Antigens, Bacterial ; genetics ; metabolism ; Bacterial Proteins ; genetics ; metabolism ; Child ; Child, Preschool ; DNA, Bacterial ; genetics ; Gastritis ; pathology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections ; microbiology ; pathology ; Helicobacter pylori ; genetics ; Humans ; Immunohistochemistry ; Peptic Ulcer ; microbiology ; pathology ; Polymerase Chain Reaction

Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA s- and m- region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacA s1/m2 genotype and gastritis cases, and a significant correlation between vacA s1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacA s1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*genetics ; Bacterial Proteins/*genetics ; DNA, Bacterial/genetics ; Female ; Gastritis/genetics/microbiology/pathology ; Genotype ; Helicobacter Infections/*epidemiology/*microbiology/pathology ; Helicobacter pylori/*genetics/isolation & purification ; Humans ; Male ; Middle Aged ; Peptic Ulcer/genetics/microbiology/pathology ; Polymerase Chain Reaction ; Saudi Arabia ; Virulence Factors/genetics ; Young Adult

OBJECTIVETo determine the influence of Helicobacter pylori (H. pylori) on gastric cancer-related antigen MG7 expression.

METHODSThe H. pylori infection and the expression level of antigen MG7 in gastric mucosa were determined by HE stain, PCR, ELISA and immunohistochemistry in 291 patients with H. pylori-related conditions, among whom 34 were followed-up.

RESULTSNo significant difference was found between H. pylori-negative and H. pylori-positive intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium in positive rate of antigen MG7 expression. There was significant difference between H. pylori-negative and H. pylori-positive superficial gastritis in the positive rate of MG7 expression (P < 0.05). During follow-up, one of 3 H. pylori-negative cases turned to be H. pylori-positive, and its MG7 expression turned to be higher at the same time. Three of 31 H. pylori-positive patients were discovered as having early gastric cancer, among whom one with antigen MG7 expression (+ + +) was found to have a reduced Mg7 expression accompanied with H. pylori eliminutied after operation.

CONCLUSIONThere is correlationship between H. pylori infection and MG7 expression in superficial gastritis. Although the MG7-positive lesions with H. pylori infection shows a benign nature in morphology, they also have the potential risk of developing into gastric cancer. Therefore, they should be followed up, during which special attention should be paid to patients with increased MG7 expression.

Antibodies, Bacterial ; blood ; Antigens, Neoplasm ; biosynthesis ; DNA, Bacterial ; genetics ; Enzyme-Linked Immunosorbent Assay ; Gastric Mucosa ; metabolism ; microbiology ; pathology ; Gastritis ; metabolism ; microbiology ; Helicobacter Infections ; metabolism ; microbiology ; Helicobacter pylori ; genetics ; growth & development ; immunology ; Humans ; Immunohistochemistry ; Polymerase Chain Reaction ; Stomach Diseases ; metabolism ; microbiology ; Stomach Ulcer ; metabolism ; microbiology

OBJECTIVETo clarify the role of these cyclins in human gastric cancer.

METHODS38 gastric cancer patients, 29 first degree relatives of gastric cancer patients, as well as 18 healthy subjects were included. The mRNA expression of cyclins D1, D2, D3 and E in gastric biopsies was evaluated by RT-PCR analysis using specific primers. Histomorphological features such as intestinal metaplasia, atrophy, H. pylori infection and severity of gastritis were determined by the updated Sydney System.

RESULTSSignificant mRNA overexpression was found for cyclins D2, D3 and E compared with healthy normal specimen, but cyclin D1 expression was not different between tumor and normal tissues. In addition, cyclin D2 and D3 overexpression was significantly more frequent in first degree relatives than in healthy controls (P < 0.05). Among the various pathological findings, the overexpression of cyclins D2 and E was associated with intestinal metaplasia, and the overexpression of cyclin D3 was associated with intestinal metaplasia as well as atrophy. The overexpression of cyclins D2 and D3 was significantly correlated with H. pylori infection. No correlation was observed between the overexpression of cyclin D1 and any pathological variables.

CONCLUSIONThe overexpression of cyclins D2, D3 and E is a frequent event in patients with gastric cancer and their first degree relatives and may be an early event in gastric carcinogenesis.

Adult ; Aged ; Aged, 80 and over ; Cyclin D1 ; genetics ; Cyclin D2 ; Cyclin D3 ; Cyclin E ; genetics ; Cyclins ; genetics ; Family Health ; Gastritis ; genetics ; Gene Expression Regulation, Neoplastic ; Helicobacter Infections ; genetics ; microbiology ; Helicobacter pylori ; growth & development ; Humans ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Stomach ; metabolism ; microbiology ; pathology ; Stomach Neoplasms ; genetics ; pathology

OBJECTIVETo establish an animal model of gastric cancer by long-term infection of Helicobacter pylori (H.pylori) and to elucidate the pathogenesis by proteomics analysis.

METHODSFifty male Mongolian gerbils (4-5 week-old and weighted 60-100 g) were infected with H.pylori and the gastric tissues were obtained after the infection at 3, 6, 12 and 24 months. Histological changes were evaluated by H-E staining of the gastric tissue sections. Detection of H.pylori was performed by in-vitro culture of fresh gastric tissue samples, PCR amplification of H.pylori 16s rRNA and localization by silver staining. In addition, proteins extracted from gastric tissue samples were subjected to two-dimensional electrophoresis (2-DE) at various infection time points. Protein spots with increased quantity over the course of H.pylori infection were selected and analyzed by LC-MS/MS. Finally, differentially expressed proteins between human gastric cancer tissue samples and lymph nodes were analyzed by real-time RT-PCR.

RESULTSColonization of H.pylori was observed in gastric tissue of gerbils as early as 3 months after H.pylori infection, and persisted till 24 months. Pathological examination of infected animals showed various histological changes including acute gastritis, atrophic gastritis, intestinal metaplasia and gastric carcinoma. Seventy-eight differentially expressed proteins were identified by proteomics analysis, among which 36 proteins were up-regulated and 42 were down-regulated. Analyzed by LC-MS/MS, ten proteins were identified, including lactate dehydrogenase, ATP synthase, fatty acid-binding protein, COX5B, peroxiredoxin-4, peroxide reductase, transgelin, succinyl-CoA ligase, keratin and protein disulfide-isomerase A2, among which transgelin, ATP synthase and lactate dehydrogenase were highly expressed in human gastric carcinoma and lymph nodes.

CONCLUSIONSH.pylori infection induces the expression of transgelin, ATP synthase and lactate dehydrogenase, implying possible roles in the pathogenesis of gastric diseases including cancer.

Animals ; Disease Models, Animal ; Gastritis ; microbiology ; pathology ; Gerbillinae ; Helicobacter Infections ; complications ; metabolism ; Helicobacter pylori ; genetics ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Male ; Metaplasia ; Microfilament Proteins ; metabolism ; Muscle Proteins ; metabolism ; Proteomics ; Proton-Translocating ATPases ; metabolism ; RNA, Ribosomal, 16S ; analysis ; Stomach Neoplasms ; metabolism ; microbiology ; Tandem Mass Spectrometry