• Journal of Life Science
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• v.11 no.2
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Journal of Gastric Cancer
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• v.16 no.3
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• pp.152-160
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• 2016

Purpose: Endoscopic diagnosis of gastric cancer (GC) that emerges after eradication of Helicobacter pylori may be affected by unique morphological changes. Using comprehensive endoscopic imaging, which can reveal biological alterations in gastric mucosa after eradication, previous studies demonstrated that Congo red chromoendoscopy (CRE) might clearly show an acid non-secretory area (ANA) with malignant potential, while autofluorescence imaging (AFI) without drug injection or dyeing may achieve early detection or prediction of GC. We aimed to determine whether AFI might be an alternative to CRE for identification of high-risk areas of gastric carcinogenesis after eradication. Materials and Methods: We included 27 sequential patients with metachronous GC detected during endoscopic surveillance for a mean of 82.8 months after curative endoscopic resection for primary GC and eradication. After their H. pylori infection status was evaluated by clinical interviews and $^{13}C$-urea breath tests, the consistency in the extension of corpus atrophy (e.g., open-type or closed-type atrophy) between AFI and CRE was investigated as a primary endpoint. Results: Inconsistencies in atrophic extension between AFI and CRE were observed in 6 of 27 patients, although CRE revealed all GC cases in the ANA. Interobserver and intraobserver agreements in the evaluation of atrophic extension by AFI were significantly less than those for CRE. Conclusions: We demonstrated that AFI findings might be less reliable for the evaluation of gastric mucosa with malignant potential after eradication than CRE findings. Therefore, special attention should be paid when we clinically evaluate AFI findings of background gastric mucosa after eradication (University Hospital Medical Information Network Center registration number: UMIN000020849).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7763-7768
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• 2014

Background: Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. Materials and Methods: The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Results: Association analysis of studied allelic variants and the development of gastritis in H. pylori-positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-Т that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). Conclusions: The data from the current study showed that the genotype IL-1B -511Т/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7467-7472
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• 2013

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

• Journal of Microbiology
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• v.44 no.6
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• pp.660-664
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• 2006

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3%, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9%) patients, the s1m2 in 22 (37.2%), and the s2m2 in 14 (23.7%), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.4
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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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.4
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• pp.227-235
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• 2017

Purpose: Crohn's disease (CD) can involve any site of the gastrointestinal tract (GIT). However, the characteristics of upper GIT involvement in CD are unclear, especially in the Eastern pediatric population. This study aimed to estimate the prevalence of upper GIT involvement and identify the clinical features of Korean children with CD. Methods: This was a retrospective multicenter cohort study that included 52 pediatric patients with CD who underwent esophagogastroduodenoscopy and biopsy. The clinical symptoms and endoscopic and histologic features of the upper GIT were identified according to the presence or absence of upper gastrointestinal symptoms. Results: Among the 52 patients, upper GIT involvement was noted in 50.0% (26/52). The mean age at CD diagnosis was $14.1{\pm}2.1$ years. Gastric ulcer was the most common lesion (19.2%) found on upper GIT endoscopy, followed by duodenal ulcers (15.4%). Chronic inflammation was the most common histopathologic feature (75.0%), followed by gastric erosion (17.3%). Granuloma was found in 9.6% of patients. Helicobacter pylori infection was identified in 5.8% of patients. Endoscopic and histologic findings were not significantly different, but the mean values of erythrocyte sedimentation rate ($60.7{\pm}27.1$ vs. $43.0{\pm}27.6mm/h$, p=0.037) and C-reactive protein ($16.5{\pm}28.2$ vs. $6.62{\pm}13.4mg/dL$, p=0.014) were significantly different between patients with and without upper gastrointestinal CD symptoms. Conclusion: Upper GIT involvement was relatively common in pediatric patients with CD irrespective of upper gastrointestinal symptoms, and H. pylori infection was relatively uncommon. The results of this study should aid the establishment of regional guidelines for upper GIT examination.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.11
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• pp.5094-5101
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• 2011

In order to investigate recurrence rate and risk factors for recurrence of gastric cancer after curative resection, we examined blood biochemical profile and clinicopathological features of 386 gastric cancer patients by using medical charts and data of hospital cancer registry from September 2010 to May 2011. Chi-square test and logistic regression analyses were performed to identify risk factors. The recurrence rate of all gastric cancer patients was 2.6%; The recurrence rate by gender was 3.45% in male and 0.89% in female, and that was 4 times higher in male than in female. On univariate logistic regression analyses, lymph node metastases(OR=8.793), Helicobactor pylori infecton(OR=6.495), abnormal total cholesterol(OR=14.333) were related to recurrence. On multivariate logistic regression analyses, lymph node metastases and H. pylori infection were very important risk factors for recurrence of gastric cancer. In conclusion, lymph node metastases, H. pylori infection, and total cholesterol control were very important to prevent recurrence of gastric cancer, and it needs to monitor blood biochemical (C-reactive protein, carcinoembryonic antigen, etc) for the early detection of gastric cancer recurrence.

• Journal of Gastric Cancer
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• v.1 no.1
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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.

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.3
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• pp.186-197
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• 2018

Background/Aims: To investigate the predictive factors for improvement of atrophic gastritis (AG) and intestinal metaplasia (IM). Materials and Methods: A total of 778 subjects were prospectively enrolled and followed up for 10 years. Histological analysis of AG and IM was performed by using the updated Sydney system. To find the predictive factors for reversibility of AG and IM, 24 factors including genetic polymorphisms and bacterial and environmental factors were analyzed. Results: In all subjects, the predictive factor by multivariate analysis for improvement of both antral and corpus AG was successful eradication. The predictive factors for improvement of antral IM were age and successful eradication. The predictive factor for improvement of corpus IM was successful eradication. In patients with Helicobacter pylori infection, age and cagA were predictive factors for improvement of AG and IM. In patients with H. pylori eradication, monthly income and cagA were predictive factors for improvement of AG and IM. Conclusions: H. pylori eradication is an important predictive factor of regression of AG and IM and would be beneficial for the prevention of intestinal-type gastric cancer. Young age, high income, and cagA are additional predictive factors for improving AG and IM status. Thus, various factors affect the improvement of AG and IM.