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Objective: To compare serum levels of pepsinogen I (PGI), pepsinogen II (PGII), and gastrin-17 (G-17) among patients with gastritis, gastric ulcer, and gastric cancer, and to assess the effectiveness of these biomarkers individually and in combination for screening gastric cancer., Methods: Serum levels of PGI, PGII, and G-17 were measured using enzyme-linked immunosorbent assay (ELISA) in 50 patients with gastric cancer, 60 with chronic gastritis, and 60 with gastric ulcer from February 2020 to June 2021. The diagnostic value of these biomarkers was analyzed through sensitivity, specificity, and ROC curve assessments., Results: Serum PGI levels were significantly lower in patients with advanced gastric cancer compared to those with early gastric cancer (P < .05), while PGII and G-17 levels were significantly higher in advanced-stage patients (P < .05). The combined ROC curve analysis of PGI, PGII, and G-17 yielded an area under the curve (AUC) of 0.933, indicating higher diagnostic accuracy than any of the markers alone. Statistically significant differences were noted between the combined and individual tests (Z = 2.376, P < .05). Patients with PGI levels lower than 17.21 ng/ml had a worse prognosis compared to those with higher levels. Similarly, patients with PGII levels greater than 74.65 ng/ml and G-17 levels greater than 17.03 pmol/L had poorer prognoses. Additionally, higher G-17 levels were associated with significantly lower serum PGI levels., Conclusions: Patients with low expression of PGI have a poorer prognosis, and those with high expression of PGII and G-17 also have a poor prognosis. Combining the three indicators has clear value for the screening and prognostic evaluation of gastric cancer, making it worthy of clinical promotion and application.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study., Methods: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire., Results: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p  = 0.001)., Conclusions: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

OBJECTIVE To identify minimally invasive biomarkers to help differentiate dogs with gastric carcinoma from those with chronic gastritis. DESIGN Prospective study. ANIMALS 15 dogs with gastric carcinoma, 29 dogs with chronic gastritis, and 7 healthy dogs. PROCEDURES Dogs with clinical signs of upper gastrointestinal tract disease for > 14 days that underwent gastroscopy or necropsy for collection of gastric biopsy specimens for histologic evaluation were prospectively enrolled. Gastric carcinoma and chronic gastritis were diagnosed on the basis of histologic findings. Additionally, gastric biopsy specimens were collected endoscopically from 7 healthy (control) dogs while they were anesthetized for a routine neutering procedure. Prior to being anesthetized for gastroscopy or euthanized, all dogs underwent a physical examination, and a blood sample was collected for quantification of select serum biomarker concentrations. Histologic findings, body condition score (BCS), and serum biomarker concentrations were compared among the 3 groups. RESULTS Dogs with gastric carcinoma were significantly older and had a significantly lower BCS, lower serum folate concentration, and greater serum C-reactive protein (CRP) concentration, compared with dogs with chronic gastritis and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age > 8 years, BCS < 4, serum CRP concentration > 25 mg/L, and an abnormally low serum folate concentration might be useful noninvasive biomarkers for identification of dogs with gastric carcinoma. For underweight older dogs with signs of upper gastrointestinal tract disease and high serum CRP and low serum folate concentrations, gastric biopsy specimens should be obtained and evaluated so that a prompt definitive diagnosis can be made and appropriate treatment initiated.

Aims: The aim of the study was to evaluate the rationale of blood pepsinogen (PG) testing in population based screening settings., Methods: Participants from a cross-sectional population-based study of cardiovascular risk factors in Latvia were invited to participate in the current study. Pepsinogen I and II were measured in blood samples taken during the initial study and at follow-up; upper gastrointestinal endoscopy was performed. There were three groups of patients: with moderately decreased (PG I< 70 ng/ml and PG I/PG II ratio < 3), with strongly decreased (PG I< 30 ng/ml and PG I/PG II ratio < 2), and with normal PG level. Biopsy with H. pylori detection was performed (updated Sydney system)., Results: Results from 259 patients were analyzed. Pepsinogens were decreased in 133 (51.4%), H. pylori was positive in 177 (66.0%) cases. Mean age was significantly lower in patients with normal compared to strongly decreased PG level group (52.8 vs. 64.1 years, p<0.001). Prevalence of severe corpus atrophy was higher in the strongly decreased compared to the normal PG test group: 7.0% vs. 0%; the same tendency was noted in the distribution of OLGA stages III-IV - 10.5% and 0.0%, OLGIM stages III-IV - 3.5% and 0%, and low-grade dysplasia - 15.8% and 2.4% (p<0.05). Two cases of gastric cancer were found; both presented decreased PG levels. A strong association between H. pylori eradication and PG ratio dynamics was found (p<0.05)., Conclusions: All high-risk lesions were found in the decreased PG test groups; two cancer cases were revealed. However, PG demonstrated low specificity and low value of repeated testing. The value of PG as a sole test for gastric cancer risk is limited.

Gastrin acts physiologically as a gut hormone to stimulate acid secretion after meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin level happens under various conditions including Zollinger-Ellison syndrome, antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As acid suppressive therapy causes hypergastrinemia, the association between acid suppressive therapy and gastric neuroendocrine cell tumor (NET) has been discussed during the past 30 years. In this review article, the definition of hypergastrinemia and the related disorders including acid suppressive therapy and gastric NET are discussed., (© 2018 Japanese Gastroenterological Association Published by S. Karger AG, Basel.)

Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators., Methods: Gastritis (n=58) and gastric cancer (n=31) patients were evaluated and compared with H. pylori-positive asymptomatic controls (n=46), for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis., Results: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold (OR=4.62, 95% CI=1.50-14.22), which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold (OR=9.70, 95% CI=2.06-45.69). A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold (OR=9.07, 95% CI=1.99-42.0) for HP-NAP-seropositive subjects and was drastically amplified (OR=33.64, 95% CI=2.06-548.68), when double-positive (HP-NAP seropositive/IL-4 -590 T carrier) subjects were examined against double negatives (HP-NAP seronegative/IL-4 -590 CC)., Conclusion: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility.

Circular RNAs are new type of endogenous RNAs, which play an important role in the regulation of gene expression and indicate a great capacity in clinical diagnosis and treatments of diseases. However, the role of circular RNAs in gastric cancer remains unknown. In this study, we chose hsa&#95;circ&#95;0006633 as the target circular RNA and measured its levels in human gastric cancer tissues, plasma, and gastric cell lines by real-time quantitative reverse transcription polymerase chain reaction. Hsa&#95;circ&#95;0006633 levels at multiple stages of gastric tumorigenesis were then explored, and its relationships with clinicopathological features were analyzed as well. We found that the expression levels of hsa&#95;circ&#95;0006633 in four gastric cancer cell lines, HGC-27, SGC-7901, MGC-803, and AGS, were downregulated than those in normal gastric mucosal epithelial cell line GES-1. Then, we further detected that it was downregulated in 79.2% (76/96) gastric cancer tissues compared with the adjacent non-tumorous tissues. The lower expression of hsa&#95;circ&#95;0006633 was associated with cancer distal metastasis ( p = 0.037) and tissue carcinoembryonic antigen level ( p = 0.041). In addition, hsa&#95;circ&#95;0006633 expression was significantly decreased in gastritis and dysplasia tissues comparing with the healthy control. Moreover, plasma hsa&#95;circ&#95;0006633 levels were significantly increased in gastric cancer compared with healthy control. Our data imply that hsa&#95;circ&#95;0006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for screening gastric cancer.

Background/aims: Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients., Materials and Methods: One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels., Results: The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (p<0.001). The presence of corpus atrophy (p=0.026, OR: 5.03, CI 95%: 1.21-20.88, β=1.61) and presence of enterochromaffin-like cell hyperplasia (p=0.017, OR: 6.59, CI 95%: 1.4-31.08, β=1.88) were found as risk factors associated with serum chromogranin A level., Conclusion: Factors influencing raised serum chromogranin A levels in autoimmune gastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

Carcinoma antigen 72-4 is a cell surface glycoprotein produced by gastric carcinoma cells. In the case presented, Helicobacter pylori infection induced an inappropriate elevation of this tumour antigen in a 66-year-old female patient, reaching values seen with gastric carcinomas. Extragastric sources of CA 72-4 elevation were ruled out. The elevation slowly returned to normal levels after two courses of triple and sequential eradication therapy, causing considerable anxiety for the patient and several costly examinations., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To explore the alteration and clinical significance of interleukin 23 (IL-23) and pepsinogen 1 (PG1) in the sera and tissues of patients with gastric diseases., Methods: The study collected the tissues of chronic superficial gastritis, chronic atrophic gastritis with intestinal metaplasia, gastric cancer as wells as the peripheral blood samples from the patients suffering from the three kinds of gastric diseases. Immunohistochemical staining was performed to detect IL-23 expression in the gastric involved tissues from these patients. The concentrations of serum PG1 were determined by time-resolved fluoroimmunoassay and the levels of serum IL-23 were detected by ELISA. The relationships between the serum IL-23 and PG1 in chronic atrophic gastritis with intestinal metaplasia tissues or gastric cancer tissues were analyzed by Pearson correlation analysis., Results: Compared with the chronic superficial gastritis tissues, the expression of IL-23 significantly increased in chronic atrophic gastritis with intestinal metaplasia tissues and gastric cancer tissues, so did the serum IL-23. Nevertheless, the expression level of serum PG1 significantly decreased in chronic atrophic gastritis with intestinal metaplasia group and gastric cancer group. There was a negative correlation between IL-23 and PG1 in the chronic atrophic gastritis with intestinal metaplasia group or in gastric cancer group., Conclusion: Enhanced expression of IL-23 occurred in chronic atrophic gastritis with intestinal metaplasia tissue and gastric cancer tissue, and serum IL-23 had a negative correlation with PG1.

Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence.

Gastric cancer is a heterogeneous disorder; genetic factors, H. pylori infection and various environmental factors contribute to its development. Advanced atrophic corpus-predominant gastritis provides the histological base for its genesis. Low socio-economic status and poor hygienic conditions, smoking habits, heavy alcohol consumption, high salt and low intake of vegetables and fruits are important external factors for the occurrence of gastric cancer. For its prevention, the eradication of H. pylori infection at an early age is mandatory for subjects at high risk or those living in areas with high prevalence of gastric cancer. Given that an increased serum level of Pepsinogen II is a good biomarker for the presence of gastritis, it seems reasonable to screen all infected subjects at risk of gastric cancer with increased serum pepsinogen II at an early age (at around 30 years) to eradicate H. pylori. An endoscopy should be performed for subjects at an older age (40 years and older), when increased serum pepsinogen II level is associated with decreased serum pepsinogen I and pepsinogen I to II ratio.

Background: The search for better non-invasive biomarkers for gastric cancer remains ongoing. We investigated the predictive power of serum trefoil factor (TFF) levels as biomarkers for gastric cancer in comparison with the pepsinogen (PG) test., Methods: Patients with gastric cancer, chronic atrophic gastritis (CAG) or chronic non-atrophic gastritis (CNAG), and healthy people were recruited. Serum concentrations of TFFs, PG I, and PG II, as well as the presence of antibodies against Helicobacter pylori, were measured by enzyme-linked immunosorbent assays (ELISA). Receiver operating characteristics (ROC) were used to compare the predictive powers of the selected factors., Results: The serum concentrations of TFF1, TFF2, and TFF3 in the control groups were significantly lower than those in the gastric cancer group with the exception of TFF2 which was elevated in CAG. The area under the ROC curve for TFF3 was greater than that for the PG I/II ratio (0.81 vs 0.78). TFF3 also had a significantly higher predictive power for distinguishing gastric cancer than the PG test (odds ratio: 10.33 vs 2.57). Moreover, combining the serum TFF3 and PG tests for gastric cancer had better predictive power than either alone., Conclusions: Serum TFF3 may be a better predictor of gastric cancer than the PG test, while the combined testing of serum PG and TFF3 could further improve the efficacy of gastric cancer screening.

Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

Background: Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients., Materials and Methods: Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers., Results: Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86)., Conclusions: Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas.

Irrespective of its etiology, long-standing, non-self-limiting gastric inflammation (mostly in Helicobacter pylori-associated cases) is the cancerization ground on which epidemic (intestinal-type) gastric carcinoma (GC) can develop. The natural history of invasive gastric adenocarcinoma encompasses gastritis, atrophic mucosal changes, and intraepithelial neoplasia (IEN). The topography, the extent and the severity of the atrophic changes significantly correlate with the risk of developing both IEN and GC. In recent years, both noninvasive (serological) tests and invasive (endoscopy/biopsy) procedures have been proposed to stratify patients according to different classes of GC risk. As a consequence, different patient-tailored GC secondary prevention strategies have been put forward. This review summarizes the histological features of H. pylori-related gastritis and the natural history of the disease. Histological and serological strategies to assess GC risk as well as the clinical management of atrophic gastritis patients are also discussed., (© 2014 S. Karger AG, Basel.)

Background: Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer., Methods: Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II., Results: Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation., Conclusions: Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

Purpose: To evaluate the significance of MAGE-A3 novel immunodominant epitopes in serological diagnosis of gastric cancer., Methods: B cell, CTL, and Th epitopes of MAGE-A3 were analyzed using computer-assisted techniques. Three possible immunodominant epitope peptides located at 5aa-23aa (QRSQHCKPEEGLEARGEAL), 112aa-131aa (KVAELVHFLLLKYRAREPVT), and 232aa-246aa (EGREDSILGDPKKLL) with potential B cell-dominant epitope, high-score HLA-A2 and A24 restriction CTL epitope, and HLA-DRB restriction Th epitope were selected. After optimized by prokaryotic codon, these genes were expressed as Trx-His-tag recombinant proteins in Escherichia coli and purified by Ni-NTA agarose beads. Three recombinant proteins were identified by Western blotting using His-tag monoclonal antibody and the serum antibodies from the patient of gastric cancer. The level of specific antibodies in the sera from 210 patients with gastric cancer, 56 patients with chronic gastritis, and 116 healthy controls was further analyzed by indirect ELISA., Results: Three MAGE-A3 epitope recombinant proteins about 20 kDa molecular weight were specifically recognized by His-tag monoclonal antibody and the serum of gastric cancer patients. ELISA based on the epitope recombinant protein indicated that gastric cancer patients had significantly higher reactivity to these immunodominant epitope proteins compared with chronic gastritis and healthy individuals (P < 0.05). Furthermore, the serum antibody positive rate in the gastric cancer group was also significantly higher than that in the chronic gastritis patients and healthy controls (P < 0.05), while there was no significant difference in gastritis group and the healthy control group (P > 0.05)., Conclusions: These study results demonstrated that these three predictive epitopes may be potential targets for applications in the design of serological diagnosis tools for gastric cancer.

Objective: To determine the distributions of six Helicobacter pylori (Hp)-specific antibodies in a high-risk population of gastric cancer (GC) and explore the relationship between Hp virulence factors and precancerous gastric lesions., Methods: Based on the two intervention trials conducted in Linqu County, the seropositivities for CagA, VacA, GroEL, UreA, HcpC and GGT were assessed by recombinant immunoassay (recomLine) in 623 participants with H. pylori infection determined by (13)C-urea breath test ((13)C-UBT) and/or enzyme linked immunosorbent assay (ELISA)., Results: In a total of 623 participants were detected by recomLine analysis, of which 594 were Hp-positive. The seropositivities rates of CagA, VacA, GroEL, UreA, HcpC and GGT were 84.0%, 38.2%, 66.7%, 17.7%, 58.8% and 42.8%, respectively. A total of 523 participants were determined as type I infection of Hp, accounting for 88.1%. Compared with superficial gastritis (SG), the infection rate of Hp type I was higher in the chronic atrophic gastritis (CAG) (P = 0.001)., Conclusions: The results of this population-based study suggest that the virulence factors of Hp may be related to the development of GC in a Chinese high-risk population. The recomLine analysis may serve as a tool for identification of Hp strains and prediction of high-risk population of GC.

Background and Objective: The aim of this study was to investigate the association between serum pepsinogens, serum gastrin, serum vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status in patients with various gastric precancerous lesions., Methods: One hundred and sixty two consecutive patients with various gastric lesions [38 (23.5%) H. pylori positive chronic non-atrophic gastritis, 45 (27.8%) autoimmune gastritis, 42 intestinal metaplasia and 37 dysplasia] were enrolled into the study. Serum pepsinogen I and II, gastrin 17, vascular endothelial growth factor, interleukin-1 Beta, toll-like receptor-4 levels, H. pylori Cag A status were evaluated., Results: H. pylori was positive in 98 (60.5%) patients and 38 of these patients were Cag A positive. Serum pepsinogen level was significantly lower in patients with autoimmune atrophic gastritis compared to the patients with non-atrophic chronic gastritis (p<0.001), intestinal metaplasia (P<0.001) and dysplasia (P=0.002). Mean serum gastrin was 1209.6±268.48 pg/mL in patients with autoimmune atrophic gastritis and 234.95±184.018 pg/mL in patients with chronic non-atrophic gastritis. Mean toll-like receptor-4 level was 0.56±0.098 ng/mL in patient with dysplasia, and this value was higher compared to patients with chronic non-atrophic gastritis (P=0.007), autoimmune atrophic gastritis (P=0.003) and intestinal metaplasia (P=0.006). Interleukin-1 Beta level was significantly lower in patients with dysplasia compared to patients with chronic non-atrophic gastritis (P=0.034)., Conclusions: Serum pepsinogens, serum gastrin and H. pylori Cag A status are important tests in detecting gastric precancerous lesions. However, toll-like receptor-4 may be a sensitive test to differentiate the patients with dysplasia from the other precancerous gastric lesions. Non-invasive tests are sensitive in the diagnosis of gastric precancerous lesions., (Copyright © 2012. Published by Elsevier Masson SAS.)

The study included 120 patients with pre-cancer conditions of the stomach and 30 patients with gastric cancer stage II-IV. The ELISA method in the blood serum was used to determine the markers of the infection caused by Herpes simplex virus (HSV) types 1 and 2, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The majority of the patients exhibited high titers of markers of Herpesvirus mixed infection. These data allow recommending the determination of IgG antibodies to antigens of herpesviruses in patients with the diseases of the stomach and assigning the appropriate antiviral drugs.

Background & Aims: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied, and the mechanisms by which FA exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression, and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers., Methods: Hypergastrinemic mice infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements, and immunohistochemistry with anti-5-methylcytosine. We also profiled gene expression in the same tissues., Results: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and immunohistochemistry for lymphocyte markers., Conclusions: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to prevent global loss of methylation and suppress inflammation., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The role of Helicobacter pylori status and serum zinc value in gastric disease patients and healthy controls were investigated. Cases used in this work were 45 gastric cancer patients, 44 with peptic ulcers, 52 suffering gastritis and 64 healthy controls, all diagnosed histologically with the controls undergoing medical checkups. Helicobacter pylori status and serum levels of Zn were determined by 13C-urea breath test and flame atomic absorption spectrophotometer, respectively. Our study showed that Helicobacter pylori infection has no change in gastritis, peptic ulcer and gastric cancer group, on the contrast, serum levels of Zn were significantly reduced in gastritis, peptic ulcer and gastric cancer group, compared with healthy controls, and the higher the Zn levels are, the more increased risk of gastric cancer. Helicobacter pylori infection is a cause of gastritis, peptic ulcers and even gastric cancer, while serum zinc level is an indicator of protection of gastric membranes against damage.

Background and Aim:   To study the low-molecular-weight metabolites in blood plasma of patients with the progressive disease, gastric cancer, and to characterize different stages from chronic superficial gastritis (CSG) to chronic atrophic gastritis (CAG), intestinal metaplasia (IM), gastric dysplasia (DYS) and finally gastric cancer (GC)., Methods:   We applied gas chromatography time-of-flight mass spectrometry (GC/TOF-MS) to determine metabolites levels in plasma obtained from 80 patients including 19 with CSG, 13 with CAG, 10 with IM, 15 with DYS and 22 with GC (nine preoperation and 13 postoperation). Principal component analysis (PCA) and statistics were used to differentiate the stages and to identify the markers of gastric cancer., Results:   Totally, 223 peaks were detected in GC/TOF-MS and 72 compounds were authentically identified. CSG showed distinct difference from the other groups of CAG, IM, DYS and GC, whose plots clustered closely. IM clustered closely to GC, suggesting similar metabolic patterns of them. Fifteen identified metabolites contributed most to the differentiating between CSG and GC, and characterized different stages of GC. Statistics revealed elevated levels of 2-Hydroxybutyrate, pyroglutamate, glutamate, asparagine, azelaic acid, ornithine, urate, 11-eicosenoic acid, 1-monohexadecanoylglycerol and γ-tocopherol, while downregulation of creatinine, threonate in GC group, indicating that GC patients were obviously involved in oxidative stress, and perturbed metabolism of amino acids and fatty acids., Conclusion:   The metabolic phenotype of CSG is significantly different from GC, while that of IM is similar to it. The discriminatory metabolites characterizing progressive stages from CSG to GC might be the potential markers to indicate a risk of GC., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background and Aim: Serum pepsinogen II (sPGII) is underutilized and considered an inconspicuous biomarker in clinical practice. We refocused on this neglected but novel biomarker and conducted the present study, aiming to elucidate the normal level of sPGII in healthy Chinese patients and to investigate the clinical utility of sPGII for gastric disease screening., Methods: In 2008-2009, a total of 2022 participants from northern China were selected and enrolled in the study. sPGII and Helicobacter pylori (H. pylori)-immunoglobulin G were measured with ELISA., Results: sPGII showed a normal value of 6.6 microg/L in a total of 466 patients with endoscopically- and histologically-normal stomachs. A small sex difference was observed: the average value of sPGII was 7 microg/L and 6 microg/L in males and females, respectively (P < 0.001). In the differentiation between healthy and diseased (endoscopically-diseased stomach or gastritis/atrophic gastritis in endoscopic biopsies) stomach mucosae, the best sPGII cut-off value was 8.25 microg/L (sensitivity 70.6%, specificity 70.8%). In screening the H. pylori seropositivity, the optimum cut-off sPGII value was 10.25 microg/L (sensitivity 71.6%, specificity 70.1%)., Conclusions: We demonstrated that the mean values of sPGII in a healthy Chinese population are 7 microg/L and 6 microg/L for males and females, respectively. sPGII significantly increases in diseased and H. pylori-infected stomach, and the best sPGII cut-off value is 8.25 microg/L in the differentiation between patients with healthy and diseased stomach mucosae. Furthermore, Chinese patients with sPGII greater than 10.25 microg/L are at greater risk of various H. pylori-related gastropathies, and are therefore prior candidates for gastro-protection therapy., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objective: To detect the expression levels of transcription factors and associated cytokines of Th17 and Treg cells in peripheral blood mononuclear cells (PBMC) of patients with gastric cancer, and explore the possible pathological mechanism of these cells involved in the development of gastric cancer., Methods: The mRNA levels of RORgammat, FoxP3 in PBMC were determined by quantitative real-time PCR (QRT-PCR) from 57 patients with gastric cancer, 31 patients with benign gastric illness and 40 healthy people. The concentration of IL-17, IL-23, TGF-beta, IL-10 in plasma were detected by enzyme linked immunosorbent assay (ELISA)., Results: Compared with healthy volunteers, patients with gastric cancer showed higher levels of RORgammat and FoxP3 in PBMC (P < 0.05). The ratio of FoxP3/RORgammat in gastric cancer group was higher than that in the volunteer group and benign gastric illness group (P < 0.05). The ratio of FoxP3/RORgammat was higher in advanced disease than early disease (P < 0.05). The expressions of IL-17, IL-23, TGF-beta and IL-10 were higher in patients with gastric cancer than that in healthy volunteers (P < 0.05). In addition, The expression of TGF-beta and IL-10 were significantly increased in the advanced disease group than that in the early group (P < 0.05), but IL-17 and IL-23 was not significantly changed between the two groups (P > 0.05)., Conclusion: There are higher levels of Th17 and Treg cells in gastric cancer patients, and it also shows a persistent predominant tendency of Treg cells and a reduced tendency of Th17 cells in advanced disease. Detecting the expression of Th17/Treg transcription factor and related cytokines would contribute to the diagnosis and prediction of the disease development and prognosis.

MG7 is a gastric cancer-specific MAb with high specificity and sensitivity. By using MG7 MAb, we found that MG7Ag was increasingly detected in superficial gastritis, atrophic gastritis, intestinal metaplasia, atypical hyperplasia, and gastric cancer, indicating that MG7Ag could be considered an important early warning molecule of gastric cancer and MG7 MAb could be used as a tool for screening gastric cancer. We have developed a new and sensitive system, immuno-realtime PCR, for detection of MG7Ag in the serum. The use of qIPCR assays enabled the detection of MG7Ag in complex biological samples that were poorly accessible by conventional immunoassays.

Background: Recently, several authors reported on the Protein Chip approach to analyze serum. They used SELDI-TOF-MS (surface enhanced laser desorption/ionization-time of flight-mass spectrometry) to identify patients with cancers of various origins in a highly sensitive and specific manner. In the current study, a similar approach was employed to analyze the serum of patients with various stages of gastric cancer., Methods: Control serum specimens from patients with gastritis (n = 19) and those with gastric cancer (Stage I: n = 6, Stage II or III: n = 6, Stage IV: n = 6, total: n = 18) were collected and analyzed by the Protein Chip biomarker system (Bio-Rad, Japan), a platform for SELDI-TOF-MS, and protein profiles were obtained and compared. The cation exchange chip (CM10) and the anion exchange chip (Q10) were used for processing before TOF-MS., Results: nine proteins were significantly over-expressed (P < 0.05, Student t-test) in patients with gastric cancer compared to patients with gastritis. Among them, four protein masses with 2929 m/z, 3293 m/z, 3371 m/z, and 4213 m/z were found to be differentially expressed solely in patients suffering from peritoneal dissemination. All peaks were processed on CM10 chips. Employing one data mining method, CART (classification and regression trees), gastric cancer patients with peritoneal dissemination were successfully separated from those who had no peritoneal seeding., Conclusion: A validation study with a larger number of samples is mandatory; however, the detected peaks here might be candidates for biomarkers of peritoneal dissemination and/or gastric cancer. Moreover, further analysis of these four proteins might be helpful in revealing the mechanism of peritoneal dissemination, which at present has no cure.

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.

Background/aims: Diffuse-type gastric carcinoma is associated with a poor prognosis. However, the clinical behavior of diffuse-type gastric cancer is not fully understood. The aim of this study is to distinguish the behaviors of early diffuse-type gastric carcinomas by sub classifying tumors according to their histologic features., Methodology: A total of 114 cases of diffuse-type early gastric cancer were studied retrospectively. We analyzed and compared the resected cancer specimens according to the histologic components: as poorly differentiated adenocarcinoma component-present (poor+) versus poorly differentiated adenocarcinoma component-absent (poor-). Helicobacter pylori status was evaluated by Giemsa staining and IgG serology. We assessed the degree of cancer invasion and compared background status of gastritis in accordance with the updated Sydney System criteria and serologic markers., Results: In comparison to the poor+ cancers, the poor- cancers had a significantly larger portion of cells confined to the mucosa (p=0.002). Only 8 of the 114 cases were regarded as H. pylori-negative. Although we could not detect any serologic markers specific for gastritis with poor+ cancer, but the serum levels of gastrin was slightly higher in patients with poor+ cancers than in those with poor- cancers., Conclusions: The biologic behavior of poor+ gastric carcinoma is worse than that of poor- carcinoma. There is a close relation between H. pylori infection and carcinogenesis of poorly differentiated adenocarcinoma.

Objective: The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non-atrophic gastritis, preneoplastic lesions, and gastric cancer., Methods: We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay., Results: We included 618 patients, 368 with non-atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non-atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA., Conclusions: This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases.

We evaluated the topography of histological gastritis, which may be risk factors for gastric cancer (GCa). A total of 530 Helicobacter pylori-positive patients underwent diagnostic upper-gastrointestinal endoscopy. Biopsy specimens were obtained from the gastric antrum and body to assess the grade of gastritis. Subjects were divided into four groups by the topography of active gastritis (antrum predominant gastritis, AP; pan-gastritis with or without corpus atrophy, Pan-1 and Pan-2; and corpus predominant gastritis, CP). A higher prevalence of GCa followed the order of Pan 2-->CP-->Pan 1-->AP. The age of patients decreased in the same order. When we set Pan 2 and CP as a high-risk group, the sensitivity and specificity for GCa detection were 77.3 and 54.7%, which were superior to the serum criteria using pepsinogens. These suggest that topography of histologic gastritis is an important marker to identify the high-risk group.

Background/aims: Immune response against Helicobacter pylori is important for the course and outcome of infection. We conducted study looking for the difference in anti H. pylori IgG and IgA between patients with intestinal type of gastric cancer, superficial and atrophic gastritis., Methodology: For this study, 133 patients infected with H. pylori were enrolled: 50 with superficial gastritis, 42 with atrophic gastritis and 41 with gastric cancer. Anti H. pylori IgG and IgA ELISA tests were performed. The difference in antibody titers of IgG and IgA, frequency of IgA > IgG ratio and combination of low IgG and IgA > IgG ratio were analyzed., Results: The patients with gastritis had higher titer of IgG that the patients with gastric cancer (p < 0.01). The patients with superficial gastritis had higher titer of IgA than the patients with gastric cancer (p < 0.05). IgA > IgG ratio is more frequent in patients with gastric cancer than in the patients with superficial gastritis (p < 0.01). Low IgG and IgA > IgG is more frequent in the patients with gastric cancer than in the patients with gastritis (p < 0.01)., Conclusions: The patients with gastric cancer elicit different anti H. pylori IgG and IgA response than the patients with superficial and atrophic gastritis. Low IgG and IgA predominance seems characteristic for gastric cancer.

Objective: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17 level and to study the diagnostic value of serum gastrin-17 in gastric precancerous lesions and gastric cancer., Methods: Serum gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology., Results: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum gastrin-17 level was markedly higher in people>or=60 years old than that in younger age groups. The serum gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group., Conclusions: In people over 60 years of age, the serum gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum gastrin-17 level, whereas H. pylori infection is usually associated with its increment.

Background: Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1beta-511 polymorphisms are suspected to be risk factors for gastric cancer., Methods: A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1beta-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups., Results: The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10-4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4-6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50-0.81; P = 0.014)., Conclusions: A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1beta-511 C/C genotype may be independent risk factors for gastric cancer in Thais.

SELDI mass spectrometry was used to investigate protein expression in sera of patients with gastric cancer and gastritis compared to normal volunteers. Differences in peak morphology and intensity were observed in regions of 5910 Da, 5084 Da, 6640 Da and 8691 Da. Patients with gastric cancer exhibited an up-regulation of the 5910 Da peak and a down-regulation of the 8691 Da peak compared to the healthy volunteers; there was also some bi-partitioning and tri-partitioning at the 5084 Da peak. When comparing the sera of these cancer patients with those of gastritis, the former had an up-regulation of the 5910 Da peak and a down-regulation of the 6640 Da peak. This is the first report showing that SELDI sera analysis may be useful in the screening of gastric lesions.

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.

Background/aim: Helicobacter pylori infection is associated with the development of atrophic gastritis and increased gastric epithelial proliferation that is important in developing gastric carcinoma. Some countries with a high prevalence of H. pylori infection have high gastric cancer rates, whereas in others these rates are low. Several theories have been advanced to explain this phenomenon. One of these explanations is that the concurrent parasitic infection that is common in the African population might alter the immune response to H. pylori infection and reduce the incidence of atrophic gastritis. The aim of the present study was to assess whether concurrent Schistosoma mansoni infection with H. pylori has an effect on gastric mucosal injury in view of cell proliferation, apoptosis, pathological changes, nitric oxide (NO), oxyradicals and antioxidant capacity status., Patients/methods: Between April 2001 and March 2002, 73 patients were subjected to upper gastrointestinal endoscopy for dyspepsia and liver cirrhosis in the National Liver Institute, Menoufiya University. Biopsies were obtained from any lesion as well as from apparently healthy mucosa. Specimens were preserved in RNA later solution, and then kept at -80 degrees C until utilized for estimation of DNA-flow cytometric assay, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), NO and lipid peroxidation (LPO) product--malondialdehyde (MDA). Diagnosis of bilharziasis was done by stool analysis, or by sigmoidoscopy and rectal snip., Results: Of the 73 patients, 48 were H. pylori-positive, 34 of them were positive and 14 were negative for S. mansoni. Of the 25 H. pylori-negative cases, 18 were positive and 7 were negative for S. mansoni. Concurrent infection with S. mansoni occurred in 34 patients and they had reduced DNA S-phase (7.57 +/- 4.99 vs. 14.5 +/- 3.11, P = 0.001), reduced proliferation activity (9.95 +/- 3.95 vs. 16.78, P < 0.004) and reduced apoptosis (21.83 +/- 11.64 vs. 26.0 +/- 8.31, P > 0.05) compared with H. pylori infected patients alone., Conclusions: The results demonstrate that concurrent helminthes infection may modify the inflammatory response to gastric H. pylori infection manifested by the reduction of oxyradical-induced DNA-damage, apoptosis and cellular proliferation activity, and the increase in antioxidant production. Concurrent S. mansoni infection may have a protective effect against the possible progression of H. pylori-induced gastritis towards gastric carcinoma.

Gastric cancer remains the second biggest cause of cancer death worldwide. The most common type of gastric cancer, the intestinal type, is usually preceded by chronic atrophic gastritis. Gastritis serology is therefore of crucial importance for population-based screening and prevention studies. Helicobacter pylori serum antibodies can adequately diagnose inflammation of the gastric mucosa, but the serological diagnosis of atrophic gastritis is more hazardous. Many tests have been used for this purpose, either alone or in various combinations. Depending on the population, pepsinogens and gastrin often have a high specificity but low sensitivity for the diagnosis of atrophic gastritis, whereas antibodies against H. pylori or CagA have a high sensitivity but low specificity. A combination of two tests, e.g. H. pylori antibodies and pepsinogen I, may balance this issue and provide adequate screening tools, although there is a clear need for further improvement and simplification of serological testing for atrophic gastritis.

Serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients were compared with values for age matched healthy subjects. Serum superoxide dismutase and serum malondialdehyde were analyzed spectrophotometrically whereas plasma ascorbic acid was determined by colorimetric method. Significant increase in serum superoxide dismutase and serum malondialdehyde and significant decrease in plasma ascorbic acid were observed in H. pylori gastritis and gastric cancer patients compared to control subjects. The concentration of serum superoxide dismutase and serum malondialdehyde was significantly higher and plasma ascorbic acid was significantly lower in gastric cancer as compared to H. pylori gastritis patients. Our results demonstrate that a correlation existed between the concentration of serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients.

Objective: To investigate the relation between serum level of interleukin-8 (IL-8), nitrogen monoxide (NO) and Helicobacter pylori (HP) infection, as well as the possible molecular mechanism of HP infection causing the imbalance of apoptosis and proliferation in gastric epithelial cells, which may lead to oncogenesis in stomach., Methods: Serum IL-8 level was detected with enzyme-linked immunosorbent assay (ELISA). Serum NO was detected with chrome reduction method using plated copper., Results: Serum level of IL-8 were 22.50 +/- 1.87 pg/ml in the normal tissue, 34.99 +/- 7.89 pg/ml in superficial gastritis, 65.27 +/- 10.60 pg/ml in atrophic gastritis and 94.84 +/- 11.09 pg/ml in gastric cancer (P < 0.01). Serum level of NO in the atrophic gastritis group (39.93 +/- 5.43 micromol/L) was significantly higher than that in the gastric cancer group (37.02 +/- 4.13 micromol/L) (P < 0.05). The differences in the other groups were not significant. IL-8 and NO levels in the HP(+) group were significantly higher than those in the HP(-) group (77.30 +/- 20.92 pg/ml vs 39.16 +/- 14.40 pg/ml, P < 0.01; 39.77 +/- 5.57 micromol/L vs 35.35 +/- 5.24 micromol/L, P < 0.01). Serum levels of IL-8 and NO in the cytotoxin-associated gene A protein (CagA)(+)HP group were significantly higher than those in the CagA(-)HP group (83.45 +/- 16.92 pg/ml vs 66.24 +/- 23.21 pg/ml, P < 0.01; 40.97 +/- 4.59 micromol/L vs 37.62 +/- 6.58 micromol/L, P < 0.05). Serum levels of IL-8 and NO showed positive correlation between superficial gastritis and atrophic gastritis groups (r = 0.881, r = 0.995), whereas no correlation was found in the normal or gastric cancer groups., Conclusion: Serum levels of IL-8 and NO are correlated with CagA(+)HP strain infection. Combined detection of serum level of IL-8, NO and HP-CagA will contribute to the early diagnosis of precancerous lesion in the stomach.

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.

We report the case of a 63 year-old female who presented with a seven-year history of epigastric pain and a sudden overall deterioration. Gastroscopy demonstrated inflammatory aspect and ulceration in the antrum and fundus. Histology showed a lymphocytic infiltrate consistent with low grade mucosa-associated lymphoid tissue lymphoma and cytomegalovirus gastritis. There was no evidence of Helicobacter pylori infection. Other investigations demonstrated two pulmonary foci consistent with lymphomatous infiltration and a reduced CD4 + T-lymphocyte count (85/mm3). Other screening tests including HIV serology were negative. This case of idiopathic CD4 lymphopenia, in conjunction with the other rare cases in the literature, allows us to reevaluate this condition and its unusual clinical presentation with two opportunistic pathologies.

Background: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis., Methods: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years., Results: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates., Conclusions: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis.

Low intake of foods rich in vitamin C is associated with an increased risk of gastric cancer, and geographic variation in average vitamin C intake, therefore, could explain some of the wide international variation in gastric cancer rates. This multicentre study investigated the relationships between plasma levels of vitamin C, as an indicator of vitamin C intake, and gastric cancer rates, markers of gastritis and other socio-demographic variables. Fasting plasma samples from about 1,400 individuals from 9 centres in 7 countries worldwide were assayed for total vitamin C using a fluorometric assay. There was no association between average plasma vitamin C levels and either gastric cancer mortality or incidence rates in the populations studied. Therefore, variation in fasting plasma vitamin C levels, as an indicator of consumption of vitamin C, does not appear to explain any of the wide geographic variation in gastric cancer rates. Furthermore, there was no association between plasma vitamin C levels and Helicobacter pylori infection, low serum levels of pepsinogen A (as a marker of severe chronic atrophic gastritis) or the presence of DNA adducts in blood leukocyte DNA. Multivariate models showed that fasting plasma vitamin C levels were associated positively with female sex, higher levels of education, never having smoked and increasing height and negatively with number of cigarettes smoked per day and increasing weight. This suggests not only that gender and tobacco smoking, in particular, are important predictors of plasma vitamin C levels but also that their effects are consistent throughout the developed world.

A nested case-control study was carried out to investigate the association between Helicobacter pylori infection and gastric cancer risk in Taiwan. A total of 29 patients newly affected with gastric cancer and 220 healthy controls matched with cases on age, sex and residence were selected from a cohort of 9,775 men recruited from 1984 through 1986. Frozen serum samples collected at recruitment examination were tested for IgG antibodies against Helicobacter pylori by an enzyme-linked immunosorbent assay. The average interval between serum collection and cancer diagnosis was 3.1 years. Gastric cancer cases had a higher seropositive prevalence (69%) than matched controls (59%) giving an odds ratio of 1.6 (95%) confidence interval = 0.7-2.6). Compared with previous nested case-control studies, Helicobacter pylori infection in early childhood may be a risk factor for gastric cancer. However, a long induction period seems required for gastro-carcinogenesis associated with Helicobacter pylori infection.