Gastric cancer is the second most common cause of cancer-related death in the world. A growing body of evidence indicates that inflammation is closely associated with the initiation, progression, and metastasis of many tumors, including those of gastric cancer. In addition, approximately 60% of the world's population is colonized by Helicobacter pylori, which accounts for more than 50% of gastric cancers. While the role of inflammation in intestinal and colonic cancers is relatively well defined, its role in stomach neoplasia is still unclear because of the limited access of pathogens to the acidic environment and the technical difficulties isolating and characterizing immune cells in the stomach, especially in animal models. In this review, we will provide recent updates addressing how inflammation is involved in gastric malignancies, and what immune characteristics regulate the pathogenesis of stomach cancer. Also, we will discuss potential therapeutics that target the immune system for the efficient treatment of gastric cancer.
Adaptive Immunity/*immunology ; B-Lymphocytes/immunology ; Cytokines/immunology ; Gastritis/immunology ; Helicobacter Infections/immunology ; Helicobacter pylori/immunology ; Humans ; Immunity, Innate/*immunology ; Immunotherapy/methods ; Receptors, Cytokine/immunology ; Stomach Neoplasms/diagnosis/*immunology/therapy ; T-Lymphocytes/immunology ; Tumor Microenvironment/*immunology

Eosinophils ; immunology ; Food Hypersensitivity ; etiology ; Gastritis ; etiology ; Humans ; Infant ; Male ; Milk Hypersensitivity ; complications ; immunology ; Milk Proteins ; immunology

OBJECTIVETo 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.

METHODSBased 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).

RESULTSIn 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).

CONCLUSIONSThe 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.

Adult ; Antibodies, Bacterial ; blood ; Female ; Gastritis ; blood ; immunology ; microbiology ; Gastritis, Atrophic ; blood ; immunology ; microbiology ; Helicobacter Infections ; blood ; immunology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Precancerous Conditions ; blood ; immunology ; microbiology ; Stomach Neoplasms ; blood ; immunology ; microbiology

In vitro subcultures of bacteria can lead to genetic and phenotypic changes. This study aimed at investigating the effect of repeated subcultures on the adhesion, motility, cytotoxicity, and gastric inflammation caused by Helicobacter pylori. H.pylori SS1 strain was subcultured 64 times on agar plates containing Brucella broth and 5% bovine calf serum. The adhesion, motility, cytotoxicity, and gastric inflammation produced in Mongolian gerbils were compared between the first and 64th subcultured strain. The adhesion rates, following 3 hr exposure of AGS cells to either the first strain or the 64th-transferred strain, were 21% and 12%, respectively. The motility of the 64th-transferred strain decreased significantly when compared to the 1st strain (9.1 mm vs. 15.1 mm). The cytotoxicity index tended to be higher in the first strain than in the 64th-transferred strain (73.7% vs. 69.2%). The initial infection rate on the gerbils showed no difference between the two strains. However, chronic gastric inflammation of the first strain-infected gerbils was somewhat more severe than that of the 64th-transferred strain-infected gerbils. Therefore, the use of repeatedly subcultured strains of H. pylori in virulence experiments can lead to different results from thoses of the original strain.
Animals ; Bacterial Adhesion ; Gastritis/immunology/*microbiology ; Gerbillinae ; Helicobacter Infections/immunology/*microbiology ; Helicobacter pylori/growth & development/*pathogenicity ; Male ; Virulence

OBJECTIVES: Clinical presentation of Helicobacter pylori (H. pylori) infection has marked variation mainly due to the strain diversity and host susceptibility. Although H. pylori is identified as a major risk factor for gastric and duodenal ulcers, the ulcerogenic or pathogenic strain has not been documented yet. The objective of this study was to investigate antigenic types of the ulcerogenic strain of H. pylori. METHODS: The sera of 64 patients were tested by Western blot using Helicoblot 2.0 for six major anti-H. pylori antibodies, together with CLO test and histological examination of gastric biopsy tissues. Thirty-five, nine and 20 patients had duodenal ulcer, gastric ulcer and chronic active gastritis, respectively. The antigenic types of H. pylori were analyzed in 54 patients with positive H. pylori infection. In this study, H. pylori was divided into four serotypes according to the presence and absence of CagA and VagA: type I; CagA (+) and VacA(+), type Ia: CagA (+) and VacA(-), type Ib: CagA(-) and VacA(+), and type II: CagA(-) and VacA(-). RESULTS: There was no difference in the number of bands for six antigens: 3.2 +/- 1.4, 3.0 +/- 1.2 and 3.1 +/- 1.4 in 35 duodenal ulcer, 7 gastric ulcer and 12 chronic gastritis, respectively. The band with 119 kDa was 90.7%, which was the most common band with the order of 35, 30, 26.5, 89 and 19.5 kDa. Type I, la and Ib were positive in 22.2, 42.6 and 27.8%, respectively, which were significantly higher than type II (p < 0.05). There was no difference in the positive rates of four urease subtypes between the four serotypes.
Adult ; Aged ; Antigens, Bacterial/classification* ; Antigens, Bacterial/analysis ; Blotting, Western ; Chronic Disease ; Comparative Study ; Duodenal Ulcer/pathology ; Duodenal Ulcer/microbiology* ; Duodenal Ulcer/immunology ; Gastric Mucosa/pathology ; Gastric Mucosa/microbiology ; Gastritis/pathology ; Gastritis/microbiology ; Gastritis/immunology ; Helicobacter Infections/immunology* ; Helicobacter pylori/immunology* ; Human ; Middle Age ; Serotyping ; Stomach Ulcer/pathology ; Stomach Ulcer/microbiology* ; Stomach Ulcer/immunology ; Substances: Antigens, Bacterial

A serologic test for antibodies is useful for diagnosis of Helicobacter pylori(H.pylori) infection in children. We evaluated the reliability of H.pylori IgG antibody titer in grading the severity of infection in children. We surveyed the sero-prevalence of H.pylori infection in 300 healthy school children (13 to 15 years old). Thirty-four percent(102 of 300 children) were sero-positive for H.pylori. Of the 102 sero-positive children, 70 underwent gastroscopic examination. Ninety percent of sero-positive children(63 of 70 children) were proven to be H.pylori infected. All children with H.pylori infection had histologically proven gastritis, and its severity did not correlate with the IgG antibody titer. Although a serologic test is useful to identify H.pylori infection in children, it can not predict the severity of H.pylori associated gastritis.
Adolescent ; Antibodies, Bacterial/*blood ; Gastritis/diagnosis/immunology/*microbiology ; Helicobacter Infections/diagnosis/*immunology ; Helicobacter pylori/*immunology ; Human ; Immunoglobulin G/*blood ; Support, Non-U.S. Gov't

OBJECTIVETo explore the immune mechanism of moxibustion on protecting gastric mucosa injury.

METHODSForty healthy SD rats were randomly divided into four groups: a blank group, a model group, a moxibustion acupoint group and a moxibustion non-acupoint group, 10 rats in each one. Eight days before model establishment, moxibustion at "Zusanli" (ST 36), "Zhongwan" (CV 12), "Guanyuan" (CV 4), "Pishu" (BL 20) and "Weishu" (BL 21) was applied in the moxibustion acupoint group while these acupoints' controlled points were selected in the moxibustion non-acupoint group, and no treatment was given in the model group, once a day in three groups for continuous 16 days. The helicobacter pylori (Hp) model was established by intragastric administration of Hp. HE staining microscopic examination was used to observe inflammation severity in gastric mucosa, and enzyme-linked immunosorbent assay (ELISA) was adapted to measure content of heat shock protein (HSP) 72, TNF-alpha and IL-1beta, and real-time quantitative PCR was used to measure the expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA and MyD88 mRNA in peripheral blood mononuclear cells, and western blot method was used to measure content of NFkappaB and IkappaBalpha in peripheral blood mononuclear cells.

RESULTSCompared with the blank group, the expression of HP could be seen in the smear of gastric mucosa by Gram's staining in the model group; the inflammation severity score was obviously increased as well as content of serum HSP 72 and TNF-alpha and IL-1beta in gastric tissue; and expression of TLR2, 4 mRNA, CD14 mRNA, MyD88 mRNA, NFkappaB was increased (P < 0.01), but the expression of IkappaBalpha was reduced (P < 0.05). After the moxibustion, the inflammation severity score was reduced in the moxibustion acupoint group, and the content of serum HSP 72 was increased, and the expression of TNF-alpha and IL-1beta in gastric tissue and expression of TLR2 mRNA, TLR4 mRNA, CD14 mRNA, MyD88 mRNA and NFkappaB were reduced (P < 0.01), but the expression of IkappaBalpha was increased (P < 0.05). The differences between the moxibustion non-acupoint group and the model group were not significant (P > 0.05).

CONCLUSIONThe pretreatment of moxibustion at acupoints could induce the over expression of serum HSP 72. By combining TLR 2 and 4 receptors to trigger receptor signal transduction pathways, the releases of downstream signal substances are regulated; as a result, the releases of related immune substances are regulated to relieve the gastric mucosa injury of rats with HP gastritis.

Acupuncture Points ; Animals ; Female ; Gastritis ; immunology ; therapy ; Helicobacter Infections ; genetics ; immunology ; therapy ; Helicobacter pylori ; physiology ; Humans ; Interleukin-1beta ; genetics ; immunology ; Male ; Moxibustion ; NF-kappa B ; genetics ; immunology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; genetics ; immunology

BACKGROUND/AIMS: This study was designed to investigate the role of gastric acid in the extent of H. pylori-induced gastritis. METHODS: Twenty eight mice were innoculated with live H. pylori. They were allocated into four groups. Mice in group I received no treatment, group II mice were treated with sham injection, group III received 125microgram/kg body weight of pentagastrin, while group IV received 250microgram/kg body weight of pentagastrin subcutaneously three times a week. After 7 months, the mucosal pH, H. pylori density, neutrophils and monocytes infiltration, and the degree of atrophy were assessed in the stomach. RESULTS: In the gastric body, the densities of H. pylori were not different among groups. The degree of neutrophil infiltration was significantly lower in group IV compared to other groups (p<0.05). The degree of monocyte infiltration was also significantly lower in group IV than group III (p<0.05). In the gastric antrum, there was no significant difference of the H. pylori density, neutrophil and monocyte infiltration, and degree of atrophy among the groups. The mice with the gastric mucosal pH lower than mean of 3.2 had significant lower level of H. pylori density (1.4 vs. 2.4, p=0.04), and infiltration of neutrophils (0.9 vs. 2.3, p=0.018), and monocytes (1.2 vs. 1.8; p=0.011) than the those with mucosal pH above 3.2 in the body of stomach. CONCLUSIONS: Gastric acid plays a role in suppressing the proximal propagation of H. pylori-induced gastritis to the body of stomach.
Animals ; Female ; Gastric Acid/*metabolism ; Gastric Mucosa/pathology ; Gastritis/immunology/*microbiology ; Helicobacter Infections/*immunology/microbiology ; *Helicobacter pylori/isolation & purification ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred C57BL ; Models, Animal

Antibodies, Bacterial ; blood ; Antigens, Bacterial ; biosynthesis ; Bacterial Proteins ; biosynthesis ; Carrier Proteins ; biosynthesis ; Gastritis ; microbiology ; Helicobacter Infections ; immunology ; Helicobacter pylori ; immunology ; isolation & purification ; Humans ; Recombinant Proteins ; biosynthesis

OBJECTIVETo study the correlation between the Th1/Th2 balance in the peripheral blood and Pi-Wei damp-heat syndrome (PDS) in chronic gastritis (CG).

METHODSFifty-one patients with CG of PDS were recruited, including 22 cases with predominant damp (PDS-D), 9 case with predominant heat (PDS-H), and 20 case with simultaneous onset of damp and Heat (PDS-DH). Besides, 10 healthy volunteers were recruited as the healthy control group. H. pylori (HP) infection was detected by fast urea enzyme, and the expressions of Th1 type cytokines interferon-gamma (IFN-gamma), interleukin-12 (IL-12), and Th2 type cytokines interleukin-4 (IL-4), interleukin-10 (IL-10) in serum were detected by luminex technology.

RESULTSThe HP infection rate was 41.18% (21/51) in the PDS patients, obviously higher than that in the healthy control group (10.00%,1/10), showing statistical difference (P<0.05). The HP infection rate was 45.45% (10/22) in PDS-D, 22.22% (2/9) in PDS-H, and 45.00% (9/20) in PDS-DH. The HP infection rate in PDS-D and PDS-DH was significantly higher than that of the healthy control group, showing statistical difference (P<0.05). There was no statistically significant difference in the expressions of peripheral blood IFN-gamma, IL-12, IL-4, and IL-10 between the PDS patient group and the healthy control group (P>0.05). But the expressions of IFN-gamma and IL-12 showed an increasing trend in the PDS patient group, while the expression of IL-4 showed a decreasing trend. The expressions of IFN-gamma, IL-12, IL-4, and the ratios of IFN-gamma/IL-4 and IL-12/IL-4 were also higher in PDS-DH group than in the PDS-D group and the PDS-H group, but with no statistical significance (P>0.05).

CONCLUSIONThe occurrence of Pi-Wei damp-heat CG was possibly correlated with the imbalance of Th1/Th2. Damp and heat pathogen might be important pathogenic factors leading to Th1 type cytokine immunoreaction.

Adult ; Case-Control Studies ; Chronic Disease ; Cytokines ; blood ; Female ; Gastritis ; diagnosis ; immunology ; pathology ; Helicobacter Infections ; diagnosis ; immunology ; pathology ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology