• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.231-240
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• 2007

It has been reported the higher incidence rate of gastric cancer in our country. Helicobacter pylori (H. pylori), that exhibited a higher infection rate among Korean people, has been known as a cofactor to cause cancer. Therefore, the aim of this study was to identify correlations among overexpressions of COX-2 (Cyclooxygenase-2) gene, p53 mutation and cell proliferation index related to H. pylori. Taking 28 cases of gastric cancer with H. pylori detection, immunohistochemical staining for COX-2, p53 and Ki-67 were performed. In the H. pylori positive group, the well differentiated type and diffuse type of gastric cancer were distributed in larger area and the expression rate of COX-2 was revealed high. The H. pylori negative group showed higher p53 expression than that of the positive group. However, the statistical correlation between H. pylori and histopathological factors was not observed. The significantly higher expression of COX-2 had were observed in both well differentiated type and the intestinal type of gastric cancer. Although there were no statistical significances, this showed a higher inclination of manifest in the early gastric cancer. p53 exhibited a higher tendency of expression in the well differentiated, moderately differentiated and the intestinal type of gastric cancers including the early gastric cancer. Ki-67 was expressed in a significantly higher fashion along with the increase of age. In addition, it was significantly expressed in well differentiated type and intestinal type of gastric cancer. Therefore, these results suggest that H. pylori, COX-2, p53, and Ki-67 influences on the new occurrence of gastric cancer and its development procedures. In the future, the more researches would be required to focus on a larger category relative to gene expressions in gastric cancer.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2006.08a
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• pp.26-26
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• 2006

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5583-5586
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• 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 Veterinary Science
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• v.21 no.3
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• pp.39.1-39.15
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• 2020

Background: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. Objectives: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. Methods: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. Results: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. Conclusions: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.63-68
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• 2002

위의 parietal cell 혹은 대식세포와 유사한 세포 내부에서 H. pylori가 발견된다는 보고가 있기는 하나 일반적으로 H. pylori는 Shigella와 같은 침습성 세균은 아닌 것으로 알려져 있다. 그럼에도 불구하고 H. pylori에 감염된 위점막에는 많은 수의 호중구를 위시한 염증세포의 침윤이 관찰되는데 H. pylori가 위상피세포에 부착할 경우 위상피세포를 자극하여 interleukin-8을 위시한 cytokine을 발현케하고 이에 의하여 호중구 등의 염증세포가 몰려들게 된다. 한편 고유층에 몰려든 호중구에서는 다시 interleukin-8을 위시한 일련의 호중구 활성화 chemokine을 분비하여 염증반응을 증폭해 나갈 것이다. 호중구에서 발현되는 myeloperxidase나 활성산소 등도 위점막의 조직 손상에 기여할 것이다. 위상피세포를 덮고 있는 점액층은 위상피세포를 보호한다고 알려져 있으나 H. pylori 감염의 경우 점액층에 의하여 H. pylori의 운동성이 증가하고 이것이 위상피세포로부터의 cytokine 발현을 자극하여 염증반응을 증폭하는 데 관여할 가능성도 있다. H. pylori는 위상피세포에 대하여 apoptosis를 유도함과 동시에 고유층에 몰려든 호중구에 대하여는 apoptosis를 억제케하여 궁극적으로 염증반응을 증폭 및 지속시켜 나가는 쪽으로 작용한다. 한편 H. pylori는 위상피세로로부터 COX-2의 발현을 증가시키는데 이는 위상피세포의 APOPTOSIS를 억제하는 방향으로 작용한다. 이외에 H. pylori의 urease에 의하여 발생한 암모니아나 H. pylori 자신이 분비하는 세포독소가 세포 손상을 유발할 가능성도 있다. 상술한 여러 독성 인자들 중 어느 하나가 단독으로 작용하기보다는 여러 인자가 같이 동시에 또는 시차를 두고 작용할 가능성이 많다고 생각된다.

• Nutritional Sciences
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• v.9 no.3
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• pp.152-158
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• 2006

Helicobacter pylori (H. pylori) infection rapidly stimulated either COX-2 or 5-LOX and released arachidonic acid metabolites that have been considered as pivotal mediators in H. pylori-induced inflammatory responses. To determine whether red ginseng extract (RGE) can suppress the biosynthesis of 5(S)-hydroxyeicosatetraenoic acids (HETE), a precursor metabolite of leukotrienes B4 (LTB4) in H. pylori-provoked inflammatory responses in gastric epithelial cells, the biosynthesis of monohydroxy fatty acids was measured using radioactive arachidonic acid and validated by RP-HPLC using non-radioactive AA as substrate in AGS cells cocultured with H. pylori (ATCC 43504) with or without pretreatment of RGE. Among three known major HETEs, H. pylori infection specifically induced the biosynthesis of $^{14}C-5(S)-HETE$ rather than the complex of $^{14}C-15S-/^{14}C-12(S)-HETE$ from $^{14}C-AA$, concomitantly obtained by HPLC(p<0.01). RGE, 1 to $100{\mu}g/ml$, selectively suppressed H. pylori-stimulated $^{14}C-5(S)-HETE$ production implying the attenuation of 5-lipoxygenase activity, of which was similar to known LOX inhibitor NDGA $(10{\mu}M)$ (p<0.01). However, the amount of 5(S)-HETE was significantly reduced by higher dose of RGE $(100{\mu}g/ml)$ (p<0.05). These results indicated that LOX pathway might be one of principle pathogenic mechanisms of H. pylori and red ginseng could be a nutraceutical against H. pylori infection through inhibiting action of LOX activity.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.227-236
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• 2006

Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

• Korean Journal of Food Science and Technology
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• v.48 no.5
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• pp.502-507
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• 2016

This study was designed to investigate the beneficial effects of fermented Rhus verniciflua stem bark extract (RVSBE) on the stomach. We evaluated RVSBE for its antimicrobial activity against Helicobacter pylori (H. pylori), along with its ability to reduce the viability of human gastric cancer AGS cells. In addition, its anti-inflammatory effect was examined by evaluating nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. RVSBE showed antimicrobial activity, as 2.0 mg of the extract produced a clear inhibition zone of 4.0 mm. RVSBE inhibited the growth of AGS cells by 20% at concentrations ranging from 0.25-1.0 mg/mL. Regarding the anti-inflammatory effects of RVSBE, at 0.1-1.0 mg/mL, the extract showed more than 75% inhibition of NO production. In addition, cells treated with 0.25 mg/mL RVSBE showed a 25% decrease in iNOS mRNA levels compared to those in the LPS-treated cells. These results suggest that RVSBE may have significant inhibitory effects on inflammatory mediators, and therefore, may be a potential anti-inflammatory candidate.

• BMB Reports
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• v.36 no.1
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2863-2868
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• 2014

Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigated for association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene for GC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10, 2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874 cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG (odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18, and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07, 95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysis by Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58, 95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions: This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GC in Asians and Indians.