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Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4
<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>
Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J‐,S.,Park, J‐,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5
<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. Acta Neurol Scand: 2011: 123: 325–331. © 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</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.
Optical Properties and Glass-forming Region of the K2O-Sm2O3-TeO2 Glass System
K. S. Hong,Y. J. Cha,M. G. Ha,최세용,J. P. Kim,B. S. Lee,정의덕,김현규,P. H. Borse 한국물리학회 2014 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.65 No.9
The optical properties and the glass-forming region of the K2O-Sm2O3-TeO2 glass system arestudied. In the K2O-Sm2O3-TeO2 system, only the 5K2O-5Sm2O3-90TeO2 composition gives atransparent glass. The refractive index, n, and the optical band-gap energy, Eg, of the 5K2O-5Sm2O3-90TeO2 glass are n = 2.04 ± 0.003 and Eg = 3.2 eV, respectively. A single Sm2Te6O15phase is found to be formed by a two-step thermal treatment process at 370 C for 5 h and 390 Cfor 5 h. This is the first report on the crystallization and the preparation of the K2O-Sm2O3-TeO2glass system.
Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9
<P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>
Foxp3 is a key downstream regulator of p53-mediated cellular senescence
Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2
<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>
Hong, S.,Yim, U.H.,Ha, S.Y.,Shim, W.J.,Jeon, S.,Lee, S.,Kim, C.,Choi, K.,Jung, J.,Giesy, J.P.,Khim, J.S. Pergamon Press 2016 CHEMOSPHERE - Vol.144 No.-
Bioaccessibility of toxic substances in sedimentary residual oil is a crucial factor that needs to be considered for accurate risk assessments posed by oil spills. However, information on oil weathering processes and bioaccessibility of residual oil is often not sufficient and clear. In the present study, bioaccessibility of aryl hydrocarbon receptor (AhR)-active polycyclic aromatic hydrocarbons (PAHs) in coastal sediments near the site of the Hebei Spirit oil spill (Korea, 2007) was assessed by Tenax extraction in effect-directed analysis (EDA). Sediment samples collected 6 years after the oil spill were extracted using Soxhlet or Tenax, and EDA was performed using a battery of H4IIE-luc bioassay and GC/MSD analysis. Concentrations of PAHs and alkyl-PAHs in Soxhlet extracts ranged from 210 to 53,000 μg kg<SUP>-1</SUP> dry mass. However, concentrations of PAHs and alkyl-PAHs in Tenax extracts were approximately 20-fold less compared to those in Soxhlet extracts. In Soxhlet and Tenax extracts, the major AhR-active PAHs were identified as C1-chrysene, C3-chrysene, and C4-phenanthrene. Concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQ<SUB>PAHs</SUB>) explained 31% and 60% of the bioassay-derived TCDD-EQ concentrations in Soxhlet and Tenax extracts, respectively. Overall, bioaccessibility of PAHs and alkyl-PAHs in sedimentary residual oils depended on hydrophobicity (log K<SUB>ow</SUB>) and degree of weathering of crude oil. The results of the present study provide further evidence in support of the biological and ecological recoveries of oil spill sites.
Pollen morphology of the tribe Sorbarieae (Rosaceae)
Song, J. H.,Moon, H. K.,Hong, S. P. Springer Science + Business Media 2016 Plant systematics and evolution Vol.302 No.7
<P>The pollen morphology of the tribe Sorbarieae (Adenostoma, Chamaebatiaria, Sorbaria, and Spiraeanthus) and two related genera Gillenia and Lyonothamnus was investigated by light, scanning electron, and transmission electron microscopy. Sorbarieae pollen was monad, tri-colporate, small to medium in size (P = 10.2-40.0 mu m, E = 10.8-32.4 mu m), and oblate to prolate in shape (P/E = 0.74-1.88). The sexine ornamentation was striate, but four different types could be divided: striate-psilate, striate-plicate, striate-microechinate, and striate-perforate. The pollen wall stratification typically consisted of unbranched columellae and a continuous endexine. As an additional palynological characteristic, orbicules (small sporopollenin granules) were observed in all taxa and thus a possible synapomorphic character of Sorbarieae as a whole. The pollen characteristics are useful to recognize certain taxa. Gillenia is the only genus with both a pore flap on the aperture and the perforated sexine. Lyonothamnus has a significantly thick exine and relatively larger pollen grains, which is compared to that of Sorbarieae. Some quantitative characteristics (e.g., pollen and colpus size, exine thickness, and ridge width of striae) identified using principal components analysis (PCA) may have diagnostic importance among the taxa in the tribe.</P>