• Title/Summary/Keyword: helicobacter pylori

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Directed Evolution of Soluble α-1,2-Fucosyltransferase Using Kanamycin Resistance Protein as a Phenotypic Reporter for Efficient Production of 2'-Fucosyllactose

  • Jonghyeok Shin;Seungjoo Kim;Wonbeom Park;Kyoung Chan Jin;Sun-Ki Kim;Dae-Hyuk Kweon
    • Journal of Microbiology and Biotechnology
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    • v.32 no.11
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    • pp.1471-1478
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    • 2022
  • 2'-Fucosyllactose (2'-FL), the most abundant fucosylated oligosaccharide in human milk, has multiple beneficial effects on human health. However, its biosynthesis by metabolically engineered Escherichia coli is often hampered owing to the insolubility and instability of α-1,2-fucosyltransferase (the rate-limiting enzyme). In this study, we aimed to enhance 2'-FL production by increasing the expression of soluble α-1,2-fucosyltransferase from Helicobacter pylori (FucT2). Because structural information regarding FucT2 has not been unveiled, we decided to improve the expression of soluble FucT2 in E. coli via directed evolution using a protein solubility biosensor that links protein solubility to antimicrobial resistance. For such a system to be viable, the activity of kanamycin resistance protein (KanR) should be dependent on FucT2 solubility. KanR was fused to the C-terminus of mutant libraries of FucT2, which were generated using a combination of error-prone PCR and DNA shuffling. Notably, one round of the directed evolution process, which consisted of mutant library generation and selection based on kanamycin resistance, resulted in a significant increase in the expression level of soluble FucT2. As a result, a batch fermentation with the ΔL M15 pBCGW strain, expressing the FucT2 mutant (F#1-5) isolated from the first round of the directed evolution process, resulted in the production of 0.31 g/l 2'-FL with a yield of 0.22 g 2'-FL/g lactose, showing 1.72- and 1.51-fold increase in the titer and yield, respectively, compared to those of the control strain. The simple and powerful method developed in this study could be applied to enhance the solubility of other unstable enzymes.

Chemoquiescence with Molecular Targeted Ablation of Cancer Stem Cells in Gastrointestinal Cancers

  • Jong-Min Park;Young-Min Han;Migyeong Jeong;Eun Jin Go;Napapan Kangwan;Woo Sung Kim;Ki Baik Hahm
    • 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.

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Gastric Adenocarcinoma of Fundic-gland Type Diagnosed and Treated by Endoscopic Mucosal Resection (내시경 점막 절제술로 진단 및 치료했던 위바닥샘형 선암)

  • Sung Eun Kim;Seun Ja Park;Moo In Park;Won Moon;Jae Hyun Kim;Kyoungwon Jung;Bang Ju Kim;Hee Kyung Chang
    • 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.

Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake

  • Rino Hasegawa;Kenshi Yao;Takao Kanemitsu;Hisatomi Arima;Takayuki Hirase;Yuuya Hiratsuka;Kazuhiro Takeda;Kentaro Imamura;Kensei Ohtsu;Yoichiro Ono;Masaki Miyaoka;Takashi Hisabe;Toshiharu Ueki;Hiroshi Tanabe;Atsuko Ohta;Satoshi Nimura
    • Clinical Endoscopy
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    • v.57 no.1
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    • pp.65-72
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    • 2024
  • Background/Aims: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. Methods: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. Results: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). Conclusions: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Biological and Antimicrobial Activity of Vaccinium oldhami Fruit (정금나무(Vaccinium oldhami) 열매의 생리활성 및 항균활성)

  • Chae, Jung-Woo;Jo, Bun-Sung;Joo, Sung-Hyun;Ahn, Dong-Hyun;Chun, Sung-Sook;Cho, Young-Je
    • 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 $200{\mu}g/mL$.

Biological Activity of Chamomile (Matricaria chamomilla L.) Extracts (캐모마일(Martricaria chamomilla L.)의 생리활성)

  • Cho, Young-Je;Yoon, So-Jung;Kim, Jeung-Hoan;Chun, Sung-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.4
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    • pp.446-450
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    • 2005
  • The biological activity of water and ethanol extracts from Chamomaile for functional food source were examined. Total phenol contents in the $60\%$ ethanol extracts $(24.98\pm0.20\;mg/g)$ from Chamomaile leaf was higher than those of water extracts $(23.64\pm0.35\;mg/g)$ The major phenolic compound by HPLC were rosemarinic acid and Quercetin. $60\%$ ethanol extracts had higher content of these phenolics than water extacts. Electron donating ability showed $91.05\%$ in the water extracts and $95.49\%$ in the $60\%$ ethanol extracts. Antioxidant protection factor (PF) showed $0.71\pm0.02 $ in the water extracts and $1.48\pm0.03 $ in the $60\%$ ethanol extracts. The water extracts of Chamomaile leaves did not have antimicrobial activity against H. pylori, but the $60\%$ ethanol extracts revealed the slight antimicrobial activity as 9.42 mm of clear zone. Angiotensin converting enzyme inhibition was $57.98\%$ in water extracts and $91.36\%$ in $60\%$ ethanol extracts. Xanthine oxidase activity was $73.48\%$ in water extracts and $81.96\%$ in $60\%$ ethanol extracts. The results suggest that Chamomailes extract may be useful as potential source as antioxidant, angiotensin converting enzyme and xanthine oxidase inhibitors.

Epidemiological Patterns of Cancer Incidence in Southern China: Based on 6 Population-based Cancer Registries

  • Liu, Jie;Yang, Xu-Li;Li, Ai;Chen, Wan-Qing;Ji, Lu;Zhao, Jun;Yan, Wei;Chen, Yi-Ying;Zhu, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1471-1475
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    • 2014
  • Background: The epidemiological patterns of cancer incidence have been investigated widely in western countries. Nevertheless, information is quite limited in Jiangxi province, southern China. Materials and Methods: All data were reported by 6 population-based cancer registries in Jiangxi Province. The results were presented as incidence rates of cases by site (ICD-10), sex, crude rate (CR), age-standardized rates (ASRs) and truncated incidence rate (TR) per 100,000 person-years, using the direct method of standardization to the world population. Results: 8,765 new cancer cases were registered in our study during the period 2009-2011. Diagnosis of cancer was based on histopathology in 61.0%, clinical or radiology findings in 4.87% and death certificate only (DCO) in 3.0% of the cases. The median age at diagnosis was 62.0 years (mean, 61; standard deviation, 15). The ASRs were 170.8 per 100,000 for men and 111.2 for women. The ASRs for all invasive cancers from the urban areas (145.7 per 100,000) was higher than that of rural areas (137.1). Incidence rates for lung cancer were higher in rural (35.8) than in urban areas (27.0). Similarly, relatively high rates were observed for stomach cancer in rural (20.1) relative to urban areas (15.5). Conclusions: Our results reveal that the most common cancers were breast and lung in women and lung and liver in men. Interestingly, this study suggested a higher incidence rates for lung and stomach cancer in rural males than in urban population, which may suggest other potential causes, such as over-consumption of smoked meats and high prevalence of Helicobacter pylori infection, respectively. Public education and the promotion of healthy lifestyles should be actively carried out.

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

  • Lim, Hyeon Woo;Kim, Tae Hyun;Choi, Il Ju;Kim, Chan Gyoo;Lee, Jong Yeul;Cho, Soo Jeong;Eom, Hyeon Seok;Moon, Sung Ho;Kim, Dae Yong
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.193-201
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    • 2016
  • Purpose: To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods: Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results: All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, $D_{max}$ and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and $D_{mean}$ and V15 for right kidney and $D_{mean}$ for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion: Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.

A Case Report of Disseminated Extranodal Marginal Zone B-Cell Lymphoma of MALT Manifested by Solitary Pulmonary Nodule (고립성 폐결절로 발현한 파종성 림프절 외 변연부 B-세포 림프종 1예)

  • Cho, Joon Hyun;Jung, Jong Pil;Cha, Hee Jeong;Park, Chang Ryul;Kim, Sung Ryul;Kim, Hawk;Park, Jin Woo;Woo, Soon Joo;Eum, Eun A;Lee, Ki Young;Jegal, Yang Jin
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.2
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    • pp.171-177
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    • 2006
  • Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is usually indolent. Although it was reported recently that about 20-30% cases of MALT lymphoma presented with a disseminated disease at diagnosis, it was described as a disease localized at diagnosis and remaining stable for a prolonged period. However, only a few cases of MALT lymphoma involved the lung and gastrointestinal tract all at once. We report a case of a 73-year-old man with disseminated MALT lymphoma. He presented with non-productive cough, initial chest radiograph showed a nodule in the right lower lobe. The diagnosis of stage IV MALT lymphoma was made by CT scan, video-assisted thoracoscopic excisional biopy, gastrofiberscopic biopsy and bone marrow biopsy. The lymphoma involved the lung, stomach and bone marrow at the time of diagnosis. Because he refused chemotherapy, he discharged after Helicobacter pylori eradication without chemotherapy. Regular follow-up examination did not show any evidence of disease progression over 22 months.