• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.14
• /
• pp.5583-5586
• /
• 2014

Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrence may link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is not clear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes our discovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells. We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantly enhance apoptosis, and this upregulation was triggered by COX-2 inhibition. Furthermore, we found that microRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancer tissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis among H. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulating cell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNA targeted therapy in the future.

• Journal of Ginseng Research
• /
• v.44 no.1
• /
• pp.79-85
• /
• 2020

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• Korean Journal of Microbiology
• /
• v.41 no.3
• /
• pp.177-182
• /
• 2005

H. pylori strains were isolated from antral biopsies taken during upper endoscopy in 114 dyspeptic patients with no previous therapy against H. pylori. Rapid urease test, PCR amplification of SSA and cagA gene for H. pylori detection, and Western blot for CagA expression detection were performed. H. pylori infected patients were treated with omeprazole, clarithromycin (a macrolide), and amoxicillin. At 6 weeks after the discontinuation of therapy, the bacterial eradication rate was determined by endoscopy. The resistance rate to clarithromycin and amoxicillin was $20.2\%$ and $0.0\%$, respectively. The clarithromycin resistance was mainly caused by the A2142G mutation in the 23S rRNA gene of H. pylori. MICs of clarithromycin for the A2142G mutant isolates were significantly higher than MICs for the A2143G mutant isolates. H. pylori eradication was obtained in all patients with clarithromycin-susceptible isolates but not in patients with clarithromycin-resistant isolates (P = 0.0001). These results did not appear to be biased by any differences in CagA expression. The resistance of H. pylori to clarithromycin included in the therapeutic regimens is the most important reason for treatment failure. H. pylori antimicrobial susceptibility testing of the gastric biopsy culture should be performed before choosing the first triple therapy in infected patients and the increase in prevalence of clarithromycin resistance in Korea was problematic.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.979-984
• /
• 2016

The incidence rate of stomach cancer in Bali, Indonesia, is estimated to be strikingly lower than that in Japan. We conducted an on-site ecological study to investigate the association between the stomach cancer incidence and Helicobacter pylori (H. pylori) infection. Recruiting 291 healthy persons (136 men and 155 women) from the general population in Bali, Indonesia, we conducted a urea breath test (UBT) to examine H. pylori infection, along with a pepsinogen test to detect chronic atrophic gastritis and urine analysis to estimate sodium and potassium excretion. UBT positivities were 9% (2-15, 95% confidence interval) for men and 7% (1-12) for women, and positive cases for H. pylori IgG antibodies were 1% (0-3) for men and 3% (0-5) for women, significantly lower than the respective values in Japan. Positive pepsinogen tests in Bali were 0% (0-0) for men and 1% (0-4) for women, also significantly lower than the Japanese figures. Computed values for daily salt excretion were $13.3{\pm}4.1g$ (mean${\pm}$SD) for men and $11.1{\pm}3.1g$ for women, as high as corresponding Japanese consumption values. Moreover, the estimated potassium excretion was $3.2{\pm}0.7g$ for men and $2.8{\pm}0.6g$ for women in Bali, significantly higher than the figures in Japan. There were no associations across genetic polymorphisms of IL-beta, TNF-alpha, and PTPN11 with UBT positivity. The low incidence of stomach cancer in Bali may thus mainly be due to the rare H. pylori infection. Namely, the bacterium infection seems to be a critical factor for gastric cancer rather than host or other environmental factors.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.4 no.2
• /
• pp.191-198
• /
• 2001

Purpose: This study was undertaken to investigate the seroepidemiologic pattern of Helicobacter pylori (H. pylori) and hepatitis A virus (HAV) infections in children. Methods: A total of 315 serum samples were obtained from healthy children, living in Gwangju and Chonnam area. All serum samples were assayed for H. pylori IgG level using enzyme immunoassay techniques. HAV IgG level in serum were tested by a competitive radio-immunoassay in 215 subjects. The age-specific seroprevalence of H. pylori and HAV was separately analysed. The concordance of seropositivity and seronegativity between H. pylori and HAV infection was examined by the kappa statistic analysis. Results: Seropositivity was found in 17.5% (55/315) and 30.2% (65/215) of the subjects for H. pylori and HAV, respectively. Cross-tabulation of these data showed that 21 subjects (9.8%) were seropositive and 135 (62.8%) were seronegative for both H. pylori and HAV, 15 (7.0%) were seropositive for only H. pylori and 44 (20.5%) for only HAV. The seroprevalence of H. pylori and HAV increased significantly with age. There was a slight agreement between H. pylori and HAV seropositivity (${\kappa}$=0.26). Conclusion: This study shows a slight similarity in the concordance of seropositivity and seronegativity between H. pylori and HAV infection and provides evidence that H. pylori and HAV may share a common mode of transmission.

• 대한위암학회:학술대회논문집
• /
• 2002.04a
• /
• pp.18-23
• /
• 2002

• 대한위암학회:학술대회논문집
• /
• 2002.04a
• /
• pp.3-8
• /
• 2002

• 대한위암학회:학술대회논문집
• /
• 2002.04a
• /
• pp.24-28
• /
• 2002

• Journal of Gastric Cancer
• /
• v.2 no.2
• /
• pp.59-62
• /
• 2002

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.3 no.2
• /
• pp.151-159
• /
• 2000

Purpose: Recently, a wide application of gastrofiberscopy in the pediatric group have revealed that nodular duodenitis is not an uncommon disease in children and is suspected to be associated with H. pylori infection. The aim of this retrospective study was to investigate the clinical and histopathologic features in children with nodular duodenitis, and to assess the correlations beween both. Methods: During a period of 5 years (Jan. 1995~Dec. 1999), we investigated clinical, endoscopic and histopathologic features of 39 consecutive patients diagnosed as having nodular duodenitis at Pediatric department of Seoul Red Cross Hospital. In 35 children with nodular duodenitis endoscopic biopsy specimens were stained with Hematoxylin & Eosin and Giemsa's stain, and were graded according to the criteria outlined by Triadafilopoulos, Whitehead et al., and Prieto et al.. Statistical analyses were performed with Graph PAD InStat. Results: The prevalence rate of nodular duodenitis was 17.1% and the most frequent chief complaint was abdominal pain (69.2%). Endoscopically grade 1 was the most common (45.7%) and nodular gastritis was coexistent in 28.3%. The most common histology of the duodenum was grade 2 (54.3%), and the most common histologic score of the stomach was 2 (42.9%). H. pylori was found in the duodenum in 37.1%, and in the stomach in 31.4%. The correlation coefficient between the endoscopic grade and the histologic grade of nodular duodenitis was 0.3983 (p=0.0178). And the correlation coefficient between the histologic grade and the grade of H. pylori colonization in the duodenum was 0.5154 (p=0.0018). Conclusion: There was significant correlation between the endoscopic grade and the histologic grade of nodular duodenitis, and was also significant correlation between the histologic grade and the grade of H. pylori colonization in the duodenum. Therfore H. pylori infection should be regarded as an etiologic factor of nodular duodenitis.