Cheol Min Shin

Prevalence of Primary and Secondary Antimicrobial Resistance of Helicobacter pylori in Korea from 2003 through 2012

Antimicrobial resistance of Helicobacter pylori (H. pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H. pylori isolates to antibiotics and to characterize the risk factors associated with antimicrobial resistance in Korea.

Stomach cancer risk in gastric cancer relatives: interaction between Helicobacter pylori infection and family history of gastric cancer for the risk of stomach cancer.

Goals To identify the risk of gastric cancer in first-degree relatives of gastric cancer patients, and to determine if there is an interaction between Helicobacter pylori (H. pylori) infection and family history of gastric cancer in gastric carcinogenesis. Background It is unclear to what degree a family history of gastric cancer is associated with stomach cancer risk in Korea. Study From May 2003 to July 2008, 428 gastric cancer patients and 368 controls were included in the analyses. Logistic regression models including age, sex, family history of gastric cancer, residency during childhood, smoking, monthly income, spicy food diet and H. pylori status were evaluated to estimate the odds ratios (ORs) of developing gastric cancer. Results Adjusted OR for gastric cancer increased 3-fold for subjects reporting first-degree relatives with gastric cancer [OR 2.85, 95% confidence interval (CI): 1.83-4.46]. The association was strong in the 40 to 59 years age group (OR 4.00, 95% CI: 2.06-7.76), and became weaker in subjects older than 60 years of age (OR 1.81, 95% CI: 0.95-3.46). Compared with the uninfected subjects without a family history, subjects with both a family history and H. pylori infection had a 5-fold increased risk (OR 5.32, 95% CI: 2.76-10.25). Conclusions After adjusting for environmental factors and H. pylori infection, a family history of gastric cancer remained independently associated with gastric cancer. The interaction between H. pylori infection and family history of gastric cancer might be a rationale for H. pylori eradication in the gastric cancer relatives as a strategy to prevent gastric cancer.

Clinical Outcomes of Two-Week Sequential and Concomitant Therapies for Helicobacter pylori Eradication: A Randomized Pilot Study

The eradication rate with PPI‐based standard triple therapy for Helicobacter pylori infection has fallen considerably. One recent innovation is sequential therapy with PPI and three antibiotics, but the complexity of this regimen may reduce its usability. Concomitant administration of nonbismuth quadruple drugs (concomitant therapy) is also an effective treatment strategy. To investigate which regimen is a reasonable choice for Korean population, we performed two pilot studies with sequential and concomitant therapies.

Helicobacter pylori‐Negative Gastric Cancer in South Korea: Incidence and Clinicopathologic Characteristics

Background and Aim:  It is difficult to determine the exact incidence rate of Helicobacter pylori (H. pylori) infection‐negative gastric cancer (HPIN‐GC) because H. pylori detection rates decrease with the progression of gastric atrophy and intestinal metaplasia. The aim of this study was to evaluate the incidence and clinicopathologic characteristics of HPIN‐GC in South Korea.

Ten-day sequential therapy is more effective than proton pump inhibitor-based therapy in Korea: A prospective, randomized study

Background and Aims:  The eradication rate of proton pump inhibitor (PPI)‐based triple therapy for Helicobacter pylori (H. pylori) infection has decreased, mainly due to increasing antibiotic resistance, especially against clarithromycin. It has been reported that a 10‐day sequential strategy can produce good outcomes. The aim of this prospective study was to assess the efficacy of sequential therapy as the first‐line treatment for the eradication of H. pylori in Korea.

Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis

CpG island hypermethylation is frequently found during gastric carcinogenesis. We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative methylation‐specific PCR in 459 patients with gastric cancer (GC), 137 with dysplasia, and 248 controls. Controls were divided into four subgroups sorted by current H. pylori infection status (active vs past or negative infection) and the presence of intestinal metaplasia (IM). In controls, active H. pylori infection significantly increased methylation levels in THBD, LOX, and HAND1 (all P < 0.001), and hypermethylation of THBD, HAND1, and APC was associated with IM. Aberrant DNA hypermethylation was correlated well with activity of H. pylori‐associated gastritis. However, methylation levels in LOX, HAND1, THBD, and p41ARC remained increased in cases with past H. pylori infection compared to those that were H. pylori negative (all P < 0.05). Hypermethylation of THBD, and possibly p16, was significantly associated with GC, regardless of the status of current H. pylori infection (all P < 0.05). These results suggest that aberrant DNA hypermethylation caused by H. pylori‐associated gastritis occurs in a gene‐specific manner along gastric carcinogenesis, which can be persistent even after the disappearance of H. pylori. Aberrant methylation of THBD might provide a link between H. pylori infection and development of GC. (Cancer Sci 2010)

Validation of diagnostic tests for Helicobacter pylori with regard to grade of atrophic gastritis and/or intestinal metaplasia.

Background and Aims:  To evaluate the validity of the biopsy‐based tests (histology, culture, and urease test) and serology in detecting current Helicobacter pylori infection against a background of atrophic gastritis (AG) or intestinal metaplasia (IM).

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.

Effect of Helicobacter pylori Eradication on Functional Dyspepsia

Background/Aims This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses. Methods A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated. Results Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (< 50%) of 12.5% and 11.9%; and refractory response of 25.0% and 6.0%, respectively (P = 0.015). In addition, the responder group (complete + satisfactory response) at 1 year showed improvement of activity and chronic inflammation in both the antrum and corpus (all P < 0.001). Multivariate analysis showed that H. pylori eradication (OR, 5.81; 95% CI, 1.07-31.59) and symptom improvement at 3 month (OR, 28.90; 95% CI, 5.29-157.82) were associated with the improvement of dyspepsia at 1 year. Among the successfully eradicated FD patients (n = 67), male (P = 0.013) and higher initial BMI (P = 0.016) were associated with the improvement of dyspepsia at 1 year. Conclusions H. pylori eradication improved FD symptoms, as well as gastritis at 1 year, suggesting that inflammation mediates FD.

c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells.

MicroRNAs (miRNAs) regulate post‐transcriptional gene expression in various physiological and pathological processes, including viral infections. The miR‐17‐92 cluster encodes six miRNAs (miR‐17‐5p, miR‐18a, miR‐19a, miR‐19b, miR‐20a, and miR‐92a‐1) which are transactivated by c‐Myc. Because hepatitis B virus transactivates c‐Myc, the interaction between the miR‐17‐92 cluster and HBV replication was examined in this study. Inducing HBV replication in a human hepatoma cell line increased miR‐17‐5p, miR‐20a and miR‐92a‐1 expression. HBV‐induced overexpression of miR‐17‐92 was reversed by c‐Myc knockdown. Antisense peptide nucleic acids against miR‐20a and miR‐92a‐1 augmented HBV replication. A computational analysis yielded potential binding sites for miR‐20a and miR‐92a‐1 in the HBV genome. The direct interaction between these two miRNAs and target regions in HBV transcripts was confirmed by luciferase reporter analysis. These results demonstrated negative feedback suppression of HBV replication by the miR‐17‐92 polycistron. J. Med. Virol. 85: 969–978, 2013.