• Journal of Digestive Cancer Research
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• v.4 no.1
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• pp.1-9
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• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

• Journal of Digestive Cancer Research
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• v.11 no.3
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• pp.165-170
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• 2023

Gastric cancer is histologically classified into two types. One is the intestinal and diffuse type according to Lauren's classification, and the other is the differentiated and undifferentiated type based on Nakamura's classification. In 2007, Japanese groups proposed a new type of well-differentiated gastric adenocarcinoma in the gastric fundic glands with distinct endoscopic and clinicopathologic features. This is gastric adenocarcinoma of the fundic-gland type (GA-FG), a rare variant of gastric cancer. In a 2012 Korean study, of 6,000 cases of gastric cancer tissues, only three cases of GA-FG were identified. GA-FG is usually located in the upper third of the stomach and not known to be associated with the Helicobacter pylori infection. We herein report a case of GA-FG diagnosed in a 63-year-old man. A gastric polyp was incidentally detected during an upper endoscopy screening while conducting a health check-up, and he was diagnosed with GA-FG after an endoscopic mucosal resection (EMR) was conducted for diagnostic and therapeutic purposes. Our case suggests that for both diagnostic and therapeutic purposes, EMR may be beneficial in case of gastric polyps with suspected GA-FG.

• Clinical Endoscopy
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• v.56 no.4
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• pp.391-408
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• 2023

With an aging population, the number of patients with difficulty in swallowing due to medical conditions is gradually increasing. In such cases, enteral nutrition is administered through a temporary nasogastric tube. However, the long-term use of a nasogastric tube leads to various complications and a decreased quality of life. Percutaneous endoscopic gastrostomy (PEG) is the percutaneous placement of a tube into the stomach that is aided endoscopically and may be an alternative to a nasogastric tube when enteral nutritional is required for four weeks or more. This paper is the first Korean clinical guideline for PEG developed jointly by the Korean College of Helicobacter and Upper Gastrointestinal Research and led by the Korean Society of Gastrointestinal Endoscopy. These guidelines aimed to provide physicians, including endoscopists, with the indications, use of prophylactic antibiotics, timing of enteric nutrition, tube placement methods, complications, replacement, and tube removal for PEG based on the currently available clinical evidence.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.1-6
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• 2012

This study was carried out to investigate the biological activity and antimicrobial activity of Vaccinium oldhami fruit extracts. ABTS radical cation decolorization and the antioxidant protection factor (PF) of extracts as $92.7{\pm}4.1%$ and $3.6{\pm}1.6$ PF were higher than a BHT of $200{\mu}g/mL$ as $52.4{\pm}1.9%$ and $2.0{\pm}0.8$ PF, and the TBARS of extracts was $74.4{\pm}2.9%$ with $200{\mu}g/mL$. The hypertension inhibitory activity of extracts from Vaccinium oldhami fruit indicated the activities of $28.6{\pm}0.6%$ with $200{\mu}g/mL$, and anti-gout activity was $43.3{\pm}0.8%$ with $200{\mu}g/mL$. Antimicrobial activity was found in Vaccinium oldhami fruit extracts on Helicobacter pylori, Staphylococcus epidermidis, Staphylococcus aureus, Eschericia coli and Propionebacterium acne. This activity was illustrated as 24 mm, 28 mm, 13 mm, 26 mm and 16 mm clear zones with $200{\mu}g/mL$ respectively, and the elastase inhibitory activity which is related to the wrinkle cause was observed in extracts as $52.7{\pm}0.9%$ with $200{\mu}g/mL$.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.228-237
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• 2005

Purpose: We investigated the impacts of the methylation states of the P16 and the hMLH1 genes on pathogenesis and genetic expression of stomach cancer and their relationships with Helicobater pylori infection, and with other clinico-pathologic factors. Material and Methods: In our study, to detect protein expression and methylation status of the P16 and the hMLH1 genes in 100 advanced gastric adenocarcinomas, used immunohistochemical staining and methylation-specific PCR (MSP) and direct automatic genetic sequencing analysis. Results: Methylation of the P16 gene was observed in 19 out of 100 cases (19%) and in the 18 of those cases (94.7%) loss of protein expression was seen. We were sble to show that loss of P16 gene expression was related to methylation of the P16 gene (kappa coefficient=0.317, p=0.0011). Methylation of the hMLH1 gene was observed in 27 cases (27%), and in 24 cases of those 27 cases (88.8%), loss of protein expression was seen, which suggested that loss of protein expression in the hMLH1 gene is related to methylation of hMLH1 gene (kappa coefficient=0.675, P<0.0001). Also methylation of the hMLH1 gene was related to age, size of the mass, and lauren's classification. Conclusion: We found that methylation of DNA plays an important role in inactivation of the P16 and the hMLH1 genes. The methylation of the hMLH1 genes is significantly related to age, size of the mass, and lauren's classification.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.133-139
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• 2009

Purpose: In spite of many reports about Helicobacter pylori infection in children with functional gastrointestinal disorders, there are few reports about the influence of H. pylori infection to functional dyspepsia and gastric motility. Therefore, we studied the influence of H. pylori infection on gastric myoelectrical activity in children with functional dyspepsia. Methods: Between August 2006 and December 2008 upper gastrointestinal endoscopies with biopsies, the rapid urease test and/or $^{13}C$ urea breath test, and electrogastrography (EGG) were performed on 63 patients with histologic chronic gastritis; patients with chronic disorders were excluded. Comparisons about gastric myoelectrical activities were made between H. pylori-positive children (n=25) and H. pylorinegative children (n=38). Results: The percentage of pre- and post-prandial normogastria was relatively lower in H. pylori-positive children than H. pylori-negative children (80% vs. 65%, and 80% vs. 68%, respectively). Compared to H. pylori-negative children, H. pylori-positive children had lower postprandial predominant power (8.18${\pm}$22.36 dB and 32.20${\pm}$24.18 dB, respectively; p<0.01) and a lower power ratio (${\delta}P$; -1.28${\pm}$6.18 vs. +4.62${\pm}$5.93, respectively; p<0.01). Conclusion: It was suggested that the gastric myoelectrical activity in children with chronic gastritis can be influenced by H. pylori infection. Thus, this study indicates that H. pylori infection may be predictable in children with functional dyspepsia through analyzing the EGG parameters, and treatment may be considered in H. pylori-positive children with impaired gastric activity, especially in the lower prevalence area.

• 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.

• Journal of Gastric Cancer
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• v.13 no.4
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• pp.232-241
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• 2013

Purpose: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. Materials and Methods: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. Results: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. Conclusions: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.

• The Journal of the Korean Society for Microbiology
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• v.34 no.6
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• pp.533-542
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• 1999

H. pylori produces urease abundantly amounting to 6% of total protein of bacterial mass. Urease genes are composed of a cluster of 9 genes of ureC, ureD, ureA, ureB, ureI, ureE, ureF, ureG, ureH. Production of H. pylori urease in E. coli was studied with genetic cotransformation. Structural genes ureA and ureB produce urease apoprotein in E. coli but the apoprotein has no enzymatic activity. ureC and ureD do not affect urease production nor enzyme activity ureF, ureG, and ureH are essential to produce the catalytically active H. pylori urease of structural genes (ureA and ureB) in E.coli. The kinetics of activation of H. pylori urease apoprotein were examined to understand the production of active H. pylori urease. Activation of H. pylori urease apoprotein, pH dependency, reversibility of $CO_2$ binding, irreversibility of $CO_2$ and $Ni^{2+}$ incorporation, and $CO_2$ dependency of initial rate of urease activity have been observed in vitro. The intrinsic reactivity (ko) for carbamylation of urease apoprotein co expressed with accessory genes was 17-fold greater than that of urease apoprotein expressed without accessory genes. It is concluded that accessory genes function in maximizing the carbamylating deprotonated ${\varepsilon}$-amino group of Lys 219 of urease B subunit and metallocenter of urease apoprotein is supposed to be assembled by reaction of a deprotonated protein side chain with an activating $CO_2$ molecule to generate ligands that facilitate productive nickel binding.