• BMB Reports
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• 제36권1호
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• pp.82-94
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• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

• 생명과학회지
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• 제10권6호
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• pp.630-639
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• 2000

The gastric pathogen Helicobacter pylori(H. pylori) establishes long-term chronic infection that can lead to atrophic gastritis, intestinal metaplasia, and gastric cancer. H. pylori, which express cytotoxic genes is now recohnized as a cause of peptic ulcer and is also a major risk factor for the development of gastric adenocarcinoma. We performed this study 1) to assess the detection rate of H. pylori according to direct investigation of bacteria of gastric biopsy specimen and two serologic tests of GAP test and Helico blot 2.0 system in the symptomatic and non-symptomatic group 2) to evaluate and compare the efficacy of two serologic tests of GAP test and Helico blot 2.0 system for the diagnosis of H. pylori infection. Forty-nine patients were positive for H pylori infection based on direct investigation of bacteria by histology. The detection rates of H. pylori infection based on direct investigation of bacteria by histology. The detection rates of H. phlori were significantly lower in gastric cancer than in other gastroduodenal disease(p<0.05). The concordance of two serologic tests of GAP test and Helico blot 2.0 system is poor. There was no statistically significant difference between the expression rate of CagA and VacA in the symptomatic and non-symptomatic group. Although Helico blot 2.0 system may not displace GAP test, it was a very sensitive serologic test for the diagnosis of H. pylori infection and it was used to detect IgG antibodies to H. pylori-specific antigens, including CagA, VacA and the various urease subunit. Our data suggest that further investigation is needed to determine whether or not the serologic expression of cytotoxic gene may be clinical usefulness of diagnostic methods in the gastroduodenal disease.

• Journal of Gastric Cancer
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• 제15권4호
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• pp.246-255
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• 2015

Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.

• Journal of Ginseng Research
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• 제38권1호
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• pp.8-15
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• 2014

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-${\kappa}B$. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-$1{\beta}$, and iNOS; protein level of phospho-$I{\kappa}B{\alpha}$(which reflects the activation of NF-${\kappa}B$); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-$1{\beta}$, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of $I{\kappa}B{\alpha}$ and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of poly-morphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pyloriinduced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-$1{\beta}$, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.142-154
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• 2021

Purpose: Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Materials and Methods: Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Results: Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Conclusions: Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.

• Clinical Endoscopy
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• 제57권2호
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• pp.181-190
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• 2024

Background/Aims: Radiofrequency ablation (RFA) is the first-line therapy for dysplastic Barrett's esophagus (BE). Therefore, cryotherapy has emerged as an alternative treatment option. This study aimed to compare the efficacies of these two techniques based on the rates of complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Adverse events and recurrence have also been reported. Methods: An electronic search was conducted using the Medline (PubMed), Embase, LILACS, and Google Scholar databases until December 2022. Studies were included comparing cryotherapy and RFA for treating dysplastic BE with or without early esophageal neoplasia. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Three retrospective cohort studies involving 627 patients were included. Of these, 399 patients underwent RFA, and 228 were treated with cryotherapy. There was no difference in CE-IM (risk difference [RD], -0.03; 95% confidence interval [CI], -0.25 to 0.19; p=0.78; I²=86%) as well as in CE-D (RD, -0.03; 95% CI, -0.15 to 0.09; p=0.64; I²=70%) between the groups. The absolute number of adverse events was low, and there was no difference in the recurrence rate. Conclusions: Cryotherapy and RFA were equally effective in treating dysplastic BE, with or without early esophageal neoplasia.

• Journal of Digestive Cancer Research
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• 제8권2호
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• pp.81-90
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• 2020

배경 및 목적: Helicobacter pylori (H. pylori) 제균 치료는 위암 발병률을 줄이는 것으로 알려져 있다. 그러나 만성 위축성 위염, 장상피화생 및 이형성증이 있는 일반 집단에서도 위암의 발생 위험을 예방할 수 있는지에 대해서는 여전히 논란의 여지가 있다. 우리는 포괄적인 메타분석을 통해 이에 대한 연구를 수행해 보고자 한다. 방법: 2019년 12월까지 H. pylori 제균 치료가 위암에 미치는 영향을 평가한 논문들을 PubMed, KoreaMed, EMBASE 및 Cochrane Library에서 검색하였다. 전암성 병변(만성 위축성 위염/장상피화생/이형성증), 지역(아시아/비아시아) 및 추적관찰기간에 따라 하위 집단 분석을 수행하였다. 모든 데이터는 Review Manager 5.3으로 분석하였다. 결과: 본 연구에서는 총 6편의 전향적 무작위 연구가 최종 분석에 포함되었다. 전체 집단에서 H. pylori 제균 치료는 위암 발생 위험을 유의하게 감소시켰다(위험비[RR]=0.56; 95% 신뢰구간[CI]: 0.41-0.77, p<0.01). 또한, 하위 집단 분석을 보면, H. pylori 제균 치료는 아시아 지역과 10년 이상의 추적관찰을 시행한 집단에서 위암 발생 위험을 현저하게 감소시키는 것을 보여주었다(RR=0.54, 95% CI: 0.39-0.75, p<0.01 및 RR=0.51; 95% CI: 0.35-0.73, p<0.01). 그러나, 전암성 병변 유무에 따른 하위 집단 분석에서는 유의한 결과가 도출되지 않았다(전암성 병변이 있는 군, RR=0.86, 95% CI: 0.47-1.59, p=0.63; 전암성 병변이 없는 군, RR=0.42, 95% CI: 0.02-7.69, p=0.56). 결론: H. pylori 제균 치료는 일반 집단, 특히 아시아 지역에서 위암 발생 위험을 낮춘다. 제균 치료의 위암 예방 효과는 10년 이상 장기간 추적관찰 하였을 때 유의하다. 한편, 전암성 병변이 있는 일반 집단에서 위암 예방을 위해 H. pylori 제균 치료를 시행하는 것은 아직 근거가 명확하지 않아 권고하기 어렵다. 따라서 앞으로 이에 대한 더 많은 연구가 필요하다.

• Journal of Gastric Cancer
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• 제1권1호
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• pp.55-59
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• 2001

Purpose: Several studies of an endoscopic mucosal resection(EMR) have been reported, but reports about benign protruding lesions that arise at the scar of EMR for early gastric cancer (EGC) or a gastric adenoma are rare. The purpose of this study was to elucidate endoscopic and histological characteristics of benign protruding lesions which arise at the scar of an EMR for EGC and a gastric flat adenoma. Materials and Methods: In 101 lesions (73 gastric flat adenomas and 28 EGCs) from 96 patients, 16 lesions developed new protruding lesions that arose at the scar of the EMR. We retrospectively analyzed the endoscopic findings of initial and protruding lesions, and several other clinical factors (H. pylori infection, eradication therapy, and proton pump inhibitor (PPI) or H2-blocker use). Results: 1. The mean duration until detection of the protruding lesion was 8.9 months ($1.5\∼27$). Protruding lesions arose at the scar of the EMR in 1 of 28 EGCs ($3.6\%$) and from 15 of 73 gastric flat adenomas ($20.5\%$). All of the patients were men. 2. With respect to the endoscopic findings, the shapes of the protruding lesions were as follows: 10 Yamada (Y) I, 4 Y-II, 1 Y-III, and 1 flat lesion. Histological examination of the protruding lesions revealed regenerating hyperplasia in 5 lesions, intestinal metaplasia in 5, and both in 6. 3. The incidence of these lesions was higher in cases of tubular adenomas with focal high-grade dysplasia than in cases of tubular adenomas without dysplasia (p<0.05). 4. The incidence of H. pylori infection was higher in patients ($81.7\%$) who developed a protruding lesion than in those ($51.8\%$) who did not develop (p=0.029); also, the incidence of use of PPI was higher in those patients (p=0.045). However, eradication therapy for H. pylori and duration of use of PPI or H2-blocker showed no difference between groups. Conclusions: It may be possible that the potential hyperplasia that may reside in normal mucosa surrounding EGC or a gastric adenoma might awaken during the healing process of the EMR ulcer and develop to benign protruding lesions. And, H. pylori and PPI might also be related to the development of the protruding lesions.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제5권1호
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• pp.1-10
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• 2002

목적: 소아기는 알코올이나 약물 등에 의한 자극이 거의 없는 시기로 H. pylori 감염의 자연 경과와 단기간의 영향을 연구하기에 적합한 시기이다. 최근 H. pylori 감염의 기전으로 중요시되고 있는 위상피세포 증식과 세포사에 대해 소아에서 알아보고자 하였다. 방법: 1996년 5월부터 2001년 6월까지 이화여자대학교 목동병원 소아과에서 소화기 증상으로 내시경을 시행하여 H. pylori 감염으로 진단된 58예와 감염 음성 40예를 대상으로 하였다. H. pylori 감염 양성은 조직학적으로 H. pylori 균이 관찰되고, CLO 검사와 ureC PCR이 전부 양성인 경우로 하였다. 위생검 조직에서 개정된 시드니 체계를 이용하여 조직 소견을 분석하고, proliferating cell nuclear antigen (PCNA) 발현으로 위 상피세포 증식의 정도를, in situ terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) 방법으로 세포사의 정도를 조사하였다. 결과: 1) H. pylori 감염 양성에서 다핵형 중성구의 활동성(P=0.000), 만성 염증(P=0.000), 상피손상(P=0.000), 림프여포(P=0.000)의 정도가 감염 음성에 비하여 유의하게 높았다. H. pylori 감염 양성에서 장형화생은 관찰되지 않았다. 2) H. pylori 감염 양성에서 세포 증식 지표는 $67.8{\pm}18.13$으로, 음성 $54.8{\pm}14.46$에 비하여 유의하게 높았다(P=0.000). 세포 증식 지표는 H. pylori 밀도가 증가할수록(r=0.277, P=0.007), 다핵형 중성구의 활동성이 증가할수 (r=0.280, P=0.007), 만성염증이 증가할수록(r=0.284, P=0.006) 증가하였다. 3) 세포사 지표는 H. pylori 감염 양성에서 $0.44{\pm}0.447$, 음성에서 $0.14{\pm}0.196$으로 감염 양성에서 음성보다 유의하게 높았다(P=0.000). 세포사 지표는 H. pylori 밀도가 증가할수록(r=0.472, P=0.000), 다핵형 중성구의 활동성이 증가할수록(r=0.370, P=0.001), 만성 염증이 증가할수록(r=0.483, P=0.000) 증가하였다. 4) 세포 증식 지표가 증가할수록 세포사 지표는 유의하게 증가하였다(r=0.353, P=0.003). 결론: H. pylori 감염 소아에서 세포 증식 지표와 세포사 지표가 유의하게 증가하였으며 상관성도 유의하였다. 이는 소아에서 위 상피세포 증식과 세포사가 H. pylori의 병인에 중요함을 시사하며, 앞으로 세포 증식과 세포사의 기전, 유발 요인 외에 다른 병독 인자와의 관련성에 대한 연구가 필요하리라 생각된다.