• BMB Reports
• /
• 제40권2호
• /
• pp.142-150
• /
• 2007

Epigenetic alterations, represented by aberrant DNA methylation, are deeply involved in human cancers. In gastric cancers, tumor-suppressor genes are inactivated more frequently by promoter methylation than by mutations. We recently showed that H. pylori infection, a potent gastric carcinogenic factor, induces methylation of specific genes in the gastric mucosae. When the methylation levels were analyzed in the gastric mucosae of healthy volunteers, cases with a single gastric cancer, and cases with multiple gastric cancers, who have increasing levels of risks for gastric cancers, there was a significant increasing trend in the methylation levels among the individuals without current H. pylori infection. This finding unequivocally showed the presence of an epigenetic field for cancerization. The degree of the field defect was measured more conveniently using methylation levels of marker genes than using those of tumor-suppressor genes. The presence of an epigenetic field for cancerization has been indicated for liver, colon, Barrett's esophageal, lung, breast, and renal cancers. Since decreased transcription is involved in the specificity of methylated genes, it is likely that specific genes are methylated according to carcinogenic factors. These findings emphasize the usefulness of DNA methylation as a marker for past exposure to carcinogens and future risk of cancer development.

• 한국미생물·생명공학회지
• /
• 제46권3호
• /
• pp.261-268
• /
• 2018

Differences in host ethnicities and geographical distributions may influence the genetic variation and pathogenesis of Helicobacter pylori strains, particularly with respect to those with a high risk of gastric cancer and in Asian Enigma regions. We simultaneously identified H. pylori virulence-associated genes involved in inflammation and cell damage in Thai and Korean dyspeptic patients. The virulence-associated gene cagA, cagA genotypes (East Asian and Western type cagA), vacA genotypes (s- and m-), oipA, and sabA were detected in Thai and Korean dyspeptic patients by polymerase chain reaction (PCR), real-time PCR, and DNA sequence analysis. Comparisons between the two regions showed that cagA, East Asian type cagA, and vacA s1/m1 in Korean dyspeptic patients occurred at rates of 100%, 86.67%, and 88.89%, respectively (p < 0.05). The oipA- and sabA-positive samples were significantly more predominant in the Korean population (95.56%, 91.11%) than in the Thai population (32%, 34%). DNA sequence analysis revealed differences in the patterns of cytosine-thymine dinucleotide repeats of oipA and sabA among the two populations of dyspeptic patients. Our results indicate that the H. pylori strains detected in the two regions were divergent, and strains colonizing the Korean dyspeptic patients may be more virulent than those in the Thai population. Our data may help explain H. pylori pathogenesis in Asian Enigma areas with a low gastric cancer incidence. However, other factors involving H. pylori infection in these two regions should be further analyzed.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• 제16권2호
• /
• pp.123-126
• /
• 2013

$M\acute{e}n\acute{e}$trier's disease is a rare protein-losing gastropathy characterized by hypertrophic gastric fold, foveolar hyperplasia, and hypoproteinemia with resulting peripheral edema. It is clinically evident as nonspecific gastrointestinal symptoms, including abdominal discomfort, nausea and vomiting, abdominal pain, weight loss, diarrhea, and edema. Pediatric $M\acute{e}n\acute{e}$trier's disease usually has an insidious onset and progressive, chronic clinical course and it spontaneously resolves in weeks or months. The pathogenesis of $M\acute{e}n\acute{e}$trier's disease is not clearly understood. $M\acute{e}n\acute{e}$trier's disease is thought to be associated with some gastric infections. But the cause of $M\acute{e}n\acute{e}$trier's disease is unknown, an association with cytomegalovirus (CMV) and Helicobacter pylori has been suggested. In Korea, We present the first a case of pediatric $M\acute{e}n\acute{e}$trier's disease with positive evidence of CMV and H. pylori.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권17호
• /
• pp.7911-7916
• /
• 2015

Serum anti-Helicobacter pylori antibodies and pepsinogens (PGs) have been used as gastric cancer screening and gastric mucosal status markers. Nepal is a low risk country for gastric cancer. However, the mountainous populace in the northern region culturally linked to Tibet as well as Bhutan, a neighboring country, have a high risk of GC. We collected gastric biopsy specimens and sera from 146 dyspeptic patients living in Kathmandu, Nepal. We also examined the sera of 80 volunteers living in the mountainous regions of the Himalayas. The optimal cut-off was calculated for serum biomarkers against the histology. Kathmandu patients (43.8%) were serologically positive for H. pylori infection, which was significantly lower than that for the mountainous (61.3%, P = 0.01). The same results also found in the prevalence of PG-positivity, PG I levels and PG I/II ratios (P = 0.001, P<0.0001 and P = 0.03, respectively). Moreover, the PG I/II ratios were significantly, and inversely correlated with the OLGA score (r = -0.33, P<0.009). The low incidence of gastric cancer in Nepal can be attributed to low gastric mucosal atrophy. However, the mountainous subjects have high-risk gastric mucosal status, which could be considered a high-risk population in Nepal.

• Journal of Gastric Cancer
• /
• 제14권3호
• /
• pp.196-203
• /
• 2014

Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. Materials and Methods: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: nonulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1996년도 춘계학술대회
• /
• pp.197-197
• /
• 1996

Helicobacter pylori (H. pylori) is a microaerophilic spiral bacterium and infection by it in the human stomach causes gastritis, furthermore, it is considered to be involved in the pathogenesis of peptic ulcers and the development of gastric carcinoma. We assessed the inhibitory activity of new antiulcer drugs against Helicobacter pylori. The activities of new antiulcer agents against Helicobacter pylori strains were determined by the standard agar dilution method with blood agar base #2, supplemented with 5% sheep blood and 4 antibiotics to support growth of these organisms. They were inoculated by multipoint inoculator and incubated at 37$^{\circ}C$ for 3 days under microaerophilic atmosphere. The MIC of antiulcer agents was the lowest concentration that inhibited visible growth of these organisms. According to results of various biochemical tests, these bacteria were identified as Helicobacter pylori strains. And the MIC results showed that the strains were very susceptible to omeprazole and YJA20379s. Some of YJA20379s were more potent than omeprazole. These results suggest that our new antiulcer drugs have potent inhibitory activity against Helicobacter pylori, so that our new antiulcer drugs might be useful for the clinical eradication of gastrointestinal Helicobacter pylori.

• Parasites, Hosts and Diseases
• /
• 제59권4호
• /
• pp.363-368
• /
• 2021

Despite the synergistic effect of Opisthorchis viverrini and Helicobacter pylori co-infection on pathogenesis of severe hepatobiliary abnormalities (HBA) including advanced periductal fibrosis and replace with cholangiocarcinoma (CCA) have been established, the immune response to H. pylori in O. viverrini infected population has never been explored. Hence, this study aimed to investigate the antibody responses to 2 immunogenic H. pylori proteins in O. viverrini-infected patients with HBA and CCA. The risk analysis by multinomial logistic regression revealed that GroEL seropositivity was associated with higher risks of hepatobiliary abnormalities and CCA with adjusted odds ratios (95% confidence intervals) of 2.11 (95% CI=1.20-3.71, P=0.008) and 2.13 (95% CI=1.21-3.75, P=0.009), respectively. These findings indicate that GroEL seropositivity might be a biomarker for early detection of O. viverrini associated HBA and CCA.

• Journal of Ginseng Research
• /
• 제36권2호
• /
• pp.135-145
• /
• 2012

Previously, we reported that Helicobacter pylori-associated gastritis and gastric cancer are closely associated with increased levels of hydrogen sulfide ($H_2S$) and that Korean red ginseng significantly reduced the severity of H. pylori-associated gastric diseases by attenuating $H_2S$ generation. Because the incubation of endothelial cells with $H_2S$ has been known to enhance their angiogenic activities, we hypothesized that the amelioration of $H_2S$-induced gastric inflammation or angiogenesis in human umbilical vascular endothelial cells (HUVECs) might explain the preventive effect of Korean red ginseng on H. pylori-associated carcinogenesis. The expression of inflammatory mediators, angiogenic growth factors, and angiogenic activities in the absence or presence of Korean red ginseng extracts (KRGE) were evaluated in HUVECs stimulated with the $H_2S$ generator sodium hydrogen sulfide (NaHS). KRGE efficiently decreased the expression of cystathionine ${\beta}$-synthase and cystathionine ${\gamma}$-lyase, enzymes that are essential for $H_2S$ synthesis. Concomitantly, a significant decrease in the expression of inflammatory mediators, including cyclooxygenase-2 and inducible nitric oxide synthase, and several angiogenic factors, including interleukin (IL)-8, hypoxia inducible factor-1a, vascular endothelial growth factor, IL-6, and matrix metalloproteinases, was observed; all of these factors are normally induced after NaHS. An in vitro angiogenesis assay demonstrated that NaHS significantly increased tube formation in endothelial cells, whereas KRGE pretreatment significantly attenuated tube formation. NaHS activated p38 and Akt, increasing the expression of angiogenic factors and the proliferation of HUVECs, whereas KRGE effectively abrogated this $H_2S$-activated angiogenesis and the increase in inflammatory mediators in vascular endothelial cells. In conclusion, KRGE was able to mitigate $H_2S$-induced angiogenesis, implying that antagonistic action against $H_2S$-induced angiogenesis may be the mechanism underlying the gastric cancer preventive effects of KRGE in H. pylori infection.

• Clinical and Experimental Pediatrics
• /
• 제49권3호
• /
• pp.268-272
• /
• 2006

목 적 : Helicobacter pylori 재감염률은 내시경적 생검만이 가능했던 시대에는 $^{13}C$-요소 호기 검사의 출현 이후에 비해 높게 보고되었다. 소아는 일반적으로 침습적인 내시경적 생검을 시행하기 용이치 않다. 본 연구는 $^{13}C$-요소 호기 검사와 내시경적 생검에 의한 재감염률을 비교하고, 그 차이에 영향을 미치는 인자를 찾고자 하였다. 방 법 : H. pylori 감염으로 치료받고 박멸이 확인된 소아들을 대상으로 하였다. 박멸 확인 후 18개월이 경과한 시점에 재감염을 확인하기 위하여 내시경적 생검(n=34명, 평균 연령 $11.5{\pm}3.7$세) 혹은 $^{13}C$-요소 호기 검사를(n=38명, 평균 연령 $10.0{\pm}3.6$세) 시행하였다. 첫 진단 시 내시경적 생검으로 위전정부 및 체부에서 세 절편을 채취하여 urease 검사, Giemsa 염색 및 Warthin-Starry 염색이 모두 양성으로 나오거나 생검 조직에서 H. pylori균이 배양된 경우 감염된 것으로 판정하였고, 박멸 치료 1-3개월 후 모든 검사상 음성인 경우 박멸된 것으로 판정하였다. $^{13}C$-요소 호기 검사는 최소 4시간 금식 후 75 mg의 $^{13}C$-요소를 주스에 섞어 마시도록 하는데, 복용 전 및 30분 후 Helikit(Isodiagnostika, Alberta, Canada)를 이용하여 숨을 불어넣도록 하고 delta $^{13}C$ per mil이 4.00 이상일 때를 양성으로 판독하였다. 결 과 : 내시경적 생검을 시행하였을 때 재감염률은 35.3%(12/34)였다. 내시경적 생검을 받은 모두가 당시 복부 증상이 있어 $^{13}C$-요소 호기 검사를 시행한 경우에 비해 복부 증상이 있는 경우가 유의하게 많았다(P=0.000). $^{13}C$-요소 호기 검사를 시행하였을 때 재감염률은 13.2%(5/38)였다. 추적 관찰 시 복부 증상이 있는 경우 재감염률이 유의하게 높았으며(P=0.008), 성별(P=0.694), 연령별(P=0.827). 궤양과 비궤양 간(P=0.730), 치료 방법 간에는(P=0.087) 재감염률에 차이를 보이지 않았다. 결 론 : 한국 소아에서 H. pylori 박멸 후 18개월이 경과하였을 때 비침습적인 $^{13}C$-요소 호기 검사를 이용한 재감염률은 13.2%이다. 내시경적 생검은 정확하나 침습적이어서 특히 무증상인 소아의 경우 이를 기피할 확률이 높아, 순응도에 따라 많은 영향을 받는다. 소아에서 재감염률 조사를 평가할 때에는 비침습적이면서 간편한 방법인가를 고려하여야 할 것이다.

• 한국미생물학회:학술대회논문집
• /
• 한국미생물학회 2002년도 추계학술대회
• /
• pp.180-182
• /
• 2002

Substantial genomic diversity has been expected among clinical isolates of H. pylori. We have suggested that the two complete H. pylori genomes already sequenced may be insufficient for providing a discriminatory tool for typing clinical isolates as well as an insight into the genomic diversity, which enable to establish strategy for control of H. pylori infection. In this study, we determine the nucleotide sequence of the entire genome of Korean strain 51 and compare it with two reported genomic sequences to suggest validity for extensive genomic sequencing of H. pylori. The genome of H. pylori 51 consists of a circular chromosome with a size of 1,591,297 bp, which is corresponding to $95.4\%\;and\;96.8\%$ of the 26695 and J99 chromosome length, respectively. We predict that there are 1,454 open reading frames (ORFs) in 51, representing $91.4\%\;and\;97.2\%$ of the reported numbers of ORF of 26695 and J99, respectively. In contrast to 26695 and J99 that have 123 and 65 strain-specific genes, respectively, of the 1,454 genes, only 39 genes are unique to 51. Differences in genomic organization between 51 and each foreign strain were greater than between 2 foreign strains in pair wise entire sequence alignments by BLASTN. Particularly, the extent of genomic rearrangement observed between 51 and 26695 is higher than between 51 and J99. Multiple sequence alignment of orthologous genes among 3 strains showed that 51 is genetically closer to 26695 rather than J99. Phylogenetic analysis of nonsynonymous and synonymous mutation indicated J99 has the longest branch length in the unrooted phylogenetic tree, suggesting that J99 has higher mutation rate than the other 2 strains.