Effect of Helicobacter pylori VacA on gene expression of gastric cancer cells

AIM: To determine the effect of Helicobacter pylori VacA on gene expression of gastric cancer cells. METHODS: Gene expression profile of a gastric cancer cell line, SGC7901, after challenged by VacA^+ and VacA^- H pylori broth culture supernatants (BCS), was detected by the cDNA microarray technique. Cytoskeleton changes of SGC7901 and HeLa cells were observed through high-resolution laser scanning confocal microscopy. RESULTS: A total of 16 000 cDNA clones were detected. The percentage of genes with heterogeneous expression in SGC7901 cells challenged by VacA^+ BCS reached 5%, compared with that challenged by VacA^- BCS. There were 865 genes/EST with 2-fold differential expression levels and 198 genes/EST with 3-fold differential expression levels. Most of these genes were involved in vital cell events including signal transduction, regulation of gene expression, cytoskeleton, apoptosis, stress response and inflammation, cell cycle and tumor development. Cells co-cultured with VacA^+ BCS showed collapsed and disrupted microtubular cytoarchitecture. CONCLUSION: VacA^+ BCS can disrupt cytoskeletal architecture, likely through affecting the expression of cytoskeleton-associated genes, directly induce the expression of tumor promoter-related genes and inhibit the expression of tumor suppressor genes, thus favoring the development of tumors. VacA^+ BCS can also alter the expression of inflammation and stress response genes. This suggests that VacA may play an important role in the pathogenicity of H pylori.

The vacA i1 genotype of Helicobacter pylori is associated with peptic ulcer and gastric cancer:A meta-analysis

There are two genotypes of the vacA intermediate region, il and i2; however, the association between the genotypes and gastroduodenal disease remains to be elucidated. The aim of this article was to investigate the interaction between the genotypes and H. py/ori-associated diseases such as chronic gastritis, peptic ulcer disease （PUD） and gastric cancer. Methods： The meta-analysis was performed in Review Manager 4.2.2. Results： Eleven （ten articles and one abstract） met the inclusion criteria and were included. The il genotype increased the risk of PUD （OR = 1.70, 95% CI： 1.24-2.33, P 〈 0.001） and gastric cancer （OR = 3.90, 95% CI： 2.64-5.78, P 〈 0.001）. Sub-analysis showed that the il genotype was significantly associated with gastric ulcers （OR = 2.59, 95% CI： 1.05-6.35, P = 0.040）, but not with duodenal ulcers （OR = 1.04, 95% CI： 0.61-1.76, P = 0.90）. In addition, the association between the il genotype and PUD and GC existed in studies not only from Europe but also Asia, except for the association between the il genotype and PUD in Asian population. Conclusion： The vacA il genotype is associated with an increased risk of the development of peptic ulcer disease （mainly gastric ulcer） and gastric cancer. In geographical distribution, the association between the il genotype and PUD and GC existed in studies not only from Europe but also Asia, except for the association between the il genotype and PUD in Asian population.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.