• Journal of Gastric Cancer
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• 제2권2호
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Journal of Digestive Cancer Research
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• 제10권1호
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• pp.9-15
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• 2022

Proton pump inhibitors (PPIs), a potent gastric acid inhibitor, are widely used in gastric acid-related diseases such as gastroesophageal reflux disease and peptic ulcer, and are known as the most frequently used drugs worldwide. However, as the frequency of use increases, the number of cases of long-term PPI therapy without clear indications is increasing. Recently, there have been concerns about the risk of gastric cancer in patients with long-term PPI users. Potential mechanisms for the association between PPI and gastric cancer include enterochromaffin-like cell proliferation due to hypergastrinemia caused by gastric acid suppression, progression of atrophic gastritis, and corpus-predominant type through interaction with Helicobacter pylori (H. pylori) infection. Several epidemiologic studies showed controversial results on the issue, and it is difficult to prove a causal relationship between PPI and gastric cancer. Nevertheless, long-term PPI should be administered cautiously based on individual risk-benefit profile, specifically among those with history of H. pylori infection, in high-risk region of gastric cancer.

• Journal of Digestive Cancer Research
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• 제12권1호
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• pp.6-14
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• 2024

Gastric cancer is the 4th leading cause of death worldwide. The primary cause of gastric cancer is known to be Helicobacter pylori (H. pylori). The advancement of molecular biology has enabled the identification of microbiomes that could not be confirmed through cultivation, and it has been revealed that the microbial communities vary among normal mucosa, atrophic gastritis, intestinal metaplasia, and gastric cancer. It has also been confirmed that the composition of the microbial community differs depending on the presence or absence of H. pylori. Whether changes in the microbiome are causative factors in the carcinogenesis process is not yet clear. Experiments using animal models and in vitro studies on the role of microbes other than H. pylori in the carcinogenic process are underway, but the data is still insufficient.

• 대한핵의학회지
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• 제39권6호
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• pp.456-463
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• 2005

목적: FDG PET에서 위(stomach)에 보이는 다양한 FDG 섭취 양상들이 임상적으로 어떠한 의미가 있는지 알아보고 유의한 병변의 특징적 양상을 밝혀 내어 좀 더 정확한 PET 판독을 유도하여 임상적 처치에 도움이 되고자 하였다. 대상 및 방법: 2003년 6월에서 2004년 8월까지, 15개월 동안 FDG PET과 위 내시경을 모두 시행한 위 절제술을 받지 않은 피검자들 중에서 두 검사간 간격이 1주일 이내인 총 38명을 대상으로 하여 후향적으로 연구하였다. PET 영상의 분석은 섭취 정도의 측면에서 시각적 섭취 정도와 max.SUV를 사용하였고, 섭취 모양의 측면에서 국소적, 미만성, 비대칭성의 섭취 양상을 인자로 분석하였다. 내시경 소견은 악성 병변, 염증성 병변, 비염증성 병변, 정상 소견으로 분류하였고, 염증성 병변은 다시 궤양, 위염(만성위염, 기타위염)으로 분류하였다. 통계적 분석은 t-test와 Mann Whitney test를 이용하였다. 결과: 악성 병변의 경우 시각적 섭취 정도에서 grade 4,5, max.SUV $7.95{\pm}4.38$로 높은 섭취 정도를 보였으며, 섭취 양상은 국소적 섭취 양상이었다. 이러한 기준에 따른 결과는 다른 병변들과 유의한 차이를 보였다. 염증성 병변, 비염증성 병변, 정상 소견에서는 시각적 섭취 정도가 grade$1{\sim}5$까지 다양하게 분포하였으며, 섭취 양상도 국소적, 미만성, 비대칭적인 다양한 양상이었다. 이러한 양성 염증성 병변, 비염증성 병변, 정상 소견 병변들 간에는 섭취 정도와 양상의 인자들 사이에 유의한 차이를 보이지 않았다. 결론: 위의 악성 병변은 양성 병변에 비해 높은 FDG 섭취 정도를 보이고 섭취 양상에 있어서는 대개가 국소적 섭취 양상이었다. 그러나 위의 양성 병변과 정상에서는 다양한 정도의 섭취 정도와 섭취 양상을 보여 주었고, 각 병변들간에 또는 정상의 생리적 섭취와 구별할 수 있는 소견은 제시하기 어려웠다.

• 대한상부위장관⦁헬리코박터학회지
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• 제18권4호
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• pp.247-257
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• 2018

Background/Aims: The aim of this study was to analyze the trend of the prevalences of atrophic gastritis (AG) and intestinal metaplasia (IM) from 2011 to 2016~2017 in Korea. And, the risk factors of AG and IM were compared between 2011 and 2016~2017. Materials and Methods: A total of 4,023 subjects in 2011 and 2,506 subjects in 2016~2017 were enrolled. AG and IM were diagnosed on the basis of endoscopic findings. Multivariate analysis was performed for risk factors of AG and IM. Seventeen factors were analyzed. Results: The seroprevalence of Helicobacter pylori decreased from 2011 (59.8%; 2,407/4,023) to 2016~2017 (51.6%; 1,293/2,506; P<0.001). The prevalence of AG decreased from 2011 to 2016~2017 (P=0.018), but that of IM increased (P<0.001). The risk factors of AG in 2011 were male sex, old age, H. pylori immuoglobulin G (IgG) positivity, family history of gastric cancer (GC), and high-salt diet. For IM in 2011, the risk factors were male sex, old age, H. pylori IgG positivity, and family history of GC. Risk factors of AG in 2016~2017 were old age, H. pylori IgG positivity, and country of residence. For IM in 2016~2017, the risk factors were male sex, old age, family history of GC, high fasting glucose level (${\geq}126mg/dL$), H. pylori IgG positivity, and low income level. Conclusions: The difference in prevalence trends of AG and IM between 2016~2017 and 2011 could be the result of the different risk factors of AG and IM, such as decreased prevalence of H. pylori infection.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5199-5205
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• 2013

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

• Journal of Gastric Cancer
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• 제5권3호
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• pp.158-162
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• 2005

목적: 위암환자의 임상적 특성과 수술 전 혈중 pepsinogen I/II 비율의 결과를 비교 분석하여 위암 발생과 혈중 pepsinogen의 변화와의 관련성 및 혈중 pepsinogen의 위암 진단의 이용 가능성 여부를 밝히는 것이 본 연구의 목적이다. 대상 및 방법: 분당차병원에서 절제술을 받은 103명의 위선암 환자를 대상으로 수술 전 혈중 pepsinogen I과 II를 측정하고, 이 결과를 종양의 임상 및 조직학적 요소와 비교 분석하였다. 결과: Pepsinogen I/II 비율의 평균치는 mucinous type, 종양 주위에 위축이 있는 경우 및 종양이 큰 경우에 감소하였으며 종양주위에 위축이 있는 환자에서도 종양이 클수록 의미 있게 감소하였다. 암세포가 고분화를 보이는 환자가 인환세포암 환자에 비하여 pep I/II이 의미 있게 감소하였으나 종양의 위치,침윤도, 림프절 전이 여부 및 Lauren분류에 따른 종양의 아형은 pep I/II의 변화와 의미 있는 관련을 보이지 않았다. 결론: 본 연구의 결과는 혈중 pepsinogen과 점막위축 정도와의 연관성은 증명하였지만 이 결과만으로 pepsinogen과 위암의 전암 병소의 연관성이나 일차점진의 유용성을 논하기는 부족하다고 생각된다.

• Journal of Digestive Cancer Reports
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1571-1574
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• 2015

Background: Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, and may inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determine the effect of treatment on subsequent gastric precancerous lesion development. Materials and Methods: We prospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasia atrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy to treat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at follow up two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greater curvature, angularis, body of stomach and fundus. Results of these biopsies were compared before and after treatment. Results: Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotic therapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reduction of the atrophic lesions (p=0.01), but not metaplasia. Conclusions: Treatment of H. pylori likely is an effective therapy in preventing the development of subsequent gastric premalignant lesions.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권sup1호
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• pp.83-92
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• 2008

Helicobacter pylori is the causative agent of chronic gastritis and has a role in the pathogenesis of peptic ulcer diseases, and gastric cancer. There have been reports suggesting a close link between these gastroduodenal disorders and a state of vitamin C deficiency. In this paper, the past, present and future perspectives on H. pylori infection and vitamin C will be discussed under the following view points. Since the ecological niche of H. pylori is the mucus layer and intercellular junctions of the gastric epithelium, the various kinds of host inflammatory cells motivated by the local and systemic immune responses cannot eliminate the microorganisms. When the invading foreign body is not removed, despite full activation of defense mechanisms, adverse consequences of the immune responses develop on the host gastric mucosa. The reasons for the body vitamin C depletion could be explained as follows; 1) the increased vitamin C consumption by increased oxygen free radical production through the prolonged hypersensitivity reactions in the gastric mucosa, 2) the increased vitamin C oxidation by the nitrite which is formed from nitrate reduction by the intragastric bacteria proliferated in the hypochlorhydric gastric cavity, 3) the strong ${\gamma}$-glutamyltranspeptidase activity of H. pylori which depletes the glutathiones in gastric mucosa. Depletion of glutathiones in the stomach favors irreversible oxidative destruction of ascorbic acid. Both persistent inflammatory burdens in the stomach by H. pylori and resultant vitamin C depletions synergistically and uninhibitedly might aggravate the hypothetical sequence of gastric carcinogenesis: atrophic gastritis${\rightarrow}$intestinal metaplasia${\rightarrow}$dysplasia${\rightarrow}$gastric adenocarcinoma. High intake of vitamin C could reverse the hypothetical sequence of the gastric carcinogenesis via direct and indirect effects on H. pylori and host-parasite relationships.