• Toxicological Research
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• 제34권4호
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• pp.291-296
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• 2018

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

• Journal of Chest Surgery
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• 제23권1호
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• pp.95-106
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• 1990

Between May 1979 and April 1989, 213 patients with esophageal injuries visited the Department of the Thoracic and cardiovascular surgery Department, Yonsei University College of Medicine. There were 159 non perforated esophageal injuries accompanied by hematemesis, and 54 perforated esophageal injuries. The causes of non perforated esophageal injuries were Mallory-Weise Syndrome [%], corrosive esophagitis [54], esophageal carcinoma [4], foreign bodies [2], sclerotherapy due to esophageal varices [3]. The causes of perforated esophageal injuries were esophageal anastomosis[13], malignancies[17], esophagoscopy or bougienage[5], chest trauma[5], foreign bodies[5], paraesophageal surgery[3], others[6] In esophageal perforation due to foreign bodies, esophagoscopy or bougienage, there were 6 cervical esophageal perforations and 9 thoracic esophageal perforations. There were no mortalities in the treatment of the cervical esophageal perforations and 5 deaths resulted in the treatment of 9 thoracic esophageal perforations. And four of six patients with thoracic esophageal perforations died in the initiation of treatment over 24 hours, after trauma. There were another 12 deaths in the patients with chest trauma, malignancies or chronic inflammation except esophageal injuries due to foreign bodies or instruments during the hospital stay or less than 30 days after esophageal injuries. One patient with esophageal carcinoma died due to bleeding and respiratory failure after irradiation. Another patient with esophago gastrostomy due to esophageal carcinoma died of sepsis due to EG site leakage. One patient with a mastectomy due to breast cancer followed by irradiation died of sepsis due to an esophagopleural fistula. Two patients with Mallory-Weiss syndrome died; of hemorrhagic shock in one and of respiratory failure due to massive transfusion in the other. One patient with TEF died of respiratory failure and another died of pneumonia and respiratory failure. One patient with esophageal perforation due to blunt chest trauma died of brain damage accompanied with chest trauma.

• 동의생리병리학회지
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• 제23권4호
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

• Journal of Nutrition and Health
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• 제39권1호
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• pp.18-27
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• 2006

Smoking is well known to be associated with increased indices of tree radical-mediated damage of DNA, indicating that smoking may exacerbate the initiation and propagation of oxidative stresses, which are potential underlying processes in the pathogenesis of many diseases. The purpose of this study was to evaluate whether a daily regimen of green vegetable drink supplementation to smokers can be protective against endogenous lymphocytic DNA damage and whether it could enhance other antioxidant status. Twenty nonsmokers and nineteen smokers aged 23-60 were given 240 ml of green vegetable drink every day for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The 8 weeks of green vegetable drink consumption resulted in a significant decrease (p = 0.000, by paired t-test) in lymphocyte DNA damage expressed by TL (before: $63.13{\pm}1.05$ vs after: $37.86{\pm}10.83$, before: $66.73{\pm}1.24$ vs after: $36.51{\pm}1.13$), TM (before: $14.55{\pm}0.61$ vs after: $6.61{\pm}0.25$, before: $15.36{\pm}0.45$ vs after: $6.65{\pm}0.38$) and $\%$ DNA in tail (before: $19.7{\pm}0.41$ vs after: $16.6{\pm}0.37$, before: $20.6{\pm}0.31$ vs after: $17.1{\pm}0.5$) in both nonsmokers and smokers respectively. Vitamin C and TRAP level was not significantly changed after the supplementation. In conclusion, these results support the hypothesis that green vegetable drink exert a cancer-protective effect partially via a decrease in oxidative damage to DNA.

• 생약학회지
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• 제35권3호통권138호
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• pp.250-254
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• 2004

Helicobacter pylori (H. pyroli) infection it associated with type B gastritis, peptic uler disease, and gastric cancer. The vacuolation of cells induced by H. pylori is thought to be essential for the initiation and maintenance of gastric infection. The roles of H. pylori cytotoxin, urease, and ammonia in the vacuolation of HeLa cells were determined. H. pylori toxin induced vacuolation of HeLa cells. Korean and Japanese radishes significantly prevented the vacuolation of HeLa cells induced by H. pylori toxin. The urease activity in vacuolated cells was also decreased with Korean and Japanese radishes. H. Pylori toxin-induced vacuolation was inhibited by vacuolar type ATPase inhibitors (bafilomycin and N-ethylmaleimide). However, further investigation is required to determine the mechanisms of radish for the inhibition of vacuole formation of eukaryotic cells in response to the H. pylori toxin.

• Journal of Microbiology and Biotechnology
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• 제22권5호
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• pp.721-728
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• 2012

The human papillomavirus (HPV) is the main cause of cervical cancer in developing countries. Rapid diagnosis and initiation of treatment of the HPV infection are critical. Various methods have been employed to reduce the immunogenicity of antibodies targeting HPV serotypes. Nanobodies are the smallest fragments of naturally occurring single-domain antibodies with their antigen-binding site compromised into a single domain. Nanobodies have remarkable properties such as high stability, solubility, and high homology to the human VH3 domain. In this study, a phagemid library was employed to enrich for nanobodies against the L1 protein of the human papilloma virus. Binding reactivity of the selected clones was evaluated using phage enzyme-linked immunosorbent assay (phage-ELISA). Finally, two nanobodies (sm5 and sm8) with the best reactivity against the Gardasil vaccine and the purified HPV-16 L1 protein were expressed and purified using a $Ni^+$-NTA column. The accuracy of expression and purification of the nanobodies was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting assays. In vitro studies demonstrated that neutralization was achieved by the selected nanobodies. The ease of generation and unique features of these molecules make nanobodies promising molecules for the new generation of HPV diagnosis and therapy.

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• Mass Spectrometry Letters
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• 제12권3호
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• pp.66-75
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• 2021

Interleukin-4 (IL-4) and IL-13 are cytokines secreted by immune cells. Cytokines induce the proliferation of macrophages or promote the differentiation of secretory cells. The initiation and progression of allergic inflammatory diseases, such as asthma, are dependent on cytokines acting through related receptor complexes. IL-4 and IL-13 are N-glycoproteins. Glycan structures in glycoproteins play important roles in protein folding, protein stability, enzymatic function, inflammation, and cancer development. Therefore, the glycan structure of IL-4 and IL-13 needs to be elucidated in detail for the development of effective therapies. We report the first attempt to characterize the site-specific N-glycosylation of recombinant IL-4 and IL-13 via liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The tandem mass spectra of intact N-glycopeptides were identified using the Integrated GlycoProteome Analyzer (I-GPA) platform, which can automatically and rapidly analyze multiple N-glycopeptides, including their glycan composition and amino acid sequences. The recombinant IL-4 and IL-13 were identified with amino acid sequence coverages of 84% and 96%, respectively. For IL-4, 52 glycoforms on one N-glycosylation site were identified and quantified. In IL-13, 232 N-glycopeptides from three N-glycosylation sites were characterized, with the site Asn52 being the most extensively glycosylated (~80%). The complex glycans were the most abundant glycan on IL-4 and IL-13 (~96% and 91%, respectively), and the biantennary glycans were the most abundant in both recombinant IL-4 and IL-13 proteins.

• 대한본초학회지
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• 제34권6호
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• pp.117-124
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• 2019

Objective : Broccoli is edible green plant that has a wide variety of health benefits including cancer prevention and cholesterol reduction. However, leaves of broccoli are not eaten and are mostly left as waste. This study was conducted to evaluate the effects of the broccoli leaf extract (BLE) on prostaglandin E₂ (PGE₂) production related to nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-activated macrophages. Methods : BLE was prepared by extracting dried leaf with ethanol. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PGE₂ and inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Expression level of each protein was monitored by Western blot analysis. Results : In LPS-activated Raw264.7 cells, PGE₂ release into culture medium was dramatically enhanced compared to control cells. However, increased PGE₂ was attenuated dose-dependently by treatment with BLE. Inhibition of PGE₂ production by BLE was due to the suppression of cyclooxygenase-2 (COX-2) expression determined by Western blot analysis. BLE also inhibited the production of inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Inhibition at PGE₂ and cytokine was mediated from inhibition of nuclear translocation of NF-κB due to the repression of inhibitory kappa B alpha (IκBα) phosphorylation and degradation. Conclusion : This study showed that BLE exerted inhibitory activities against PGE₂, which is critical for the initiation and resolution of inflammatory responses, and that inhibition of PGE₂ was mediated by suppression of NF-κB signaling. These results suggest that the waste broccoli leaves could be used for controlling inflammation.

• 대한영상의학회지
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• 제85권1호
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• pp.77-94
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• 2024

고령의 환자에서 척추에 단일 병소의 병변을 만나게 되면 골전이를 가장 먼저 염두하게 된다. 골전이는 어느 부위든 가능하지만 척추체에서 가장 많이 발생한다. 그러나 항상 골전이에 전형적인 영상 소견을 보이지 않을 수도 있고 단일 병소로 발견하게 되면 다른 모방하는 병변과 감별이 어려울 수 있다. 그러면 원발암의 진단 및 치료가 늦어지게 된다. 본 종설에서는 골전이의 영상검사 및 임상지침에 대해서 살펴보고 골전이 외에도 고령 환자에서 척추에 단일 병소로 생길 수 있는 다양한 질환들의 영상 소견 및 감별 포인트에 대해서 알아보고자 한다.