Gastric Ulcer Tissues Research Articles

To study the Helicobacter pylori infection in peptic ulcer

Helicobacter pylori is a gram negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. Its major in the human pathogen that produces inflammation of the stomach and etiologically related to the duodenal ulcer, gastric ulcer, gastric cancer and mucosa-lymphoid tissue. It is weakens the protective mucous coating of the stomach and duodenum, thus allowing acid to get through to the sensitive lining beneath. Both the acid and the bacteria irritate the lining and cause a sore, or ulcer. Helicobacter treated with a combination of antibiotics plus a proton pump inhibitor. Peptic ulcer is characterized by discontinuation in the inner lining of the gastrointestinal tract because of the gastric acid secretion or pepsin. It extends into muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. Peptic means that cause of the problem is due to the acid. It is most common causes in the peptic ulcers are infection with the bacterium and causes the long-term use of the non-steroidal anti-inflammatory drugs. Gastric ulcer occurs in the stomach. Duodenal ulcer occurs in the first part of the small intestine. The interplay of gastritis phenotype related to the bacterium colonization and resulting acid secretion.

Gastrointestinal microbiome in the context of Helicobacter pylori infection in stomach and gastroduodenal diseases.

Infectious origins of a set of severe gastroduodenal diseases viz. gastritis, duodenal ulcer, gastric ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma were appreciated only after the discovery of H. pylori in 1983. In the past two decades, however, findings from many laboratories suggest that apart from H. pylori, several of the trillions of microbes that populate the human gastrointestinal tract and form microbiomes of the respective niches (like oral microbiome, esophageal microbiome, gastric microbiome and intestinal microbiome) may also participate in maintaining the healthy state of stomach and duodenum. Dysbiosis leading to alteration in the relative abundance of the key gastrointestinal microbes is associated with severe gastric diseases. For instance, an increased abundance of genera like Leptotrichia, Prevotella and Veillonella in gastric microbiome and a decreased abundance of Bifidobacterium in intestinal microbiome are associated with gastric cancer. H. pylori infection, apart from causing direct harm to the gastric epithelium by its virulence proteins like vacuolating cytotoxin A (VacA) and cytotoxin associated gene A (CagA), is also capable of triggering dysbiosis in stomach and intestinal microbiomes. In this chapter, we have discussed the possible roles of bacteria, viruses, fungi, archaea, protozoa and helminths in human gastrointestinal tracts in the context of H. pylori infection in stomach and various gastroduodenal diseases.

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis.

Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.

Effectiveness of the polyphenols-rich Sedum dendroideum infusion on gastric ulcer healing in rats: Roles of protective endogenous factors and antioxidant and anti-inflammatory mechanisms

Ethnopharmacological relevancePeptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. Aim of the studyHere, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. Material and methodsRats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. ResultsOral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1β levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. ConclusionsThe gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.

Evaluation of the gastroprotective effects of Chihuahua propolis on indomethacin- induced gastric ulcers in mouse

The aim of this work was to evaluate the gastroprotective activity of a Mexican propolis on indomethacin-induced gastric ulcers in a mouse model. The following contents of the ethanolic extract of propolis of Chihuahua (EEPCh) were determined: antioxidant activity (SA50), total phenolic content (TPC), total flavonoid content (TFC), and chemical composition by HPLC-DAD and HPLC-MS, as well as acute toxicity by OECD Guideline 423. Gastric lesions were induced by intragastric indomethacin treatment in male ICR mice. As the positive control, omeprazole was administered, and three doses of EEPCh were evaluated (50, 150 and 300 mg/kg). Gastric mucosal injury, histological changes and mucosal content were evaluated by means of H&E and PAS staining. For homogenized gastric tissues, the following were evaluated: TBARS, MPO, and PGE2 levels; SOD and GPx antioxidant enzymatic activity; and the concentrations of the proinflammatory cytokines, TNF-α, IL-1β and IL-6. EEPCh had a significant SA50 of 41.55 µg/mL. The TPC of EEPCh was 860 mg GAE/g, and its TFC was 49.58 mg QE/g. Different phenolic compounds were identified in the extract and were not toxic. The EEPCh doses decreased mucosal damage and histological injuries, maintained the mucosal content and reduced the TBARS, MPO and concentrations of proinflammatory cytokines in gastric ulcer tissues. The 150 and 300 mg/kg doses increased the SOD activity and maintained the PGE2 content. Only the 300 mg/kg dose increased the GPx activity. The results of this study suggest that EEPCh displays gastroprotective effects by means of its antioxidant activity and anti-inflammatory effects and promotes ulcer protection through the maintenance of mucosal content and PGE2 levels.

Prevalence and genotyping of Helicobacter pylori in endoscopic biopsy samples from a Chinese population

AbstractBackground:Helicobacter pyloriinhabit the gastric mucosa of humans and are associated with several gastrointestinal diseases which include gastric cancer, peptic ulcer, chronic gastritis and gastric mucosa-associated lymphoid tissue lymphoma.Helicobacter pyloriexhibit a high degree of genetic variability and are associated with its epidemiological, pathological characteristics and dynamics of transmission. The objective of the study was to determine the prevalence and genetic heterogeneity ofH. pyloriisolated from endoscopic biopsy samples from a Chinese population.Methods:Gastric biopsy samples from 86 patients (males, 55; females, 35) who presented to the endoscopic section for various gastrointestinal abnormalities were collected. The samples were subjected to a real-time polymerase chain reaction (PCR) and microbial culture for the isolation ofH. pylori. Further, the isolates were subjected to randomly amplified polymorphic DNA (RAPD) and restriction fragment length polymorphism (RFLP) analysis.Results:Of the 86 gastric biopsy samples, 61 (70.9%) samples were positive for rapid urease test and 37 (43%) samples (28 from male and nine from female) grewH. pylori. Among the biopsy samples subjected to real-time PCR, 39 (45.3%) samples were found to be positive forH. pylori.The RAPD analysis yielded 15 different patterns (four to 17 different sized fragments per strain). The phylogenetic analysis of RAPD yielded 22 clusters at a similarity level ranging from 63% to 100%. RFLP analysis yielded nine different patterns (two to six different sized fragments per strain). Two major restriction patterns were identified, of which 14 (37.8%) strains forms the most common pattern (genotype I) followed by five (13.5%, genotype II) strains with an intra-strain similarity of 100%.Conclusions:The overall prevalence ofH. pyloriwas 45.3%. Despite reports on the declining trend in the prevalence ofH. pyloriinfections, our prevalence rate was still higher than those reported from other developed countries. However, further studies involving a large sample size and covering more regions of China is highly warranted.

Gastroprotective effect and mode of action of methanol extract of Sphenodesme involucrata var. paniculata (C.B. Clarke) Munir (Lamiaceae) leaves on experimental gastric ulcer models

Sphenodesme involucrata var. paniculata (C. B. Clarke) Munir, endemic to South Asia, is used by tribal for alleviation from abdominal disorders, inflammation and body pain. However, the gastroprotective properties of this species have not yet been studied. The leaves of S. involucrata were extracted by Soxhlet extraction using different solvents successively and the extracts were analyzed for antioxidant and anti-Helicobacter pylori activities using different in vitro assays. The chemical composition of methanol extract of S. involucrata (MESi) was analysed by gas chromatography-mass spectrometry (GC–MS). The gastroprotective action of the MESi at the doses of 100, 200, and 400 mg/kg were evaluated in absolute ethanol, acidified ethanol (EtOH/HCl) and nonsteroidal anti-inflammatory drug (NSAID) induced rat experimental models. To elucidate the mode of antiulcerogenic action, the antisecretory parameters (gastric juice volume, pH, and total acidity) and the catalase (CAT) and superoxide dismutase (SOD) enzymes activity and malondialdehyde (MDA) level were evaluated in gastric ulcer tissue. Also the stomachs of the animals were subjected to histological assessment. MESi presented a high antioxidant activity in several oxidants in vitro systems (DPPH•, ABTS•+ and FRAP) and it demonstrated a good spectrum of inhibitory activity against H. pylori growth (MIC, 100 μg/mL). GC–MS analysis of MESi indicated the presence of twenty one compounds, among them phenol (21.84%), hexadecanoic acid (15.96%), (9E, 12E)-9, 12-octadecadienoyl chloride (11.15%) and palmitic acid-β-monoglyceride (8.80%) were found higher. MESi (100, 200 and 400 mg/kg, p.o.) produced significant reduction (p < 0.01) of lesion area in the ethanol, acidified ethanol and indomethacin-induced ulcer models. In the pylorus ligation induced ulcer model, the treatment with MESi significantly altered the gastric secretion by decreasing total gastric juice volume and gastric acidity as well as by increasing the gastric pH. MESi pre-treatment significantly (p < 0.05) restored the depleted activity of SOD, CAT enzymes and reduced MDA levels in the gastric tissue as well as the histological analysis of the stomachs of the animals showed that the MESi also prevents local action of offensive factors. Collectively, the present study results suggest that the methanol extract of S. involucrata leaves demonstrates gastroprotective action, supporting the folkloric usage of the plant to treat gastro-intestinal disturbances.

Fucosyltransferase-4 and Oligosaccharide Lewis Y Antigen as potentially Correlative Biomarkers of Helicobacter pylori CagA Associated Gastric Cancer.

H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n=128, 176), gastric ulcer (n=174, 213), and gastric cancer (n=323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97%) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p-EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P<0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R-0.62, -0.74), FUT4 (R-0.81, -0.76) and LeY (R-0.82, -0.70) in gastric tissues and serum (P<0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.

Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers.

Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE) was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20), 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05) smaller ulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. This study showed that the gastroprotective effect of MECE is achieved through inhibition of gastric juice secretion and ulcer lesion development, stimulation of mucus secretion, elevation of gastric pH, reduction of reactive oxygen species production, inhibition of apoptosis in the gastric mucosa, and modulation of inflammatory cytokines.

Protective effect of Cupressus sempervirens extract against indomethacin-induced gastric ulcer in rats.

Cupressus sempervirens (C. sempervirens) belongs to the family Cupressaceae. It is widspread in Northern Africa, Greece, Turkey, North America, Cyprus and Syria. Cupressuflavone is the major ingredient of the plant leave extract. The aim of the present study was to evaluate the antiulcerogenic activity of the extract of C. sempervirens leaves in gastric ulcer tissues induced by indomethacin. The results of the present study revealed that indomethacin significantly decreased glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) levels, while it increased significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyl (PC) levels in gastric tissue. Furthermore, indomethacin decreased p53 expression, while it increased bcl-2 expression in gastric tissue. Pretreatment with 5%, 10% & 20% of the LD50 of C. sempervirens and cupressuflavone of indomethacin-treated rats restored all the above parameters to approach normal values. C. sempervirens at the highest dose was more effective than the two lower doses. C. sempervirens proved more potent than cupressuflavone. In conclusion, C. sempervirens exerted antiulcerogenic activity and the effect was dose-dependent and related to the cupressuflavone ingredient of the plant leave extract.

Efficacy of standard triple therapy versus bismuth-based quadruple therapy for eradication of Helicobacter Pylori infection

Helicobacter Pylori is the main cause of gastric ulcer, adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Up to now, different regimens have been used for Helicobacter pylori (H.pylori) eradication to find the most potent and cost-effective regimen with less side effects. The aim of this study was to investigate the efficacy of standard triple therapy versus quadruple therapy for eradication of H. pylori. In a randomized clinical trial, 110 patients with H.pylori infection were randomly assigned into two groups of triple or quadruple therapy. The first group received standard triple therapy regimen with clarithromycin, amoxicillin and omeprazole and the second group received bismuth-based quadruple therapy regimen. At the end of study, stool antigen assay was used to confirm H.pylori eradication. The mean age of patients was 41.58 ± 11.98 years and 50.9% of them were male. Side effects of treatment with triple therapy were observed in 49.1% of cases. H.pylori eradication rate with triple and quadruple therapy regimen was 54.5% and 72.7% respectively but the difference was not statistically significant.Results showed that the efficacy of triple therapy was comparable to that of bismuth-based quadruple therapy regimen. However, due to the better compliance of triple therapy regimen, it is recommended for the first line treatment. Quadruple therapy could be used as an alternative treatment when triple therapy fails.

The effect of Dioscorea opposita polysaccharide in the treatment of rats with gastric ulcer and its influence on the level of EGF in gastric ulcer tissues

Objective To observe the therapeutic effect of Dioscorea opposita polysaccharide on gastric ulcer in rats,and to investigate the effects of Dioscorea opposita polysaccharide on level of epidermal growth factor （ EGF） in stomach tissues .Methods 50 rats were randomly divided into five groups [ A group （ normal control group ） , B group（model group）,C group（Dioscorea opposita polysaccharide group ）,D group（teprenone group）].The healing condition of gastric ulcer and EGF level were observed and compared .Results （1）The ulcer index of C group was obviously reduced compared with B group （P〈0.01）.（2）Between C group and A group,the significant difference existed in the level of EGF（P〈0.05）,while the difference was not statistically significant between C group and D group（P〉0.05）.Conclusion Dioscorea opposita polysaccharide has protective effects for gastric mucosa .The mechanism of protection may be related to promote synthesis of EGF . Key words: Ipomoea batatas ; Polysaccharides ; Stomach ulcer; Epidermal growth factor; Rats

Upregulation of MicroRNA 181c Expression in Gastric Cancer Tissues and Plasma

To test the microRNA-181c (miR-181c) expression in tissues and plasma of gastric cancer (GC) cases, analyze any correlations, and explore the possibility of miR-181c as a potential molecular marker for GC diagnosis. Relative miR-181c expression levels in cancers and plasma from 30 GC patients was tested using reverse transcription?real-time fluorescent quantitation PCR and compared to that in samples from 30 gastric ulcer and 30 chronic gastritis patients. The miR-181c expression level in the GC tissues was significantly higher than that in the gastric ulcer and chronic gastritis tissues (P = 0.000), as was the miR-181c expression level in the GC plasma (P = 0.000). We determined that miR-181c expression in GC plasma was positively correlated to its expression in the GC tissues (P = 0.000). The expression of miR-181c is upregulated in GC tissues and plasma, and the miR-181c expression level in GC plasma is positively correlated to that in the corresponding cancer tissues. Plasma miR-181c is possibly a new serological marker for GC diagnosis.

Correlation of hK6 expression with tumor recurrence and prognosis in advanced gastric cancer

BackgroundHuman kallikrein gene 6 (KLK6) is a member of the human kallikrein gene family (Kallikreins, KLKs). Human kallikrein-related peptidase 6 (hK6) is a trypsin-like serine protease encoded by the KLK6, has been reported to be highly expressed in several cancers including gastric cancer. In this study, we investigated the the correlation of hK6 expression with clinicopathological characteristics, tumor recurrence and prognosis in advanced gastric carcinoma after curative resection.MethodsWe retrospectively analyzed the clinical data of 129 cases advanced gastric cancer after curative gastrectomy. The expression of hK6 in advanced gastric cancer tissues compared to adjacent noncancerous tissues were examined, and the relationship between hK6 expression and clinicopathological characteristics was evaluated. In additional, these patients were followed up to investigate the relationship between hK6 expression and the survival time.ResultsThe positive rate of hK6 expression was significantly higher in advanced gastric cancer tissue, than that in adjacent noncancerous and gastric ulcer tissues (36.5%, 33.3%, respectively, P < 0.001). There was a close relationship between hK6 expression and TNM stage (P = 0.005), vascular invasion (P = 0.037) and perineural invasion (P = 0.035). Furthermore, patients with hK6 positive showed significantly higher recurrence and poorer prognosis than those with hK6 negative. Multivariate analysis showed that hK6 expression was a significant independent factor for tumor recurrence and overall survival.ConclusionhK6 is overexpressed in advanced gastric cancer tissues. Its clinical utility may be used as an unfavorable indicator in predicting tumor recurrence and prognosis for advanced gastric cancer after operation. This study also suggests that hK6 might be a potential therapeutic target for gastric cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8558403578787206

Expression and biological significance of human kallikrein 6 in gastric cancer tissues

Aim of the studyThis study aims to investigate the expression of human kallikrein 6 (hK6) in gastric cancer, gastric ulcer and normal gastric mucosa tissues and its biological significance.Material and methodsThe expression of hK6 in 15 normal gastric mucosa (NGM) tissues, 15 gastric ulcer (GU) tissues and 55 gastric carcinoma (GC) tissues was respectively detected by immunohistochemistry. The correlations between the expression of hK6 and the clinical pathological parameters of gastric cancer were also analyzed.ResultsHuman kallikrein 6 was mainly expressed in cytoplasm. The positive rate of hK6 was significantly higher in gastric cancer tissues than that in gastric ulcer or normal gastric mucosa tissues (70.9%, 40% and 20%, respectively, p < 0.01). With the increase of the invasion depth of gastric cancer cells, aggravation of TNM stage and development of lymph node metastasis, the expression of hK6 increased significantly (p < 0.05 and p < 0.01). There was no obvious correlation between the expression of hK6 and sex, age, tumor diameter, histodifferentiation degree or primary pathological location of gastric cancer (p > 0.05).ConclusionsThe overexpression of hK6 is related to the depth of invasion, lymph node metastasis and clinical stage of gastric carcinoma, which suggests that hK6 may act as a new marker of gastric cancer biological behavior.

Antiulcer Effect of Bark Extract of Tabebuia avellanedae: Activation of Cell Proliferation in Gastric Mucosa During the Healing Process

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.

P056 Amelioration of indomethacin-induced gastric injury by hydroxy-omeprazole

Introduction Stomach ulcer is an illness that affects a considerable number of people worldwide. We investigated the effect of hydroxy-omeprazole on indomethacin-induced gastric injury in mice. Methods Gastric injury was induced by oral injection of indomethacin. Hydroxy-omeprazole (3 mg/kg) was given to B6 mice once daily for up to 7 days; the first dose was given 6 h after indomethacin administration. The mice were sacrificed on the fourth and seventh days, 4 h after administering the last dose of the samples. Results Total immunoglobulin G and A levels were increased in sera and fecal extracts of mice administrated with indomethacin and hydroxy-omeprazole compared with mice administrated with indomethacin alone.In histopathological analysis, immune cell infiltration on indomethacin-induced ulcerated gastric tissues was prevented by administration of hydroxy-omeprazole.In addition, hydroxy-omeprazole suppressed gene expression of inflammatory cytokines including COX, IL-1band IL-6 in indomethacin-induced ulcerated gastric tissues. Conclusion These results suggest that hydroxy-omeprazole ameliorated gastric injury by inhibiting expression of inflammatory cytokines.

Expressions of MMPs and TIMP-1 in Gastric Ulcers May DifferentiateH. pylori-Infected from NSAID-Related Ulcers

Background. Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. Aims. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. Methods. The 126 gastric ulcer patients (H. pylori infected n = 46; NSAID related n = 30; combined with two factors n = 50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Results. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (P < 0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (P < 0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1 than H. pylori-infected gastric ulcers (P < 0.05). Conclusions. H. pylori-infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID-related ulcers. In patients with the two combined factors, ulcer location and MMP-7 and MMP-9 intensities are similar to NSAID use.

Down-regulation of TM4SF is associated with the metastatic potential of gastric carcinoma TM4SF members in gastric carcinoma

BackgroundThe aim of this study was to clarify the clinical significance of TM4SF members CD9, CD63 and CD82 in human gastric carcinoma.MethodsBy employing RT-PCR and immunohistochemistry, we studied the expression of CD9, CD63 and CD82 in 49 paired tissue specimens of normal gastric mucosa and carcinoma. All tissues were obtained from patients who underwent curative surgery.ResultsAll normal gastric epithelium and gastric ulcer tissues strongly expressed transcripts and proteins of CD9, CD63 and CD82 as compared with corresponding controls. We found a significant correlation between CD63 mRNA level and different pM statuses (P = 0.036). Carcinomas in M0 stage revealed a stronger expression of CD63 than carcinomas in M1 stage. Expression of CD9 protein was found significantly stronger in pN0, pM0 than in advanced pN stages (P = 0.03), pM1 (P = 0.013), respectively. We found the relationship between CD63 expression, gender (p = 0.09) and nodal status (p = 0.028), respectively. Additionally, advanced and metastasized tumor tissues revealed significantly down-regulated CD82 protein expression (p = 0.033 and p = 0, respectively), which correlated with the tumor pTNM stage (p = 0.001).ConclusionThe reduction of CD9, CD63 and CD82 expression are indicators for the metastatic potential of gastric carcinoma cells. Unlike their expression in other tumor types, the constitutive expression of CD63 may indicate that this factor does play a direct role in human gastric carcinogenesis.

Weak up-regulation of serum response factor in gastric ulcers in patients with co-morbidities is associated with increased risk of recurrent bleeding

BackgroundSerum response factor (SRF) is crucial for gastric ulcer healing process. The study determined if gastric ulcer tissues up-regulate SRF and if such up-regulation correlated with co-morbidities and the risk of recurrent bleeding.MethodsUlcer and non-ulcer tissues were obtained from 142 patients with active gastric ulcers for SRF expression assessed by immunohistochemistry. Based on the degree of SRF expression between these two tissue types, SRF up-regulation was classified as strong, intermediate, and weak patterns. The patients were followed-up to determine if SRF up-regulation correlated to recurrent bleeding.ResultsGastric ulcer tissues had higher SRF expression than non-ulcer tissues (p < 0.05). Patients with strong SRF up-regulation had lower rates of stigmata of recent hemorrhage (SRH) on the ulcer base than the others (p < 0.05). Multivariate logistic regression confirmed that co-morbidities and weak SRF up-regulation were two independent factors of recurrent gastric ulcer bleeding (p < 0.05). Combining both factors, there was an 8.29-fold (95% CI, 1.31~52.62; p = 0.03) higher risk of recurrent gastric ulcer bleeding.ConclusionsSRF expression is higher in gastric ulcer tissues than in non-ulcer tissues. Weak SRF up-regulation, combined with the presence of co-morbidities, increase the risk of the recurrent gastric ulcer bleeding.