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Atrophic antral gastritis was found to show an absolute decrease in gland volume with higher expression of the gastric transcription factor Shh, i.e. absolute atrophy and that concurrent with the replacement of the specialized gastric epithelium by the intestinal MUC2-producing one, i.e. metaplastic atrophy. In atrophic multifocal gastritis along absolute and metaplastic atrophy, there are foci of the proliferative metaplastic epithelium, i.e. hyperproliferative metaplastic atrophy that is prevalent in atrophic pangastritis. The molecular characteristics of hyperproliferative metaplastic atrophy are varying: in some foci of metaplasia, the high proliferative activity of the epithelium is concomitant with the hyperexpression of P53, a marker of DNA damage, the lower expression of the intestinal transcription factor CDX-2, and the low level of Cpp32, an indicator of apoptosis. Whether such structures can be identified at the launching pad for tumor growth in atrophic pangastritis is discussed.

Objective: To observe clinical efficacy of Huazhuo Jiedu Recipe (HJR) on chronic atrophic gastritic precancerosis (CAGP), and its effect on contents of lactic acid, total acid, free acid, and nitrite in the gastric juice, as well as tumor markers in gastric juice and blood., Methods: Two hundred and twenty-nine patients with CAGP were randomly assigned to two groups, the 119 patients in the treated group orally took HJR and the 110 patients in the control group orally took Weifuchun Tablet. The therapeutic course for all was three months, two courses in total. The therapeutic efficacy, changes of gastric acid contents before and after treatment were observed, and the tumor markers in the gastric juice and blood were detected using electrochemical luminescence immunoassay., Results: The pathological effective rate was 83.2% (99/119) in the treated group and 60.9% (67/110) in the control group, showing significant difference between the two groups (P <0.05). The total acids and free acids in the gastric juice were significantly improved, contents of lactic acid and nitrite were significantly lowered in the two groups. Both contents of carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen72-4 (CA72-4), and carbohydrate antigen125 (CA125) in the gastric juice and serum were significantly lowered after treatment in the treated group (P<0.05). Compared with the normal control group, the therapeutic effect was more obvious in the treated group (P<0.05)., Conclusions: HJR could stimulate the gastric membranous secretion, enhance contents of total acids and free acids. It could prevent the further progress of CAGP by decreasing contents of lactic acid and nitrite in the gastric juice, and lowering contents of CEA, CA19-9, CA72-4, and CA125 in the gastric juice and serum.

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of gastric cancer. Our study aimed to investigate the correlation of RUNX3 methylation, expression and the risk of advanced gastric lesions, based on a high-risk population in Linqu County, Shandong Province, China. Methylation status of RUNX3 was determined by methylation-specific polymerase chain reaction, and expression was detected by immunohistochemical analysis in 1113 subjects with different gastric lesions. Results showed that the frequency of RUNX3 methylation was significantly increased in subjects with advanced gastric lesions. The odds ratios (ORs) were 2.09 [95% confidence interval (CI): 1.49-2.94] for intestinal metaplasia (IM), 3.22 (95% CI: 2.33-4.47) for indefinite dysplasia (Ind DYS) and 2.03 (95% CI: 1.23-3.37) for dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. Stratified analysis indicated that the frequency of RUNX3 methylation was higher in subjects with Helicobacter pylori infection (OR, 2.74; 95% CI: 2.00-3.76). Moreover, there was a reverse grade-response relationship between the level of RUNX3 expression and risk of gastric lesions. Among subjects with mild, moderate or heavy expression, the risk was decreased by 41, 59 or 80% for IM (P(trend) < 0.0001); 40, 64 or 74% for Ind DYS (P(trend) < 0.0001) and 28, 59 or 51% for DYS (P(trend) = 0.045), respectively. Furthermore, RUNX3 expression was negatively associated with increased frequency of RUNX3 methylation (OR, 0.76; 95% CI: 0.59-0.98). These findings suggest that RUNX3 may play important roles in the development of advanced gastric lesions.

Systemic leucocyte-induced oxidative stress in prolonged occupational exposure to dust modifies oxidative metabolism of neutrophils and RBC, causes inflammatory and destructive, autoimmune processes in gastric lining and possible subsequent occupational gastropathies. To verify gastropathies caused by technogenic dust aerosols, search of preclinical biologic markers of gastric lining damage is essential. The article presents main steps in occupational gastropathies formation, trigger mechanisms, leading pathogenetic factors of gastric lining damage and of atrophic fundus gastritis. Using the mentioned complex of biomarkers in gastric lining state monitoring among workers at periodic and thorough medical examination is main item in forecasting individual risk of occupational gastropathies and in possible approach to their prevention and treatment.

Background: Ghrelin is a hormone produced by neuroendocrine cells of gastric mucosa. Its concentration changes in cases of Helicobacter pylori (H. pylori) infection of stomach, but the relation between the expression of plasma and mucosal ghrelin content and H. pylori infection is not completely defined. This study was designed to determine the changes in plasma and gastric mucosa ghrelin concentrations in diseases of gastric mucosa depending upon the H. pylori infection., Material/methods: The following groups were included; Group 1. patients with gastric cancer and concomitant H. pylori infection (N=25); Group 2. patients with antral gastritis with H. pylori infection and concomitant duodenal peptic ulcer (N=18); Group 3. patients with atrophic gastritis of both the fundus and the body of the stomach without H. pylori infection (N=10); Group 4. control group consisting of patients without morphological and histological lesions of gastric mucosa and without H. pylori infection (n=25). Endoscopic biopsies of gastric mucosa of fundus, body and pyloric region were obtained in all tested groups. In patients suffering from gastric cancer biopsies of tumor were also taken. The ghrelin concentrations were measured by specific RIA. Biopsy specimens were examined to assess ghrelin mRNA expression in intact gastric mucosa and gastric cancer., Results: The study showed significant influence of H. pylori infection on ghrelin plasma concentrations. The highest ghrelin concentrations were found in patients of the group 2 (average 503 pg/mL (95% CI: 285-886). Ghrelin concentrations were found to fall to the lowest values in the group 3 (average 144 pg/mL (95% CI: 93-222). In the group 1, the ghrelin concentration averaged 203 pg/mL (95% CI: 161-257), while in the group 4 (control group) - 255 pg/mL; 95% (CI: 160-406). The study proved that gastric cancer does not exert any ghrelin-production activity, as confirmed by RT-PCR examination of biopsy specimens of the cancer., Conclusions: This study shows that the presence of H. pylori in the stomach with peptic ulcer increases plasma ghrelin levels, whereas in gastric cancer and atrophic gastritis it is accompanied by a marked decrease in plasma and cancer tissue levels of ghrelin.

Aim: To investigate let-7a expression and analyze the correlation between let-7a and progression of gastric mucosa cancerization., Methods: The tissue microarray was constructed previously in 52 cases of human gastric carcinoma, 17 cases of chronic atrophic gastritis (atypical hyperplasia) and 11 cases of normal gastric tissue, and tissue microarrays combined with in situ hybridization were used to detect the expression of let-7a., Results: The positive rates of let-7a in normal gastric tissue, chronic atrophic gastritis and gastric carcinoma were 90.9%, 88.2% and 86.5%, respectively, without significant differences among the groups (P > 0.05). However, an intense signal of let-7a was observed in gastric epithelial cells, whereas a less intense signal was found in gastric atypical hyperplasia epithelial cells and a weak signal in gastric carcinoma epithelial cells. The expression of let-7a decreased along with the progression of gastric mucosa cancerization (P < 0.05). In the group of gastric carcinoma, the expression of let-7a was even significantly lower in gastric carcinomas with lymph node metastasis than in those without metastasis (P < 0.05)., Conclusion: Gastric carcinoma has relatively lower expression of let-7a. Reduced let-7a may be a fundamental factor in the formation and lymph node metastasis of gastric carcinoma.

The purpose of the investigation was to study a correlation between gastric secretory function and the gastric juice levels of nitric oxide (NO) in patients with upper digestive tract diseases. One hundred and seventy-four patients with upper digestive tract diseases were examined to solve the set tasks. Analysis of the correlation between gastric juice NO levels and gastric secretion volume in patients with gastroduodenal diseases indicated that no correlation was found in the level of end products of gastric juice NO metabolism and total acidity as an aggression factor. At the same time, there was a positive correlation between the gastric juice of NO and the volume of basal and stimulated gastric secretion. Since during gastric juice secretion, blood supply of the gastric mucosal is increased due its dilated microvessels, NO is most likely to cause dilatation and accordingly a gastric secretion stimulant. Therefore, by taking into account that provision of sufficient gastric mucosal blood supply is one of the protective means in gastroduodenal diseases, it may be suggested that in this case NO performs a positive role, by participating in gastric protection.

Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental biology and cancer biology. The association between Shh and cancer development in general is well established but the functional role of Shh in the development and progression of gastric cancer specifically is largely unknown. Bone marrow-derived stem cells, specifically mesenchymal stem cells (MSCs) infiltrate and engraft into the gastric mucosa in response to the chronic inflammatory environment of Helicobacter infection. In this review, MSC infiltration and changes in the cytokine and cellular profiles of later-stage chronic environments will be tied into their interactions with the Shh pathway. We will discuss how these changes shape tumorigenesis and tumor progression in the gastric mucosa. The current review focuses on the Shh signaling pathway and its role in the development of gastric cancer, specifically in response to Helicobacter pylori infection. We follow with an in-depth discussion of the regulation of the Hedgehog pathway during acute and chronic gastric inflammation with a focus on signaling within the MSC compartment.

Objectives: To evaluate the expression of Ki-67 protein in stomach mucosa in H. pylori-associated chronic atrophic gastritis according to the stage of atrophy., Materials and Methods: The immunohistochemical and histological study of gastric mucosal biopsies from dyspeptic patients was performed. The new international system of gastric musocal atrophy staging (OLGA) was used., Results: The rates of cellular proliferation increase along the rising of the stage of stomach mucosal atrophy in Hpylori-associated chronic atrophic gastritis., Conclusions: In H. pylori-associated chronic atrophic gastritis, the acceleration of the cellular renewal was revealed, proportional to a stage of gastric mucosal atrophy that implies the increase of risk of development of precancerous changes.

Objective: To investigate the role of transforming growth factor beta1 (TGFbeta1) in the development of Helicobacter pylori (H.pylori)-associated non-metaplastic atrophic gastritis., Methods: The expressions of TGFbeta1, CD68 and smooth muscle actin(SMA) were detected immunohistochemically in 10 patients with mild non-atrophic gastritis, 30 patients with mild non-metaplastic atrophic gastritis, and 32 patients with severe non-metaplastic atrophic gastritis having H.pylori infecion. Meanwhile, three cases of mild non-atrophic gastritis and 4 cases of severe non-metaplastic atrophic gastritis were observed with electron microscope., Results: The count of TGFbeta1 positive cells per high-power field (HPF) in severe non-metaplastic atrophic gastritis group (53 +/- 22) was significantly higher than that in mild non-atrophic gastritis group(22+/-9/HPF) and mild non-atrophic gastritis group(0-3/HPF, P<0.01). The count of CD68 positive cells in severe non-metaplastic atrophic gastritis group (23+/-7/HPF) was significantly higher than that in mild non-atrophic gastritis group (13+/-6/HPF) and mild non-atrophic gastritis group(0-3/HPF, P<0.01). Correlation analysis showed that the expressions of TGFbeta1 and CD68 had a moderate correlation in each group (r=0.634, P<0.01; r=0.699, P<0.01). Compared with mild non-atrophic gastritis, SMA-positive myofibroblasts and smooth muscle cells in the lamina propria increased in mild and severe non-metaplastic atrophic gastritis. Ultrastructurally, the proliferation of fibroblasts in gastric lamina propria was observed in mild non-atrophic gastritis, while the proliferation of fibroblasts and presence of myofibroblasts could be observed in mild non-metaplastic atrophic gastritis, and there was a parallel phenomenon between myofibroblasts and fibroblasts, as well as smooth muscle cells., Conclusion: Our findings indicate that TGFbeta1 expression increases with severity of H.pylori- associated non-metaplastic atrophic gastritis, suggesting that TGFbeta1 might play an important role in the development of non-metaplastic atrophic gastritis.

Aim: Sodium/iodide symporter (NIS) is a transmembrane protein that mediates the transport of I(-). The aim was to evaluate the immunohistochemical expression of the human homolog of NIS (hNIS) in a wide spectrum of gastric lesions., Materials and Methods: Seventy-seven samples were stained immunohistochemically with a monoclonal antibody for hNIS, including 14 with normal gastric mucosa, 14 with chronic atrophic gastritis with foveolar hyperplasia, 15 with chronic atrophic gastritis with intestinal metaplasia, 6 with chronic atrophic gastritis with atypical regenerative hyperplasia, 8 with chronic atrophic gastritis with dysplasia, 15 with invasive adenocarcinoma, 3 with well-differentiated neuroendocrine tumor, and 2 with gastrointestinal stromal tumors (GISTs)., Results: hNIS stained the basolateral cytoplasmic portion of foveolae in normal mucosa, in 13 cases of chronic atrophic gastritis with foveolar hyperplasia, and in only 1 case of regenerative atypical hyperplasia. hNIS was consistently absent in intestinal metaplasia, in dysplastic glands, and in the cells constituting invasive carcinoma, well-differentiated neuroendocrine tumors, and GIST., Conclusion: It seems that lack of hNIS can be useful in distinguishing foveolar hyperplasia from dysplastic glands.

Objective: To explain the accumulation of (18)F-2-deoxy-2-fluoro-glucose ((18)FDG) on positron emission tomography (PET) in the stomach and differences in its pattern, we focus on the accumulation pattern in association with endoscopic findings of the gastric mucosa and Helicobacter pylori (Hp) infection., Methods: Of 599 cases undergoing (18)FDG-PET examinations, we retrospectively analyzed the pattern of (18)FDG accumulation in the stomach, findings of upper gastrointestinal endoscopy, and Hp infection. The pattern of (18)FDG accumulation was classified into three groups: localized accumulation only in the fornix (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group B, 49 patients), and no accumulation (Group C, 191 patients)., Results: Regarding the relation between Hp infection and (18)FDG accumulation, Hp infection was positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with significant differences (p < 0.001). Regarding the relation between (18)FDG accumulation and gastric mucosal inflammation, when Groups A and B were compared with Group C, nearly half of the cases in the former groups had papular redness with a significantly higher frequency of redness and erosion. Three cases found to have malignant tumor were limited to the former groups. One MALT lymphoma case was also found in the same group. Accumulation of (18)FDG largely corresponded to mucosal inflammation including superficial gastritis and erosive gastritis, and therefore the main cause of non-specific (18)FDG accumulation was considered to be inflammatory mucosa (mainly redness). The accumulation pattern was not associated with atrophic changes of the gastric mucosa or with Hp infection, but with mucosal inflammatory changes, including redness and erosion localized to the fornix., Conclusions: Accumulation of (18)FDG in the stomach suggests a high probability of the presence of inflammatory change in the gastric mucosa forming a background for the development of cancer or malignant lymphoma, and thus requires further endoscopic examinations.

Type A chronic atrophic gastritis (CAG) is increased in type 1 diabetic patients (DM1). To address this issue, we determined and analyzed the number of peripheral blood regulatory T cells (Tregs) in 15 DM1-CAG patients, 15 DM1 patients without associated autoantibodies (DM1) and 15 healthy controls by flow cytometry and compared gastric Tregs expression (CD4+Foxp3+/CD4+) in DM1-CAG patients with that observed in 10 control Helicobacter pylori CAG-infected biopsies. The percentage of peripheral Tregs was higher in DM1-CAG patients compared to DM1 and controls (CD4+Foxp3+: 7.67 +/- 1.91% vs. 5.38 +/- 1.57% and 5.65 +/- 1.76%, P < 0.001, respectively), with no differences between DM1 and controls. Gastric mucosal Tregs were higher in H. pylori CAG than in DM1-CAG patients (31.31 +/- 5.52% vs. 7.68 +/- 3.70%; P < 0.001). Data suggest that Tregs are stimulated in patients with more than one autoimmune disease (DM1 + CAG) in an ineffectual attempt to control autoimmune response and that the number of Tregs in gastric mucosa implicated in the chronification of gastritis differs according to the etiology.

Background and Objective: Human pepsinogen C (PGC) is an aspartic protease synthesized in gastric mucosa. PGC gene insertion/deletion polymorphism, which is located between exon 7 and 8, has been found to associate with gastric cancer (GC) susceptibility. This study was to investigate the relationship between PGC polymorphism with protein expression of PGC in gastric mucosa and serum., Methods: PGC insertion/deletion polymorphism was evaluated by PCR, followed by direct DNA sequencing in 493 cases of GC, atrophic gastritis (AG), gastric erosion ulcer (GEU) and superficial gastritis (SG). PGC protein expression in gastric mucosa was measured by immunohistochemistry. The serum PGC level was determined by enzyme-linked immunosorbent assay (ELISA)., Results: In accordance with the following order SG-->GEU-->GA-->GC, the frequency of PGC homozygous allele 1 was gradually increased, which was higher in GC than in SG (P=0.018); while the protein expression of PGC in gastric mucosa was gradually decreased (P<0.01), along with a gradual decrease in the strong positive rate of PGC (P<0.05) except for SG vs. GEU. The serum level of PGC was significantly lower in SG than in GU(P=0.000) and GC(P=0.000). The frequency of PGC homozygous allele 1 was negatively correlated to PGC protein expression in gastric mucosa (r=-0.1085, P=0.023). From homozygous allele 1 to heterozygous allele 1, and to other genotypes, the PGC positive rate was gradually increased in gastric mucosa, with significant differences between homozygous allele 1 and other genotypes (P=0.009); while the strong-positive rate of PGC was gradually decreased only in SG group (P=0.047)., Conclusion: PGC gene insertion/deletion polymorphism is negatively related to PGC protein expression in gastric mucosa, but is not related to the serum PGC level.

The gastrointestinal peptide hormone gastrin is responsible for initiating the release of gastric acid in the stomach in response to the presence of food and/or humoral factors such as gastrin releasing peptide. However, it has a role in the growth and maintenance of the gastric epithelium, and has been implicated in the formation and growth of gastric cancers. Hypergastrinemia resulting from atrophic gastritis and pernicious anemia leads to hyperplasia and carcinoid formation in rats, and contributes to tumor formation in humans. Additionally, gastrin has been suspected to play a role in the formation and growth of cancers of the colon, but recent studies have instead implicated gastrin processing intermediates, such as gastrin-17-Gly, acting upon a putative, non-cholecystokinin receptor. This review summarizes the production and chemical structures of gastrin and of the processing intermediate gastrin-17-Gly, as well as their activities in the gastrointestinal tract, particularly the promotion of colon cancers.

Sonic hedgehog (Shh) is an essential regulator of patterning processes throughout development, and CDX proteins act as the master regulators for intestinal development and differentiation. Shh and CDX2 seem to be interdependently linked with cellular differentiation through different signal cascades. We have recently shown that the loss of Shh and aberrant expression of CDX2 in Helicobacter pylori (H. pylori)-associated atrophic gastritis can be modified by H. pylori eradication prior to incomplete intestinal metaplasia. On the other hand, abnormal signaling of the hedgehog pathway has been reported in gastric cancer, especially diffuse-type cancer and advanced gastric cancer, and Shh acts as a proliferation factor in both the normal mucosa and malignant lesions. CDX2 expressed in the early stage of gastric carcinogenesis is associated with the intestinal phenotypic region and thus with a better outcome. However, it remains unclear how Shh and CDX2 are involved with intestinal transformation and further carcinogenesis.

Background: The Updated Sydney System (USS) is used to evaluate chronic gastritis and chronic atrophic gastritis (CAG) due to H. pylori infection. Here, we investigated USS scores and gastric juice pH levels in H. pylori infection-positive or -eradicated patients with remnant stomach after surgery., Methods: Gastric juice pH levels were measured using pH test-tape in 197 patients (112 H. pylori-positive and 85 H. pylori-negative after eradication) who had undergone distal gastrectomy and conventional H. pylori eradication therapy., Results: In H. pylori infection-positive remnant stomach cases, gastric juice pH showed a reverse correlation with pepsinogen I/II ratio, and H. pylori infection-negative patients following eradication showed associations with the degree of atrophy and intestinal metaplasia at both the anastomosis and in the corpus. Further, pH levels in these patients were normalized time depending after the eradication in the remnant stomach., Conclusions: Eradication therapy for the remnant stomach contributes to the possible improvement of stomach conditions by controlling the pH level of gastric juice. This effect will be protective against the risk of secondary stomach carcinogenesis in the remnant stomach.

Helicobacter pylori persistently colonize the human stomach and have been linked to atrophic gastritis and gastric carcinoma. Although it is well known that H. pylori infection can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood. Here we show that VacA permeabilizes the apical membrane of gastric parietal cells and induces hypochlorhydria. The functional consequences of VacA infection on parietal cell physiology were studied using freshly isolated rabbit gastric glands and cultured parietal cells. Secretory activity of parietal cells was judged by an aminopyrine uptake assay and confocal microscopic examination. VacA permeabilization induces an influx of extracellular calcium, followed by activation of calpain and subsequent proteolysis of ezrin at Met(469)-Thr(470), which results in the liberation of ezrin from the apical membrane of the parietal cells. VacA treatment inhibits acid secretion by preventing the recruitment of H,K-ATPase-containing tubulovesicles to the apical membrane of gastric parietal cells. Electron microscopic examination revealed that VacA treatment disrupts the radial arrangement of actin filaments in apical microvilli due to the loss of ezrin integrity in parietal cells. Significantly, expression of calpain-resistant ezrin restored the functional activity of parietal cells in the presence of VacA. Proteolysis of ezrin in VacA-infected parietal cells is a novel mechanism underlying H. pylori-induced inhibition of acid secretion. Our results indicate that VacA disrupts the apical membrane-cytoskeletal interactions in gastric parietal cells and thereby causes hypochlorhydria.

Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status., ((c) 2008 Wiley-Liss, Inc.)

Background and Aims: The metabolic profile and morphologic aspects of normal and pathologic human gastric mucosa were studied. The aim of the present research was the application of ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) to the human gastric tissue to get information on the molecular steps involved in gastric carcinogenesis and the identification of biochemical markers useful for the development of in vivo MRS methodologies to diagnose gastric pathologies in clinical situations., Methods: Twelve normal subjects, five with autoimmune atrophic gastritis, five with Helicobacter pylori infection, and five with adenocarcinoma were examined. Ten biopsies were taken during endoscopy from each patient. Specimens from carcinoma were also obtained during gastrectomy. Of the 10 biopsies, 4 were used for histologic evaluation, 4 were fixed in glutaraldehyde and processed for transmission and scanning electron microscopy, and 2 were immersed in liquid nitrogen and stored at -85 degrees C for monodimensional and bidimensional ex vivo HR-MAS MRS analysis., Results: Ex vivo HR-MAS MRS identified glycine, alanine, free choline, and triglycerides as possible molecular markers related to the human gastric mucosa differentiation toward preneoplastic and neoplastic conditions. Ultrastructural studies of autoimmune atrophic gastritis and gastric adenocarcinoma revealed lipid accumulations intracellularly and extracellularly associated with a severe prenecrotic hypoxia and mitochondria degeneration., Conclusions: This is the first report of synergic applications of ex vivo HR-MAS MRS and electron microscopy in studying the human gastric mucosa differentiation. This research provides useful information about some molecular steps involved in gastric carcinogenesis. The biochemical data obtained on gastric pathologic tissue could represent the basis for clinical applications of in vivo MRS.

Objective: Claudin-2 is an important component of the tight junction (TJ) of epithelial cells, and its protein expression between many tumours is significantly different. It is unclear if Claudin-2 overexpression is a trigger or a consequence during carcinogenesis. The multistage tissues of gastric carcinogenesis provides us a valuable model for determining tumourigenicity., Methods: This paper investigated, for the first time, claudin-2 expression in the pathological paraffin tissues of sinus ventriculi from gastroscopic biopsy. To determine claudin-2 expression in gastric carcinogenesis by immunochemical ABC technique., Results: Altogether, 108 chronic superficial gastritis, 55 chronic atrophic gastritis, 109 intestinal-type metaplasia, 93 dysplasia and 52 gastric intestinal-type adenocarcinoma samples were analyzed. Results indicated that the percentage of claudin-2-positive cases was 0% for chronic superficial gastritis (0/108), 0% for chronic atrophic gastritis (0/55), 0% for intestinal-type metaplasia (0/109), 35.87% for dysplasia (33/92), and 73.47% for gastric intestinal-type adenocarcinoma (36/49) respectively, primarily in the cell membrane, and gradually increased in the multistage process of gastric carcinogenesis (P<0.001)., Conclusions: This suggests that claudin-2 protein overexpression may be closely correlated to gastric carcinogenesis.

Sonic hedgehog (Shh) is recognized as one of the main morphogens that regulates cell differentiation during early development of the stomach. In the adult stomach, Shh is expressed and secreted from the acid-producing parietal cells, where it is believed to play an essential role in gastric tissue homeostasis and normal differentiation of the epithelium. The present Themes article focuses on reviewing the literature and controversies surrounding the processing and secretion and the role of Shh in the adult stomach.

Objective: To study the relationship of TCM syndrome type of gastric mucosal epithelial growth factor (EGF), vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) in patients with chronic atrophic gastritis (CAG) for exploring the essence of TCM type and providing a theoretical basis of clinical treatment., Methods: TCM syndrome type of 200 patients with diagnosis of CAG confirmed by fibro-gastroscope and pathological examination were differentially classified, and the expressions of EGF, VEGF and PCNA in different types were determined using immunohistochemistry., Results: Patients were differentiated as Pi-Wei deficiency type (Type I ) in 72; Gan-Wei disharmony type (Type II ) in 43; Pi-deficiency with qi stagnation type (Type III) in 32; Wei-yin deficiency type (Type IV) in 24; Pi-Wei damp-heat type (Type V) in 14; and Wei-collateral stasis obstruction type (Type VI) in 5. The difference of PCNA expression level between Type II with Type I , III and IV was significant (P < 0.05). No significant difference in expression levels of EGF and VEGF was found among the 6 types (P > 0.05)., Conclusion: Type I and II were the dominant TCM syndrome types in CAG patients; the high expression of PCNA might be a diagnostic evidence for Gan-Wei disharmony syndrome.

Unlabelled: The infection of H. pylori causes inflammatory lesions in gastric mucosa--until atrophic gastritis, intestinal metaplasia, dysplasia (precancerous states) and finally to gastric cancer or lymphoma. The mechanism of mentioned disturbances is complicated, no doubt that nitric oxide plays here very important role. It is proved, that H. pylori causes essential oxygen metabolism disturbances by activation of inflammatory infiltration's cells to oxide reactive forms as nitric oxide formation. Nitric oxide as oxide radical could react with other free radicals and contribute to oxidative lesions of gastric mucosa and alterations of its structure. The aim of the study was try to answer the question: 1. Is this the relationship between NO metabolites concentrations in gastric juice and morphological state of gastric mucosa? 2. Does H. pylori eradication influence on NO metabolites concentrations in gastric juice? 3. Does H. pylori eradication influence on grade of inflammatory lesions in gastric mucosa?, Material and Methods: The study included 75 subjects between of 21 to 60 years, infected with H. pylori with diagnosed (according to the Sydney system) different stages of chronic gastritis progression. The type of inflammation, activity, the presence of atrophy, intestinal metaplasia and H. pylori infection were assessed. The study group was divided into 3 subgroups: group I--25 subjects with chronic active gastritis, group II--25 subjects with chronic atrophic gastritis without intestinal metaplasia, group III--25 subjects with chronic atrophic gastritis with intestinal metaplasia. Control group comprised 20 healthy subjects, without H. pylori infection. In each patient during gastroscopy 5 biopsy specimens for histopathologic examination and for urea test and 3 ml gastric juice were collected. The concentration of nitric oxide metabolites in gastric juice was determined with spectrophotometric method, based on Griess reaction. H. pylori infection was detected using fast urea test (CLO--test), confirmed by histopathological examination (stained Giemsa method) and non-invasive urea breath test (UBT-13C). In H. pylori--infected patients the above mentioned investigations were performed three times -before, in 8 weeks and in 12 months after antibacterial treatment's finish. In antibacterial therapy we use 7-days three-drugs therapy (omeprasole, amoksycillin and clarythromycin)., Results: The concentration of nitric oxide metabolites in gastric juice in healthy subjects was 6.81 +/- 2.23 micromol. In patients with chronic gastritis, H. pylori infected was significantly higher--in patients with chronic active gastritis was 9.29 +/- 2.19 micromol/l, in patients with chronic atrophic gastritis--10.25 +/- 2.31 micromol/l (p < 0.01), in patients with intestinal metaplasia--11.89 +/- 2.46 micromol/l (p < 0.01). 8 weeks after antibacterial treatment's finish the concentration of nitric oxide metabolites in gastric juice in each group decreased and were: in patients with chronic active gastritis was 8.18 +/- 1.63 micromol/l, in patients with chronic atrophic gastritis--10.02 +/- 2.28 micromol/l, in patients with intestinal metaplasia--10.83 +/- 2.32 micromol/l. The differences were not statistically significant. 12 months after antibacterial treatment's finish the concentration of nitric oxide metabolites in gastric juice in each group decreased and were: in patients with chronic active gastritis was 6.90 +/- 1.43 micromol/l, in patients with chronic atrophic gastritis--7.22 +/- 2.01 micromol/l, in patients with intestinal metaplasia--7.56 +/- 1.98 micromol/l. The differences were statistically significant--p < 0.05, p < 0.01. 8 weeks after antibacterial treatment's finish in each patient also the gastroscopy was performed and another biopsy specimen for histopathologic examination were collected. Only in group I in microscopic image the decreased of inflammation intensity was find (both in antrum and in corpus)--however the differences were not statistically significant. In the other groups the alterations in gastric mucosa do not improve significantly. The gastroscopy was performed again in 12 months after antibacterial treatment's finish. In group I the significant decrease or regression of inflammatory infiltration (in corpus and in antrum) was found. Also in group II the significant decrease of the grade of atrophy and similarly in III group the improvement of histopathological state were observed., Conclusions: 1. The increase of NO metabolites concentration demonstrates positive correlation with grade of inflammatory lesions in gastric mucosa. 2. The effective antibacterial therapy causes the decrease of NO metabolites concentration in gastric juice, especially in patients with chronic active gastritis. 3. Eradication influence on decrease of grade of lesions' progression in gastric mucosa just in 12 months after effective antibacterial therapy.

Background: Mitochondrial dysfunction is one of the most characteristic properties of the cancer cell. However, it is not known whether oxidative energy metabolism has already become altered in conditions of atrophic gastritis, a precancerous state of gastric disease. The purpose of our study was to comparatively characterize oxidative phosphorylation (OXPHOS) in the atrophic and nonatrophic gastric corpus mucosa., Methods: Mucosal biopsies were taken from 12 patients with corpus dominant atrophic gastritis and from 12 patients with nonatrophic mucosa (controls). One part of the tissue samples was permeabilized with saponin for analysis of the function of the respiratory chain using high-resolution respirometry, and another part was used for histopathological examination. The serum level of pepsinogen I (S-PGI) was determined with a specific enzyme immunoassay (EIA)., Results: Compared to the control group, the maximal capacity of OXPHOS in the atrophy group was almost twofold lower, the respiratory chain complex I-dependent respiration, normalized to complex II-dependent respiration, was reduced, and respiratory control by ADP in the presence of succinate was increased in the atrophic corpus mucosa. In the whole cohort of the patients studied, serum S-PGI level correlated positively with complex I-dependent respiration or complex I-dependent to complex II-dependent respiration ratio., Conclusions: Corpus dominant atrophic gastritis is characterized by decreased respiratory capacity and relative deficiency of the respiratory complex I of mitochondria in the mucosa, the latter defect probably limiting mitochondrial ATP production and energetic support of the secretory function of the zymogenic mucosal cells.

Background & Objective: The individual genetic susceptibility is important in the development of gastric cancer. The 1082G/A single nucleotide polymorphism (SNP) of interleukin-10 (IL-10), an immune suppressor gene, became a research hot spot in this field. This study was to analyze the distribution of IL-10-1082G/A SNP in a population from northern China, and explore its correlation to the susceptibility to gastric cancer., Methods: Blood samples were taken from 983 subjects in a high risk area of gastric cancer and 533 in a low risk area. The genotype of IL-10-1082G/A was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum level of anti-Helicobacter pylori (H. pylori) IgG was measured by enzyme-linked immunosorbent assay. Matched by sex and age, 111 specimens of normal gastric mucosa (NOR), 111 specimens of superficial gastritis (GS), 111 specimens of gastric erosion ulcer (GEU), 111 specimens of atrophic gastritis (AG) and 111 specimens of gastric cancer (GC) were selected to analyze the correlation of IL-10-1082G/A SNP to the susceptibility to gastric cancer., Results: The detection rates of IL-10-1082 AA, AG, GG genotypes in the 1516 subjects were 88.5%, 10.9% and 0.6%, respectively. There were no differences in region and sex distribution of IL-10-1082AG+GG genotype between the high and low risk areas of gastric cancer. The detection rate of IL-10-1082 AG+GG genotype was significantly higher in gastric cancer than in benign lesions and normal mucosa (19.8% vs. 9.7% and 6.3%, P=0.003). As compared with the subjects with IL-10-1082 AA genotype and without H.pylori infection, the subjects with AG+GG genotype and without H.pylori infection [odds ratio (OR)=3.3, 95% confidence interval (CI)=1.3-8.6], the subjects with AA genotype and H.pylori infection (OR=4.3, 95% CI=2.0-9.5) and the subjects with AG+GG genotype and H. pylori infection [OR=2.5, 95% CI=2.1-3.1] had higher susceptibility to gastric cancer, but there was no significant difference between every 2 of the 3 groups (P>0.05)., Conclusions: The susceptibility to gastric cancer is higher in the subjects with IL-10-1082 AG+GG genotype. There is no synergism between IL-10-1082G/A SNP and H.pylori infection.

Levels were assayed and compared of metabolic enzymes--thymidine and adenosine--in gastric mucosa tissues and blood serum from patients with gastric ulcer disease and gastric cancer (age--30-60 yrs). Enzymatic levels matched to the highest degree in cases of ulcer disease aggravated by chronic atrophic gastritis and precancerous alterations (dysplasia, metaplasia). Elevated concentrations of thymidine kinase and phosphorylase and adenosine desaminase were identified both at foci of ulceration (p > 0.001, p > 0.05, respectively) and in blood serum in all age brackets. Moreover, blood serum assay confirmed the view that changes in serum enzyme levels are suggestive of those in tissue enzymatic profile. Our data established a direct correlation between accumulated effect of level changes, on the one hand, and risk of neoplastic transformation of gastric mucosa in ulcer patients, on the other.

Sonic hedgehog (Shh) is not only essential to the development of the gastrointestinal tract, but is also necessary to maintain the characteristic acid-secreting phenotype of the adult stomach. Gastrin is the only hormone capable of stimulating gastric acid and is thus required to maintain functional parietal cells. We have shown previously that gastrin-null mice display gastric atrophy and metaplasia prior to progression to distal, intestinal-type gastric cancer. Because reduced levels of Shh peptide correlate with gastric atrophy, we examined whether gastrin regulates Shh expression in parietal cells. We show here that gastrin stimulates Shh gene expression and acid-dependent processing of the 45-kDa Shh precursor to the 19-kDa secreted peptide in primary parietal cell cultures. This cleavage was blocked by the proton pump inhibitor omeprazole and mediated by the acid-activated protease pepsin A. Pepsin A was also the protease responsible for processing Shh in tissue extracts from human stomach. By contrast, extracts prepared from neoplastic gastric mucosa had reduced levels of pepsin A and did not process Shh. Therefore processing of Shh in the normal stomach is hormonally regulated, acid-dependent, and mediated by the aspartic protease pepsin A. Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing.

Objective: To explore the relationship between TCM syndrome type and gastric mucosa cell proliferation related controlling gene protein in chronic atrophic gastritis (CAG)., Methods: Expressions of cell proliferation related controlling gene protein, including proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR) and c-myc, from gastric mucosa of CAG model rats with different syndrome types were measured by immunohistochemistry and the changes of them before and after TCM intervention were also analyzed by image analysis., Results: Protein expressions of PCNA, EGFR and c-myc in gastric mucosa of CAG model rats with different syndrome types (Pi-deficiency type, Gan-stagnation type and dampness-heat type) were different to some extent, and all of them reduced significantly after TCM intervention in the model rats of all syndrome types., Conclusion: Expressions of cell proliferation related controlling gene protein in gastric mucosa of CAG model rats of different syndrome types were different to some extent, which provides a certain experimental evidence for revealing the essence of TCM syndrome type of CAG and judging the prognosis of various types.

Background/aims: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach., Methods: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization., Results: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern., Conclusions: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepatology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion.

The subjects of the study were 104 patients with Helicobacter pylori (HP)-associated gastric pathology, including 30 patients with gastric ulcer (GU), 30 patients with chronic atrophic gastritis (CAG), 20 patients with CAG plus adenomatous polyps (AP), and 24 patients with gastric cancer (GC). All the subjects were examined dynamically; the comparison group consisted of 12 practically healthy people. The study revealed that GU, CAG, AP, and GC were consequent stages of gastric mucosal epithelial cell regeneration disorder which manifested by the fact that the apoptotic activity of these cells was lower than their proliferation rate, and this difference grew with time; the reflection of this was the growth of Ki-67 and Bcl-2 expression. HP eradication improved the process of cell regeneration. Epithelial cell apoptosis/proliferation ratio tended to normalize, which suggests that the processes of mucosal atrophy and metaplasia, and initial signs of gastric mucosal dysplasia in patients with HP-associated pathology may be reversible.

Background: The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia., Aim: To examine CDX2 expression in the non-cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia., Methods: Sixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining., Results: Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7-18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001)., Conclusions: Loss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.

Background: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion., Aim: To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease., Methods and Materials: Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO., Results: Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R(2) = 0.62)., Conclusion: Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

Background: Gastric-acid secretion is reduced in Helicobacter pylori-positive fundic atrophic gastritis, but it is restored by the eradication. However, changes in the distribution of acid-secreting mucosa after the eradication remain unknown. Congo red chromoendoscopy is capable of visualizing the acid-secreting fundic mucosa., Objective: To evaluate the effect of H pylori eradication on the distribution of acid-secreting mucosa in the fundus by using Congo red chromoendoscopy., Design: An assessment of the distribution of acid-secreting mucosa by the visualized images of Congo red chromoendoscopy and a histologic evaluation of biopsy specimens were performed before and 1 and 7 months after the eradication. The areas of the acid-secreting mucosa in the lesser and greater curvatures of the fundus were evaluated semiquantitatively., Patients: Thirty-seven patients positive for H pylori and with fundic atrophic gastritis., Results: The area of the acid-secreting mucosa increased in 27 cases (73%) by 1 month after eradication, and in 32 cases (86%) by 7 months. This expansion of the acid-secreting mucosa coincided with the improvement of inflammatory changes rather than with that of the mucosal atrophy and was more prominent on the greater curvature than on the lesser curvature., Conclusions: The acid-secreting mucosa in the fundus expanded in most cases with fundic atrophic gastritis after H pylori eradication, which could be responsible for the increase in acid secretion after the treatment. Regional differences in the recovery of local acid secretion may be associated with site-specific susceptibility to the development of gastric cancer after successful eradication.

The aim of the study was to investigate the relationship between gastritis and leptin and ghrelin in elderly patients. Patients older than 75 years undergoing an endoscopy were included. We reported data on nutritional status and Helicobacter pylori infection diagnosis (serology, 13C-urea breath test, culture, histology, and polymerase chain reaction on gastric biopsies). Gastric messenger RNA expression of leptin and ghrelin were quantified by real-time polymerase chain reaction. Sixty-two patients were included (84.7 +/- 5.2 years). H. pylori infection was associated with decreased gastric expression of leptin (p = .021), ghrelin (p =.002), and plasma ghrelin levels (p = .018). Atrophy was associated with decreased gastric leptin (p = .007) and ghrelin (p = .02). H. pylori infection correlated negatively with patient energy intake (r = -0.36; p = .001) and body mass index (r = -0.34; p = .018). The negative association between ghrelin and H. pylori infection may be related to a higher prevalence of atrophy and raises the possibility that H. pylori may be contributing to undernutrition in some older people.

Objective: To investigate the expression of peroxisome proliferators-activated receptor-gamma (PPAR-gamma) and cyclooxygenase-2 (COX-2) in Helicobacter pylori (Hp)-associated gastric mucosal lesions and the relations among them., Methods: Two-step immunohistochemical staining was used to detect the expression of PPAR-gamma and COX-2 proteins in the gastric biopsy specimens from 209 patients with lesions of gastric mucosa, including 75 cases of chronic superficial gastritis (CSG), 24 cases of chronic atrophic gastritis (CAG), and 90 cases of intestinal metaplasia (MI) and dysplasia (DYS), and from 20 subjects with normal gastric mucosa negative in Hp as controls. In addition, 36 CSG patients were followed up for 10 years to observe the changes of expression of PPAR-gamma and COX-2., Results: (1) The expression of COX-2 protein in the glandular cells of the CSG, CAG, and IM + DYS groups were 42.7%, 45.8%, and 61.1% respectively, all significantly higher than that of the control group (20%, P < 0.01 or 0.05). The expression of COX-2 protein in the inflammatory cells of the CSG, CAG, and IM + DYS groups were 32%, 29.2%, and 36.7% respectively, all significantly higher than that of the control group (0%, all P < 0.05). (2) In the CSG and IM + DYS groups the expression levels of COX-2 in both the inflammatory and glandular cells were both significantly higher in the Hp-positive patients than in the Hp-negative patients (P < 0.05 or 0.01). (3) The expression of PPAR-gamma protein in the glandular cells of the CSG, CAG, and IM + DYS groups were 18.7%, 29.2%, and 45.6% respectively, all significantly higher than that of the control group (0%, all P < 0.01); and the expression levels of PPAR-gamma protein in the inflammatory cells of the CSG, CAG, and IM + DYS groups were 22.5%, 20.8%, and 22.2% respectively, all significantly higher than that of the control group (0%, P < 0.05 or 0.01). (4) In the CSG and IM + DYS groups the expression levels of PPAR-gamma in the inflammatory cells of the Hp-positive patients were both significantly higher than those of the Hp-negative patients (both P < 0.01); and the. expression levels of PPAR-gamma in the glandular cells of the Hp-positive patients were both significantly higher than those of the Hp-negative patients (both P < 0.01). (5) The expression level of COX-2 in the inflammatory cells of the CSG patients with a persistent Hp infection after a period of ten years was 33.3%, significantly lower than that a decade before (38.9%, P < 0.05). However, the expression level of PPAR-gamma in the inflammatory cells of the patients with a persistent Hp infection after a period of ten years was 30.6%, not significantly different from that a decade before (33.3%, P > 0.05). (6) The expression levels of COX-2 and PPAR-gamma in the glandular cells of the CSG patients with a persistent Hp infection after a period of ten years were 55.6% and 30.6% respectively, both significantly higher than those a decade before (47.2% and 22.2%, both P < 0.01). (7) In all Hp-negative disease groups the expression level of COX-2 in the inflammatory cells was not significantly correlated with the expression level of PPAR-gamma in the inflammatory cells(r = 0.006 and 0.149, P > 0.05) In the Hp-negative disease groups, the expression level of COX-2 in the glandular cells was significantly positively correlated with the expression level of PPAR-gamma in the glandular cells in the IM + DYS group (r = 0.336, P < 0.05), however, not significantly correlated with the expression level of PPAR-gamma in the glandular cells in both CAG and CSG groups (r = 0.035 and 0.126, both P > 0.05). (8) In both the inflammatory cells and glandular cells the COX-2 expression was significantly positively correlated with the PAR-gamma expression in all disease groups with Hp positivity (r = 0.348 and 0.645, P < 0.05 or 0.01)., Conclusion: (1) Hp infection induces the overexpression of COX-2 and PPAR-gamma in the inflammatory and glandular cells within gastric mucosa, thus participating in the pathogenesis of gastric cancer (2) The expression of COX-2 induces by Hp is related to acute inflammation caused by Hp infection. In the glandular cells, significant increase of COX-2 and PPAR-gamma expression implies that along with time the expression of COX-2 and PPAR-gamma may change in advance of the morphological changes of the gastric mucosa.

The authors investigated p27 expression in 21 cases of high-grade gastric adenocarcinoma with portions of signet ring cell differentiation, by comparing that in 11 cases of chronic atrophic gastritis with Helicobacter pylori and in 5 cases of the intact gastric mucosa. The mean age of patients with gastric adenocarcinoma was 67.7 years (35-86 years); there were 9 males and 12 females. All tumors were of T3 N1-2 M0 stage. Helicobacter pylori was found in 3 of the 21 patients. The investigations indicated a great difference (by 2.4-7.6 times) and a statistically significant decrease in p27 expression in the adenocarcinoma cells as compared to the comparison groups. However, there was no significant correlation between the lower level of p27 expression and the prognosis in patients with adenocarcinoma.

Objective: To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms., Methods: Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E) and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (microm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE(2), EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue., Results: Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+/-0.28) microg/L, EGF in CAG (2.24+/-0.83) microg/L was significantly higher (P<0.05). The levels of PGE(2) and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in the nucleus of epithelial cells. The former was higher positively expressed in atrophic gland, while the later was higher positively stained in normal gastric tissue. bcl-2 protein was positively stained in the cytoplasma in atrophic gastric gland, while very weakly stained in normal gastric tissue., Conclusion: The pathological findings in gastric gland accorded with the Houston diagnostic criteria of antrum-predominant CAG. CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. There was high protein expression of oncogene, while inhibitor of suppressor gene in CAG rats indicated high trend of carcinogenesis.

Objective: To study the level of expression of Caspase-3 protein in precancerous lesions of stomach and its relation to gastric carcinogenesis., Methods: Formalin-fixed paraffin embedded tissues from 184 cases of gastric mucosa biopsy and surgically removed specimens, including gastric cancer (GC, N = 20), chronic atrophic gastritis (CAG, N = 6), atrophic gastritis with intestinal metaplasia (IM, N = 31), atrophic gastritis with dysplasia (DYS, N = 114) and normal controls (N = 13) were examined for expression of Caspase-3 protein and Ki-67 index by SABC immunohistochemistry, and for apoptosis by TdT-mediated dUTP biotin nick end labeling (TUNEL) method. Caspase-3, Ki-67 and TUNEL index were compared in different stages of gastric precancerous lesions and their correlation was analyzed., Results: The positive index of Caspase-3 protein in severe DYS (29.8% +/- 3.9%) showed no significant difference compared with that in GC (26.9% +/- 3.0%, P > 0.05), but was significantly lower than that in low (58.3% +/- 4.2%) and moderate grade DYS (50.4% +/- 4.8%), CAG (68.3% +/- 3.3%) and IM (70.9% +/- 4.3%, P < 0.05). Caspase-3 positive index was significantly correlated with that of apoptosis detected by TUNEL (r = 0.94, P < 0.05). Ki-67 index in Caspase-3 protein positive group (18.3% +/- 2.2%) was significantly lower than that in Caspase-3 negative group (48.9% +/- 3.1%, P < 0.05)., Conclusion: Caspase-3 protein expression was upregulated in CAG with or without IM and low or moderately low in DYS, while down-regulated in severe DYS and gastric carcinoma, and significantly positively correlated with cell apoptosis. It is suggested that down-regulated expression of Caspase-3 protein somehow contributes to gastric carcinogenesis through an imbalance between cell apoptosis and proliferation.

Polarized immune response to Helicobacter pylori and induction of chronic inflammation may increase the risk of gastric atrophy and adenocarcinoma. We studied the association of the response of IgG1 and IgG2 antibodies to H. pylori with grade of gastric chronic inflammation and atrophy in a population with a high prevalence of H. pylori, and compared these data with the data obtained from the study of gastric cancer patients, as well as with the data for CagA positivity. Altogether, 114 persons from two adult population samples from Estonia and 45 consecutive gastric cancer patients were studied. All patients were positive for the H. pylori antibody determined by ELISA. Adenocarcinoma was classified histologically according to the Laurén's system. The response of the IgG subclasses to H. pylori (acid glycine-extracted whole cell proteins) was determined by ELISA and the results were compared with the ELISA results for the recombinant fragment of the CagA protein. Helicobacter pylori IgG level was lower in atrophic gastritis compared with nonatrophic gastritis (chronic inflammation) (p=0.001). In the group of cancer patients, the response of IgG and IgG1 was lower compared with both gastritis groups (p=0.01 and p=0.0002 for IgG, and p=0.001 and p=0.0005 for IgG1). IgG2 was lower for gastric cancer localized in the corpus (p=0.03). In conclusion, atrophic gastritis and gastric cancer were associated with a significant decline in IgG and IgG1 response to H. pylori compared with nonatrophic gastritis. Higher value of CagA antibodies was seen in gastric cancer and in gastric atrophy compared with nonatrophic gastritis; in gastric cancer patients, IgG1 response to H. pylori was correlated with CagA status.

Objective: To research the regulative effect of mica monomer granule preparation on the expression of gene associated with cancer in gastric mucosa tissue of experimental chronic atrophic gastritis (CAG) rats., Method: To treat experimental CAG rats using mica monomer granule preparation with three different dosage-high, moderate and low level respectively. To observe the expression changes of mutant antioncogene-p53 gene-protein, oncogene p21, antioncogene p16 and anti-apoptosis gene bcl-2 in gastric mucosa of CAG rats by two-step ways of EnVision system in immunohistochemical method., Result: There was the tendency that mica monomer granule preparation with three different dosage could decrease the expression of p53 as well as p21, and mica had the obvious regulative effects on deletion of p16 and high-expression of bcl-2. It could also alleviate the inflammation of gastric mucosa and promote the regeneration of gland., Conclusion: The treatment and reversion action of mica on chronic atrophic gastritis is probably related with the regulative effect on the expression of gene associated with cancer.

Background & Objective: Intestinal metaplasia (IM) is thought as the precancerous lesion of gastric carcinoma, and CDX2 gene plays important roles in development and differentiation of intestinal epithelium, and maintenance of intestinal phenotype. Recent studies found that CDX2 were expressed aberrantly in IM of chronic atrophic gastritis (CAG) and some gastric carcinomas, which implied that CDX2 may play an important role in IM formation and gastric carcinogenesis. This study was to investigate the roles of CDX2 in the development and progression of IM and gastric carcinogenesis, and determine the correlation of IM to gastric carcinogenesis., Methods: A tissue microarray containing 46 cases of CAG with IM, 40 cases of gastric carcinoma, and 32 cases of IM foci in paracancerous tissues was constructed. High iron diamine/alcian blue (HID/AB) and HE staining were used to classify IM and gastric carcinoma, and the expression of CDX2 protein and mRNA in different gastric lesions was assessed with immunohistochemistry and in situ hybridization, respectively., Results: The proportion of type III IM was significantly higher in IM foci in paracancerous tissues than in CAG with IM (56.25% vs. 21.74%, P<0.01). The positive rates of CDX2 protein were 69.56% in IM foci in CAG, 53.13% in IM foci in paracancerous tissues, and 42.50% in gastric carcinomas, and the positive rates of CDX2 mRNA were 63.04%, 46.87%, and 35.00%, respectively. The positive rates were significantly lower in gastric cancer than in IM in CAG (P<0.01), but there was no significant difference between gastric cancer and IM foci in paracancerous tissues (P>0.05). The expression of CDX2 protein and mRNA was significantly higher in intestinal-type gastric cancer than in diffuse-type gastric cancer (54.55% vs. 27.78%, 45.45% vs. 22.22%, P<0.05). The expression of CDX2 protein was significantly lower in type III IM than in type I IM (46.42% vs. 79.31%, P<0.05)., Conclusions: CDX2 may play important roles in the development and progression of IM and gastric carcinogenesis.

The effects of helminth infection on humoral IgG responses and clinical outcome of gastric Helicobacter pylori infection are unknown. IgG and IgG subclass responses to H. pylori and serum pepsinogen I/II ratio, a marker of gastric atrophy, were investigated in a Schistosoma japonicum prevalent Chinese population. H. pylori, CagA and IgG subclass responses were assayed by ELISA. Serum pepsinogen I and pepsinogen II were assayed by ELISA and the pepsinogen I/II ratio determined. In 150 subjects, infection with S. japonicum and H. pylori was 55.3% and 51.3%, respectively. H. pylori IgG titres and CagA seropositivity were significantly lower (P<0.05) in co-infected subjects, and differences in H. pylori IgG isotype responses were evident. In H. pylori positives, a significantly higher (P<0.05) pepsinogen I/II ratio was observed in co-infected subjects. The difference between S. japonicum positive and negative subjects was only evident in H. pylori CagA seronegative subjects. In conclusion, S. japonicum co-infection with H. pylori is associated with alterations in IgG responses to H. pylori and less gastric atrophy.

Background and Aims: Bcl-2 protein prolongs cell survival in the face of classical apoptotic stimuli, and is considered to be a suppressor of apoptosis. Bax plays a key role in apoptosis by accelerating cell death after an apoptotic stimulus. The aim of our study was to determine the roles of the Bax proapoptotic gene and the Bcl-2 antiapoptotic gene in the carcinogenesis of gastric cancer., Methods: One hundred and forty-five gastric biopsy specimens of chronic gastritis, atrophic gastritis, intestinal metaplasia and gastric dysplasia were studied. Using immunohistochemical methods, Bax and Bcl-2 protein expression was observed., Results: Bax was expressed in epithelial cells in all cases of chronic gastritis. Bax was not detected in 26% of specimens of atrophic gastritis. As intestinal metaplasia develops, Bax is further suppressed. In biopsy samples with dysplasia, Bax expression was demonstrated only in 12% of biopsy samples. Although Bcl-2 protein was not detected in chronic gastritis, aberrant expression was found in gastric epithelial intestinal metaplasia and dysplasia., Conclusions: The suppression of Bax and overexpression of Bcl-2 protein is an early event in gastric tumorigenesis, before gastric dysplastic changes occur.