too early but probably sometimes too late after the patients pass a "point of no return". Large prospective long term studies are necessary to prove this and identify new reliable markers for gastric cancer development. PMID:17036380

Vieth, Michael; Stolte, Mandred

2006-10-14

195

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

196

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

197

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

198

Type I Helicobacter pylori Lipopolysaccharide Stimulates Toll-Like Receptor 4 and Activates Mitogen Oxidase 1 in Gastric Pit Cells  

Microsoft Academic Search

oxidase. These cells spontaneously secreted about 10 nmol of superoxide anion (O2 2 )\\/mg of protein\\/h under LPS-free conditions. They expressed the mRNA and protein of Toll-like receptor 4 (TLR4) but not those of TLR2. LPS from type I H. pylori at 2.1 endotoxin units\\/ml or higher stimulated TLR4-mediated phosphory- lations of transforming growth factor b-activated kinase 1 and its

TSUKASA KAWAHARA; SHIGETADA TESHIMA; AYUKO OKA; TOSHIRO SUGIYAMA; KYOICHI KISHI; KAZUHITO ROKUTAN

2001-01-01

199

Synthesis and investigation of anti-inflammatory activity and gastric ulcerogenicity of novel nitric oxide-donating pyrazoline derivatives  

Microsoft Academic Search

A group of 3,5-diaryl-2-pyrazoline derivatives were prepared via the reaction of various chalcones with hydrazine hydrate in ethanol. A group of NO-donating-2-pyrazoline derivatives were synthesized by carrying a nitrate ester group or an oxime group onto the prepared pyrazoline derivatives through different spacers. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced rat paw edema and compared to

Mai E. Shoman; Mohamed Abdel-Aziz; Omar M. Aly; Hassan H. Farag; Mohamed A. Morsy

2009-01-01

200

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

201

Gastric emptying in patients with fundal gastritis and gastric cancer.  

PubMed Central

Gastric emptying was compared in patients with gastric cancers and fundal gastritis to determine its value in identifying patients at high risk of gastric cancer. Gastric emptying was measured by the acetaminophen absorption method, and the extent of fundal gastritis was determined by the endoscopic Congo red test. The results showed that gastric emptying was significantly slower in patients with severe fundal gastritis than in those without. Gastric emptying in patients with differentiated adenocarcinomas was significantly slower than in those with undifferentiated adenocarcinoma, its value being similar to that in patients with severe fundal gastritis. The Congo red test showed that the incidence of severe fundal gastritis was significantly greater in patients with differentiated adenocarcinomas than in those with undifferentiated cancers. These findings suggest that delayed gastric emptying may allow prolonged contact between dietary carcinogens and the stomach. PMID:2370013

Tatsuta, M; Iishi, H; Okuda, S

1990-01-01

202

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

203

Gastric ulcers evoke hyperexcitability and enhance P2X receptor function in rat gastric sensory neurons.  

PubMed

Tissue inflammation contributes to the development of hyperalgesia, which is at least in part due to altered properties of primary afferent neurons. We hypothesized that gastric ulcers enhance the excitability of gastric sensory neurons and increase their response to purinergic agonists. The rat stomach was surgically exposed, and a retrograde tracer [1.1'-dioctadecyl-3,3,3,'3-tetramethylindocarbocyanine methanesulfonate (DiI)] was injected into the wall of the distal stomach. Kissing ulcers (KUs) were produced by a single injection of acetic acid (0.1 ml for 45 s; 60%) into the clamped gastric lumen. Saline injection served as control. Gastric nodose ganglion (NG) or dorsal root ganglion (DRG) cells were harvested 7 days later and acutely dissociated for whole cell recordings. Based on whole cell capacitance, gastric DRG neurons exhibited larger cell size than NG neurons. Significantly more control gastric DRG neurons compared with NG counterparts had TTX-resistant action potentials. Almost all control NG neurons (90%) compared with significantly less DRG neurons (< or =38%) responded to ATP or alpha,beta-metATP. Whereas none of the control cells exhibited spontaneous activity, about 20% of the neurons from KU animals generated spontaneous action potentials. KUs enhanced excitability as shown by a decrease in threshold for action potential generation, which was in part due to an increased input resistance. This was associated with an increase in the fraction of neurons with TTX-resistant action potentials and cells responding to capsaicin and purinergic agonists. KU doubled the current density evoked by the P2X receptor agonist alpha,beta-metATP and slowed decay of the slowly desensitizing component of the current without affecting the concentration dependence of the response. These data show that KU sensitizes vagal and spinal gastric afferents by affecting both voltage- and ligand-gated channels, thereby potentially contributing to the development of dyspeptic symptoms. PMID:15673552

Dang, K; Bielfeldt, K; Lamb, K; Gebhart, G F

2005-06-01

204

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

205

BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)\\/Akt pathway  

Microsoft Academic Search

Up-regulation of bone morphogenetic proteins (BMPs) and their receptors by tumor is an important hallmark in cancer progression, as it contributes through autocrine and paracrine mechanisms to tumor development, invasion, and metastasis. Generally, increased motility and invasion are positively correlated with the epithelial-mesenchymal transition (EMT). The purpose of the present study was to determine whether BMP-2 signaling to induce gastric

Myoung Hee Kang; Jun Suk Kim; Ji Eun Seo; Sang Cheul Oh; Young A. Yoo

2010-01-01

206

The role of sensory C-fibers in response of vagal afferent stimulation by gastric distension in rats with experimental chronic gastric ulcer.  

PubMed

There is growing evidence that gastric vagal afferent input may contribute to the altered sensations associated with gastrointestinal disorders. The aim of our study was to evaluate gastric vagal afferents (VA) activity in rats with experimental gastric ulcer and ulcer healing. The study was carried out on rats with gastric ulcer (GU), including, a group with perivagal capsaicin pretreatment (CAP), a group with capsaicin administration in gastric ulcer (CAP+GU) animals and control rats. In all rats electrical VA activity was recorded and analysed. In GU rats recordings were carried out in chronic ulcer and ulcer healing. In GU and CAP+GU groups gastric balloon distensions with vagal recording was performed on 3(rd) day after ulcer induction. Usually, experimental GU healed spontaneously within 2 weeks. Three days after acetic acid application when GU fully develop, the frequency of the basal VA activity was almost 3-times higher than in the control intact rats and remained elevayed until 4(th) week after ulcer induction. VA response to gastric distension increased concomitantly with increased balloon volume in both GU and control animals, but it was several times higher in GU rats. Perivagal capsaicin application decreased the frequency of spontaneous VA activity and decreased the response of VA to gastric distension. In CAP+GU, spontaneous activity as well as the response to gastric distension were higher than in CAP rats. Our study shows that GU induced inflammatory changes increase sensitivity of gastric VA. Capsaicin-sensitive vagal afferent fibers may play some role in this phenomenon. Peripheral sensitization of VA persists even when gastric ulcer is completely healed. PMID:18812637

Zurowski, D; Dobrek, ?; Bugajski, A; Thor, P J

2008-08-01

207

Dietary Glutamate Signal Evokes Gastric Juice Excretion in Dogs  

Microsoft Academic Search

Background: Dietary-free L-glutamate (Glu) in the stomach interacts with specific Glu receptors (T1R1\\/T1R3 and mGluR1–8) expressed on surface epithelial and gastric gland cells. Furthermore, luminal Glu activates the vagal afferents in the stomach through the paracrine cascade including nitric oxide and serotonin (5-HT). Aim: To elucidate the role of dietary Glu in neuroendocrine control of the gastrointestinal phase of gastric

Raisa Khropycheva; Julia Andreeva; Hisayuki Uneyama; Kunio Torii; Vasiliy Zolotarev

2011-01-01

208

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

209

Study of Mimusops elengi bark in experimental gastric ulcers.  

PubMed

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E1), n-butanol (Ext E2), methanol (Ext E3) and aqueous (Ext E4) were studied (p.o.) against ethanol-induced gastric damage. Ext E1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg(-1)) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg(-1)) was also used as a reference standard. Ext E1 tested in mice up to the dose of 5000 mg kg(-1) (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg(-1) and its different fractions (100 mg kg(-1)) showed reduction in gastric ulceration (P < 0.05). Ext E1 at the doses of 10, 50 and 100 mg kg(-1) showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E1 at 50 and 100 mg kg(-1) doses showed significant reduction in ulcer index (P < 0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity (P < 0.05) when compared with the control group. Besides, Ext E1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) (P < 0.05), which is an indication of mucin activity. Ext E1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index (P < 0.05), score for intensity (P < 0.05) and total lesion area (P < 0.05) when compared with the control group. It can be concluded from our study that Ext E1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms. PMID:14611897

Shah, Payal J; Gandhi, Mitesh S; Shah, Mamta B; Goswami, Sunita S; Santani, Devdas

2003-12-01

210

Hydroxyl radical formation in human gastric juice.  

PubMed

The hydroxyl radical is the most potent free radical derived from oxygen, and has been implicated in damage caused to the gastroduodenal mucosa. The ability of human gastric juice to generate hydroxyl radicals has been investigated in 54 adults with endoscopically normal gastroduodenal mucosa and in 39 patients with chronic duodenal ulcer. Hydroxyl radical production was measured by the formation of formaldehyde from dimethylsulfoxide. Unlike other body fluids, this reaction could proceed without the extraneous addition of catalysts such as hydrogen peroxide (H2O2), ascorbate and iron. Measurement of H2O2, iron and ascorbate showed that these catalysts are already present in the gastric juice. There was no significant difference in the concentration of these components in gastric juice between normal subjects and patients with duodenal ulcer, except that H2O2 levels were slightly higher in duodenal ulcer patients. Although generation of free radicals has been investigated in other body fluids, this is the first reported case regarding the production of these active species in normal human gastric juice. Since hydroxyl production is not significantly enhanced in duodenal ulcer, we suggest that attention may be turned to mucosal antioxidant defences in this disease. PMID:1327262

Nalini, S; Ramakrishna, B S; Mohanty, A; Balasubramanian, K A

1992-01-01

211

Specific food structures supress appetite through reduced gastric emptying rate.  

PubMed

The aim of this study was to determine the extent to which gastric layering and retention of a meal could be used to reduce appetite using the same caloric load. Liquid (control) and semi-solid (active) meals were produced with the same protein, fat, carbohydrate, and mass. These were fed to 10 volunteers on separate days in a crossover study, and subjective appetite ratings, gastric contents, and plasma cholecystokinin (CCK) were assessed over a period of 3 h. The active meal showed food boluses in the stomach persisting for ~45 min, slower emptying rates, and lower plasma CCK levels over the first hour. After the first hour, both gastric emptying rates and plasma CCK levels were similar for both systems and slightly increased compared with the unfed situation. Despite the lower plasma CCK levels for the active meal over the first hour, this meal reduced appetite more than the control meal over the 3 h of the study. For a moderately increased plasma CCK level in the fed state, appetite was correlated with the volume of gastric contents rather than gastric emptying rates or plasma CCK. This suggests that enhanced gastric retention was the key factor in decreasing appetite and was probably mediated by a combination of intestinal nutrient sensing and increased viscosity in the stomach. PMID:23578786

Mackie, Alan R; Rafiee, Hameed; Malcolm, Paul; Salt, Louise; van Aken, George

2013-06-01

212

Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA  

PubMed Central

AIM: To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA, pathological features and clinical staging of gastric cancer. METHODS: The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by in situ hybridization. RESULTS: Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t = 0.4161, P<0.01). Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (?2 = 10.23, P<0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r = 0.3426, P<0.05). However, iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r = 0.3612, P<0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa. CONCLUSION: In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread. Inactivation of antioncogene p53 and overexpression of iNOS might play a synergetic role in the process of carcinogenesis of human gastric carcinoma. PMID:15609395

Wang, Yong-Zhong; Cao, You-Qing; Wu, Jian-Nong; Chen, Miao; Cha, Xiao-Ying

2005-01-01

213

Adoptive immunotherapy of human gastric cancer with ex vivo expanded T cells  

Microsoft Academic Search

Surgical resection of gastric cancer has made significant progress, but majority of patients with advanced gastric cancer\\u000a face relapse and die within five years. In this study, the antitumor activity of ex vivo expanded T cells against the human gastric cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3

Yeon Jin Kim; Jaeseung Lim; Jong Soon Kang; Hwan Mook Kim; Hong Kyung Lee; Hwa Sun Ryu; Jee Youn Kim; Jin Tae Hong; Youngsoo Kim; Sang-Bae Han

2010-01-01

214

Spontaneous neonatal gastric perforation  

Microsoft Academic Search

Over a 7-year period (1990-1997) spontaneous gastric perforation was diagnosed in five neonates. The mean gestational age and birth weight were 33\\/40 weeks and 1.83 kg, respectively. All patients presented with severe abdominal distention and frank pneumoperitoneum on roentgenograms. All perforations were on the anterior wall of the greater curvature and were managed by prompt laparotomy and primary closure of

Akram J. Jawad; A. Al-Rabie; Anjum Hadi; A. Al-Sowailem; A. Al-Rawaf; Bashar Abu-Touk; T. Al-Karfi; A. Al-Sammarai

2002-01-01

215

Effects of rabeprazole sodium on gastric emptying, electrogastrography, and fullness.  

PubMed

Proton pump inhibitors have been reported to delay gastric emptying, but this effect is controversial. Our aim was to determine the effect of rabeprazole sodium on several parameters of gastric function including gastric emptying, myoelectrical activity and ingested water volume required to produce fullness. Fifteen healthy males underwent assessment of solid-phase gastric emptying with the [13C] Spirulina platensis breath test as well as electrogastrography and satiety testing using a 5-min water load. Subjects were evaluated at baseline, after administration of placebo, and after rabeprazole sodium 20 mg daily for one week. No significant differences were seen between groups with respect to solid-phase gastric emptying as measured by T1/2 or T(lag). No differences were seen between baseline, placebo, and rabeprazole with respect to the number of normal electrogastrograms and the volume of water required to produce fullness. In conclusion, one week of therapy with rabeprazole sodium does not significantly alter gastric emptying, myoelectrical activity or threshold to fullness. PMID:12645792

Jones, Michael P; Shah, Dhiren; Ebert, Christine C

2003-01-01

216

Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats.  

PubMed

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes. PMID:23965296

Xu, Luo; Qu, Zhuling; Guo, Feifei; Pang, Mingjie; Gao, Shengli; Zhu, Hai; Gu, Fang; Sun, Xiangrong

2013-10-01

217

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

218

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

219

Therapeutic strategies in gastric cancer.  

PubMed

Gastric cancer continues to be a major public health problem and is the second most common cause of cancer-related deaths in the world. These statistics led the American Society of Clinical Oncology (ASCO) International Affairs Committee to choose gastric cancer as the topic for the International Symposium held at the 2003 ASCO Annual Meeting. Dr Yoshiaki Ito will discuss the role of RUNX3 in the genesis and progression of human gastric cancer. Dr Pelayo Correa will present a compelling argument on the use of Helicobacter pylori therapy and antioxidants in selected high-risk population as chemoprevention strategies for gastric cancer. The controversy regarding the role of extended lymph node dissection for gastric cancer will be discussed by Dr Cornelis J.H. Van De Velde and Dr Mitsuru Sasako. Dr Van De Velde will present the European surgical approach to gastric cancer, and Dr Sasako will review the Japanese experience. The issues of whether certain patients benefit from more aggressive surgical dissection and the potential risks compared with benefits will also be discussed. Dr John Macdonald will discuss the role of adjuvant chemotherapy and adjuvant chemoradiotherapy in resected gastric cancer, as well as the role of chemotherapy in metastatic gastric cancer. PMID:14645406

Wong, J E L; Ito, Y; Correa, P; Peeters, K C M J; van de Velde, C J H; Sasako, M; Macdonald, J

2003-12-01

220

Comparison of nuclear matrix proteins between gastric cancer and normal gastric tissue  

Microsoft Academic Search

AIM: To study the alteration of nuclear matrix proteins (NMPs) in gastric cancer. METHODS: The NMPs extracted from 22 cases of gastric cancer and normal gastric tissues were investigated by SDS-PAGE technique and the data were analyzed using Genetools analysis software. RESULTS: Compared with normal gastric tissue, the expression of 30 ku and 28 ku NMPs in gastric cancer decreased

Qin-Xian Zhang; Yi Ding; Xiao-Ping Le; Wei Zhang; Ling Sun; Hui-Rong Shi

221

Hindbrain glucoprivation effects on gastric vagal reflex circuits and gastric motility in the rat are suppressed by the astrocyte inhibitor fluorocitrate.  

PubMed

Fasting and hypoglycemia elicit powerful gastrointestinal contractions. Whereas the relationship between utilizable nutrient and gastric motility is well recognized, the explanation of this phenomenon has remained incomplete. A relatively recent controversial report suggested that astrocytes in the dorsal hindbrain may be the principal detectors of glucoprivic stimuli. Our own studies also show that a subset of astrocytes in the solitary nucleus (NST) is activated by low glucose. It is very likely that information about glucopenia may directly impact gastric control because the hindbrain is also the location of the vago-vagal reflex circuitry regulating gastric motility. Our in vivo single unit neurophysiological recordings in intact rats show fourth ventricular application of 2-deoxyglucose (2-DG) inhibits NST neurons and activates dorsal motor nucleus (DMN) neurons involved in the gastric accommodation reflex. Additionally, as shown in earlier studies, either systemic insulin or central 2-DG causes an increase in gastric motility. These effects on motility were blocked by fourth ventricle pretreatment with the astrocyte inactivator fluorocitrate. Fluorocitrate administered alone has no effect on gastric-NST or -DMN neuron responsiveness, or on gastric motility. These results suggest that glucoprivation-induced increases in gastric motility are dependent on intact hindbrain astrocytes. PMID:25100584

Hermann, Gerlinda E; Viard, Edouard; Rogers, Richard C

2014-08-01

222

Angiogenesis and Lymphangiogenesis of Gastric Cancer  

PubMed Central

Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interactions contribute functionally to tumor growth and metastasis. Activated fibroblasts and macrophages in tumor stroma play important roles in angiogenesis and tumor progression. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, platelet-derived endothelial cell growth factor, and angiopoietin. In addition, Helicobacter pylori infection increases tumor cell expression of metastasis-related genes including those encoding several angiogenic factors. We review the current understanding of molecular mechanisms involved in angiogenesis and lymphangiogenesis of human gastric cancer. PMID:20369064

Kitadai, Yasuhiko

2010-01-01

223

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

PubMed Central

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

Hady, Hady Razak; Baniukiewicz, Andrzej; Dabrowski, Andrzej; Kaminski, Fabian; Dadan, Jacek

2011-01-01

224

Update on gastric lymphoma.  

PubMed Central

Primary gastrointestinal lymphoma is an uncommon entity that can often present like classic adenocarcinoma. The most common organ site involved is the stomach. Important prognostic indicators include location of lymph node involvement, histologic subtype, lymphocyte lineage, gross size, and location of the tumor. Surgical resection is the mainstay of curative therapy. Combination chemotherapy and radiotherapy may have a role either separately or as part of a multimodality treatment program. Clinicians are encouraged to enter patients with primary gastric lymphoma into multi-institutional, cooperative group clinical trials to more clearly define the best treatment strategy. PMID:1956083

Thomas, C. R.

1991-01-01

225

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

Microsoft Academic Search

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

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

1972-01-01

226

Electrical bioimpedance and other techniques for gastric emptying and motility evaluation  

PubMed Central

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

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

2012-01-01

227

The potency of substituted benzimidazoles such as E3810, omeprazole, Ro 18-5364 to inhibit gastric H+, K(+)-ATPase is correlatedwith the rate of acid-activation of the inhibitor.  

PubMed

The half maximal inhibitory concentrations (IC50) of substituted benzimidazoles for the H+, K(+)-ATPase in hog gastric vesicles were measured by using the pyruvate kinase-lactate dehydrogenase-linked system in which hydrolysis of ATP was coupled with the oxidation of NADH. The vesicles were incubated in a solution containing a high concentration of KCl, valinomycin and Mg-ATP, and the intravesicular medium was acidified. The inhibitor was activated in the acidic medium and reacted with SH groups on the luminal (intravesicular) side of the ATPase. The active compound formed in the extravesicular medium (pH 6.11) was quenched by GSH. Under these conditions, IC50 of new compound E3810, 2[(4-(3-methoxypropoxy)-3-methylpyridine-2-yl)methyl-sulfinyl]-1H- benzimidazole sodium salt, was 0.072 microM and that of omeprazole was 0.47 microM at 25 degrees. On the other hand, the rates of formation of active compounds, tetracyclic sulfenamide derivatives, from original substituted benzimidazoles in 0.1 N HCl (k) were determined by measuring optical density at the characteristic wavelengths of the active compounds. There was a good correlation between IC50 and k for various substituted benzimidazoles including E3810, methoxy derivative of E3810, omeprazole, Ro 18-5364, H compound, picoprazole and timoprazole. This fact suggest that the rate of the formation of the acid-activated compound is a main factor determining the potency of the inhibitor. PMID:2154989

Morii, M; Takata, H; Fujisaki, H; Takeguchi, N

1990-02-15

228

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, Vesteinn; 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; LaYniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychala, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna

2014-01-01

229

Gastric ulcers in standardbred racehorses: prevalence, lesion description, and risk factors.  

PubMed

This study was performed to estimate the prevalence of gastric ulcers in Standardbred racehorses, to describe the lesion score and location, and to identify potential risk factors. Two hundred seventy-five (275) Standardbred horses from 5 training centers and 2 racetracks in Quebec, Canada, were studied. Historical data for the 2 months before examination were recorded for each horse, and the presence of gastric ulcers was determined by gastroscopy. A previously reported scoring system that used grades 0-3 for gastric lesions was used. Overall, 121 horses (44.0%; 95% CI, 38.1-50.1%) had gastric ulcers. The prevalence of gastric ulcers was significantly higher (P < .0001) in actively racing horses (63.3%; 95% CI, 54.7-71.2%) than in horses at rest. Multivariate analysis defined that horses in racing (OR = 9.29; 95% CI, 3.55-24.3) were significantly more likely to have gastric ulcers than horses at rest and that trotters (OR = 2.23; 95% CI, 1.28-3.86) were more likely to have gastric ulcers than pacers. The number of lesion sites (P < .0001) and poor body condition (P < .0001) were significantly associated with lesion scores. Gastric ulcers are highly prevalent in Standardbred racehorses. Furthermore, actively racing horses and trotters are more likely to have gastric ulcers. Also, poor body condition in Standardbred racehorses may be an indication that gastric ulcers are present and that lesion scores are high. The cause-and-effect relationship between poor body condition and the presence of gastric ulcers is unclear. PMID:12683624

Dionne, Rachel M; Vrins, André; Doucet, Michèle Y; Paré, Julie

2003-01-01

230

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

231

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

PubMed

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; Wang, Yongzhong; Cui, Hongjuan

2014-04-01

232

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

233

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

234

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

235

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma  

PubMed Central

Background There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. Methods The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. Results There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. Conclusion There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma, especially of diffuse large B-cell lymphoma. PMID:24159918

2013-01-01

236

Anticancer effects of ?-elemene in gastric cancer cells and its potential underlying proteins: A proteomic study.  

PubMed

Gastric cancer is a common malignancy with a poor prognosis. ?-elemene is a broad-spectrum anticancer drug extracted from the traditional Chinese medicinal herb Curcuma wenyujin. In the present study, we investigated the anticancer effects of ?-elemene in gastric cancer cells and the potential proteins involved. Human SGC7901 and MKN45 gastric cancer cells were treated with different concentrations of ?-elemene. Cell viability, clonogenic survival and apoptotic cell death were assessed. ?-elemene inhibited viability and decreased clonogenic survival of gastric cancer cells in a dose-dependent manner. Apoptosis induction contributed to the anticancer effects. We then employed a proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), to detect the proteins altered by ?-elemene. In total, 147 upregulated proteins and 86 downregulated proteins were identified in response to ?-elemene treatment in SGC7901 gastric cancer cells. Among them, expression of p21-activated protein kinase?interacting protein 1 (PAK1IP1), Bcl-2-associated transcription factor 1 (BTF) and topoisomerase 2-? (TOPII?) were validated by western blot analyses and the trends were consistent with iTRAQ results. Top pathways involved in ?-elemene treatment in SGC7901 gastric cancer cells included ribosome signaling, peroxisome proliferator-activated receptors (PPARs) signaling pathway, regulation of actin cytoskeleton, phagosome, biosynthesis and metabolism of some amino acids. Collectively, our results suggest a promising therapeutic role of ?-elemene in gastric cancer. The differentially expressed proteins provide further insight into the potential mechanisms involved in gastric cancer treatment using ?-elemene. PMID:25333415

Liu, Jun-Song; He, Shi-Cai; Zhang, Zheng-Liang; Chen, Rui; Fan, Lin; Qiu, Guang-Lin; Chang, Shuai; Li, Liang; Che, Xiang-Ming

2014-12-01

237

Genomic profile analysis of diffuse-type gastric cancers  

PubMed Central

Background Stomach cancer is the third deadliest among all cancers worldwide. Although incidence of the intestinal-type gastric cancer has decreased, the incidence of diffuse-type is still increasing and its progression is notoriously aggressive. There is insufficient information on genome variations of diffuse-type gastric cancer because its cells are usually mixed with normal cells, and this low cellularity has made it difficult to analyze the genome. Results We analyze whole genomes and corresponding exomes of diffuse-type gastric cancer, using matched tumor and normal samples from 14 diffuse-type and five intestinal-type gastric cancer patients. Somatic variations found in the diffuse-type gastric cancer are compared to those of the intestinal-type and to previously reported variants. We determine the average exonic somatic mutation rate of the two types. We find associated candidate driver genes, and identify seven novel somatic mutations in CDH1, which is a well-known gastric cancer-associated gene. Three-dimensional structure analysis of the mutated E-cadherin protein suggests that these new somatic mutations could cause significant functional perturbations of critical calcium-binding sites in the EC1-2 junction. Chromosomal instability analysis shows that the MDM2 gene is amplified. After thorough structural analysis, a novel fusion gene TSC2-RNF216 is identified, which may simultaneously disrupt tumor-suppressive pathways and activate tumorigenesis. Conclusions We report the genomic profile of diffuse-type gastric cancers including new somatic variations, a novel fusion gene, and amplification and deletion of certain chromosomal regions that contain oncogenes and tumor suppressors. PMID:24690483

2014-01-01

238

Multimodal treatment of gastric cancer  

PubMed Central

Gastric cancer is the second leading cause of death from malignant disease worldwide. Although complete surgical resection remains the only curative modality for early stage gastric cancer, surgery alone only provides long-term survival in 20% of patients with advanced-stage disease. To improve current results, it is necessary to consider multimodality treatment, including chemotherapy, radiotherapy and surgery. Recent clinical trials have shown survival benefit of combining different neoadjuvant or adjuvant protocols compared with surgery with curative intent. Furthermore, the implementation of chemotherapy with novel targeted agents could play an important role in the multimodal management of advanced gastric cancer. In this paper, we focus on a multidisciplinary approach in the treatment of gastric cancer and discuss future strategies to improve the outcome for these patients. PMID:24829622

Proserpio, Ilaria; Rausei, Stefano; Barzaghi, Sabrina; Frattini, Francesco; Galli, Federica; Iovino, Domenico; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo; Pinotti, Graziella

2014-01-01

239

Gastric Cancer Prevention by Demethylation  

PubMed Central

Niwa et al. report in this issue that treatment with the DNA demethylation agent 5-aza-2?-deoxycytidine decreases the incidence of gastric cancers in an animal model of Helicobacter pylori-promoted gastric cancer. This provocative study underscores the importance of changes in DNA methylation that contribute to the origin of inflammation-related cancers. The findings also raise the exciting possibility of cancer prevention by altering DNA methylation events early during tumorigenesis. PMID:23559450

Schneider, Barbara G.; Peek, Richard M.

2013-01-01

240

Lymph nodes in gastric cancer.  

PubMed

Surgery is the only curative therapy for gastric cancer and controversy still exist on the extend of surgery. As the lymphatic distribution of stomach is very complex, the determination of the actual lymph node involvement is important for making the decision in order to avoid complications. Sentinel node navigation surgery has recently been introduced in gastrointestinal tract cancer. Present article reviews the detection techniques of lymph nodes and significance of lymphadenectomies in gastric cancer. PMID:18720367

Ozmen, M Mahir; Ozmen, Fusun; Zulfikaroglu, Bari?

2008-11-01

241

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

242

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

243

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

PubMed Central

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

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

2013-01-01

244

mTOR-dependent Modulation of Gastric Nesfatin-1/NUCB2  

PubMed Central

Background Nesfatin-1, an 82 amino acid peptide derived from the prohormone nucleobindin-2 (NUCB2), is a novel satiety hormone acting through a leptin-independent mechanism in the hypothalamus. The mechanisms by which production of nesfatin-1/NUCB2 is regulated remain unknown. Methods Nesfatin-1/NUCB2 mRNA and immunoreactivity were examined in gastric tissue and Min-6 cells by RT-PCR and immunofluorescent staining or Western blotting. Results Nesfatin-1/NUCB2 is co-localized with pS6K1, the downstream target of mammalian target of rapamycin (mTOR), in gastric X/A like cells. A parallel relationship between gastric mTOR signaling and nesfatin-1/NUCB2 was observed during changes in energy status. Both mTOR activity and gastric nesfatin-1/NUCB2 were down-regulated by fasting, and returned to basal levels with re-feeding. In high fat diet induced obese mice, gastric mTOR signaling and nesfatin-1/NUCB2 were increased. Inhibition of the gastric mTOR signaling by rapamycin attenuated the expression of gastric nesfatin-1/NUCB2 mRNA and protein in both lean and obese mice. Attenuation of mTOR activity by rapamycin or over-expression of TSC1 or TSC2 reduced the expression of nesfatin-1/NUCB2 in Min-6 cells, suggesting a direct effect of mTOR signaling. Conclusion Gastric mTOR is a gastric energy sensor whose activity is linked to the regulation of gastric nesfatin-1/NUCB2. PMID:22508056

Li, Ziru; Xu, Geyang; Li, Yin; Zhao, Jing; Mulholland, Michael W.; Zhang, Weizhen

2012-01-01

245

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

PubMed

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

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

2013-04-01

246

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

247

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

PubMed Central

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

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

1996-01-01

248

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.

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

2015-01-01

249

Helicobacter pylori colonization critically depends on postprandial gastric conditions  

PubMed Central

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

Bucker, Roland; Azevedo-Vethacke, Marina; Groll, Claudia; Garten, Desiree; Josenhans, Christine; Suerbaum, Sebastian; Schreiber, Soren

2012-01-01

250

The role of sympathetic neurons for low susceptibility to stress in gastric lesions.  

PubMed

Stroke prone spontaneously hypertensive rats (SHRSP) were less susceptible to stress in gastric lesions than Wistar-Kyoto rats used as normotensive controls. The gastric lesions induced by water-immersion restraint (WIR) in SHRSP were aggravated by pretreatment with 6-hydroxydopamine (6-OHDA), an agent for chemical sympathectomy, following decreases in blood pressure and sympathetic nerve function. 6-OHDA treatment remarkably reduced norepinephrine content but caused increases in dopamine content and in choline acetyltransferase activity in the stomach. The mechanism of aggravation of gastric lesions in SHRSP was investigated with regard to gastric acid and motility. The pretreatment with 6-OHDA of SHRSP significantly increased the acid secretion stimulated by 2-deoxy-D-glucose indirectly acting on parietal cells via the vagus nerve, but did not change the acid secretions stimulated by carbachol, pentagastrin and histamine acting directly on parietal cells. Gastric (corpus) motility associated with WIR was completely blocked by atropine. The pretreatment with 6-OHDA in SHRSP decreased the gastric motility during WIR, which was facilitated by treatment with domperidone. These results indicate that the sympathetic hyperactivity of the stomach prevents WIR-induced gastric lesion formation mainly via the inhibition of gastric acid secretion. PMID:8321086

Shichijo, K; Ito, M; Taniyama, K; Sekine, I

1993-01-01

251

Human lysosomal acid lipase/cholesteryl ester hydrolase and human gastric lipase: site-directed mutagenesis of Cys227 and Cys236 results in substrate-dependent reduction of enzymatic activity.  

PubMed

Chemical modification studies and site-directed mutagenesis experiments have provided evidence that human lysosomal acid lipase/cholesteryl ester hydrolase (HLAL), human gastric lipase (HGL), and rat lingual lipase (RLL) are serine esterases. Loss of HLAL and HGL activity was also observed in the presence of sulfhydryl-reactive substances, suggesting that cysteines are likewise essential for substrate hydrolysis. To study the functional role of the HLAL and HGL cysteine residues, we replaced these amino acids with alanine by site-directed mutagenesis. Substitutions at positions 227 and 236, alone or together, drastically reduced hydrolytic activity in a substrate-dependent manner while the other mutants were not affected to any great extent. HLAL(Cys227-->Ala), HLAL(Cys236-->Ala), and HLAL(Cys227-->Ala, Cys236-->Ala) were essentially inactive against cholesteryl oleate, but retained about 23-39%, 28-37%, and 13-17% of catalytic activity for both triolein and tributyrin, respectively. The data obtained with the corresponding HGL mutants confirmed the importance of residues 227 and 236 in maintaining enzymatic activity towards long- and short-chain triglycerides. In order to assess the contribution of the eight amino acids delimited by Cys227 and Cys236 to lipolysis, we generated HLAL replacement mutants containing the corresponding residues 228-235 of HGL or RLL. Both HLAL chimeras were catalytically active towards all three substrates analyzed, indicating that these amino acids do not determine HLAL substrate specificity. Deletion of the eight-amino acid alpha-helix as well as disruption of its hydrophobic surface, in contrast, abolished enzymatic activity. Our studies suggest that Cys227, Cys236, and the amphipathic helix formed by residues 228-235 are essential for HLAL- and HGL-mediated neutral lipid catabolism. PMID:9323599

Lohse, P; Lohse, P; Chahrokh-Zadeh, S; Seidel, D

1997-09-01

252

Cimetidine Prevents Stress-Induced Gastric Erosions.  

National Technical Information Service (NTIS)

Acute gastric erosions following severe stress usually occur in the presence of gastric acid Cimetidine (Smith, Kline and French), an H2-receptor antagonist, inhibits both resting and stimulated acid production. This study investigated the effect of Cimet...

B. A. Levine, B. A. Pruitt, C. G. McLeod, D. K. Teegarden, K. R. Sirinek

1977-01-01

253

Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma  

PubMed Central

Background Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated. Methods In this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis and in vivo study through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated. Results YY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/?-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/?-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs. Conclusion Our data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target. PMID:24674326

2014-01-01

254

Solitary Lymph Node Metastasis in Gastric Cancer  

Microsoft Academic Search

The feasibility and diagnostic reliability of sentinel node (SN) biopsy for gastric cancer are still controversial. We studied\\u000a the clinicopathological features and localization of solitary lymph node metastasis (SLM) in gastric cancer to provide useful\\u000a information for use of the SN concept in gastric cancer. From 2000 to 2004, 3,267 patients with gastric cancer underwent D2\\u000a radical gastrectomy. The clinicopathological

Chen Li; Sungsoo Kim; Ji Fu Lai; Sung Jin Oh; Woo Jin Hyung; Won Hyuk Choi; Seung Ho Choi; Sung Hoon Noh

2008-01-01

255

Subtotal gastrectomy for gastric cancer  

PubMed Central

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

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

2014-01-01

256

Gastroprotective effects of 'Amla' Emblica officinalis on in vivo test models in rats.  

PubMed

An ethanol extract of 'Amla' Emblica officinalis Gaertn. was examined for its antisecretory and antiulcer activities employing different experimental models in rats, including pylorus ligation Shay rats, indomethacin, hypothermic restraint stress-induced gastric ulcer and necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl). Oral administration of Amla extract at doses 250 mg/kg and 500 mg/kg significantly inhibited the development of gastric lesions in all test models used. It also caused significant decrease of the pyloric-ligation induced basal gastric secretion, titratable acidity and gastric mucosal injury. Besides, Amla extract offered protection against ethanol-induced depletion of stomach wall mucus and reduction in nonprotein sulfhydryl concentration. Histopathological analyses are in good agreement with pharmacological and biochemical findings. The results indicate that Amla extract possesses antisecretory, antiulcer, and cytoprotective properties. PMID:12403160

Al-Rehaily, A J; Al-Howiriny, T A; Al-Sohaibani, M O; Rafatullah, S

2002-09-01

257

Gastric Cancer: Epidemiology and Risk Factors  

Microsoft Academic Search

The incidence of gastric cancer is decreasing and lies between 10 and 15 new cases per 100,000 population per year in most Western countries. Peak age is between 60 and 80 years. While distal gastric cancers account for the overall decrease in gastric cancer, tumors in the proximal stomach (cardia and esophagogastric junction) are on the rise. Recognized risk factors

Guenter J. Krejs

2010-01-01

258

Diagnostic dilemma of gastric intramural air.  

PubMed

Emphysematous gastritis and gastric emphysema remain the two most important differential diagnoses of intramural gastric air bubbles, both differing vastly in their clinical presentation, radiographic findings, management and prognosis. This report discusses a case of gastric emphysema along with the importance of reaching an accurate clinical diagnosis early in the disease course. PMID:25245715

Misro, A; Sheth, H

2014-10-01

259

Helicobacter pylori eradication for gastric cancer prevention  

Microsoft Academic Search

Gastric cancer is the second most common fatal malignancy in the world. Its incidence is high in East Asia. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have established a strong\\u000a causal relationship between H. pylori infection and gastric cancer. H. pylori eradication is therefore likely to be one of the most promising

Ting Kin Cheung; Harry H. X. Xia; Benjamin C. Y. Wong

2007-01-01

260

Selective cyclooxygenase (COX) inhibition causes damage to portal hypertensive gastric mucosa: roles of nitric oxide and NF-kappaB.  

PubMed

Portal hypertension (PHT) is associated with increased susceptibility of the gastric mucosa to injury by a variety of factors, including nonsteroidal anti-inflammatory drugs (NSAIDs) that nonselectively inhibit both isoforms of cyclooxygenase (COX-1 and -2). PHT gastric mucosa also has excessive nitric oxide (NO) production that contributes to the general increased susceptibility to injury. Using a rat model of PHT, we studied whether selective COX inhibition, which does not damage normal (normotensive) gastric mucosa, is sufficient to cause PHT gastric damage and, if so, whether and how excessive NO is involved. Indomethacin, a nonselective NSAID, caused 2.4-fold more gastric injury to PHT vs. normotensive sham-operated (SO) control rats. Neither NS-398 nor celecoxib, selective COX-2 inhibitors, caused gastric damage in either SO or PHT rats. SC-560, a selective COX-1 inhibitor, did not cause gastric damage in SO rats but dose-dependently caused gastric damage in PHT rats. There was a compensatory increase in COX-2 expression and activity in SC-560-treated SO rats but not SC-560-treated PHT rats. Partial inhibition of NO production restored gastric COX-2 expression and activity levels in SC-560-treated PHT rats to those of SC-560-treated SO rats, by a mechanism consistent with induction of NF-kappaB, and significantly reduced gastric damage. These studies indicate that, in contrast to normotensive gastric mucosa, inhibition of COX-1 alone is sufficient to cause PHT gastric damage as a result of excessive NO that prevents the induction of NF-kappaB and the compensatory increase in COX-2. PMID:15845610

Akahoshi, Tomohiko; Tanigawa, Tetsuya; Sarfeh, I James; Chiou, Shiun-Kwei; Hashizume, Makoto; Maehara, Yoshihiko; Jones, Michael K

2005-07-01

261

Lack of modulation of gastric emptying by dietary nitrate in healthy volunteers.  

PubMed

Nitric oxide produced endogenously in vagal neurons modulates gastrointestinal motor activity as an important non-adrenergic and non-cholinergic neurotransmitter. Other than through endogenous biosynthesis, a high concentration of nitric oxide also occurs by chemical reactions within the stomach in the presence of gastric acid through the entero-salivary re-circulation of dietary nitrate. Although dietary nitrate can be a potential source of nitric oxide in the human stomach, there has been no report on the effect of dietary nitrate on gastric motor function. The aim of this study is to investigate the effect of dietary nitrate on gastric emptying, one of the major parameters for the gastric motor function. Fifteen healthy volunteers underwent a placebo-controlled (310 mg sodium nitrate or placebo), double-blind, crossover trial. Since a sufficient amount of gastric acid is essential for dietary nitrate-derived nitric oxide generation in the stomach, the same protocol was repeated after 1-week treatment with a proton pump inhibitor, rabeprazole. Gastric emptying was evaluated by (13)C-octanoate breath test. The sodium nitrate ingestion did not affect gastric emptying either prior to or during rabeprazole treatment, although rabeprazole treatment itself significantly delayed gastric emptying, being independent of the dietary nitrate load. Confirmation of the delayed gastric emptying with rabeprazole indicates the sensitivity of the breath test employed in the present study. In conclusion, despite the potential nitrogen source of exogenous nitric oxide, the ingestion of 310 mg sodium nitrate, which is equivalent to the average daily intake of Japanese adults, does not affect gastric emptying in healthy volunteers. PMID:19398876

Terai, Shiho; Iijima, Katsunori; Asanuma, Kiyotaka; Ara, Nobuyuki; Uno, Kaname; Abe, Yasuhiko; Koike, Tomoyuki; Imatani, Akira; Ohara, Shuichi; Shimosegawa, Tooru

2009-05-01

262

Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats  

PubMed Central

We investigated the mechanism underlying the protective effects of ginger against gastric damage induced by aspirin in rats. Gastric mucosal lesions were produced by orally administering 200 mg/kg aspirin suspended in 1% carboxymethylcellulose solution to pyloric-ligated male Wistar rats. Ginger powder (200 mg/kg) markedly reduced the aspirin-induced gastric hemorrhagic ulcer area. The total acidity of gastric juice was not significantly influenced by aspirin or ginger. Ginger powder did not affect the aspirin-induced reduction in mucosal prostaglandin E2 (PGE2) content; however, it did ameliorate the aspirin-induced increases in mucosal activity of the inducible form of NO synthase (iNOS) and plasma tumor necrosis factor (TNF)-? and interleukin (IL)-1? levels. In the next experiment, high and low doses of 6-gingerol and 6-shogaol were used instead of ginger powder in the same experimental model to examine their roles in the anti-ulcer mechanism of ginger. Both 6-gingerol and 6-shogaol reduced aspirin induced ulcer formation, mucosal iNOS and plasma TNF-? and IL-1? levels. In conclusion, ginger powder prevents the aspirin induced gastric ulcer formation by reducing mucosal iNOS activity and the plasma levels of inflammatory cytokines but does not affect gastric juice or acid production or mucosal PGE2 content. This protective effect of ginger powder against gastric ulcers may be attributable to both gingerol and shogaol. PMID:24031124

Wang, Zhongzhi; Hasegawa, Junichi; Wang, Xinhui; Matsuda, Akiko; Tokuda, Takahiro; Miura, Norimasa; Watanabe, Tatsuo

2011-01-01

263

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

264

Primary gastric mantle cell lymphoma  

PubMed Central

Mantle cell lymphoma represents 2.5–7% all of non Hodgkin's lymphomas. Stomach is the most common site of extranodal lymphoma. However, that is not the case with mantle cell lymphoma, which is extremely rare. We present a case of 71-year-old woman admitted to the Internal Clinic of the University Clinical Hospital Center Rijeka, because of stomach discomfort and melena. Endoscopy and computed tomography revealed a polyp in gastric antrum. Histopathologic, immunohistochemic and genetic methods were also performed and the results were consistent with primary gastric mantle cell lymphoma without periepigastric and/or local or distant abdominal lymph node involvement. PMID:22567215

Petranovic, Duska; Pilcic, Gorazd; Peitl, Milena; Cubranic, Aleksandar; Valkovic, Toni; Nacinovic, Antica Duletic; Lucin, Ksenija; Jonjic, Nives

2012-01-01

265

Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes  

Microsoft Academic Search

Helicobacter pylori is a Gram-negative bacterium affecting about half of the world population, causing chronic gastritis type B dominated by activated phagocytes. In some patients the disease evolves into gastric ulcer, duodenal ulcer, gastric cancer or MALT lymphoma. The pathogenesis is in part caused by the immunological response. In mouse models and in human disease, the mucosal immune response is

Mads Bennedsen; Xin Wang; Roger Willén; Torkel Wadström; Leif Percival Andersen

2000-01-01

266

Helicobacter pylori Infection Affects Eosinophilic Cationic Protein in the Gastric Juice of Patients with Idiopathic Chronic Urticaria  

Microsoft Academic Search

Background:Helicobacter pylori, the main cause of gastritis and peptic ulcer, has been associated with idiopathic chronic urticaria (ICU), an immunological skin disorder of unknown origin. Eosinophilic cationic protein (ECP) is a cytotoxic molecule secreted by the activated eosinophils involved in the pathogenesis of ICU. We assessed serum\\/gastric juice ECP levels and gastric mucosal eosinophil infiltration in ICU patients infected or

V. Ojetti; A. Armuzzi; A. De Luca; E. Nucera; F. Franceschi; M. Candelli; G. F. Zannoni; S. Danese; S. Di Caro; M. Vastola; D. Schiavino; G. Gasbarrini; G. Patriarca; P. Pola; A. Gasbarrini

2001-01-01

267

GASTRIC REFLUX IN MECHANICALLY VENTILATED GASTRIC FED ICU PATIENTS  

E-print Network

to enrollment in the study. A randomized 2-day crossover trial was conducted in a surgical and medical ICU. Mechanically ventilated gastric fed subjects were randomly assigned to 1 of the 2 HOB elevation sequences, HOB 30? for 12 hours (hrs) on day 1 and 45...

Schallom, Marilyn

2013-08-31

268

Gastric blood flow and the gastric mucosal barrier  

Microsoft Academic Search

The basic mechanisms underlying cytoprotection of gastrointestinal mucosae against damage are not understood. One hypothesis is that the initial and primary system affected by a cytoprotective agent is the local circulation of the tissue that is being protected. According to this circulatory hypothesis, a cytoprotective prostaglandin would increase gastric mucosal blood flow, thereby ameliorating the effect of topical damaging agents,

Eugene D. Jacobson

1985-01-01

269

Prognostic analysis of gastric gastrointestinal stromal tumor with synchronous gastric cancer  

PubMed Central

Background Many patients with gastric gastrointestinal stromal tumor (GIST) and synchronous gastric cancer have been described, most in single case studies. We retrospectively investigated the clinicopathologic features and prognostic effects of gastric GIST in patients with synchronous gastric cancer. Methods The study enrolled 170 patients with gastric GIST, who had undergone complete surgical resection (R0) from January 2000 to December 2011. Forty-two patients had synchronous gastric cancer (CA Group), whereas 128 did not (Non-CA Group). The clinicopathologic features and potential prognostic factors in the two groups were compared. Results Patients in the CA Group had more obvious symptoms, but a lower rate of preoperative diagnosis of gastric GIST (P <0.05). The two groups differed significantly in gender, age, greatest tumor diameter, risk stratification, tumor-associated ulcers, and CD117 and CD34 expression (P <0.05 each). Univariate analysis showed that age, risk stratification, postoperative oral imatinib and synchronous gastric cancer were predictive factors of survival (P <0.05). Cox regression analysis showed that risk stratification, postoperative oral imatinib and synchronous gastric cancer were independent predictors of survival (P <0.05). Stratified analysis showed that the 5-year overall survival rate was lower in patients with synchronous gastric cancer than in those without synchronous gastric cancer. Conclusions Gastric GIST with synchronous gastric cancer had a lower rate of preoperative diagnosis, with correct diagnosis often missed. Survival, however, depended primarily on the gastric cancer. PMID:24479763

2014-01-01

270

Delayed gastric emptying in Parkinson's disease.  

PubMed

Gastrointestinal symptoms are evident in all stages of Parkinson's disease (PD). Most of the gastrointestinal abnormalities associated with PD are attributable to impaired motility. At the level of the stomach, this results in delayed gastric emptying. The etiology of delayed gastric emptying in PD is probably multifactorial but is at least partly related to Lewy pathology in the enteric nervous system and discrete brainstem nuclei. Delayed gastric emptying occurs in both early and advanced PD but is underdetected in routine clinical practice. Recognition of delayed gastric emptying is important because it can cause an array of upper gastrointestinal symptoms, but additionally it has important implications for the absorption and action of levodopa. Delayed gastric emptying contributes significantly to response fluctuations seen in people on long-term l-dopa therapy. Neurohormonal aspects of the brain-gut axis are pertinent to discussions regarding the pathophysiology of delayed gastric emptying in PD and are also hypothesized to contribute to the pathogenesis of PD itself. Ghrelin is a gastric-derived hormone with potential as a therapeutic agent for delayed gastric emptying and also as a novel neuroprotective agent in PD. Recent findings relating to ghrelin in the context of PD and gastric emptying are considered. This article highlights the pathological abnormalities that may account for delayed gastric emptying in PD. It also considers the wider relevance of abnormal gastric pathology to our current understanding of the etiology of PD. PMID:24151126

Marrinan, Sarah; Emmanuel, Anton V; Burn, David J

2014-01-01

271

Regulation of RKIP Function by Helicobacter pylori in Gastric Cancer  

PubMed Central

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world’s population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP’s S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells. PMID:22662230

Cross-Knorr, Sam; Brilliant, Kate; Birnbaum, Faith; Rahaman, Sherida; Sedivy, John M.; Moss, Steven F.; Chatterjee, Devasis

2012-01-01

272

CEUS and strain elastography in gastric carcinoma.  

PubMed

Gastric cancer is the fourth most common type of cancer, but diagnosis is often delayed. Esophagogastroduodenoscopy is currently the gold standard for evaluating gastric cancer. Also other imaging modalities, such as computed tomography and magnetic resonance imaging are employed for identifying gastric cancer, but particularly for cancer staging. Ultrasound (US) is a first-line imaging modality used to examine organs in the abdomen, and during these examinations gastric cancer may be incidentally detected. Very few studies in the literature have investigated the role of US in gastric disease. However, more recently, some authors have reported on the use of contrast-enhanced US (CEUS) and US-elastography in gastric disease using both endoscopic and transabdominal approach. In this paper, we present a case of gastric cancer studied by CEUS and transabdominal US-elastography. PMID:24432162

Cantisani, Vito; Rubini, Antonello; Miniagio, Guglielmo

2013-07-18

273

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

PubMed Central

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

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

2012-01-01

274

Inhibitions of acid secretion by E3810 and omeprazole, and their reversal by glutathione.  

PubMed

A substituted benzimidazole ([4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methylsulfinyl)- 1H-benzimidazole sodium salt (E3810), is a gastric proton pump (H+, K(+)-ATPase) inhibitor. E3810 and omeprazole inhibited acid accumulation dose dependently as measured with aminopyrine uptake in isolated rabbit gastric glands, their IC50 values being 0.16 and 0.36 microM, respectively. The addition of exogenous reduced glutathione (GSH) to the gland suspension reactivated dose dependently the acid secretion which had been inhibited by 2 microM E3810 or omeprazole as a function of the incubation time. Furthermore, GSH at 1 and 3 mM reversed the antisecretory effect of E3810 more quickly than it did that of omeprazole. The antisecretory effect of E3810 was slightly greater than that of omeprazole in histamine-stimulated fistula dogs in vivo. The duration of the antisecretory activity of E3810 at concentrations of 2 and 4 mg/kg was shorter than that of omeprazole at the same concentrations in pentagastrin-stimulated fistula dogs. The reversal of the antisecretory activity of the inhibitors in dogs is suggested to be due to the action of endogenous extracellular GSH, in addition to de novo synthesis of the proton pump, because bullfrog gastric mucosae were found in the present study to secrete GSH into the mucosal solution at the rate of about 0.25 nmol/min/g tissue. PMID:1650210

Fujisaki, H; Shibata, H; Oketani, K; Murakami, M; Fujimoto, M; Wakabayashi, T; Yamatsu, I; Yamaguchi, M; Sakai, H; Takeguchi, N

1991-07-01

275

Remote ischemic postconditioning protects against gastric mucosal lesions in rats  

PubMed Central

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

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

2014-01-01

276

Gastric dysrhythmias and the current status of electrogastrography  

NASA Technical Reports Server (NTRS)

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

Koch, K. L.

1989-01-01

277

Gastric emptying of combined liquid-solid meals in healed duodenal ulcer  

SciTech Connect

The gastric emptying rates of combined liquid and solid radioisotopically labeled meals in 47 healed duodenal ulcer subjects and 17 healthy control subjects are compared. No significant differences were found between the groups in emptying slopes and the emptying half-times or in the percent retention values at any of the counting intervals for either the liquid or solid meals. These results are compatible with the observation that the rapid gastric emptying in many patients with duodenal ulcer is associated with the disease and that healing results in a return to normal gastric emptying rates. However, since gastric emptying rates during active ulceration were not determined in our patients, a more definitive interpretation awaits a study comparing emptying rates obtained during and after healing of active ulceration in the same patient.

Moore, J.G.; McIntyre, B.; Alazraki, N.

1985-12-01

278

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

PubMed Central

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

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

2014-01-01

279

Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80  

PubMed Central

The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80). Ginsenoside Re (20 mg/kg or 100 mg/kg) was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration) and xanthine oxidase (XO) and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue. PMID:24748832

Lee, Sena; Kim, Myung-Gyou; Ko, Sung Kwon; Kim, Hye Kyung; Leem, Kang Hyun; Kim, Youn-Jung

2013-01-01

280

VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance.  

PubMed

Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and RhoGDI2 expression is positively correlated with VEGF-C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo. Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2-overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer. PMID:24585459

Cho, Hee Jun; Kim, In-Kyu; Park, Sun-Mi; Baek, Kyoung Eun; Nam, In-Koo; Park, Seung-Ho; Ryu, Ki-Jun; Choi, Jungil; Ryu, Jinhyun; Hong, Soon-Chan; Jeong, Sang-Ho; Lee, Young-Joon; Ko, Gyung-Hyuck; Kim, Jae; Won Lee, Chang; Soo Kang, Sang; Yoo, Jiyun

2014-10-01

281

Astragalus saponins affect proliferation, invasion and apoptosis of gastric cancer BGC-823 cells  

PubMed Central

Background Astragalus memebranaceus is a traditional Chinese herbal medicine used in treatment of common cold, diarrhea, fatigue, anorexia and cardiac diseases. Recently, there are growing evidences that Astragalus extract may be a potential anti-tumorigenic agent. Some research showed that the total saponins obtained from Astragalus membranaceus possess significant antitumorigenic activity. Gastric cancer is one of the most frequent cancers in the world, almost two-thirds of gastric cancer cases and deaths occur in less developed regions. But the effect of Astragalus membranaceus on proliferation, invasion and apoptosis of gastric cancer BGC-823 cells remains unclear. Methods Astragalus saponins were extracted. Cells proliferation was determined by CCK-8 assay. Cell cycle and apoptosis were detected by the flow cytometry. Boyden chamber was used to evaluate the invasion and metastasis capabilities of BGC-823 cells. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Results The results demonstrated that total Astragalus saponins could inhibit human gastric cancer cell growth both in vitro and in vivo, in additional, Astragalus saponins deceased the invasion ability and induced the apoptosis of gastric cancer BGC-823 cells. Conclusions Total Astragalus saponins inhibited human gastric cancer cell growth, decreased the invasion ability and induced the apoptosis. This suggested the possibility of further developing Astragalus as an alternative treatment option, or perhaps using it as adjuvant chemotherapeutic agent in gastric cancer therapy. PMID:24152941

2013-01-01

282

Effects of Bidens pilosa L. var. radiata Scherff on experimental gastric lesion.  

PubMed

Bidens pilosa L. var. radiata Scherff: (BP) is a plant used as a traditional folk medicine. BP, cultivated with only green manure on Miyako Island, Okinawa prefecture, was processed to powder and is referred to as MMBP. We have reported that MMBP has antioxidant, anti-inflammatory, and anti-allergy properties. In this study, we investigated the effects of MMBP on several experimental gastric lesions induced by HCl/EtOH, a non-steroidal anti-inflammatory drug, or cold-restraint stress, comparing these results with those of rutin or anti-ulcerogenic drugs (cimetidine or sucralfate) based on the lesion index and hemorrhage from the gastric lesions. Orally administered MMBP prevented the progression of the gastric lesions. Moreover, treatment with MMBP, rutin, or sucralfate, which had potent antioxidative activity, inhibited increases in the levels of thiobarbituric acid reactive substances (TBARS) in the gastric mucosal lesions. The inhibition of the gastric mucosal TBARS content by MMBP may have been due to the antioxidant effects of MMBP. These results indicate that MMBP prevents the progression of acute gastric mucosal lesions, possibly by suppressing oxidative stress in the gastric mucosa. PMID:20526746

Horiuchi, Masako; Wachi, Hiroshi; Seyama, Yoshiyuki

2010-10-01

283

Ghrelin inhibits sodium metabisulfite induced oxidative stress and apoptosis in rat gastric mucosa.  

PubMed

This study aimed to investigate the effect of ghrelin administration on sulfite induced oxidative and apoptotic changes in rat gastric mucosa. Forty male albino Wistar rats were randomized into control (C), sodium metabisulfite (Na2S2O5) treated (S), ghrelin treated (G) and, Na2S2O5+ghrelin treated (SG) groups. Sodium metabisulfite (100 mg/kg/day) was given by gastric gavage and, ghrelin (20 ?g/kg/day) was given intraperitoneally for 5 weeks. Plasma-S-sulfonate level was increased in S and SG groups. Na2S2O5 administration significantly elevated total oxidant status (TOS) levels while depleting total antioxidant status (TAS) levels in gastric mucosa. Ghrelin significantly decreased gastric TOS levels in the SG group compared with the S group. Additionally, TAS levels were found to be higher in SG group in reference to S group. Na2S2O5 administration also markedly increased the number of apoptotic cells, cleaved caspase-3 and PAR expression (PARP activity indicator) and, decreased Ki67 expression (cell proliferation index) in gastric mucosal cells. Ghrelin treatment decreased the number apoptotic cells, cytochrome C release, PAR and, caspase-3 expressions while increasing Ki67 expression in gastric mucosa exposed to Na2S2O5. In conclusion, we suggest that ghrelin treatment might ameliorate ingested-Na2S2O5 induced gastric mucosal injury stemming from apoptosis and oxidative stress in rats. PMID:23439480

Ercan, Sevim; Basaranlar, Goksun; Gungor, Nazl? Ece; Kencebay, Ceren; Sahin, P?nar; Celik-Ozenci, Ciler; Derin, Narin

2013-06-01

284

Effect of anthocyanins on expression of matrix metalloproteinase-2 in naproxen-induced gastric ulcers.  

PubMed

Non-steroidal anti-inflammatory drugs cause gastric ulceration through a number of mechanisms including inhibition of PG synthesis, generation of reactive oxygen species (ROS) and induction of apoptosis. Recently, matrix metalloproteinases (MMP) have been suggested to play a crucial role in these mechanisms. The present study investigated the protective effect of anthocyanins isolated from black rice bran (Heugjinjubyeo) against naproxen-induced gastric mucosal injury in rats. The oral administration of anthocyanins (5, 25 or 50 mg/kg body weight) showed significant protection against naproxen (80 mg/kg body weight)-induced gastric ulcer and inhibited lipid peroxidation in the gastric mucosa. In addition, pretreatment with anthocyanins resulted in a significant increase in the activities of radical-scavenging enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Also biochemical and zymographic analyses suggested that the administration of anthocyanins gives a significant protection against naproxen-induced gastric antral ulcer through scavenging ROS and regulation of matrix metalloproteinase-2 (MMP-2) activity. The results of intracellular radical activation show that anthocyanins suppress the generation of intracellular ROS and attenuate the suppression of MMP-2 activity by naproxen. These results suggest that anthocyanins extracted from black rice may offer potential remedy of gastric antral ulceration. PMID:21733337

Kim, Sun-Joong; Park, Young Sam; Paik, Hyun-Dong; Chang, Hyo Ihl

2011-12-01

285

64Cu DOTA-Trastuzumab PET in Studying Patients With Gastric Cancer  

ClinicalTrials.gov

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer

2014-10-16

286

Advances in gastric cancer prevention.  

PubMed

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

Giordano, Antonio; Cito, Letizia

2012-09-10

287

Growth inhibition and cell-cycle arrest of human gastric cancer cells by Lycium barbarum polysaccharide  

Microsoft Academic Search

Lycium barbarum polysaccharide (LBP) is extracted from the traditional Chinese herb Lycium barbarum, and has potential anticancer activity. However, the detailed mechanisms are largely unknown. The purpose of this study was\\u000a to observe the anticancer effect of LBP on human gastric cancer, and its possible mechanisms. Human gastric cancer MGC-803\\u000a and SGC-7901 cells were treated with various concentrations of LBP

Ying Miao; Bingxiu Xiao; Zhen Jiang; Yanan Guo; Fang Mao; Junwei Zhao; Xia Huang; Junming Guo

2010-01-01

288

Anti-cancer effect of rubropunctatin against human gastric carcinoma cells BGC823  

Microsoft Academic Search

The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR) and its cytotoxic activities against human gastric\\u000a adenocarcinoma BGC-823 cells were studied both in vitro and in vivo. Rubropunctatin inhibited the proliferation of BGC-823\\u000a cells with an inhibitory concentration (IC50) of 12.57 ?M, while it exhibited no significant toxicity to normal gastric epithelial cell GES-1 at the same

Yunquan Zheng; Yanwen Xin; Xianai Shi; Yanghao Guo

2010-01-01

289

The Critical Impact of HIF-1? on Gastric Cancer Biology  

PubMed Central

Hypoxia inducible factor-1 (HIF-1) monitors the cellular response to the oxygen levels in solid tumors. Under hypoxia conditions, HIF-1? protein is stabilized and forms a heterodimer with the HIF-1? subunit. The HIF-1 complex activates the transcription of numerous target genes in order to adapt the hypoxic environment in human cancer cells. In gastric cancer patients, HIF-1? activation following extended hypoxia strongly correlates with an aggressive tumor phenotype and a poor prognosis. HIF-1? activation has been also reported to occur via hypoxia-independent mechanisms such as PI3K/AKT/mTOR signaling and ROS production. This article argues for the critical roles of HIF-1? in glucose metabolism, carcinogenesis, angiogenesis, invasion, metastasis, cell survival and chemoresistance, focusing on gastric cancer. PMID:24216696

Kitajima, Yoshihiko; Miyazaki, Kohji

2013-01-01

290

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

PubMed

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

Piché, Mathieu; Watanabe, Nobuhiro; Hotta, Harumi

2014-01-01

291

Pteridium aquilinum and its ptaquiloside toxin induce DNA damage response in gastric epithelial cells, a link with gastric carcinogenesis.  

PubMed

The multifactorial origin of gastric cancer encompasses environmental factors mainly associated with diet. Pteridium aquilinum-bracken fern-is the only higher plant known to cause cancer in animals. Its carcinogenic toxin, ptaquiloside, has been identified in milk of cows and groundwater. Humans can be directly exposed by consumption of the plant, contaminated water or milk, and spore inhalation. Epidemiological studies have shown an association between bracken exposure and gastric cancer. In the present work, the genotoxicity of P. aquilinum and ptaquiloside, including DNA damaging effects and DNA damage response, was characterized in human gastric epithelial cells and in a mouse model. In vitro, the highest doses of P. aquilinum extracts (40 mg/ml) and ptaquiloside (60 ?g/ml) decreased cell viability and induced apoptosis. ?H2AX and P53-binding protein 1 analysis indicated induction of DNA strand breaks in treated cells. P53 level also increased after exposure, associated with ATR-Chk1 signaling pathway activation. The involvement of ptaquiloside in the DNA damage activity of P. aquilinum was confirmed by deregulation of the expression of a panel of genes related to DNA damage signaling pathways and DNA repair, in response to purified ptaquiloside. Oral administration of P. aquilinum extracts to mice increased gastric cell proliferation and led to frameshift events in intron 2 of the P53 gene. Our data demonstrate the direct DNA damaging and mutagenic effects of P. aquilinum. These results are in agreement with the carcinogenic properties attributed to this fern and its ptaquiloside toxin and support their role in promoting gastric carcinogenesis. PMID:22143989

Gomes, Joana; Magalhães, Ana; Michel, Valérie; Amado, Inês F; Aranha, Paulo; Ovesen, Rikke G; Hansen, Hans C B; Gärtner, Fátima; Reis, Celso A; Touati, Eliette

2012-03-01

292

Gastric Pseudotumoral Lesion Caused by a Fish Bone Mimicking a Gastric Submucosal Tumor  

PubMed Central

Gastric complications following unintentional foreign body ingestion are extremely rare. Here, we report the case of a 59-year-old healthy woman who presented with nonspecific abdominal pain and an apparent gastric submucosal tumor that was incidentally detected by gastrofiberscopy. The patient underwent laparoscopic surgery, which revealed an intact gastric wall with no tumor invasion, deformity, or evidence of a gastric submucosal lesion. However, an impacted fish bone was found. PMID:25328766

Kim, Sang Woon; Song, Sun Kyo

2014-01-01

293

Use of lectin microarray to differentiate gastric cancer from gastric ulcer  

PubMed Central

AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different glycopatterns in gastric cancer and gastric ulcer, and the lectins MPL and VVA can be used as biomarkers. PMID:24833877

Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

2014-01-01

294

Gastric pseudotumoral lesion caused by a fish bone mimicking a gastric submucosal tumor.  

PubMed

Gastric complications following unintentional foreign body ingestion are extremely rare. Here, we report the case of a 59-year-old healthy woman who presented with nonspecific abdominal pain and an apparent gastric submucosal tumor that was incidentally detected by gastrofiberscopy. The patient underwent laparoscopic surgery, which revealed an intact gastric wall with no tumor invasion, deformity, or evidence of a gastric submucosal lesion. However, an impacted fish bone was found. PMID:25328766

Kim, Se Won; Kim, Sang Woon; Song, Sun Kyo

2014-09-01

295

Laparoscopic gatrojejunostomy for palliation of gastric outlet obstruction in unresectable gastric cancer  

Microsoft Academic Search

  Background: Gastric bypass through laparotomy is required traditionally when gastric outlet obstruction occurs secondary to\\u000a a disease process (e.g., unresectable cancer). The recent trend toward minimally invasive procedures has led us to apply laparoscopic\\u000a bypass surgery for gastric obstruction caused by unresectable advanced gastric cancer. Methods: From March 1998 to February\\u000a 2000, 78 gastrojejunostomies (GJ) (45 open [OGJ] and 33

Y.-B. Choi

2002-01-01

296

Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats  

PubMed Central

Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 ?g) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 ?g) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 ?g·kg?1·h?1 iv), vagal stimulation with 2-deoxy-d-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-d-glucose-stimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P < 0.01). Finally, nesfatin-induced Ca2+ signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dose-dependent Ca2+ increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca2+ signaling in cultured DMNV neurons. PMID:22723266

Xia, Ze-Feng; Fritze, Danielle M.; Li, Ji-Yao; Chai, Biaoxin; Zhang, Chao

2012-01-01

297

Gastric Sarcoidosis: A Rare Clinical Presentation  

PubMed Central

Gastrointestinal (GI) sarcoidosis is a very rare disease, which clinically presents along with systemic disease or as an isolated finding. Gastric sarcoidosis is the most common form of GI sarcoidosis. Symptomatic gastric sarcoidosis is rare and only few case reports have been described in the literature with well-documented histological evidence of noncaseating granulomas. We present an interesting case of gastric sarcoidosis in a 39-year-old Caucasian man with symptoms of epigastric pain and profound weight loss. His endoscopic gastric mucosal biopsies revealed noncaseating granulomas consistent with gastric sarcoidosis. Treatment with oral steroids alleviated his symptoms with no recurrence in 2 years. Gastric sarcoidosis should be considered in patients with history of sarcoidosis and GI symptoms. PMID:24368949

Tokala, Hemasri; Polsani, Karthik; Kalavakunta, Jagadeesh K.

2013-01-01

298

Molecular targeting to treat gastric cancer  

PubMed Central

Trastuzumab that targets human epidermal growth factor receptor 2 (HER2) protein is the only approved molecular targeting agent for treating gastric cancer in Japan and the outcomes have been favorable. However, trastuzumab is effective for only 10% to 20% of the population with gastric cancer that expresses HER2 protein. Molecular targeting therapy with bevacizumab against vascular endothelial growth factors (VEGF) and with cetuximab and panitumumab against the epidermal growth factors pathway that have been approved for treating colorectal cancer are not considered effective for treating gastric cancer according to several clinical trials. However, ramucirumab that targets VEGF receptor-2 prolonged overall survival in a large phase III clinical trial and it might be an effective molecular targeting therapy for gastric cancer. The significance of molecular targeting therapy for gastric cancer remains controversial. A large-scale randomized clinical trial of novel molecular targeting agents with which to treat gastric cancer is needed.

Aoyagi, Keishiro; Kouhuji, Kikuo; Kizaki, Junya; Isobe, Taro; Hashimoto, Kousuke; Shirouzu, Kazuo

2014-01-01

299

Linoleic Acid-Induced Growth Inhibition of Human Gastric Epithelial Adenocarcinoma AGS Cells is Associated with Down-Regulation of Prostaglandin E2 Synthesis and Telomerase Activity  

PubMed Central

Background: Linoleic acid is the most abundant polyunsaturated fatty acid in human nutrition and found in most vegetable oils and certain food products. In the present study, we investigated the effects of linoleic acid on the growth of human epithelial adenocarcinoma AGS cells. Methods: MTT assay, flow cytometry, RT-PCR and Western-blot analyses were used to investigate the effects and underlying mechanisms of linoleic acid on AGS cells. The effects of this compound were also tested on prostaglandin E2 (PGE2) production and telomerase activity. Results: Our data indicated that growth inhibition of AGS cells by linoleic acid treatment was associated with induction of apoptosis. Linoleic acid treatment decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of PGE2 synthesis. Linoleic acid treatment also decreased the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, and activity of telomerase, with inhibiting the expression of c-myc in a concentration-dependent manner. Conclusions: Taken together, our results indicate that linoleic acid inhibits the production of PGE2 and activity of telomerase by suppressing COX-2 and hTERT expression. PMID:25337570

Choi, Yung Hyun

2014-01-01

300

17?-Estradiol inhibition of IL-6-Src and Cas and paxillin pathway suppresses human mesenchymal stem cells-mediated gastric cancer cell motility.  

PubMed

Epidemiological studies demonstrate that the incidence and mortality of gastric cancer in women are lower than in men worldwide. Many studies have reported the delayed menopause and hormone replacement therapy are associated with a reduced risk for gastric cancer. It has been reported that endogenous estrogen lowers gastric cancer incidence in women, and cancer patients treated with estrogens have a lower subsequent risk of gastric cancer. It has been reported that estrogen decreases the progression of gastric cancer by inhibiting erbB-2 oncogene expression. Overexpression of estrogen receptor might inhibit the proliferation and invasion of MKN28 gastric cancer cells. Accumulating evidence suggests that bone marrow mesenchymal stem cells contribute to the progression of gastric cancer. However, it is unknown if 17?-estradiol (E2) treatment is sufficient to inhibit human bone marrow mesenchymal stem cells (HBMMSCs)-mediated cell motility in human gastric cancer cells. The results from human cytokine arrays have shown that HBMMSCs notably secrete interleukin 6 (IL-6) protein. Administration of IL-6-specific neutralizing antibody significantly inhibits HBMMSCs-mediated motility activity in human gastric cancer cells. Treatment of recombinant IL-6 soluble protein confirmed the role of IL-6 in mediating HBMMSCs-upregulated cell motility. IL-6 mainly upregulates motility activity via activation of Src signaling pathway in human gastric cancer cells. We further observed that E2 treatment inhibits HBMMSCs-induced cellular motility via suppressing the activation of IL-6-Src/Cas/paxillin signaling pathway in human gastric cancer cells. Collectively, these results suggest that E2 treatment significantly inhibits HBMMSCs-induced cellular motility in human gastric cancer cells. PMID:24801617

Liu, Chung-Jung; Kuo, Fu-Chen; Hu, Huang-Ming; Chen, Chiao-Yun; Huang, Yaw-Bin; Cheng, Kuang-Hung; Yokoyama, Kazunari K; Wu, Deng-Chyang; Hsieh, Shuchen; Kuo, Chao-Hung

2014-09-01

301

Risk for Gastric Cancer After Cholecystectomy  

Microsoft Academic Search

BACKGROUND:It is becoming increasingly evident that chronic inflammation may predispose cancer development. In the stomach, inflammation caused by Helicobacter pylori infection is linked to gastric cancer. Cholecystectomy is regularly followed by duodenogastric bile reflux and reactive gastritis. To test whether a noninfectious long-standing inflammation impels gastric carcinogenesis as well, we assessed the risk of gastric cancer in a large, population-based

Katja Fall; Weimin Ye; Olof Nyrén

2007-01-01

302

Gastric heterotopia causing jejunal ulceration and obstruction.  

PubMed

A young woman with persistent postprandial vomiting was found to have a high-grade proximal jejunal stricture. The stricture was surgically excised, and histopathological examination showed gastric heterotopia with localised ulceration and fibrosis. Symptomatic gastric heterotopia in the small bowel is rare, and to our knowledge this is the first report of jejunal gastric heterotopia resulting in ulceration with subsequent stricturing and obstruction. PMID:24209701

Chinnery, Galya E; Bernon, Marc M; Banderker, M Asief; Roberts, Riyaad; Krige, Jake E J

2013-11-01

303

Retarded gastric acid secretion in rats infected with larval Taenia taeniaeformis.  

PubMed

The influence of hepatic larval Taenia taeniaeformis infection on gastric acid secretory activity and gastric mucosal integrity was investigated. After 12 weeks of infection with 2,000 T. taeniaeformis eggs, the gastric pH values of control and infected rats were 4.1+/-0.6 (mean +/- SD) and 8.4+/-0.2, respectively. There was no difference in the basal acid secretion between control (1.7+/-0.7 micro Eq.H(+)/15 min) and infected (1.9+/-0.3) rats. However, infected rats failed to respond to histamine stimulation, the maximum acid output level being 2.8+/-0.4 in the infected rats, compared to 12.9+/-3.3 in control rats. Larval T. taeniaeformis infection resulted in the suppression of gastric acid secretion leading to hypergastrinemia. PMID:12172822

Oku, Y; Yamanouchi, T; Matsuda, K; Abella, J A C; Ooi, H K; Ohtsubo, R; Goto, Y; Kamiya, M

2002-09-01

304

Effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion and its antioxidant properties.  

PubMed

The effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion (I-R) injury was studied in rats. I-R injury was produced in rat stomach by applying a small clamp to the celiac artery for 30 min and by removal of the clamp for 60 min. The increase in total area of erosions in the stomach after I-R and the increase in lipid peroxides in the gastric mucosa were significantly inhibited by intragastric administration of sofalcone. In addition, sofalcone significantly inhibited the lipid-soluble free radical initiator-induced increase in lipid peroxides of the gastric mucosal homogenate, and could show scavenging action of superoxide radicals in aprotic solvent. These results showed that the protective effect of sofalcone against I-R-induced gastric mucosal injury is attributable to its antioxidant activities in the lipophilic phase. PMID:8283005

Yoshikawa, T; Nakamura, S; Takahashi, S; Naito, Y; Kondo, M

1993-01-01

305

Pathogenetic mechanisms in gastric cancer  

PubMed Central

Gastric cancer (GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis, as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways, such as gene mutations, copy number variants, aberrant gene methylation and histone modification, nucleosome positioning, and microRNAs. Some of these genetic/epigenetic alterations represent effective diagnostic and prognostic biomarkers and therapeutic targets for GC. This information has now opened unprecedented opportunities for better understanding of the molecular mechanisms of gastric carcinogenesis and the development of novel therapeutic strategies for this cancer. The pathogenetic mechanisms of GC are the focus of this review.

Shi, Jing; Qu, Yi-Ping; Hou, Peng

2014-01-01

306

Minimally invasive surgery in gastric cancer  

PubMed Central

Minimally invasive surgery for gastric cancer has rapidly gained popularity due to the early detection of early gastric cancer. As advances in instruments and the accumulation of laparoscopic experience increase, laparoscopic techniques are being used for less invasive but highly technical procedures. Recent evidence suggests that the short- and long-term outcomes of minimally invasive surgery for early gastric cancer and advanced gastric cancer are comparable to those of conventional open surgery. However, these results should be confirmed by large-scale multicenter prospective randomized controlled clinical trials. PMID:25339802

Son, Sang-Yong; Kim, Hyung-Ho

2014-01-01

307

Hypergastrinemia increases gastric epithelial susceptibility to apoptosis.  

PubMed

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy gamma-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to gamma-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans. PMID:17900712

Przemeck, S M C; Varro, A; Berry, D; Steele, I; Wang, T C; Dockray, G J; Pritchard, D M

2008-02-01

308

Gastric Bypass after Cardiac Transplantation  

Microsoft Academic Search

A 39-year-old morbidly obese male presented with severe and poorly controlled diabetes mellitus (DM) and hypertension (HBP)\\u000a as well as moderately severe obesity hypoventilation syndrome (OHS) that threatened the survival of his cardiac graft which\\u000a had been transplanted 7 years previously. A gastric bypass procedure with a 45-cm Roux-limb was performed. His OHS resolved,\\u000a his DM became undetectable off medication,

1995-01-01

309

Combining Platinums in Gastric Cancer  

Microsoft Academic Search

\\u000a The role for systemic treatment in gastric cancer has become more evident over the past years. Perioperative chemotherapy\\u000a increases the cure rates in localized stages. At the same time, palliative chemotherapy has shown to prolong survival and\\u000a maintain the patients' quality of life in advanced disease.\\u000a \\u000a \\u000a Cisplatin in combination with 5-fluorouracil with or without an anthracycline now has a definite

Florian Lordick; Dirk Jäger

310

Nicotinic receptor mediates nitric oxide synthase expression in the rat gastric myenteric plexus.  

PubMed Central

The mechanism that regulates the synthesis of nitric oxide synthase (NOS), a key enzyme responsible for NO production in the myenteric plexus, remains unknown. We investigated the roles of the vagal nerve and nicotinic synapses in the mediation of NOS synthesis in the gastric myenteric plexus in rats. Truncal vagotomy and administration of hexamethonium significantly reduced nonadrenergic, noncholinergic relaxation, the catalytic activity of NOS, the number of NOS-immunoreactive cells, and the density of NOS-immunoreactive bands and NOS mRNA bands obtained from gastric tissue. These results suggest that NOS expression in the gastric myenteric plexus is controlled by the vagal nerve and nicotinic synapses. We also investigated if stimulation of the nicotinic receptor increases neuronal NOS (nNOS) expression in cultured gastric myenteric ganglia. Incubation of cultured gastric myenteric ganglia with the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperizinium (DMPP, 10(-10)-10(-7) M), for 24 h significantly increased the number of nNOS-immunoreactive cells and the density of immunoreactive nNOS bands and nNOS mRNA bands. nNOS mRNA expression stimulated by DMPP was antagonized by a protein kinase C antagonist, a phospholipase C inhibitor, and an intracellular Ca2+ chelator. We concluded that activation of the nicotinic receptor stimulates a Ca2+-dependent protein kinase C pathway, which in turn, upregulates nNOS mRNA expression and nNOS synthesis in the gastric myenteric plexus. PMID:9525991

Nakamura, K; Takahashi, T; Taniuchi, M; Hsu, C X; Owyang, C

1998-01-01

311

Knockdown of protein tyrosine phosphatase receptor U inhibits growth and motility of gastric cancer cells  

PubMed Central

Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating ?-catenin and reducing the activation of ?-catenin signaling. Here, we investigate the expression of PTPRU protein in gastric cancer cell lines, gastric cancer tissues and respective adjacent non-cancer tissues and find that the 130kDa nuclear-localized PTPRU fragment is the main PTPRU isoform in gastric cancer cells, whereas the full-length PTPRU is relatively lowly expressed. The level of the 130kDa PTPRU is higher in gastric cancer tissues than in adjacent non-cancer tissues. Knockdown of endogenous PTPRU in gastric cancer cells using lentivirus-delivered specific shRNA results in the attenuation of cell growth, migration, invasion and adhesion. Knockdown of PTPRU also inhibits tyrosine phosphorylation and transcriptional activity of ?-catenin as well as levels of focal adhesion proteins and lysine methylation of histone H3. These results indicate that PTPRU is required for gastric cancer progression and may serve as a potential therapeutic target. PMID:25337216

Liu, Yongjie; Zhu, Zhichuan; Xiong, Zhiqi; Zheng, Jing; Hu, Zelan; Qiu, Jiangfeng

2014-01-01

312

The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high-fat diet  

PubMed Central

Background and purpose: Endocannabinoids (via cannabinoid CB1 receptor activation) are physiological regulators of intestinal motility and food intake. However, their role in the regulation of gastric emptying is largely unexplored. The purpose of the present study was to investigate the involvement of the endocannabinoid system in the regulation of gastric emptying in mice fed either a standard diet (STD) or a high-fat diet (HFD) for 14 weeks. Experimental approach: Gastric emptying was evaluated by measuring the amount of phenol red recovered in the stomach after oral challenge; CB1 expression was analysed by quantitative reverse transcription-PCR; endocannabinoid (anandamide and 2-arachidonoyl glycerol) levels were measured by liquid chromatography-mass spectrometry. Key results: Gastric emptying was reduced by anandamide, an effect counteracted by the CB1 receptor antagonist rimonabant, but not by the CB2 receptor antagonist SR144528 or by the transient receptor potential vanilloid type 1 (TRPV1) antagonist 5?-iodoresiniferatoxin. The fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine (but not the anandamide uptake inhibitor OMDM-2) reduced gastric emptying in a way partly reduced by rimonabant. Compared to STD mice, HFD mice exhibited significantly higher body weight and fasting glucose levels, delayed gastric emptying and lower anandamide and CB1 mRNA levels. N-arachidonoylserotonin (but not rimonabant) affected gastric emptying more efficaciously in HFD than STD mice. Conclusions and implications: Gastric emptying is physiologically regulated by the endocannabinoid system, which is downregulated following a HFD leading to overweight. PMID:18223666

Di Marzo, V; Capasso, R; Matias, I; Aviello, G; Petrosino, S; Borrelli, F; Romano, B; Orlando, P; Capasso, F; Izzo, A A

2008-01-01

313

The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers.  

PubMed

Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (five EGCs and four AGCs) and eight MS-stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well-known driver mutations (TP53, APC, PIK3CA, ARID1A, and KRAS) that were enriched in cancer-related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI-H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly, EGC genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between EGC and AGC genomes were not significantly different in either MSI-H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that EGC genomes were as old as AGC genomes in both MSS and MSI-H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in EGC genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25042771

Kim, Tae-Min; Jung, Seung-Hyun; Kim, Min Sung; Baek, In-Pyo; Park, Sung-Won; Lee, Sung Hak; Lee, Han Hong; Kim, Sung Soo; Chung, Yeun-Jun; Lee, Sug Hyung

2014-11-01

314

Gastric cancer: staging, treatment, and surgical quality assurance  

Microsoft Academic Search

Research described in this thesis focuses on several aspects of gastric cancer care: staging and prognostication, multimodality treatment, and surgical quality assurance.\\u000a\\u000aPART I - STAGING AND PROGNOSTICATION\\u000aCancer staging is one of the fundamental activities in oncology.6,7 For over 50 years, the TNM classification has been a standard in classifying the anatomic extent of disease.8 In order to maintain

Johannes Leen Dikken

2012-01-01

315

Effects of chronic normovolemic anemia on gastric microcirculation and ethanol-induced gastric damage in rats.  

PubMed

The effects of chronic normovolemic anemia on gastric microcirculation and gastric mucosal susceptibility to ethanol-induced gastric damage were investigated in anesthetized rats. Blood exchange by a plasma expander during four consecutive days rendered the animals anemic with a 34% decrease in the baseline hematocrit but without affecting blood volume. Chronic anemia induced a decrease in whole blood viscosity, an increase in gastric mucosal blood flow measured by hydrogen gas clearance, a decrease in gastric vascular resistance, and a decrease in gastric hemoglobin content without changes in the gastric oxygen content, the latter two parameters being measured by reflectance spectrophotometry. Gastric mucosal blood flow was lowered by intragastric administration of 100% ethanol in both anemic and control rats, but the final blood flow was significantly higher in anemic than in control animals. Macroscopic gastric damage induced by ethanol administration was significantly lower in anemic than in control rats. We conclude that chronic normovolemic anemia increases gastric mucosal blood flow and leads a protecting mechanism against gastric mucosal damage induced by absolute ethanol. PMID:8149840

Marroni, N; Casadevall, M; Panés, J; Piera, C; Jou, J M; Pique, J M

1994-04-01

316

A cephalic influence on gastric motility upon seeing food in domestic turkeys (Melagris gallopavo), great-horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis).  

PubMed

Strain gage transducers were permanently implanted on the muscular stomachs of 13 turkeys, 3 great-horned owls and 2 red-tailed hawks to monitor gastric motility before, during and after eating. Following fasting, the sight of food resulted in significant increases in gastric contractile activity in all three species. Gastric motility further increased when the birds were allowed to eat. In raptors, however, a brief interruption in gastric motility occurred immediately after eating. This is apparently analogous to receptive relaxation which occurs in the stomach of mammals. PMID:1019075

Duke, G E; Evanson, O A; Redig, P T

1976-11-01

317

Oxidative stress induces gastric submucosal arteriolar dysfunction in the elderly  

PubMed Central

AIM: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process. METHODS: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H2O2) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits. RESULTS: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H2O2 in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group. CONCLUSION: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process. PMID:24409074

Liu, Lei; Liu, Yan; Cui, Jie; Liu, Hong; Liu, Yan-Bing; Qiao, Wei-Li; Sun, Hong; Yan, Chang-Dong

2013-01-01

318

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

PubMed Central

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

Khan, Muhammad Israr; Khan, Muhammad Rashid

2013-01-01

319

D2 dissection for gastric cancer  

Microsoft Academic Search

Theodore Billroth successfully performed the first gastrectomy for cancer in Vienna in 1881. This was the beginning of modern gastric cancer surgery and provided the first real hope for cure from this form of cancer. Gastric cancer is a leading cause of cancer related mortality world wide, particularly in Central and South America, Japan and Korea, and in the Baltic

Jeffrey S. Lee; Harold O. Douglass

1997-01-01

320

Gastric emptying in diabetic autonomic neuropathy  

Microsoft Academic Search

Gastric emptying was studied in 12 diabetic patients, six with and six without objective evidence of autonomic neuropathy and in 20 non-diabetic controls, using a double isotope scinti-scanning technique which differentiated between solid and liquid emptying. Three patients with autonomic neuropathy exhibited gastric stasis, although this was detected by conventional radiology in only one. Neither the patients with stasis nor

I W Campbell; R C Heading; P Tothill; T A Buist; D J Ewing; B F Clarke

1977-01-01

321

Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole  

PubMed Central

Aim: To investigate the distribution of amoxicillin in the gastric juice and gastric mucosa of rats and to investigate the effects of proton pump inhibitor rabeprazole on amoxicillin concentrations in various compartments. Methods: One hundred and sixty anesthetized rats were divided into five groups, and given intravenously different doses of amoxicillin or amoxicillin and rabeprazole. The pH value and volume of gastric juice was aspirated were measured and separated gastric mucosa was homogenized. The concentrations of amoxicillin in the plasma, gastric juice and gastric mucosa were measured by high performance liquid chromatography (HPLC). Results: The maximum concentrations of amoxicillin in gastric juice and gastric mucosa were significantly lower than those in plasma (P<0.001). Concentrations in the glandular stomach mucosa were higher than those in the forestomach mucosa. Rabeprazole did not significantly change the pharmacokinetic parameters of amoxicillin in the plasma and did not alter gastric antibiotic clearance or the gastric transfer fraction of amoxicillin in gastric juice. However, rabeprazole did increase the amoxicillin concentration and pH value in gastric juice and reduced the volume of the gastric juice. Conclusion: Amoxicillin could penetrate the gastric mucosa and achieve therapeutic concentrations at the target site after transfer from the blood to the stomach. Rabeprazole increased the amoxicillin concentration in gastric juice by decreasing the gastric juice volume but did not affect its concentration in blood or gastric mucosa. PMID:20305682

Zheng, Hai-lun; Hu, Yong-mei; Bao, Jun-jun; Xu, Jian-ming

2010-01-01

322

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

PubMed

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

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

2014-08-28

323

Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration  

PubMed Central

Acer mono Max. sap (AmMs) is called ‘Gol-Li-Su’ or ‘Go-Lo-Soe’ in Korean, which means ‘water beneficial to the bones’. It is reported that the sap contains several types of minerals and sugars. In particular, the calcium concentration of the sap is 36.5 times higher than that of commercial mineral water. Apart from its anti-osteoporosis effect, no reports have addressed the biological activities of AmMs against degenerative diseases. In the present study, we investigated whether AmMs alleviates gastric ulcer-related symptoms in a stress-induced mouse model. To assess the effect of AmMs on gastric ulcer-like symptoms, we carried out a water immersion restraint (WIRE) test and found that AmMs has potential in alleviating gastric ulcers in a concentration-dependent manner. These results indicate that the nutritional factors of the sap mitigate the gastric ulcer-related symptoms caused by stress-induced gastric lesions in mice. AmMs-treated mice exhibited a significant decrease in the ulcer index as compared to those treated with omeprazole or L-arginine. To examine one potential mechanism underlying this effect, we performed reverse transcription-polymerase chain reaction to ascertain whether molecular markers were associated with the mitigation of the gastric lesions. Epithelial and/or tissue nitric oxide synthase (NOS) was assessed to determine whether or not the genes were down-regulated dose-dependently by the sap. The levels of these enzymes were found to be lower in the tissue samples treated with AmMs compared with the levels in the control samples. These findings collectively suggest that AmMs significantly protects the gastric mucosa against WIRE stress-induced gastric lesions, at least in part, by alleviating inducible NOS and/or neuronal NOS expression. PMID:22977586

PARK, CHUL-HONG; SON, HYUNG-U; SON, MINSIK; LEE, SANG-HAN

2011-01-01

324

Calcium/calmodulin?dependent protein kinase II enhances metastasis of human gastric cancer by upregulating nuclear factor??B and Akt?mediated matrix metalloproteinase?9 production.  

PubMed

Calcium/calmodulin?dependent protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase, involved in processes that cause tumor progression, including cell cycle regulation, apoptosis and differentiation. However, the role of CaMKII in cancer cell metastasis has not been fully elucidated. In the present study, the function of CaMKII in gastric cancer cell metastasis is reported. Firstly, it was demonstrated that the overexpression of H282R (constitutively active CaMKII) enhanced gastric cancer cell migration and invasion, and the inhibition of CaMKII activity by KN?62 decreased gastric cancer cell metastasis. Furthermore, H282R upregulated matrix metalloproteinase?9 (MMP?9) expression and production, which were dependent on CaMKII?mediated increase in nuclear factor (NF)??B and Akt activation. Finally, CaMKII activation, through phosphorylation of the Thr 286 site, was significantly increased in the metastatic gastric cancer tissues compared with non?metastatic tissues, suggesting that CaMKII has an important function in the regulation of gastric cancer cell metastasis. Collectively, the present study demonstrated that CaMKII promotes gastric cancer cell metastasis by NF??B and Akt?mediated?MMP?9 production. These findings suggest a novel function of CaMKII in the control of gastric cancer metastasis, offering a promising target for future therapeutics to treat and prevent gastric cancer metastases via the inhibition of CaMKII activity. PMID:25174603

Liu, Zhaolong; Han, Gang; Cao, Yu; Wang, Yidong; Gong, Hangjun

2014-11-01

325

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

SciTech Connect

Helicobacter pylori has been found to promote the malignant process leading to gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been identified as a potent immunogene. This study investigates the role of HpHSP60 in gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti-death activity, angiogenesis and cell migration were explored. The results showed that HpHSP60 enhanced migration by gastric cancer cells and promoted tube formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not increase cell proliferation nor was this protein able to rescue gastric cancer cells from death. Moreover, the results also indicated HpHSP60 had different effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their expression of pro-inflammatory cytokines, which are known to be important to cancer development. We propose that HpHSP60 may trigger the initiation of carcinogenesis by inducing pro-inflammatory cytokine release and by promoting angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is potentially a vigorous virulence factor that can act as a carcinogen during gastric tumorigenesis.

Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China) [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)] [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Li, Chi-Han; Yang, Shang-Chih; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China)] [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China)] [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Cheng, Tain-Lu [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)] [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)] [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

2010-02-05

326

Molecular Integrative Clustering of Asian Gastric Cell Lines Revealed Two Distinct Chemosensitivity Clusters  

PubMed Central

Cell lines recapitulate cancer heterogeneity without the presence of interfering tissue found in primary tumor. Their heterogeneous characteristics are reflected in their multiple genetic abnormalities and variable responsiveness to drug treatments. In order to understand the heterogeneity observed in Asian gastric cancers, we have performed array comparative genomic hybridization (aCGH) on 18 Asian gastric cell lines. Hierarchical clustering and single-sample Gene Set Enrichment Analysis were performed on the aCGH data together with public gene expression data of the same cell lines obtained from the Cancer Cell Line Encyclopedia. We found a large amount of genetic aberrations, with some cell lines having 13 fold more aberrations than others. Frequently mutated genes and cellular pathways are identified in these Asian gastric cell lines. The combined analyses of aCGH and expression data demonstrate correlation of gene copy number variations and expression profiles in human gastric cancer cells. The gastric cell lines can be grouped into 2 integrative clusters (ICs). Gastric cells in IC1 are enriched with gene associated with mitochondrial activities and oxidative phosphorylation while cells in IC2 are enriched with genes associated with cell signaling and transcription regulations. The two clusters of cell lines were shown to have distinct responsiveness towards several chemotherapeutics agents such as PI3 K and proteosome inhibitors. Our molecular integrative clustering provides insight into critical genes and pathways that may be responsible for the differences in survival in response to chemotherapy. PMID:25343454

Choong, Meng Ling; Tan, Shan Ho; Tan, Tuan Zea; Manesh, Sravanthy; Ngo, Anna; Yong, Jacklyn W. Y.; Yang, Henry He; Lee, May Ann

2014-01-01

327

Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer  

PubMed Central

Objective: To investigate chemoresistance of human gastric cancer to chemotherapeutic drugs in vitro and explore the relationship with Bcl-2 protein expression. Methods: Single-cell suspensions were prepared from freshly excised samples of primary gastric cancer, and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. The induction of cell death was confirmed by microscopic analysis of cell morphology. Metabolic activity and the inhibitory rate (IR) of cells were evaluated by MTT assay. Expression of Bcl-2 was determined by immunohistochemistry of gastric cancer tissue samples. Results: The IRs of cancer cells exposed to different chemotherapeutic drugs varied as follows: the IRs for TAX, CDDP and 5-FU were significantly higher than those for ADM and MMC (P < 0.01). Poorly differentiated gastric cancer cells were more sensitive than well-differentiated cells (P = 0.021). The positive rate of Bcl-2 expression was 80%, and Bcl-2 expression was significantly associated with chemoresistance to 5-FU (rs = 0.265, P = 0.041), ADM (rs = 0.425, P = 0.001) and MMC (rs = 0.40, P = 0.002). Furthermore, Bcl-2 expression was strongly associated with lymph node metastasis in gastric cancer (P = 0.009). Conclusion: Overexpression of Bcl-2 may predict a loss of the efficacy of the chemotherapy drugs 5-FU, ADM and MMC in patients with gastric cancer. PMID:24228120

Geng, Ming; Wang, Lin; Li, Peifeng

2013-01-01

328

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

PubMed Central

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

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

2014-01-01

329

Polyamines are Inhibitors of Gastric Acid Secretion  

NASA Astrophysics Data System (ADS)

The naturally occurring organic polycations such as spermine and spermidine inhibit histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro; spermine is much more potent than spermidine. Unlike the H2 receptor antagonists, the polyamines are completely ineffective from the nutrient side and are effective only from the secretory side of the chambered mucosa. The polyamine effects could be reversed by increasing K+ concentration in the secretory solution. Studies with isolated gastric microsomal vesicles demonstrate that the polyamines do not inhibit the gastric H+,K+-ATPase but greatly decrease the ATPase-mediated uptake of H+ under appropriate conditions. For the latter effects the presence of polyamine within the vesicle interior was found to be essential. Our data strongly suggest an uncoupling of the gastric H+,K+-ATPase system by the polyamines. The therapeutic potential of these and similar compounds in the treatment of hyperacidity and peptic ulcer is discussed.

Ray, Tushar K.; Nandi, Jyotirmoy; Pidhorodeckyj, Nykolai; Meng-Ai, Zhou

1982-03-01

330

TNF-?/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells.  

PubMed

Helicobacter pylori infection induces chronic inflammation that contributes to gastric tumorigenesis. Tumor necrosis factor (TNF-?) is a proinflammatory cytokine, and polymorphism in the TNF-? gene increases the risk of gastric cancer. We herein investigated the role of TNF-? in gastric tumorigenesis using Gan mouse model, which recapitulates human gastric cancer development. We crossed Gan mice with TNF-? (Tnf) or TNF-? receptor TNFR1 (Tnfrsf1a) knockout mice to generate Tnf-/- Gan and Tnfrsf1a-/- Gan mice, respectively, and examined their tumor phenotypes. Notably, both Tnf-/- Gan mice and Tnfrsf1a-/- Gan mice showed similar, significant suppression of gastric tumor growth compared with control Tnf+/+ or Tnfrsf1a+/+ Gan mice. These results indicate that TNF-? signaling through TNFR1 is important for gastric tumor development. Bone marrow (BM) transplantation experiments showed that TNF-? expressed by BM-derived cells (BMDCs) stimulates the TNFR1 on BMDCs by an autocrine or paracrine manner, which is important for gastric tumor promotion. Moreover, the microarray analysis and colony formation assay indicated that NADPH oxidase organizer 1 (Noxo1) and Gna14 are induced in tumor epithelial cells in a TNF-?-dependent manner, and have an important role in tumorigenicity and tumor-initiating cell property of gastric cancer cells. Accordingly, it is possible that the activation of TNF-?/TNFR1 signaling in the tumor microenvironment promotes gastric tumor development through induction of Noxo1 and Gna14, which contribute to maintaining the tumor cells in an undifferentiated state. The present results indicate that targeting the TNF-?/TNFR1 pathway may be an effective preventive or therapeutic strategy for gastric cancer. PMID:23975421

Oshima, H; Ishikawa, T; Yoshida, G J; Naoi, K; Maeda, Y; Naka, K; Ju, X; Yamada, Y; Minamoto, T; Mukaida, N; Saya, H; Oshima, M

2014-07-17

331

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats  

PubMed Central

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-? and interleukin (IL)-1?], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-?, IL-1?, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-?-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-?, IL-1?, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels. PMID:23969974

Nicolau, L.A.D.; Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D.; Aragao, K.S.; Barbosa, A.L.R.; Soares, P.M.G.; Souza, M.H.L.P.; Medeiros, J.V.R.

2013-01-01

332

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

PubMed Central

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 (eight men and eight women) received ethanol (0.225 g/kg body weight) orally and intravenously, and the areas under the ethanol concentration time curves were determined to calculate FPM of ethanol. In seven of these subjects, FPM of ethanol was measured after the intravenous administration of 10 mg metoclopramide (MCP) and 20 mg N-butylscopolamine (NBS) in separate experiments to either accelerate or delay GE. GE was monitored sonographically by integration of the antral area of the stomach every five minutes for 90 minutes after oral ethanol intake. In addition, gastric biopsy specimens were taken to determine ADH activity and phenotype, as well as to evaluate gastric histology. Blood was also drawn for ADH genotyping. ?Results—GE time was significantly delayed by the administration of NBS as compared with controls (p<0.0001) and as compared with the administration of MCP (p<0.0001). This was associated with a significantly enhanced FPM of ethanol with NBS compared with MCP (p = 0.0004). A significant correlation was noted between GE time and FPM of ethanol (r = 0.43, p = 0.0407). Gastric ADH activity did not significantly correlate with FPM of ethanol. ?Conclusion—FPM of ethanol is strikingly modulated by the speed of GE. Delayed GE increases the time of exposure of ethanol to gastric ADH and may therefore increase gastric FPM of ethanol. In addition, hepatic FPM of ethanol may also be enhanced as the result of slower absorption of ethanol from the small intestine. Thus a knowledge of GE time is a major prerequisite for studying FPM of ethanol in humans. ?? Keywords: first pass metabolism of ethanol; gastric emptying; alcohol dehydrogenase; ethanol metabolism; stomach PMID:9824340

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

1998-01-01

333

Risk of gastric cancer among Korean familial adenomatous polyposis patients  

Microsoft Academic Search

Gastric cancer has been recognized as an extracolonic manifestation in patients with familial adenomatous polyposis (FAP). In Korea, gastric cancer is the most common malignant neoplasm. In a recent survey, we collected data from 72 Korean patients with FAP. Among them, three (4.2 percent) were found to have associated gastric cancer. This incidence of gastric cancer in our series is

Jae-Gahb Park; Kyu Joo Park; Yoon-Ok Ahn; In Sung Song; Kyoo Wan Choi; Hong Young Moon; Sang-Yong Choo; Jin-Pok Kim

1992-01-01

334

Genetic alterations of the MYH gene in gastric cancer  

Microsoft Academic Search

Increased oxygen free radicals produced in gastric mucosa by H. pylori induce DNA damage and lead to dyspalsia and gastric cancers. However, only a small percentage of individuals that carry H. pylori develop gastric cancer, indicating that other factors are involved. We have screened a set of 95 sporadic gastric cancers for mutations and allele loss of the DNA glycosylase

Chang Jae Kim; Yong Gu Cho; Cho Hyun Park; Su Young Kim; Suk Woo Nam; Sug Hyung Lee; Nam Jin Yoo; Jung Young Lee; Won Sang Park

2004-01-01

335

Manual Acupuncture and Laser Acupuncture for Autonomic Regulations in Rats: Observation on Heart Rate Variability and Gastric Motility  

PubMed Central

This study focused on the effects of laser acupuncture (LA) and manual acupuncture (MA) at different acupoints on gastric motility and heart rate variability (HRV) simultaneously to elucidate the site specific effects of acupoints and the correlation between changes of gastric motility and low frequency/high frequency (LF/HF) ratio. Gastric motility and HRV were recorded before and during MA or LA. Stimulating PC-6 or ST-36 significantly enhanced gastric motility, while BL-21 caused no changes. In contrast, MA or LA at CV-12 significantly suppressed gastric motility. Stimulating PC-6 or ST-36 significantly increased heart rate (HR), while CV-12 or BL-21 induced no significant changes of HR. Stimulating PC-6 significantly increased LF/HF, while ST-36, CV-12, or BL-21 induced no significant effects. These results indicated that there was acupoint specificity in the effects of acupuncture on gastric motility and HRV. The stimulatory effect of MA and LA at PC-6 and ST-36 on HR was associated with sympathetic activity. The stimulatory effect of MA or LA at PC-6 or ST-36 on gastric motility was associated with vagal activity. Laser needle can be used as an alternative stimulation therapy. PMID:24348694

Yang, Zhao-Kun; Wu, Mei-Ling; Xin, Juan-Juan; He, Wei; Su, Yang-Shuai; Shi, Hong; Wang, Xiao-Yu; Hu, Ling; Jing, Xiang-Hong

2013-01-01

336

CT evaluation of gastric lymphoma.  

PubMed

The purpose of our study was to determine the value of computed tomography (CT) with a drug-induced hypotonia and water filling in the diagnosis and preoperative staging of 27 patients with gastric lymphoma (GLy) confirmed by endoscopic biopsy. CT scans were performed in a supine and prone position with drug-induced hypotonia and water-filling of stomach with 500-700 ml., and intravenous administration of a non-ionic contrast agent. the prone position and drug-induced hypotonia allowed visualization of the whole gastric wall and prevented gas artifacts, commonly present during supine imaging. CT scans were analysed with respect to the thickness of the stomach wall, rugal thickening, presence of wall infiltration, mucosal nodularity, ulcerations and tumour masses, regional tumour spread, lymph node deposits and presence of distant metastases. The most common findings in GLy were ulcers of variable size, depth and number in 43% of cases, a mass with or without an ulcer in 36% of cases, and rugal thickening in 21% of cases. According to CT results, GLy was staged in four groups: I, II1, II2, III and IV. Precise preoperative staging was achieved in 73%, overstaging in 18% and understaging in 9% of patients. The sensitivity and specificity of the technique was 93% and 85% respectively. There was low grade MALT lymphoma in 69% and high grade MALT lymphoma in 31% of cases. We believe that CT performed ussing this method is a useful non-invasive method for preoperative evaluation and staging of gastric lymphoma and should be used before surgery is planned. PMID:20087255

Gligorievski, A

2009-12-01

337

Effects of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal injuries in Sprague-Dawley rats.  

PubMed

Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control) rats were orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer control) rats were also orally administered with vehicle. Group 3 (positive control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-induced gastric mucosal injury was studied grossly and histology. The level of lipid peroxidation (malondialdehyde-MDA), superoxide dismutase (SOD) and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-induced gastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may possibly be due to its preservation of gastric wall mucus along with increased SOD activity and reduction of oxidative stress (MDA). The extract is non-toxic, even at relatively high concentrations. PMID:22395408

Ibrahim, Ibrahim Abdel Aziz; Qader, Suhailah Wasmn; Abdulla, Mahmood Ameen; Nimir, Amal R; Abdelwahab, Siddig Ibrahim; Al-Bayaty, Fouad Hussain

2012-01-01

338

Molecular events in gastric carcinogenesis  

PubMed Central

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

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

2014-01-01

339

Lymph node metastasis as a significant prognostic factor in early gastric cancer: Analysis of 1,136 early gastric cancers  

Microsoft Academic Search

Background: Gastric cancer is the most frquent cancer and the leading cause of death from cancer in Korea. Early gastric cancer has been defined as a gastric carcinoma confined to mucosa or submucosa, regardless of lymph node status, and has an excellent prognosis with a >90% 5-year survival rate. From 1974 to 1992, we encountered 7,606 cases of gastric cancer

Jin-Pok Kim; Yoon Seok Hur; Han-Kwang Yang

1995-01-01

340

Gastric tone determines the sensitivity of the stomach to distention  

Microsoft Academic Search

Background\\/Aims: Whether meal-related symptoms such as postcibal epigastric fullness and discomfort are caused by hypotonic gastric expansion or gastric hypertension is unknown. This study investigated whether symptoms in healthy individuals in response to gastric distention are produced by gastric expansion or by an increase in intragastric pressure. Methods: Increasing gastric distentions (for 5 minutes at 5-minute intervals) at fixed pressure

Ricardo Notivol; Benoit Coffin; Fernando Azpiroz; Fermín Mearin; Jordi Serra; Juan-R. Malagelada

1995-01-01

341

Imaging Findings of Gastric Diverticula  

PubMed Central

Introduction. Gastric diverticula (GD) are very rare. Computer tomographic findings in GD have been reported only as case reports previously. The aim of this study was to estimate the prevalence of GD on computed tomography (CT) and to analyze their radiological appearances. Materials and Methods. From 2006 to 2013, a total of 14,428 patients were examined by abdominal/thoracic CT at our institution. GD were diagnosed in 18 (0.12%) patients (13 women and 5 men, median age, 64 years). In 9 patients, additional endoscopy and in 7 patients upper gastrointestinal investigation with contrast medium were performed. Magnetic resonance imaging (MRI) was available for 3 cases. Results. In all patients GD were diagnosed incidentally during CT examination. The diverticula were located at the posterior wall of the gastric fundus below the esophagogastric junction. On CT, GD presented as cystic lesions with a thin wall and an air fluid level, located behind the stomach between spleen, adrenal gland, and crus of the left diaphragm. Conclusion. The prevalence of GD encountered in our CT series is 0.12%. GD demonstrate typical CT appearances, namely, cystic lesions located in the left paravertebral region. The radiologist should be familiar with this finding to avoid possible misinterpretations.

Schramm, Dominik; Bach, Andreas Gunter; Zipprich, Alexander; Surov, Alexey

2014-01-01

342

Tumor deposits in gastric carcinomas.  

PubMed

We performed this study to examine the prevalence of tumor deposits (TD) in gastric adenocarcinomas (GACa), and the relevance of their presence, size and type to clinical outcome. Ninety-six patients, histopathologically diagnosed as GACa following a total/subtotal gastrectomy were included, and clinicopathologic data were recorded. Due to the statistical analysis, the majority of TD(+) cases were of intestinal type and showed vascular invasion. In these cases, the incidence of local recurrence was significantly higher. The majority of GACa of intestinal type with TD were of high grade and showed vascular invasion. Recurrence and death were more commonly encountered among them. The recurrence-free survival (RFS) was significantly shorter in patients with TDs, which was also confirmed by multivariate analysis, and there was a significant difference between both RFS and overall survival of TD(+) and TD(-) cases of intestinal type GACa. In conclusion, in this study, we demonstrate that TDs are not infrequently observed in GACa, they are more commonly associated with the intestinal type and vascular invasive gastric cancers. Our study shows the prognostic impact of TDs, especially regarding the RFS. Therefore, the documentation of TDs might be considered for prospective studies, especially for the intestinal type GACa, a shortcoming of this study. PMID:24726262

Ersen, Ayca; Unlu, Mehtat S; Akman, Tulay; Sagol, Ozgul; Oztop, Ilhan; Atila, Koray; Bora, Seymen; Ellidokuz, Huyla; Sarioglu, Sulen

2014-09-01

343

Gastric emptying abnormal in duodenal ulcer  

SciTech Connect

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.

Holt, S.; Heading, R.C.; Taylor, T.V.; Forrest, J.A.; Tothill, P.

1986-07-01

344

Biomagnetic signatures of uncoupled gastric musculature  

PubMed Central

Gastric slow waves propagate in the electrical syncytium of the healthy stomach, being generated at a rate of approximately three times per minute in a pacemaker region along the greater curvature of the antrum and propagating distally towards the pylorus. Disease states are known to alter the normal gastric slow wave. Recent studies have suggested the use of biomagnetic techniques for assessing parameters of the gastric slow wave that have potential diagnostic significance. We present a study in which the gastric syncytium was uncoupled by mechanical division as we recorded serosal electric potentials along with multichannel biomagnetic signals and cutaneous potentials. By computing the surface current density (SCD) from multichannel biomagnetic recordings, we were able to quantify gastric slow wave propagation as well as the frequency and amplitude of the slow wave and to show that these correlate well with similar parameters from serosal electrodes. We found the dominant slow wave frequency to be an unreliable indicator of gastric uncoupling as uncoupling results in the appearance of multiple slow wave sources at various frequencies in external recordings. The percentage of power distributed in specific frequency ranges exhibited significant postdivision changes. Propagation velocity determined from SCD maps was a weak indicator of uncoupling in this work; we believe that the relatively low spatial resolution of our 19-channel biomagnetometer confounds the characterization of spatial variations in slow wave propagation velocities. Nonetheless, the biomagnetic technique represents a non-invasive method for accurate determination of clinically significant parameters of the gastric slow wave. PMID:19222760

Bradshaw, L. A.; Irimia, A.; Sims, J. A.; Richards, W. O.

2010-01-01

345

Recognition of gastric cancer by Raman spectroscopy  

NASA Astrophysics Data System (ADS)

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

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

2009-08-01

346

IL-22 Negatively Regulates Helicobacter pylori-Induced CCL20 Expression in Gastric Epithelial Cells  

PubMed Central

Helicobacter pylori is a Gram-negative bacterium that infects the human gastric mucosa and causes various gastric diseases. H. pylori infection induces the production of inflammatory chemokine CCL20 in gastric mucosa and leads to gastric inflammation. Given that the IL-22/IL-22R axis plays a critical role in the regulation of homeostasis and inflammation of epithelial cells at barrier surfaces, we investigated the effect of IL-22 on CCL20 expression induced by H. pylori. We demonstrated that H. pylori infection of the gastric epithelia-derived AGS cells significantly induced CCL20 expression and the induction was inhibited by IL-22. Functional analysis of the CCL20 promoter revealed that the H. pylori-induced CCL20 expression required the activation of NF-?B, and that IL-22 inhibited the induction by attenuating NF-?B activation. Knockdown of endogenous STAT3 by either short interfering RNAs or a short hairpin RNA significantly reduced the inhibitory effect of IL-22. Furthermore, STAT3 phosphorylation elicited by IL-22 was crucial for the inhibition of H. pylori-induced CCL20 expression. Consistent with the in vitro data showing that IL-22 negatively regulated H. pylori-induced CCL20 expression in gastric epithelial cells, studies on the tissue sections from patients with H. pylori infection also revealed an inverse association of IL-22 expression and CCL20 expression in vivo. Together, our findings suggest that IL-22 plays a role in the control of overproduction of the inflammatory chemokine and thus may protect the gastric mucosa from inflammation-mediated damage. PMID:24824519

Chen, Jia-Perng; Wu, Ming-Shiang; Kuo, Sung-Hsin; Liao, Fang

2014-01-01

347

Importance of gastric acid in gastric ulcer formation in rabbits with antibody-induced prostaglandin deficiency.  

PubMed

The role of gastric acid in the development of gastroduodenal ulcers in prostaglandin-deficient conditions is unclear. In the current study, the effect of the proton pump inhibitor omeprazole on the formation of gastric ulcers was examined in a previously validated rabbit model of antibody-induced prostaglandin deficiency. Intragastric administration of 20 mg/kg omeprazole every 12 hours caused a profound suppression of gastric acidity (i.e., pH above 5 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by passive immunization with 6-keto-prostaglandin F1 alpha antibodies. It is concluded from these observations that gastric acid plays a critical role in the formation of gastric ulcers in rabbits with antibody-induced prostaglandin deficiency. PMID:1426865

Lee, M; Aldred, K; Lee, E; Prince, M D; Feldman, M

1992-11-01

348

Relationship between gastric cancer and blood trace metal levels  

SciTech Connect

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

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

1981-06-01

349

Diabetes and gastric cancer: The potential links  

PubMed Central

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

Tseng, Chin-Hsiao; Tseng, Farn-Hsuan

2014-01-01

350

Do calories or osmolality determine gastric emptying  

SciTech Connect

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

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

1984-01-01

351

CARP Is a Potential Tumor Suppressor in Gastric Carcinoma and a Single-Nucleotide Polymorphism in CARP Gene Might Increase the Risk of Gastric Carcinoma  

PubMed Central

Background The caspase-associated recruitment domain-containing protein (CARP) is expressed in almost all tissues. Recently, the tumor-suppressive function of CARP was discovered and attracted increasing attention. This study aimed to investigate the role of CARP in the carcinogenesis of human gastric carcinoma. Methodology/Principal Findings Compared with normal gastric tissue, the downregulation of CARP expression was observed in gastric carcinoma tissue by cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line (BGC-823) was stably transfected with pcDNA3.1B-CARP or plus CARP siRNA, and we used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion assay and western blot analysis to investigate the potential anti-tumor effects of CARP. The data showed that overexpressing CARP suppressed the malignancy of gastric carcinoma BGC-823 cell line, including significant increases in apoptosis, as well as obvious decreases in cell proliferation, migration, adhesion ability, and tumor growth. The tumor-suppressive effects of CARP were almost restored by siRNA-directed CARP silence. In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive effect of CARP was also verified. A single-nucleotide polymorphism (SNP) genotype of CARP (rs2297882) was located in the Kozak sequence of the CARP gene. The reporter gene assay showed that rs2297882 TT caused an obvious downregulation of activity of CARP gene promoter in BGC-823 cells. Furthermore, the association between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352 cases and 889 controls. It displayed that the TT genotype of rs2297882 in the CARP gene was associated with an increased risk of gastric carcinoma. Conclusions/Significance CARP is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of gastric carcinoma. PMID:24870804

Hu, Yu-chang; Gan, Lu; Shi, Yi; Yang, Han-shuo; Wei, Yu-quan

2014-01-01

352

Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma  

PubMed Central

A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5?mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma. PMID:25349615

Eivaz-Mohammadi, Sahar; Tarar, Omer; Malik, Khurram; Syed, Amer K.

2014-01-01

353

The Patient Journey to Gastric Band Surgery: A Qualitative Exploration  

PubMed Central

Aims This study explored the views and experiences of obese people preparing to undergo laparoscopic gastric banding (LAGB) leading up to the time of surgery. Background Weight loss surgery (WLS) is the most successful intervention available for the treatment of morbid obesity, and LAGB is among the most commonly used procedures in bariatric surgery. So far, the patient experience of deciding to undergo LAGB has been explored rarely and predominantly retrospectively. Design Semi-structured interviews took place with 23 patients about to undergo LAGB between June 2011 and March 2012. Data were analyzed using thematic analysis. Demographic and quality of life data situated the sample within the LAGB patient population. Results Three overarching themes were described. Participants were “living with obesity,” including the physical, social, and psychological challenges and consequences of being obese. These created in them a “desire to change,” expressed in multiple unsuccessful attempts to lose weight, and a quest for information, finally focusing on WLS. Eventually, “expectations toward LAGB” were formed, mainly to hand back a measure of control that enabled them to achieve, as well as ultimately to maintain, weight loss. This active process resulted in the patients' decision to undergo LAGB. When combined, these themes outline a distinct patient journey toward gastric banding. Conclusion Knowledge of the patient journey can inform both selection and care of patients awaiting gastric band surgery and is required by all health professionals working with this patient group. PMID:24761368

Pulford, Amanda; Mahon, David; Ferguson, Yasmin; Lewis, Michael PN

2013-01-01

354

Neonatal Gastric Teratoma: A Rare Entity  

PubMed Central

Gastric Teratoma is an extremely rare neoplasm seen in children. It is mostly benign and predominantly seen in males presenting with an abdominal mass. The lung and stomach are very unusual sites for teratoma. Gastric teratoma accounts for less than 1% of all teratomas, less than 100 cases are reported in literature. We report a case in a 20-day-old infant who presented with large abdominal mass; our case is an addition to the few limited known gastric teratomas reported in the world literature. PMID:24596767

Kharga, Bikram; Kumar, Vijay; Prabhu, P. Santosh; P.T, Sundeep; John, Sijo K

2014-01-01

355

Laparoscopic management of gastric gastrointestinal stromal tumors.  

PubMed

Gastrointestinal stromal tumors (GISTs) are the most frequent gastrointestinal tumors of mesodermal origin. Gastric GISTs represent approximately 70% of all gastrointestinal GISTs. The only curative option is surgical resection. Many surgical groups have shown good results with the laparoscopic approach. There have not been any randomized controlled trials comparing the open vs laparoscopic approach, and all recommendations have been based on observational studies. The experience obtained from gastric laparoscopic surgery during recent decades and the development of specific devices have allowed the treatment of most gastric GISTs through the laparoscopic approach. PMID:25031788

Correa-Cote, Juan; Morales-Uribe, Carlos; Sanabria, Alvaro

2014-07-16

356

Laparoscopic management of gastric gastrointestinal stromal tumors  

PubMed Central

Gastrointestinal stromal tumors (GISTs) are the most frequent gastrointestinal tumors of mesodermal origin. Gastric GISTs represent approximately 70% of all gastrointestinal GISTs. The only curative option is surgical resection. Many surgical groups have shown good results with the laparoscopic approach. There have not been any randomized controlled trials comparing the open vs laparoscopic approach, and all recommendations have been based on observational studies. The experience obtained from gastric laparoscopic surgery during recent decades and the development of specific devices have allowed the treatment of most gastric GISTs through the laparoscopic approach. PMID:25031788

Correa-Cote, Juan; Morales-Uribe, Carlos; Sanabria, Alvaro

2014-01-01

357

Effects of exogenous nesfatin-1 on gastric distention-sensitive neurons in the central nucleus of the amygdala and gastric motility in rats.  

PubMed

Nesfatin-1 is a novel brain-gut peptide identified in several brain regions associated with feeding and gastrointestinal function. Our study explored the effects of nesfatin-1 in the central nucleus of the amygdala (CNA) on the activity of gastric distention (GD)-sensitive neurons, gastric motility, and the potential regulation mechanisms by the dorsal motor nucleus of the vagus (DMV). Following retrograde injection of fluorogold (FG) into the DMV, we found that nesfatin-1/FG dual-labeled neurons were detected in the CNA, which indicates that some of the nesfatin-1-immunoreactive neurons arising from the DMV may project to the CNA. Single unit discharges in the CNA were recorded extracellularly, and gastric motility was monitored by implantation of a force transducer into the stomach of conscious rats. These results showed that nesfatin-1 administration to the CNA excited most of the GD-excitatory neurons, inhibited GD-inhibitory neurons, and dose-dependently reduced gastric motility. All of the above effects induced by nesfatin-1 could be partially blocked by pretreatment with the melanocortin 3/4 receptors antagonist, SHU9119. Electrical stimulation of the DMV excited the majority of the nesfatin-1-responsive GD neurons in the CNA. Additionally, pretreatment with an anti-NUCB2/nesfatin-1 antibody in the CNA increased the firing rate of nesfatin-1-responsive GD-inhibitory neurons but decreased the firing rate in nesfatin-1-responsive GD-excitatory neurons following electrical stimulation of the DMV. Finally, a subdiaphragmatic vagotomy eliminated the diminished gastric motility induced by nesfatin-1 injection. Taken together, these findings suggest that nesfatin-1 regulates the activity of GD-sensitive neurons and gastric motility via the melanocortin pathway in the CNA. Furthermore, the DMV may be involved in this regulatory pathway. PMID:25220707

Wang, Qiaoling; Guo, Feifei; Sun, Xiangrong; Gao, Shengli; Li, Zhiling; Gong, Yanling; Xu, Luo

2014-10-17

358

The CLOCK 3111T/C SNP is associated with morning gastric motility in healthy young women.  

PubMed

Circadian locomotor output cycles kaput (CLOCK) molecule plays major roles in circadian rhythmicity and regulates daily physiological processes including digestive activity. Therefore, we hypothesized that the CLOCK 3111T/C single nucleotide polymorphism (SNP) might have adverse effects on the regulation of gastric motility. Based on the hypothesis, we investigated whether this SNP was associated with morning gastric motility. Ninety-five female university students (19.6±0.2 years) completed life-style questionnaires. Gastric motility, evaluated by electrogastrography (EGG), blood pressure (BP), and heart rate variability (HRV) were measured at 8:30 a.m. after an overnight fast. To determine the gastric motility, the spectral powers and dominant frequency (DF, a peak of the spectrum) of the EGG were calculated. No significant differences were found in breakfast frequency, energy intake, or HRV between CLOCK 3111T/C minor C allele (T/C or C/C) and T/T subjects. However, C allele carriers showed significantly lower DF than T/T subjects, suggesting slower gastric motility. Moreover, C allele carriers had a lower heart rate (HR) and tended to have lower diastolic BP compared with T/T subjects. These results support our hypothesis that this SNP is likely correlated with morning gastric motility. Such attenuated gastric and cardiovascular function that characterized CLOCK 3111C allele carriers could be affecting biological behavior in the morning. PMID:22709985

Yamaguchi, Mitsue; Kotani, Kazuhiko; Sakane, Naoki; Tsuzaki, Kokoro; Takagi, Ayaka; Wakisaka, Shiori; Moritani, Toshio; Nagai, Narumi

2012-08-20

359

Characterization of gastric and neuronal histaminergic populations using a transgenic mouse model.  

PubMed

Histamine is a potent biogenic amine that mediates numerous physiological processes throughout the body, including digestion, sleep, and immunity. It is synthesized by gastric enterochromaffin-like cells, a specific set of hypothalamic neurons, as well as a subset of white blood cells, including mast cells. Much remains to be learned about these varied histamine-producing cell populations. Here, we report the validation of a transgenic mouse line in which Cre recombinase expression has been targeted to cells expressing histidine decarboxylase (HDC), which catalyzes the rate-limiting step in the synthesis of histamine. This was achieved by crossing the HDC-Cre mouse line with Rosa26-tdTomato reporter mice, thus resulting in the expression of the fluorescent Tomato (Tmt) signal in cells containing Cre recombinase activity. As expected, the Tmt signal co-localized with HDC-immunoreactivity within the gastric mucosa and gastric submucosa and also within the tuberomamillary nucleus of the brain. HDC expression within Tmt-positive gastric cells was further confirmed by quantitative PCR analysis of mRNA isolated from highly purified populations of Tmt-positive cells obtained by fluorescent activated cell sorting (FACS). HDC expression within these FACS-separated cells was found to coincide with other markers of both ECL cells and mast cells. Gastrin expression was co-localized with HDC expression in a subset of histaminergic gastric mucosal cells. We suggest that these transgenic mice will facilitate future studies aimed at investigating the function of histamine-producing cells. PMID:23555941

Walker, Angela K; Park, Won-Mee; Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Zigman, Jeffrey M

2013-01-01

360

Involvement of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury.  

PubMed

Large-dose or long-term use of aspirin tends to cause gastric mucosa injury, which is recognized as the major side effect of aspirin. It has been demonstrated that glutamate exerts a protective effect on stomach, and the level of glutamate is critically controlled by cystine/glutamate transporter (Xc(-)). In the present study, we investigated the role of glutamate-cystine/glutamate transporter system in aspirin-induced acute gastric mucosa injury in vitro and in vivo. Results showed that in human gastric epithelial cells, aspirin incubation increased the activity of LDH and the number of apoptotic cells, meanwhile down-regulated the mRNA expression of Xc(-) accompanied with decreased glutamate release. Similar results were seen in a rat model. In addition, exogenous l-glutamate attenuated the gastric mucosa injury and cell damage induced by aspirin both in vitro and in vivo. Taken together, our results demonstrated that acute gastric mucosa injury induced by aspirin is related to reduction of glutamate-cystine/glutamate transporter system activity. PMID:24866234

Du, Jie; Li, Xiao-Hui; Zhang, Wang; Yang, Yong-Mei; Wu, Yue-Han; Li, Wen-Qun; Peng, Jun; Li, Yuan-Jian

2014-07-18

361

Experimentally induced ulcers and gastric sensory-motor function in rats.  

PubMed

Prior studies have demonstrated that inflammation can sensitize visceral afferent neurons, contributing to the development of hyperalgesia. We hypothesized that both afferent and efferent pathways are affected, resulting in changes in motor and sensory function. Kissing ulcers (KU) were induced in the distal stomach by injecting 60% acetic acid for 45 s into a clamped area of the stomach. In controls, saline was injected into the stomach. A balloon catheter was surgically placed into the stomach, and electromyographic responses to gastric distension were recorded from the acromiotrapezius muscle at various times after ulcer induction. The accommodation reflex was assessed by slowly infusing saline into the distally occluded stomach. Gastric pressure changes in response to vagal stimulation were measured in anesthetized rats. Contractile function of circular muscle strips was examined in vitro using force-displacement transducers. KU caused gastric hypersensitivity that persisted for at least 14 days. Fluid distension of the stomach led to a rapid pressure increase in KU but not in control animals, consistent with an impaired accommodation reflex. Gastric ulcers enhanced the contractile response to vagal stimulation, whereas the effect of cholinergic stimulation on smooth muscle in vitro was not changed. These data suggest that inflammation directly alters gastric sensory and motor function. Increased activation of afferents will trigger vagovagal reflexes, thereby further changing motility and indirectly activating sensory neurons. Thus afferent and efferent pathways both contribute to the development of dyspeptic symptoms. PMID:15388487

Kang, Y M; Lamb, K; Gebhart, G F; Bielefeldt, K

2005-02-01

362

Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions  

PubMed Central

The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality. PMID:22606278

Herbert, Beate M.; Muth, Eric R.; Pollatos, Olga; Herbert, Cornelia

2012-01-01

363

A Simplified Biophysical Cell Model For Gastric Slow Wave Entrainment Simulation  

PubMed Central

Gastric electrical activity, also termed slow wave activity, is generated by a class of pacemaker cells called the interstitial cells of Cajal (ICC), which are organized with decreasing intrinsic frequencies along the stomach. In the healthy stomach, slow waves of different intrinsic frequencies converge to a single frequency with a constant phase-lag, in a process called entrainment. The main aim of this study was to develop a simplified biophysical ICC model that is capable of modeling the self-excitatory behavior and standard morphology of gastric slow waves. Entrainment of gastric slow waves was simulated in a one-dimensional (1D) model, with a linear gradient of intrinsic slow wave frequencies. In a coupled 1D model, the simulated slow waves were entrained to a single frequency; whereas in an uncoupled 1D model, the simulated slow waves occurred at different frequencies, resulting in loss of entrainment. The new cell model presents an option for future large multi-scale simulations of gastric slow waves in intact ICC network and diseased conditions where the loss of entrainment may lead to slow wave dysrhythmias and diminished gastric motility. PMID:24111242

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

2014-01-01

364

Toward the Virtual Stomach: Progress in Multi-scale Modeling of Gastric Electrophysiology and Motility  

PubMed Central

Experimental progress in investigating normal and disordered gastric motility is increasingly being complimented by sophisticated multi-scale modeling studies. Mathematical modeling has become a valuable tool in this effort, as there is an ever-increasing need to gain an integrative and quantitative understanding of how physiological mechanisms achieve coordinated functions across multiple biophysical scales. These interdisciplinary efforts have been particularly notable in the area of gastric electrophysiology, where they are beginning to yield a comprehensive and integrated in-silico organ modeling framework, or ‘virtual stomach’. At the cellular level, a number of biophysically-based mathematical cell models have been developed, and these are now being applied in areas including investigations of gastric electrical pacemaker mechanisms, smooth muscle electrophysiology, and electromechanical coupling. At the tissue level, micro-structural models are being creatively developed and employed to investigate clinically significant questions, such as the functional effects of ICC degradation on gastrointestinal electrical activation. At the organ level, high-resolution electrical mapping and modeling studies are combining to provide improved insights into normal and dysrhythmic gastric electrical activation. These efforts are also enabling detailed forward and inverse modeling studies at the ‘whole body’ level, with implications for diagnostic techniques for gastric dysrhythmias. These recent advances, together with several others highlighted in this review, collectively demonstrate a powerful trend toward applying mathematical models to effectively investigate structure-function relationships and overcome multi-scale challenges in basic and clinical gastrointestinal research. PMID:23463750

O'Grady, Gregory; Gao, Jerry; Sathar, Shameer; Cheng, Leo K

2013-01-01

365

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

SciTech Connect

Proteasome inhibitor is a novel class of cancer therapeutics, of which the mechanism of action is not fully understood. It is reported that proteasome inhibitor enhances bone morphogenetic protein (BMP) signaling in osteoblasts to stimulate bone formation. BMP signaling is also an important tumor-suppressing pathway in gastric carcinogenesis. We therefore sought to determine the anti-mitogenic effect of proteasome inhibition in relation to BMP signaling in gastric cancer cells. Results showed that proteasome inhibitor MG-132 significantly suppressed the proliferation and the colony-forming ability of gastric cancer TMK1 cells. In this connection, MG-132 activated BMP signaling, manifested as an increase in Smad1/5/8 phosphorylation and up-regulation of p21{sup Waf1/Cip1} mRNA and protein expression.