SAHA, an HDAC inhibitor, overcomes erlotinib resistance in human pancreatic cancer cells by modulating E-cadherin

Park, S. J.,Kim, S. M.,Moon, J. H.,Kim, J. H.,Shin, J. S.,Hong, S. W.,Shin, Y. J.,Lee, D. H.,Lee, E. Y.,Hwang, I. Y. Springer Science + Business Media 2016 Tumour biology Vol.37 No.4

<P>Pancreatic cancer is one of the most lethal cancers and remains a major unsolved health problem. Less than 20 % of patients are surgical candidates, and the median survival for non-resected patients is approximately 3 to 4 months. Despite the existence of many conventional cancer therapies, few targeted therapies have been developed for pancreatic cancer. Combination therapy using erlotinib and gemcitabine is an approved standard chemotherapy for advanced pancreatic cancer, but it has marginal therapeutic benefit. To try to improve the therapeutic outlook, we studied the efficacy of another combination treatment and the relevance to E-cadherin in human pancreatic cancer cells. We treated two human pancreatic cancer cell lines with the histone deacetylase inhibitor (HDACi) SAHA. Interestingly, in these Panc-1 and Capan1 cells, we observed that the expression levels of E-cadherin and phosphorylated EGFR were gradually upregulated after treatment with SAHA. Furthermore, these cells underwent induced cell death after exposure to the combination treatment of SAHA and erlotinib. In Panc-1 cells, overexpression of E-cadherin activated the phosphorylation of EGFR and increased the cell sensitivity to erlotinib. In Capan1 cells, knocking down E-cadherin decreased the expression of phosphorylated EGFR, and these cells did not respond to erlotinib. Therefore, we demonstrated the efficacy of the combined treatment with SAHA and erlotinib in human pancreatic cancer cells, and we determined that the increased efficacy was due, at least in part, to the effects of SAHA on the expression of E-cadherin. Our studies suggest that E-cadherin may be a potent biomarker for pancreatic cancer.</P>

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN

Hong, S-W,Moon, J-H,Kim, J-S,Shin, J-S,Jung, K-A,Lee, W-K,Jeong, S-Y,Hwang, J J,Lee, S-J,Suh, Y-A,Kim, I,Nam, K-Y,Han, S,Kim, J E,Kim, K-p,Hong, Y S,Lee, J-L,Lee, W-J,Choi, E K,Lee, J S,Jin, D-H,Kim, Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.1

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Fabrication and Atmospheric Pressure Dependent Electrical Properties of the ZnO Nanowire Device

E.-K Kim,S. E. Moon,G. T. Kim,H. J. Ji,H.-Y. Lee,J. Park,J. H. Kwak,K.-H. Park,S. Maeng,S. J. Park,S.-W. Kim 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.51 No.II

A single ZnO nanowire device was fabricated by electron-beam lithography, and its current-voltage characteristics were recorded while varying the atmospheric pressure to test possible applications as a chemical gas sensor. Vertically well aligned ZnO nanowires were grown on GaN epilayer on c-plane sapphire {\it via} a vapor-liquid-solid (VLS) process by introducing an Au thin film (3 nm) as a catalyst. Semiconducting nanowire devices were fabricated by using photolithography and e-beam lithography, and their electrical properties were studied. To realize reliable device operation, which is a key factor for a chemical sensor, the contact resistance should be optimized. Here, we studied the contact-resistance problem by using a scanning probe microscopic tool to characterize surface-potential behaviors. To overcome the contact-resistance problem, a post thermal process was adapted to the nanowire device. Atmospheric-pressure-dependent electrical properties of the ZnO nanowire device were studied for chemical-sensor application.

2001년 11월 오염시기와 2002년 봄 황사시기 제주도 고산에서의 미량원소 농도 변화

한진석,김영성,문광주,안준영,김정은,류성윤,김영준,공부주,이석조 한국대기환경학회 2004 한국대기환경학회지 Vol.20 No.2

The chemical composition of PM_(2.5) was measured at Gosan. Jeju for two weeks each in November 2001 and spring 2002. In the latter part of the measurement period of November 2001, designated as the polluted period in this work, secondarily formed ion components as well as primarily emitted elemental carbon were high, PM_(2.5) mass concentration was also high in this polluted period compared with the yellow sand period, in which daily average of PM_(10) peaked up to 520㎍/㎥. Increase of major components of anthropogenic origin in the polluted period was not correlated with the variation in sea salt components while increase of crustal components in the yellow sand period was highly correlated with the variation in sea salt components. Trace elements were generally higher in the yellow sand period: however, toxic heavy metals such as zinc, cadmium and lead were the highest in the polluted period.

The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation

Chung, C.,Yoo, G.,Kim, T.,Lee, D.,Lee, C.S.,Cha, H.R.,Park, Y.H.,Moon, J.Y.,Jung, S.S.,Kim, J.O.,Lee, J.C.,Kim, S.Y.,Park, H.S.,Park, M.,Park, D.I.,Lim, D.S.,Jang, K.W.,Lee, J.E. Academic Press 2016 Biochemical and biophysical research communication Vol.479 No.2

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

L-ascorbic acid와 α-tocophero1이 돼지정액 성상과 체외수정란의 배발달율에 미치는 영향

박희진,김은국,위갑인,강만종,김광현,김재홍,문승주 全南大學校 農業科學技術硏究所 2001 農業科學技術硏究 Vol.36 No.-

The objective of this studys were to investigate the effect of α-tocopherol and L-ascorbic acid supplement on the boar semen characteristics and in vitro development rate of porcine oocytes. Sperm viability rate was significantly higher in α-tocopherol supplement than in control(66.6%) after 72hr of storage(P<0.05). Sperm motility was increased in treatment(80%, 93.3%, 85%) than in control(73.3%) at 12h of storage(P<0.05). Following insemination with 60h of store, morular and blastocyst on in vitro development resulted in significantly higher than control(P<0.05). After 72h of semen storage L-ascorbic addition also increased the sperm viability rate(P<0.05). Treatment as sperm motility was significantly higher than control in 72h of store(60% vs 66.6%, p<0.05). Following insemination with 60h of store treated porcine oocytes on in vitro development was increased more than control(56.8%), 59.9%, 62.8% vs 45.1%, P<0.05). Morular and blastocyst on in vitro development resulted in significantly higher than control(27.1%, 30.0%, 33.1% vs 20.0%, P<0.05). The results from this experiment indicated that α-tocopherol and L-ascorbic acid supplementation, for viability and motility in porcine semen, increased delay storing time of semen and in vitro development rate following insemination.

Improved dimensional stability of Nafion membrane modified using a layer by layer self-assembly of biophilic polymers

Lee, H.J.,Nam, E.J.,Woo, J.J.,Moon, S.H.,Lee, J. Elsevier 2012 Current Applied Physics Vol.12 No.5

The modification of perfluorinated proton exchange membranes (e.g. Nafion) utilizing a layer by layer (LbL) electrostatic assembly of oppositely charged biophilic polymers such as poly-l-lysine as positive layer and dsDNA as a negative layer is developed to protect the interface between the catalyst layer and the membrane in a low temperature fuel cell. Various physicochemical measurements including water uptake, proton conductivity and surface tension were investigated for both the as-received Nafion and the biopolymeric LbL modified Nafion. The smaller water contact angle and the less swelling characteristics of the biopolymer modified Nafion membrane was founded compared to that of as-received Nafion. This clearly indicates that the more hydrophilic surface of biopolymeric layers on Nafion plays an important role in the enhanced dimensional stability. In addition, a potential hypothesis explaining the higher proton conductivity from the LbL biopolymeric film coated Nafion is suggested.

Magnetic resonance imaging of macrophage activity in atherosclerotic plaques of apolipoprotein E-deficient mice by using polyethylene glycolated magnetic fluorescent silica-coated nanoparticles

Lee, K.,Moon, H.Y.,Park, C.,Kim, O.R.,Ahn, E.,Lee, S.Y.,Park, H.E.,Ihm, S.H.,Seung, K.B.,Chang, K.,Yoon, T.J.,Lee, C.,Cheong, C.,Hong, K.S. Elsevier 2009 Current Applied Physics Vol.9 No.1

We have recently synthesized organic dye-incorporated silica-coated core-shell magnetic nanoparticles (MFSNs) that enable the detection of both fluorescence and magnetic properties in cells and tissues by using magnetic resonance imaging (MRI). Furthermore, polyethylene glycolation of the surface of these MFSNs would render them more stable and biocompatible, and thus allow their in vivo use as a circulating agent with a long half-life. Atherosclerotic vascular diseases are the leading cause of death worldwide. A noninvasive diagnostic imaging method is required to identify vulnerable plaques prior to the occurrence of a clinical event. Macrophages are the key cellular mediators in the pathogenesis of plaque inflammation and vulnerability. We evaluated whether the use of polyethylene glycolated (PEGylated) MFSNs could help in effectively detecting the macrophage activity in the aorta of apolipoprotein E (apoE)-deficient mice. PEGylated MFSNs (Fe, 30mg/kg) were injected via the tail vein in 1.2% cholesterol-fed 30-week-old apoE-deficient mice. After 24h, ex vivo MRI was carried out. The atheromas were then observed by confocal laser scanning microscopy (CLSM), and immunohistochemical staining targeted toward the macrophages was performed. Ex vivo MRI demonstrated robust enhancement of the atherosclerotic plaques along the aortic wall. CLSM images showed accumulation of PEGylated MFSNs in the atherosclerotic plaques, and histological examination revealed the localization of MFSNs in the macrophages present in the lesion. Therefore, PEGylated MFSNs could function as an effective multimodal imaging agent in the identification of macrophage activity in atherosclerotic plaques.

대학생의 취침 전 스마트폰 사용과 수면의 질 간의 관계

김보민,김지은,김희진,문소연,문재민,송지원,양다경,이서연,정유담,허혜빈,배성희 이화여자대학교간호학회 2020 이화간호학회지 Vol.- No.54

Purpose: This study's main objectives are to examine the relationship of smartphone use at bedtime and sleep quality among college students. Methods: A sample 189 Korean college students(20-26 years old( participated in a survey about smartphone use in bed time and sleep quality. Self-reported sleep quality, daytime fatigue and insomnia were measured using the Pittsburgh Sleep Quality Index Korean version (PSQI-K). There are 3 sections of the questionnaire; 1) general information 2) sleep quality using PSQI-K 3) smartphone usage before bedtime. Data was analyzed using cross tabulation, one-way ANOVA, and independent T-Test. Results: 1. There was a difference whether they suffer from daily life due to the use of smartphones before bedtime between college student‘s sex and majors. 2. There was a difference in the main purpose of using smartphone before bedtime by age. 3. Respondents who used their smartphones before bedtime everyday showed prolonged sleep latency than those who used smartphones before bedtime less frequently. 4. There was no significant difference in the quality of sleep according to usage time and recognition on smartphone usage before bedtime and its disturbance of daily life. 5. The quality of sleep according to the purpose of smartphone usage before bedtime showed no significant difference. Conclusion: Based on the study results, there is the necessity of self-management among college students to enhance their sleep quality. Additionally, further research on the smartphone usage before bedtime is necessary due to the absence of the precedent studies and gender imbalance in the collected data.

New emergence pattern with variant porcine epidemic diarrhea viruses, South Korea, 2012-2015

Chung, H.C.,Lee, J.H.,Nguyen, V.G.,Huynh, T.M.L.,Lee, G.E.,Moon, H.J.,Park, S.J.,Kim, H.K.,Park, B.K. ELSEVIER 2016 VIRUS RESEARCH Vol.226 No.-

Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014-2015year. This study analyzed a large collection of the Spike protein coding gene to infer the spatial-temporal diffusion history of PEDV. The studying results suggested that PEDVs in Korea belonged to different genogroups. While classical G1 was continuingly circulating between provinces of Korea, the pandemic G2a were recently introduced from China and USA. By the application of Bayesian phylogeographical analysis, this study demonstrated the spatial-temporal transmission of PEDVs within Korea. Of the recent emerged G2a viruses, J3142 strains showed potential recombination breakpoint (376-2,143nt) of S1 gene between KNU1303_Korea strain_G2a (KJ451046) and 45RWVCF0712_Thailand strain_G2b (KF724935). The pandemic G2a virus was partial neutralized by the antibodies invoked by the G1- based PED vaccine virus.