Helicobacter pyloripromote gastric cancer cells invasion through a NF-κB and COX-2-mediated pathway

AIM: To examine the effects of Helicobacter pylori(Hpylori) infection on the invasiveness of gastric cancer cells,and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis.The expression of matrix metallopr-oteinase-9 (MMP-9),vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly,the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay. RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC,a nuclear factor κB (NF-κB) inhibitor;(2) the induction of MKN-45 cells invasion by Hpylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects;(3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter. CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway, as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.

Impact of Helicobacter pylori infection on ghrelin and various neuroendocrine hormones in plasma

AIM: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, influences appetite, energy balance, gastric motility and acid secretion. The stomach is the main source of circulating ghrelin. There are inconsistent reports on the influence of Helicobacter pylori (H pylori) infection on circulating ghrelin levels. We sought to elucidate the relationship between ghrelin and various peptides in plasma, with special reference to H pylori.METHODS: Plasma ghrelin levels were measured by radioimmunoassay in 89 subjects who were referred for upper gastrointestinal endoscopy, consisting of 42 H pylori infected and 47 uninfected ones. Plasma gastrin,somatostatin, leptin, insulin-like growth hormone 1 (IGF-1)and chromogranin A concentrations were also measured.Twelve patients were treated with anti- H pylori regimen.RESULTS: Ghrelin circulating levels were greatly decreased in H pylori-positive than negative individuals (194.2±90.2fmol/mL and 250.4±84.1 respectively, P＜0.05), but did not significantly alter following the cure of infection (176.5±79.5 vs 191.3±120.4). There was a significant negative correlation between circulating ghrelin and leptin levels, as well as body mass index, for the whole and uninfected population, but not in H pylori-infected patients. Plasma ghrelin concentrations correlated positively with IGF-1 in H pylori-negative group and negatively with chromogranin A in the infected group.There were no significant correlations among circulating levels of ghrelin, gastrin and somatostatin irrespective of H pylori status.CONCLUSION: H pylori infection influences plasma ghrelin dynamics and its interaction with diverse bioactive peptides involved in energy balance, growth and neuroendocrine function.

Clinical role and importance of fluorescence in situ hybridization method in diagnosis of H pylori infection and determination of clarithromycin resistance in H pylori eradication therapy

H pylori is etiologically associated with gastritis, gas-tric and duodenal ulcers, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Eradicating H pylori may convert rapidly the outcome of related diseases with the use of more accurate diagnostic molecular tests. Indeed some of the tests cannot give the evidence of current infection; H pylori can be detected by noninvasive and invasive methods, the latter requiring an endoscopy. Eradication failure is a big problem in H pylori infection. Recently, clarithromycin resistance in H pylori strains is increasing and eradicati-on therapy of this bacterium is becoming more difficult. Molecular methods have frequently been applied besides phenotypic methods for susceptibility testing to detect clarithromycin resistance due to mutations in the 2143 and 2144 positions of 23S rRNA gene. Fluorescence in situ hybridization (FISH) method on paraffin embedded tissue is a rapid, accurate and cost-effective method for the detection of H pylori infection and to determine clarithromycin resistance within three hours according to the gold standards as a non-culture method. This method can also be applied to fresh biopsy samples and the isolated colonies from a culture of H pylori, detecting both the culturable bacillary forms and the coccoid forms of H pylori, besides the paraffin embedded tissue secti-ons. This technique is helpful for determining the bac-terial density and the results of treatment where clarith-romycin has been widely used in populations to increase the efficacy of the treatment and to clarify the treatment failure in vitro.

Gastric carcinoid in a patient infected with Helicobacter pylori:A new entity?

There are four types of gastric carcinoid tumors, classified according to their histology and malignant potential. Only a few cases of carcinoid tumors in patients infected with Helicobacter pylori （H. pylor/） have been reported so far. We report a patient infected with H. pylori presenting with a small solitary gastric carcinoid tumor with very low proliferative rate and normal gas- trin levels. The tumor was endoscopically removed and the patient received an eradication therapy against H. pylori. No signs of metastatic disease have been found so far during more than 3 year of follow-up. Infection with H. pylori may cause chronic gastritis with normal or elevated gastrin levels, leading to the develop- ment of gastric carcinoids by mechanisms unrelated to gastrin. Enterochromaffin-like cell tumors related to a chronic H. pylori infection may be considered as a distinct type of gastric carcinoid tumors.

Short mucin 6 alleles are associated with H pylori infection

AIM： To investigate the relationship between mucin 6 （MUC6） VNTR length and Hpylori infection. METHODS： Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme （Pvu 11） and the length of the allele fragments was determined by Southern blotting. Hpylori infection was diagnosed by ^14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long （〉 13.5 kbp） or short （≤ 13.5 kbp） and patients were classified according to genotype [long- long （LL）, long-short （LS）, short-short （SS）]. RESULTS： 160 patients were studied （mean age 43 years, 36% were males, 58% H pylori positive）. MUC6 PvuⅡ-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6 genotype, 43% （24/56）, 57% （25/58） and 76% （11/46） were infected with Hpylori, respectively （P = 0.003）. CONCLUSION： Short MUC6 alleles are associated with H pylori infection.

Gastrin and antral G cells in course of Helicobacter pylori eradication: Six months follow up study

AIM： To assess long-term effects of Helicobacter pylori （H pylon} eradication on antral G cell morphology and function in patients with and without duodenal ulcer （DU）.METHODS： Consecutive dyspeptic patients referred to the endoscopy entered the study. Out of 39 Hpylori positive patients, 8 had DU （Hpylori ＋DU） and 31 gastritis （Hpylori＋G）. Control groups consisted of 11 uninfected dyspeptic patients （CG1） and 7 healthy volunteers （CG2）. Basal plasma gastrin （PGL）, antral tissue gastrin concentrations （ATGC）, immunohistochemical and electron microscopic characteristics of G cells were determined, prior to and 6 mo after therapy.RESULTS： We-demonstrated elevated PGL in infected patients compared to uninfected controls prior to therapy.Elevated PGL were registered in all Hpylori＋patients （Hpylori＋DU： 106.78＋22.72 pg/mL, Hpylori＋G： 74.95＋15.63,CGI： 68.59＋17.97, CG2：39.24＋5.59 pg/mL, P〈0.01）.Successful eradication （e） therapy in Hpylori＋patients lead to significant decrease in PGL （Hpylori＋DU： 59.93＋9.40 and Hpylori＋Ge： 42.36＋10.28 pg/mL, P〈0.001）. ATGC at the beginning of the study were similar in infected and uninfected patients and eradication therapy lead to significant decrease in ATGC in Hpylori＋gastritis, but not in DU patients. In the Hpylori＋DU patients, the mean number of antral G cells was significantly lower in comparison with all other groups （P〈0.01）, but after successful eradication was close to normal values found in controls. By contrast, G cell number and volume density were significantly decreased （P〈0.01） in Hpylori＋Ge group after successful eradication therapy （294＋32 and 0.31＋0.02,respectively）, in comparison to values before eradication （416~40 and 0.48~0.09）. No significant change of the G cell/total endocrine cell ratio was observed during the 6 mo of follow up in any of the groups. A reversible increase in G cell secretory function was seen in all infected individuals, demonstrated by a more prominent secretory apparatus. However, differences between DU and gastritis group were identified.CONCLUSION： H py/oriinfection induces antral G cell hyperfunction resulting in increased gastrin synthesis and secretion. After eradication therapy complete morphological and functional recovery is observed in patients with gastritis. In the DU patients some other factors unrelated to the Hpyloriinfection influence antral G cell morphology and function.

Dietary and socio-economic factors in relation to Helicobacter pylori re-infection

AIM:To examine if dietary and socio-economic factors contribute to Helicobacter pylori(H pylori)re-infection. METHODS:The population of patients consisted of subjects in whom H pylori infection had been successfully treated in the past.Patients were divided into two groups:Ⅰ-examined group(111 persons with H pylori re-infection)andⅡ-control group(175 persons who had not been re-infected).The respondents were interviewed retrospectively on their dietary habits and socio-economic factors. RESULTS:A statistically significant lower frequency of fermented dairy products(P<0.0001),vegetables (P=0.02),and fruit(P=0.008)consumption was noted among patients with H pylori re-infection as compared to those who had not been re-infected. CONCLUSION:High dietary intake of probiotic bacteria,mainly Lactobacillus,and antioxidants,mainly vitamin C(contained in fruit and vegetables),might decrease the risk of H pylori re-infection.

Efficacy of one-day quadruple therapy for H pylori infection in Chinese patients

AIM： TO compare the efficacies of one-day quadruple therapy and seven-day triple therapy in Chinese patients. METHODS： Sixty consecutive patients with nonulcer dyspepsia and confirmed H pylori infection were randomized to receive either omeprazole 40 mg, amoxycillin 1 g, and furazolidone 100 mg, all twice a day for 7 d or omeprazole 20 mg （at breakfast and dinner）, amoxicillin 1 g, furazolidone 200 mg, and colloidal bismuth subcitrate 220 mg four times for only one day. H pylori status was determined before and at least 5 weeks after therapy by endoscopy with antral and corpus biopsies for rapid urease test and histology. RESULTS： Hpyloi eradication was successful in 66.67% （20/30） patients in the 7-d group and in 36.67% （11/30） patients in the 1-day group （P = 0.037）. Side effects were induced by the treatment in 13.3% （4/30） patients of each group, but these were all self-limiting, shortlasting, and did not require any specific treatment. CONCLUSION： The one-day quadruple therapy is less effective than the one-week regimen in curing H pylori infection in Chinese patients.

ASSOCIATION OF HELICOBACTER PYLORI INFECTION WITH PRECANCEROUS LESIONS AND STOMACH CANCER:A CASE-CONTROL STUDY IN YANGZHONG COUNTY

Previous study has raised H' pylori infection as a suspected biologic risk factor for gastric cancer. Acomparative case-control study involving precancerous lesions and gastric cancer was conducted inYanzhong county, an area with one of the highest rates of gastric cancer in China to study the relatlonshipbetween the H' pylori infection and gastric cancer. Subjects in the study were all randomly selected Partici-pants of a screening program for gastric cancer sponsored by the Cancer Institute of CAMS in cooPerationwith Yangzhong county Hospital' Totally, l25 normal controls, lO8 superficial gastritis, l l1 atrophic gas-tritis and 110 gastric cancer patients were included in our study according to endoscopy and pathology re-sult. Status of H. pylori infection was evaluated by measuring Ig G antibody in plasma with ELISA assay.Our result showed Odds ratios of H' pylori infection were higher among gastritis and cancer groups, 4. 5(95 % CI 2. 5~7. 9) for superficial gastritis, 6. 3 (95% CI 3. 4~ 12) for atrophic gastritis, 3. 3 (95 % CI1. 9~5. 9) for gastric cancer. It was found in our study that consumption of pickled vegetables and drink-ing dirty water increased the relative risk of H' pylori lnfection for both precancerous lesions and gastriccancer and that H. pylori infection had higher risk of atrophic gastritis and gastric cancer for males and alsohigher risk of atrophic gastritis for olders. Our results strongIy support the casual role played by H. pyloriinfection in the carcinogenic process of gastric mucosa.