Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor

Cui, Y-H,Suh, Y,Lee, H-J,Yoo, K-C,Uddin, N,Jeong, Y-J,Lee, J-S,Hwang, S-G,Nam, S-Y,Kim, M-J,Lee, S-J Macmillan Publishers Limited 2015 Oncogene Vol.34 No.42

Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial–mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.

Mössbauer 분광법에 의한 원자로 용기재료의 비파괴적 중성자 조사평가에 대한 연구

정명모(M. M. Jung),장기상(K. S. Jang),유근배(K. B. Yoo),김길무(G. M. Kim),윤인섭(I. S. Yoon),홍치유(C. Y. Hong) 한국비파괴검사학회 2000 한국비파괴검사학회지 Vol.20 No.3

Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

Yoo, H.-S.,Kim, J. M.,Jo, E.,Cho, C.-K.,Lee, S.-Y.,Kang, H. S.,Lee, M.-G.,Yang, P.-Y.,Jang, I.-S. Spandidos Publications 2017 Oncology reports Vol.37 No.6

<P>Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagy-related genes affected by MRGX. Administration of MRGX at 100 mu g/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 mu g/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 mu g/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.</P>

Injection molding of a nanostructured plate and measurement of its surface properties

Yoo, Y.E.,Kim, T.H.,Choi, D.S.,Hyun, S.M.,Lee, H.J.,Lee, K.H.,Kim, S.K.,Kim, B.H.,Seo, Y.H.,Lee, H.G.,Lee, J.S. Elsevier 2009 CURRENT APPLIED PHYSICS Vol.9 No.2

This paper highlights recent research on the injection molding of a surface nanostructured substrate with super-hydrophobicity or dry adhesiveness. An anodic aluminum oxidation (AAO) membrane or layer on an Si wafer is used as a molding master for surface nanostructures. The AAO membrane or layer has closely packed nanoholes; depending on the AAO membrane used, the nanoholes have a diameter of around 200nm and a depth that varies from a few hundred nanometers to 60μm. This AAO master is installed directly in the injection molding tool, or the AAO holes are replicated on the nickel stamper by an electroforming process and installed in the injection molding tool. Either a high temperature (>T<SUB>g</SUB> of the molding material) mold or a rapid heating (up to 200<SUP>o</SUP>C) and cooling (<70<SUP>o</SUP>C) mold is used to fill the high aspect ratio nanoholes with thermoplastic melt for the injection molding. These high aspect ratio nanoholes are extremely difficult to fill with melt in a conventional injection molding process. This paper proposes a new simple and efficient rapid heating and cooling method that heats the stamper by means of the electrical resistance of the stamper itself. Depending on the aspect ratio of the structures and the type of master, a chemical etching or mechanical ejecting process is used to release the molded surface nanostructures. With the use of an AAO membrane and a high temperature mold, some polypropylene disks with a nanohairy surface and some polycarbonate plates with a nanopillar on the surface are injection molded at several different mold temperatures for the purpose of studying the replication of the surface nanostructures. In addition, the contact angle of the water and the adhesion force on the molded surfaces are measured to investigate the effect of the surface nanostructures on the hydrophobicity or dry adhesiveness.

Production of transgenic cloned minipig expressing HLA-G1 and DAF gene by nuclear transfer

Park K.W.,G.S.Han,K.M. Choi,S.P. Hong,J.Y. Yoo,E.J. Kim,S.H. Kim,Y.C. Park,W.K. Lee,C.G. Park,S.J. Kim,J.G. Seol 한국동물생명공학회(구 한국동물번식학회) 2007 발생공학 국제심포지엄 및 학술대회 Vol.2007 No.1

Novel and Recurrent ACADS Mutations and Clinical Manifestations Observed in Korean Patients with Short-chain Acyl-coenzyme a Dehydrogenase Deficiency

Kim, Y.-M.,Cheon, C.-K.,Park, K.-H.,Park, S. W.,Kim, G.-H.,Yoo, H.-W.,Lee, K.-A.,Ko, J. M. INSTITUTE FOR CLINICAL SCIENCE 2016 Annals of clinical and laboratory science Vol.46 No.4

<P>Short-chain acyl-CoA dehydrogenase (SCAD) catalyzes the first step in mitochondrial short-chain beta-oxidation, and its deficiency is caused by mutations in the ACADS. We sought to investigate the spectrum ACADS mutations and associated clinical manifestations in Korean patients with SCAD deficiency. The study included ten patients with SCAD deficiency from 8 unrelated families as diagnosed by biochemical profile and mutation analyses. Clinical features, biochemical data, growth, and neurodevelopmental state were reviewed retrospectively. Eight patients were found during newborn screening, and two were diagnosed by family screening. During follow-up ranging from 2 months to 4.5 years, no hypoglycemic event was noted, and the development and growth of the patients were normal, except in two siblings. One exhibited hypotonia and gross motor delay, while one girl showed cyclic vomiting until the age of two years. We identified seven different mutations of ACADS. Of these, p. E344G was the most frequent mutation with an allele frequency of 50%, followed by p. P55L with 18.8%. p. G108D and four novel mutations were identified: p. L93I, p. E228K, p. P377L, and p. R386H. Korean patients with SCAD deficiency showed heterogenous clinical features and ACADS genotype. Our data contributes to a better understanding of the distinct molecular genetic characteristics and clinical manifestations of SCAD deficiency.</P>

Effects of Solution Concentration on the Structural and Magnetic Properties of Ni0.5Zn0.5Fe₂O₄ Ferrite Nanoparticles Prepared by Sol-gel

B. S. Yoo,Y. G. Chae,Y. M. Kwon,D. H. Kim,B. W. Lee,Chunli Liu 한국자기학회 2013 Journal of Magnetics Vol.18 No.3

The Ni0.5Zn0.5Fe₂O₄ nanoparticles about 30 nm were prepared using sol-gel method with metal nitrates dissolved in 2-methoxyathanol. The concentrations of the metal nitrates are adjusted from 0.1 to 0.75 M in order to study the influence on the structural and magnetic properties. The structure and morphology characterization revealed that the crystallinity was improved and the nanoparticle size was increased with the nutrition solution concentrations up to 0.5 M. Degraded crystallinity together with decreased nanoparticle size were observed for concentration of 0.75 M. The saturation magnetization at room temperature reached maximum at 0.5 M, which can be explained by considering the crystallinity and size effect.

Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women

Choi, K. M.,Kim, T. N.,Yoo, H. J.,Lee, K. W.,Cho, G. J.,Hwang, T. G.,Baik, S. H.,Choi, D. S.,Kim, S. M. Blackwell Publishing Ltd 2009 Clinical endocrinology Vol.70 No.4

<P>Summary</P><P>Objective </P><P>Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers.</P><P>Study subjects </P><P>Thirty obese Korean women and 15 age-matched nonobese control subjects were studied.</P><P>Design </P><P>Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week.</P><P>Results </P><P>Obese women exhibited higher A-FABP levels compared to nonobese women (21·4 ± 6·4 µg/l <I>vs.</I> 13·6 ± 4·4 µg/l, <I>P</I> < 0·001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (<I>P</I> = 0·054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21·4 ± 6·4 µg/l to 19·3 ± 6·8 µg/l (<I>P</I> = 0·038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme.</P><P>Conclusion </P><P>Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.</P>

Defect reduction of SiN_x embedded m-plane GaN grown by hydride vapor phase epitaxy

Woo, S.,Kim, M.,So, B.,Yoo, G.,Jang, J.,Lee, K.,Nam, O. North-Holland Pub. Co 2014 Journal of crystal growth Vol.407 No.-

Nonpolar (10-10) m-plane GaN has been grown on m-plane sapphire substrates by hydride vapor phase epitaxy (HVPE). We studied the defect reduction of m-GaN with embedded SiN<SUB>x</SUB> interlayers deposited by ex-situ metal organic chemical vapor deposition (MOCVD). The full-width at half-maximum values of the X-ray rocking curves for m-GaN with embedded SiN<SUB>x</SUB> along [11-20]<SUB>GaN</SUB> and [0001]<SUB>GaN</SUB> were reduced to 528 and 1427arcs, respectively, as compared with the respective values of 947 and 3170arcs, of m-GaN without SiN<SUB>x</SUB>. Cross-section transmission electron microscopy revealed that the basal stacking fault density was decreased by approximately one order to 5x10<SUP>4</SUP>cm<SUP>-1</SUP> due to the defect blocking of the embedded SiN<SUB>x</SUB>. As a result, the near band edge emission intensities of the room-temperature and low-temperature photoluminescence showed approximately two-fold and four-fold improvement, respectively.

A genetic variation in microRNA target site of <i>KRT81</i> gene is associated with survival in early-stage non-small-cell lung cancer

Lee, S. Y.,Choi, J. E.,Jeon, H. S.,Hong, M. J.,Choi, Y. Y.,Kang, H. G.,Yoo, S. S.,Lee, E. B.,Jeong, J. Y.,Lee, W. K.,Lee, J.,Cha, S. I.,Kim, C. H.,Kim, Y. T.,Jheon, S.,Son, J. W.,Park, J. Y. Oxford University Press 2015 ANNALS OF ONCOLOGY Vol.26 No.6

<P>In this study, <I>KRT81</I> rs3660G>C was associated with survival of patients with NSCLC after surgical resection. Mechanistic study suggested that the G-to-C change caused reduced binding efficiency of miRNA, leading to decreased translational repression, thereby increased <I>KRT81</I> expression. The <I>KRT81</I> rs3660G>C may be a useful prognostic biomarker in early-stage NSCLC patients.</P><P><B>Background</B></P><P>MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA–mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC).</P><P><B>Methods</B></P><P>Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (<I>n</I> = 479). <I>Renilla</I> luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs.</P><P><B>Results</B></P><P>Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, <I>KRT81</I> rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50–0.85; <I>P</I> = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of <I>KRT81</I> in tumor tissues.</P><P><B>Conclusion</B></P><P>The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.</P>