1.Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells.
Eunyoung BYUN ; Bohye PARK ; Joo Weon LIM ; Hyeyoung KIM
Yonsei Medical Journal 2016;57(3):647-651
PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.
Blotting, Western
;
Caffeic Acids
;
Cell Line, Tumor
;
Cell Proliferation
;
DNA, Bacterial/analysis/genetics
;
DNA-Binding Proteins/*metabolism
;
Epithelial Cells/*metabolism
;
Gastric Mucosa/*metabolism/pathology
;
Gastritis/pathology
;
Gene Expression Regulation, Bacterial
;
Helicobacter Infections/metabolism/pathology/physiopathology
;
Helicobacter pylori/pathogenicity/physiology
;
Humans
;
NF-kappa B/antagonists & inhibitors/*biosynthesis/metabolism
;
Peptide Fragments
;
Phenylethyl Alcohol/analogs & derivatives
;
Proto-Oncogene Proteins c-jun
;
Repressor Proteins
;
Transcription Factor AP-1/*biosynthesis
;
Transcription Factors/*metabolism
;
beta Catenin/*metabolism
2.Gastric lesions in patients with Crohn's disease in Korea: a multicenter study.
Hoonsub SO ; Byong Duk YE ; Young Soo PARK ; Jihun KIM ; Joo Sung KIM ; Won MOON ; Kang Moon LEE ; You Sun KIM ; Bora KEUM ; Seong Eun KIM ; Kyeong Ok KIM ; Eun Soo KIM ; Chang Kyun LEE ; Sung Pil HONG ; Jong Pil IM ; Ja Seol KOO ; Chang Hwan CHOI ; Jeong Eun SHIN ; Bo In LEE ; Kyu Chan HUH ; Young Ho KIM ; Hyun Soo KIM ; Young Sook PARK ; Dong Soo HAN
Intestinal Research 2016;14(1):60-68
BACKGROUND/AIMS: Gastric pathology and Helicobacter pylori (H. pylori) infection among Asian patients with Crohn's disease (CD) are still unclear. We evaluated gastric histologic features and frequency of H. pylori infection in Korean patients with CD. METHODS: Among 492 patients with CD receiving upper gastrointestinal (GI) endoscopic evaluation in 19 Korean hospitals, we evaluated the endoscopic findings and gastric histopathologic features of 47 patients for our study. Histopathologic classification was performed using gastric biopsy tissues, and H. pylori infection was determined using the rapid urease test and histology. RESULTS: There were 36 men (76.6%), and the median age of patients at the time of upper GI endoscopy was 23.8 years (range, 14.2-60.5). For CD phenotype, ileocolonic disease was observed in 38 patients (80.9%), and non-stricturing, non-penetrating disease in 31 patients (66.0%). Twenty-eight patients (59.6%) complained of upper GI symptoms. Erosive gastritis was the most common gross gastric feature (66.0%). Histopathologically, H. pylori-negative chronic active gastritis (38.3%) was the most frequent finding. H. pylori testing was positive in 11 patients (23.4%), and gastric noncaseating granulomata were detected in 4 patients (8.5%). Gastric noncaseating granuloma showed a statistically significant association with perianal abscess/fistula (P=0.0496). CONCLUSIONS: H. pylori-negative chronic active gastritis appears to be frequent among Korean patients with CD. The frequency of H. pylori infection was comparable with previous studies. An association with perianal complications suggests a prognostic value for gastric noncaseating granuloma in patients with CD.
Asian Continental Ancestry Group
;
Biopsy
;
Classification
;
Crohn Disease*
;
Endoscopy
;
Gastritis
;
Granuloma
;
Helicobacter pylori
;
Humans
;
Korea*
;
Male
;
Pathology
;
Phenotype
;
Stomach
;
Urease
3.Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pylori IgG and IgA in Children.
Ji Hyun SEO ; Chun Woo LIM ; Ji Sook PARK ; Jung Sook YEOM ; Jae Young LIM ; Jin Su JUN ; Hyang Ok WOO ; Hee Shang YOUN ; Seung Chul BAIK ; Woo Kon LEE ; Myung Je CHO ; Kwang Ho RHEE
Journal of Korean Medical Science 2016;31(3):417-422
We tested correlations between anti-Helicobacter pylori IgG and IgA levels and the urease test, anti-CagA protein antibody, degree of gastritis, and age. In total, 509 children (0-15 years) were enrolled. Subjects were stratified as 0-4 years (n = 132), 5-9 years (n = 274), and 10-15 years (n = 103) and subjected to the urease test, histopathology, ELISA, and western blot using whole-cell lysates of H. pylori strain 51. The positivity rate in the urease test (P = 0.003), the degree of chronic gastritis (P = 0.021), and H. pylori infiltration (P < 0.001) increased with age. The median titer for anti-H. pylori IgG was 732.5 IU/mL at 0-4 years, 689.0 IU/mL at 5-9 years, and 966.0 IU/mL at 10-15 years (P < 0.001); the median titer for anti-H. pylori IgA was 61.0 IU/mL at 0-4 years, 63.5 IU/mL at 5-9 years, and 75.0 IU/mL at 10-15 years (P < 0.001). The CagA-positivity rate was 26.5% at 0-4 years, 36.5% at 5-9 years, and 46.6% at 10-15 years for IgG (P = 0.036), and 11.3% at 0-4 years, 18.6% at 5-9 years, and 23.3% at 10-15 years for IgA (P < 0.001). Anti-H. pylori IgG and IgA titers increased with the urease test grade, chronic gastritis degree, active gastritis, and H. pylori infiltration. Presence of CagA-positivity is well correlated with a high urease test grade and high anti-H. pylori IgG/IgA levels.
Adolescent
;
Antibodies, Bacterial/*blood
;
Antigens, Bacterial/*analysis/immunology
;
Bacterial Proteins/*analysis/immunology/metabolism
;
Blotting, Western
;
Child
;
Child, Preschool
;
Chronic Disease
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Gastritis/pathology
;
Helicobacter Infections/blood/microbiology/*pathology
;
Helicobacter pylori/isolation & purification/*metabolism
;
Humans
;
Immunoglobulin A/*blood
;
Immunoglobulin G/*blood
;
Infant
;
Infant, Newborn
;
Male
;
Severity of Illness Index
;
Urease/metabolism
4.Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy.
Hyo Joon YANG ; Seon Hee LIM ; Changhyun LEE ; Ji Min CHOI ; Jong In YANG ; Su Jin CHUNG ; Seung Ho CHOI ; Jong Pil IM ; Sang Gyun KIM ; Joo Sung KIM
Journal of Korean Medical Science 2016;31(7):1075-1081
It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy.
Adult
;
Aged
;
Anti-Bacterial Agents/therapeutic use
;
Biopsy
;
Female
;
Follow-Up Studies
;
Gastric Mucosa/*pathology
;
Gastritis/diagnosis/etiology/microbiology
;
Gastroscopy
;
Helicobacter Infections/complications/*diagnosis/drug therapy
;
Humans
;
Lymphoma, B-Cell, Marginal Zone/complications/*diagnosis/pathology
;
Male
;
Middle Aged
;
Republic of Korea
;
Retrospective Studies
5.Analysis of the efficacy of gastric cancer screening in rural population in Henan Province.
Meng ZHANG ; Xin LI ; Shaokai ZHANG ; Qiong CHEN ; Shuzheng LIU ; Lanwei GUO ; Jianbang LU ; Xibin SUN
Chinese Journal of Oncology 2016;38(1):73-77
OBJECTIVETo analyze the efficacy of endoscopic screening for gastric cancer in rural population in high risk areas of upper gastrointestinal cancer in Henan province.
METHODSSubjects aged 40-69 years in the high risk areas were selected to participate in the endoscopic screening based on the cluster sampling, and screening-positive subjects were sampled for pathological examination. The data of screening were summarized and the detection rates of severe chronic atrophic gastritis, severe intestinal metaplasia, low grade intraepithelial neoplasia, high grade intraepithelial neoplasia, early and middle-late cancer were calculated, and the constituent ratio of early cancer cases was calculated. The detection rates and early diagnosis rates for the first round screening and follow-up screening were compared.
RESULTSIn the 5 years, a total of 88 263 subjects were endoscopically examined in the first round screening and 4 004 subjects were diagnosed with low grade intraepithelial neoplasia or above (the detection rate was 4.54%), in which 3 256 cases were with low grade intraepithelial neoplasia (the detection rate of 3.69%), 366 cases with high grade intraepithelial neoplasia (the rate of 0.41%), 199 cases with early cancer (the rate of 0.22%) and 183 cases with middle-late cancer (the rate of 0.21%). The number of cases of high grade intraepithelial neoplasia and early cancer was 565 and the early diagnosis rate was 75.53%. 1 894 subjects with severe chronic atrophic gastritis, severe intestinal metaplasia and low grade intraepithelial were followed up with a compliance of 66.32%. A total of 45 cases of early cancer were diagnosed, with a detection rate of 2.38% and early diagnosis rate of 100%. The detection rate and early diagnosis rate in the follow-up screening were both statistically significantly higher than that in the first round screening (P<0.01 for both).
CONCLUSIONThe efficacy of endoscopic screening for gastric cancer is significant in high risk areas of upper gastrointestinal cancer, and improving the quality of follow-up screening will achieve a better performance of the screening.
Adult ; Aged ; Carcinoma in Situ ; diagnosis ; pathology ; China ; Chronic Disease ; Early Detection of Cancer ; statistics & numerical data ; Gastritis, Atrophic ; diagnosis ; Gastroscopy ; Humans ; Mass Screening ; Middle Aged ; Rural Population ; Stomach Neoplasms ; diagnosis ; pathology
6.Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia.
Xu-Dong TANG ; Li-Ya ZHOU ; Shu-Tian ZHANG ; You-Qing XU ; Quan-Cai CUI ; Li LI ; Jing-Jing LU ; Peng LI ; Fang LU ; Feng-Yun WANG ; Ping WANG ; Li-Qun BIAN ; Zhao-Xiang BIAN
Chinese journal of integrative medicine 2016;22(1):9-18
OBJECTIVETo assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients.
METHODSThis was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument.
RESULTSDysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%.
CONCLUSIONSMoluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].
Chronic Disease ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Gastritis, Atrophic ; drug therapy ; microbiology ; pathology ; Gastroscopy ; Helicobacter pylori ; drug effects ; Humans ; Male ; Middle Aged ; Treatment Outcome
7.New monoclonal antibody-based test for Helicobacter pylori urease in gastric tissue.
Do Hyun KIM ; Ho Dong KIM ; Hyeuk PARK ; Seung CHOI ; Jae Won BEOM ; Woo Jong KIM ; Chang Kook PARK ; Young Jik LEE ; Ju Young PARK ; Hyung Rag KIM ; Chul PARK ; Young Eun JOO ; Young Do JUNG
The Korean Journal of Internal Medicine 2016;31(1):40-45
BACKGROUND/AIMS: To evaluate a new monoclonal antibody for Helicobacter pylori urease in gastric tissue. METHODS: A total of 107 volunteers were enrolled. All subjects underwent a 13C-urea breath test and esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia. Six biopsy specimens in the gastric antrum and body were obtained for a rapid urease test and histology. The new monoclonal antibody-based H. pylori urease test (HPU) was performed to rapidly and qualitatively detect urease in two biopsy specimens. RESULTS: H. pylori infection was diagnosed in 73 subjects. The sensitivity and specificity of the HPU was 89% and 74%, respectively. The subjects were divided into two groups: one with true-positive and true-negative HPU results (n = 90) and the other with false-positive and false-negative HPU results (n = 17). Across all subjects, ammonia levels were 900.5 +/- 646.7 and 604.3 +/- 594.3 mumol/L (p > 0.05), and pH was 3.37 +/- 1.64 and 2.82 +/- 1.51 (p > 0.05). Sensitivity was higher in the presence of atrophic gastritis or intestinal metaplasia. CONCLUSIONS: HPU detected H. pylori in approximately 10 min. Gastric aspirate ammonia and pH levels did not affect the test results. Sensitivity was good in the presence of atrophic gastritis or intestinal metaplasia.
Adult
;
Antibodies, Monoclonal/*immunology
;
Bacterial Proteins/*analysis/immunology
;
Biomarkers/analysis
;
Biopsy
;
False Negative Reactions
;
False Positive Reactions
;
Female
;
Gastritis, Atrophic/*diagnosis/microbiology
;
Helicobacter Infections/*diagnosis/microbiology
;
Helicobacter pylori/*enzymology/immunology
;
Humans
;
*Immunologic Tests
;
Male
;
Metaplasia
;
Middle Aged
;
Predictive Value of Tests
;
Pyloric Antrum/*microbiology/pathology
;
Reproducibility of Results
;
Time Factors
;
Urease/*analysis/immunology
;
Workflow
8.Acute gastritis associated with Epstein-Barr virus infection in a child.
Ji Mok KIM ; Chun Woo SONG ; Kyu Sang SONG ; Jae Young KIM
Korean Journal of Pediatrics 2016;59(Suppl 1):S68-S71
Infectious mononucleosis is Epstein-Barr virus (EBV) inducing a self-limiting clinical syndrome characterized by fever, sore throat, hepatosplenomegaly, and generalized lymphadenopathy. Gastrointestinal symptoms of EBV infection are nonspecific and occur rarely. EBV inducing acute gastrointestinal pathology is poorly recognized without suspicion. Careful consideration is needed to diagnose gastric involvement of EBV infection including gastric lymphoma, gastric cancer, and gastritis. A few recent cases of gastritis associated with EBV infection have been reported in adolescents and adults. However, there is no report of EBV-associated gastritis in early childhood. We experienced a rare case of 4-year-old girl with EBV gastritis confirmed by in situ hybridization.
Adolescent
;
Adult
;
Child*
;
Child, Preschool
;
Epstein-Barr Virus Infections
;
Female
;
Fever
;
Gastritis*
;
Herpesvirus 4, Human*
;
Humans
;
In Situ Hybridization
;
Infectious Mononucleosis
;
Lymphatic Diseases
;
Lymphoma
;
Pathology
;
Pharyngitis
;
Stomach Neoplasms
9.Differences in Features and Course of Mucosal Type Eosinophilic Gastroenteritis between Korean Infants and Children.
Bong Seok CHOI ; Suk Jin HONG ; Suk Hyun PARK ; Heng Mi KIM ; Byung Ho CHOE
Journal of Korean Medical Science 2015;30(8):1129-1135
Eosinophilic gastroenteritis (EGE) is a disorder characterized by eosinophilic infiltration of the bowel wall and various gastrointestinal (GI) manifestations. This study aimed to evaluate the characteristics of EGE in infants and children. A total of 22 patients were diagnosed with histologic EGE (hEGE) or possible EGE (pEGE). Serum specific IgE levels, peripheral eosinophil counts, and endoscopic biopsies were carried out. In the hEGE group (n = 13), initial symptoms included hematemesis, abdominal pain, and vomiting. Three of the subjects had normal endoscopic findings. Eight patients were categorized into the infant group and 5 into the child group. All patients in the infant group showed clinical improvement after switching from cow's milk feeding to special formula or breast feeding. The infant group showed a higher eosinophil count in the gastric mucosal biopsy than the child group. In the pEGE group (n = 9) initial symptoms included hematemesis, abdominal pain, and vomiting. Seven patients in this group showed a good response to treatment with restriction of the suspected foods and/or the administration of ketotifen. Both hEGE and pEGE groups showed clinical improvement after restriction of suspected foods in the majority of cases and also showed a similar clinical course. EGE should be considered in the differential diagnosis of patients with chronic abdominal pain, vomiting, and hematemesis of unknown cause. The infant group may have a better prognosis than the child group if treated properly.
Child
;
Child, Preschool
;
Diagnosis, Differential
;
Disease Progression
;
Endoscopy, Gastrointestinal/*methods
;
Enteritis/*pathology/*therapy
;
Eosinophilia/*pathology/*therapy
;
Female
;
Gastritis/*pathology/*therapy
;
Humans
;
Infant
;
Infant, Newborn
;
Intestinal Mucosa/*pathology
;
Male
;
Republic of Korea
;
Treatment Outcome

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