metallothionein and Helicobacter-Infections

Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions.. Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection.. MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers.. Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.

Topics: Cyclin-Dependent Kinase Inhibitor p21; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metallothionein; Metaplasia; Precancerous Conditions; Stomach Neoplasms

Overall, 50 and 30 gastric antral biopsy samples of gastric cancer (case group) and gastritis (control group) patients were included into study, respectively. All biopsy samples were collected considering the exclusion criteria including patients with a history of consumption of tobacco, alcohol, and anti-. A negative correlation was revealed between age and clinical manifestations with the ΔCt value of the. The results of the current study opened a view for more investigation on the stunning roles of

Topics: Bacterial Proteins; Biopsy; Case-Control Studies; DNA, Complementary; Focal Adhesion Kinase 1; Gastric Mucosa; Gastritis; Gene Expression; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Metallothionein; Stomach Neoplasms

Metallothionein (MT), a low-molecular-weight protein with a high affinity for divalent heavy metal ions, is involved in many pathophysiological processes, including metal homeostasis, detoxification, cell proliferation and protection against oxidative damage. We previously found that MT in gastric mucosa plays a role in protecting against Helicobacter pylori (H. pylori)-induced gastritis at the early stage of infection. H. pylori-induced chronic gastric inflammation is shown to be associated with gastric carcinogenesis. Thus, to examine whether gastric MT contributes to protection against H. pylori-induced chronic inflammation, we compared histological changes in the gastric mucosa of MT-null and the wild-type mice at 53 weeks after inoculation three times with H. pylori SS1. As a result, we observed disruption of the gastric mucosa in MT-null mice, but not in the wild-type mice, even at the late stage of H. pylori-infection. Evaluation of pathological changes in gastric specimens by the updated Sydney grading system revealed that scores related to chronic inflammation and polymorphonuclear cell activity were higher in infected MT-null mice than those in the wild-type mice. Furthermore, a higher score for metaplasia was also observed in the MT-null stomach. These results suggested that MT might be involved in protecting against H. pylori-induced gastric chronic inflammation associated with carcinogenesis.

Topics: Animals; Chronic Disease; Disease Progression; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Male; Metallothionein; Mice; Stomach Neoplasms

Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy.. Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years.. MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05).. The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.

Topics: Anti-Bacterial Agents; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Metallothionein; Stomach Neoplasms

Infection with the gastric pathogen Helicobacter pylori (H. pylori) causes chronic gastritis, peptic ulcer, and gastric adenocarcinoma. These diseases are associated with production of reactive oxygen species (ROS) from infiltrated macrophages and neutrophiles in inflammatory sites. Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that can act not only as a metal-binding protein, but also as a ROS scavenger. In the present study, we examined the role of MT in the protection against H. pylori-induced gastric injury using MT-null mice. Female MT-null and wild-type mice were challenged with H. pylori SS1 strain, and then histological changes were evaluated with the updated Sydney grading system at 17 and 21 wk after challenge. Although the colonization efficiency of H. pylori was essentially the same for MT-null and wild-type mice, the scores of activity of inflammatory cells were significantly higher in MT-null mice than in wild-type mice at 17 wk after challenge. Histopathological examination revealed erosive lesions accompanied by infiltration of inflammatory cells in the infected MT-null mice but not in wild-type mice. Furthermore, activation of NF-kappaB and expression of NF-kappaB-mediated chemokines such as macrophage inflammatory protein-1alpha and monocytes chemoattractant protein-1 in gastric cells were markedly higher in MT-null mice than in wild-type mice. These results suggest that MT in the gastric mucosa might play an important role in the protection against H. pylori-induced gastric ulceration.

Topics: Animals; Chemokine CCL2; Chemokine CCL3; Chemotaxis, Leukocyte; Cytoprotection; Disease Models, Animal; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Leukocytes; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Reactive Oxygen Species; Stomach Ulcer; Time Factors

Metallothionein (MT) expression was investigated in pregnant mice infected with H. pylori or H. felis and their fetuses and pups. Mice, healthy or infected with H. pylori or H. felis (n = 18/group), were sacrificed 2 weeks after impregnation or 4 weeks postpartum. Pups were sacrificed as fetuses, after birth, or at ages 11 or 28 days. Whole fetuses, stomachs, small intestines, and livers were assayed for MT. MT was increased (P<0.05) by two- and threefold in fetuses from H. pylori- and H. felis-infected mothers, respectively, compared to control fetuses. Stomach MT of H. felis-infected pregnant mice, and newborns and 28-day pups from H. felis-infected mothers, was elevated (P<0.05) twofold compared to that of control mice and pups. Liver MT was decreased (P<0.05) in H. felis-infected mice 4 weeks postpartum (18%) and in their 11-day (69%) and 28-day (53%) pups, while small intestinal MT was decreased in H. felis-infected pregnant mice (17%), H. felis-infected mice 4 weeks postpartum (19%), and their 11-day pups (35%), compared to control mice. H. felis infection altered MT levels of pregnant mice, their fetuses and pups, and mice postpartum, which may be a response to the marked inflammation.

Topics: Animals; Animals, Newborn; Female; Fetus; Helicobacter felis; Helicobacter Infections; Helicobacter pylori; Metallothionein; Mice; Mice, Inbred C57BL; Postpartum Period; Pregnancy

Topics: Animals; Anti-Bacterial Agents; Croton; Gene Expression; Helicobacter Infections; Helicobacter pylori; Liver; Metallothionein; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Phytotherapy; Plant Extracts; Stomach

Mucosal damage by H. pylori infection is mainly caused by neutrophils producing large quantities of reactive oxygen species (ROS). Metallothionein (MT) an intracellular, low-molecular, cysteine-rich protein, which is inducible by dietary zinc (Zn), has been implicated in sequestering ROS. This study examines the effects of Zn supplementation on Helicobacter colonisation and associated gastritis and the relationship with gastric MT levels.. C57Bl/6 mice were inoculated with either 10(8) H. pylori or H. felis and were infected for 4 weeks or 6 and 12 weeks, respectively. Mice infected with H. pylori (4 weeks) or H. felis (6 weeks) were treated with either Zn acetate (ZnA; 1 mg/ml), or Zn sulphate (ZnSO4; 5 mg/ml) for 2 weeks with 0.1 ml oro-gastric gavage twice daily. H. pylori load and H. felis colonisation density were determined by culture and microscopy, respectively. MT levels and H. felis-induced gastritis were also determined.. Zn treatment showed no significant difference in Helicobacter load and gastric MT, however, ZnSO4 treatment showed a significant (p<0.05) increased in gastric MT in H. felis infected mice. Both Zn-treated groups showed a significant (p<0.05) difference in gastritis score in the antrum of the stomach within the basal and submucosal compartments compared to H. felis-infected controls.. We found that H. felis-induced gastritis can be attenuated by short-term treatment of Zn. This observation suggests that Zn alone may be effective for the suppression of gastric mucosal inflammation induced by Helicobacter.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gastritis; Helicobacter felis; Helicobacter Infections; Metallothionein; Mice; Mice, Inbred C57BL; Stomach; Zinc Acetate; Zinc Sulfate

Helicobacter pylori a primary cause of gastritis and peptic ulcer disease, is associated with increased production of reactive oxygen species within the gastric mucosa. Metallothionein (MT), a low-molecular-weight, cysteine-rich, metal-binding ligand, has been shown to sequester reactive oxygen species and reduce tissue damage. This study investigates the role of MT in H. pylori-induced gastritis in mice.. Control (MT+/+) and MT-null (MT-/-) mice were inoculated with either 1 x 108H. pylori or H. felis, and were infected for 4, 8 and 16 weeks or 8 weeks, respectively. H. pylori load was determined by culture. Myloperoxidase activity and MT levels were also determined.. The stomachs of H. felis-infected mice were more severely inflamed than those of H. pylori-infected mice. H. felis-induced gastritis was more severe (p =.003) in MT-/- than in MT+/+ mice. MT-/- mice also had higher (60%; p <.05) H. pylori loads than MT+/+ mice 4 weeks after infection but not 8 or 16 weeks after infection. Myloperoxidase activity with H. pylori was similar between MT+/+ and MT-/- mice. Thirty-three per cent greater (p <.05) myloperoxidase activity was observed in MT-/- than in MT+/+ mice infected with H. felis. In MT+/+ mice infected with H. pylori, liver MT was increased by 33 and 39% (p <.05) at 8 and 16 weeks, respectively, whereas gastric MT increased by 46% (p <.05) at 4 weeks and declined to baseline levels at 8 and 16 weeks.. Mice lacking MT are more susceptible to H. pylori colonization and gastric inflammation, indicating that MT may be protective against H. pylori-induced gastritis.

Topics: Animals; Colony Count, Microbial; Gastric Mucosa; Gastritis; Helicobacter felis; Helicobacter Infections; Helicobacter pylori; Liver; Metallothionein; Mice; Mice, Knockout; Peroxidase; Reactive Oxygen Species; Stomach