Establishment and characterization of cell lines from three human thyroid carcinomas: Responses to all-trans-retinoic acid and mutations in the BRAF gene

Koh, C.S.,Ku, J.L.,Park, S.Y.,Kim, K.H.,Choi, J.S.,Kim, I.J.,Park, J.H.,Oh, S.K.,Chung, J.K.,Lee, J.H.,Kim, W.H.,Kim, C.W.,Cho, B.Y.,Park, J.G. North-Holland 2007 Molecular and cellular endocrinology Vol.264 No.1

We report the characteristics of three cell lines (designated, SNU-80, SNU-373 and SNU-790), which were established from two papillary carcinomas and one anaplastic carcinoma obtained from three Korean thyroid carcinoma patients. All cell lines grow as adherent cells. Electron microscopy characteristically showed cytoplasmic invaginations of nuclei and intranuclear cytoplasmic inclusions. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and SNU-790 cells positivity for CK-19. All lines were free of mycoplasma or bacteria and were proven unique by DNA fingerprinting analysis. The p15 and p16 genes are deleted in the SNU-790 line. Mutations of the p53 gene were found in two lines (SNU-80 and SNU-373), but no mutations in the RET or MEN1 genes were observed. Mutations of the BRAF gene were found in the SNU-80 (G468R) and the SNU-790 (V599E) cell lines, but no mutations in the K-ras gene were present. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and no evidence of the production of thyroglobulin or calcitonin was observed. The cell lines were unable to trap radioactive iodine but did not contain TSH receptor. In addition, we investigated the mRNA expression levels of Tg, TSHR, TTF-1, PAX-8, NIS, IL-6, and LIF, and of the α, β and γ retinoic acid receptors in these cell lines. IL-6 was down-regulated in all three cell lines by all-trans-retinoic acid treatment. RAR-α was expressed but RAR-β was not expressed in the three cell lines, and RAR-γ was not expressed in SNU-790. Interestingly, RAR-β (SNU-80 and SNU-373) and RAR-γ (SNU-790) was up-regulated by all-trans-retinoic acid treatment. We believe that these well-characterized thyroid carcinoma cell lines may be useful tools for investigations on the biological characteristics of thyroid carcinoma, particularly for investigations related to gene alterations, especially of the BRAF gene. These cell lines may also be useful for redifferentiation therapy studies on thyroid carcinoma using all-trans-retinoic acid.

Direct electrochemistry of glucose oxidase immobilized on carbon nanotube for improving glucose sensing

Hyun, K.,Han, S.W.,Koh, W.G.,Kwon, Y. Pergamon Press ; Elsevier Science Ltd 2015 International journal of hydrogen energy Vol.40 No.5

In this research, we suggest an enzyme immobilization structure that glucose oxidase (GOx) is coated on carbon nanotube (CNT) and quantify an optimal condition for the immobilization. Physical adsorption of GOx to CNT is used as the method for GOx immobilization on CNT (GOx/CNT). Cyclic voltammetry (CV) is served to evaluate catalytic activity and direct electrochemistry, while SEM is used to confirm the formation of GOx/CNT. To investigate the catalytic activity and the optimal loading of GOx, its peak current and electron transfer rate constant, k<SUB>s</SUB>, are measured. In both ways, 2 mg mL<SUP>-1</SUP> GOx shows best results and its k<SUB>s</SUB> is 1.14s<SUP>-1</SUP>. From the relationship between scan rate and peak current, it is also revealed that this structure is (i) controlled by surface reaction and (ii) quasi-reversible. Regarding redox reaction of GOx, peak potential is linearly varied with pH with slope of -51 mV/pH. The slope indicates a typical two-electron reaction that is a desirable reaction pathway. GOx-catalyzed glucose oxidation reaction (GOR) is also investigated by reacting different concentrations of glucose with GOx/CNT layer. Peak current for GOR linearly increases with glucose concentration, proving that increase in glucose concentration promotes GOR. Therefore, GOx/CNT leads to high sensitivity of glucose (53.5 μAmM<SUP>-1</SUP>cm<SUP>-2</SUP>). When it comes to long term stability, activity of GOx/CNT is measured and 86% of the activity is maintained even after two weeks, indicating that long term stability of GOx is excellent.

Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae plant essential oils and their constituents against Japanese termite (Reticulitermes speratus Kolbe)

Seo, S.M.,Kim, J.,Kang, J.,Koh, S.H.,Ahn, Y.J.,Kang, K.S.,Park, I.K. Academic Press 2014 Pesticide biochemistry and physiology Vol.113 No.-

This study investigated the fumigant toxicity of 4 Asteraceae plant essential oils and their constituents against the Japanese termite Reticulitermes speratus Kolbe. Fumigant toxicity varied with plant essential oils or constituents, exposure time, and concentration. Among the tested essential oils, those from Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus punctulatus at 2days after treatment. In all, 15, 24, 19, and 9 compounds were identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus, respectively, by using gas chromatography, gas chromatography-mass spectrometry, or open-column chromatography. The identified compounds were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide, sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus essential oils were tested to determine the mode of their action. The IC<SUB>50</SUB> values of (+)-α-pinene, (-)-limonene, (-)-α-pinene, β-pinene, and β-phellandrene against Japanese termite AChE were 0.03, 0.13, 0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.

Influence of the sintering temperature and Ag₂O dopants on microstructure and piezoelectric properties of 0.94(K_0.5Na_0.5)NbO₃-0.06LiNbO₃ lead-free ceramics

Chae, M.S.,Koh, J.H.,Lee, S.K. Elsevier Sequoia 2014 JOURNAL OF ALLOYS AND COMPOUNDS Vol.587 No.-

In this paper, the non-stoichiometric compositions of (1-x)0.94(K<SUB>0.5</SUB>Na<SUB>0.5</SUB>)NbO<SUB>3</SUB>-0.06LiNbO<SUB>3</SUB>+xmol% Ag<SUB>2</SUB>O (where x=0, 0.05, 0.07, 0.08, 0.1 and 0.15, respectively) ceramics were fabricated as a function of the amount of Ag<SUB>2</SUB>O addition. The effects of Ag<SUB>2</SUB>O dopants and sintering temperature on the phase, the microstructure and piezoelectric properties of (1-x)0.94(K<SUB>0.5</SUB>Na<SUB>0.5</SUB>)NbO<SUB>3</SUB>-0.06LiNbO<SUB>3</SUB>+xmol% Ag<SUB>2</SUB>O ceramics were investigated. The 0.94(K<SUB>0.5</SUB>Na<SUB>0.5</SUB>)NbO<SUB>3</SUB>-0.06LiNbO<SUB>3</SUB> ceramics doped with Ag<SUB>2</SUB>O (x=0.07) were well sintered at 1040<SUP>o</SUP>C for 2h. The ceramics with x=0.07 exhibit optimum piezoelectric properties of d<SUB>33</SUB>=272pC/N, k<SUB>p</SUB>=37.9%, P<SUB>r</SUB>=25.2μC/cm<SUP>2</SUP>, and E<SUB>c</SUB>=30.7kV/cm.

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding

Lee, K M,Choi, W I,Koh, D I,Kim, Y J,Jeon, B N,Yoon, J H,Lee, C E,Kim, S H,Oh, J,Hur, M W Springer Science and Business Media LLC 2012 Oncogene Vol.31 No.11

<P>The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box#3 (bp, -55 to -63) and the MIZ-1-binding elements, MRE-A (bp, -90 to -64) and MRE-B (bp, -27 to -17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp, -95 to -100) and #3 (bp, -55 to -63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.</P>

Recurrent rare earth element mineralization in the northwestern Okcheon Metamorphic Belt, Korea: SHRIMP U-Th-Pb geochronology, Nd isotope geochemistry, and tectonic implications

Cheong, C.s.,Kim, N.,Yi, K.,Jo, H.J.,Jeong, Y.J.,Kim, Y.,Koh, S.M.,Iizuka, T. Elsevier 2015 Ore geology reviews Vol.71 No.-

Rare earth element (REE) mineralization is hosted within Neoproterozoic alkaline metaigneous rocks in the northwestern part of the Okcheon Metamorphic Belt (OMB), a polymetamorphosed fold-and-thrust belt transecting the Paleoproterozoic Gyeonggi and Yeongnam Massifs in the southern Korean Peninsula. The principal carrier phase of REEs is allanite. Allanite grains can be subdivided into several types based on the texture and mineral assemblage including quartz, K-feldspar, biotite, britholite, apatite, fergusonite, andradite, magnetite, zircon, titanite and fluorite. Electron microprobe analysis of allanite clearly distinguishes sample-to-sample variations in total REEs, Ca, Al, Fe and Y but the textural varieties from each rock sample do not show marked differences in those elements. Sensitive high-resolution ion microprobe dating of allanite and zircon reveals a complex history of multistage mineralization. Allanite grains from REE ores yielded Late Ordovician (444.6+/-8.0Ma), Permian to Triassic (ca. 300-220Ma) and Early Jurassic (199-183Ma) <SUP>208</SUP>Pb/<SUP>232</SUP>Th ages. These multiple age components often coexist in single grains showing slight differences in backscattered electron brightness. The Ordovician components have distinctly higher Th/U than the younger domains in the same rock sample. The cores and rims of zircon from a syenite hosting REE ore bodies yielded Neoproterozoic (858.2+/-6.3Ma) and Early Jurassic (ca. 190Ma) <SUP>206</SUP>Pb/<SUP>238</SUP>U ages, respectively. The Early Jurassic ages (194-187Ma) also obtained from zircon grains from granites taken from dykes occurring close to the ores and a drill core indicate the correspondence between granitic magmatism and REE mineralization. The Neoproterozoic zircon inheritance (weighted mean=853.9+/-3.8Ma) in these granites is in sharp contrast to the dominant Paleoproterozoic inherited zircon from the widespread earliest Middle Jurassic granites enclosing the mineralized zone. The geotectonic significance of the Late Ordovician event recorded in the allanite, as well as in detrital zircon from the OMB, is still unclear but its temporal coincidence with intraplate volcanism and arc-related igneous activity, respectively, reported from the southwestern edge of the adjacent Taebaeksan Basin and the southwestern Gyeonggi Massif is noteworthy. The following Permian-Triassic and Early Jurassic mineralization events are probably linked to the continental suturing between the North and South China blocks and subsequent post-orogenic magmatism, and arc magmatism resulting from the paleo-Pacific plate subduction, respectively. Sub-grain Sm-Nd isotopic analyses of allanite by laser ablation multiple collector ICPMS yielded initial ε<SUB>Nd</SUB> values plotting along the Nd isotopic evolution path of the Neoproterozoic metaigneous rocks, indicating that REEs originating from the host rock have been recycled during multistage mineralization events. The profound differences in inherited zircon ages and Nd isotopic compositions between the Early and Middle Jurassic granites may reflect the presence of a major thrust-bounded crustal structure beneath the OMB.

Hydrogeochemical interpretation of South Korean groundwater monitoring data using Self-Organizing Maps

Choi, B.Y.,Yun, S.T.,Kim, K.H.,Kim, J.W.,Kim, H.M.,Koh, Y.K. Elsevier 2014 Journal of geochemical exploration Vol.137 No.-

The National Groundwater Monitoring Network (NGMN) of South Korea provides data since 1995 to monitor the water level and quality of groundwater on a national scale. Major ions such as Ca, Mg, Na, K, HCO<SUB>3</SUB>, Cl, SO<SUB>4</SUB> and NO<SUB>3</SUB> have been monitored since 2008 to assess groundwater quality. Hydrochemical data of bedrock groundwater samples collected from 299 monitoring stations in 2009 were examined using the Self-Organizing Map (SOM) approach. Based on hydrochemical characteristics, bedrock groundwater is clustered into two groups and six subgroups. Group I containing 70.2% of groundwater samples (and monitoring stations) is characterized by lower TDS values and NO<SUB>3</SUB> concentrations than Group II, indicating that Group I waters are less affected by contamination. Subgroup I-1 (39.1%) represents Ca-HCO<SUB>3</SUB>-type groundwater with relatively low pH, TDS and concentrations of most ions compared with groundwater of Subgroups I-2-1 (26.1%) and I-2-2 (5.0%). Subgroup I-2-2 represents a moderately alkaline, F-rich, Na-HCO<SUB>3</SUB>-type groundwater. Group II records either anthropogenic or natural processes. Subgroup II-1 (16.1%) contains groundwater with low values of TDS, HCO<SUB>3</SUB> and pH, and moderately high NO<SUB>3</SUB> concentrations due to nitrification, while groundwater of Subgroups II-2-1 and II-2-2 is characteristically high in Ca and Mg. Subgroup II-2-1 is also very high in SO<SUB>4</SUB> and HCO<SUB>3</SUB> but very low in NO<SUB>3</SUB>, while Subgroup II-2-2 is substantially enriched in Cl and NO<SUB>3</SUB>. The hydrochemistry of groundwater of Subgroup II-2-1 likely results from dissolution of carbonates and gypsum in clastic sedimentary rocks and is affected by dissolution of pyrite and/or S-bearing fertilizers in crystalline rocks. The enrichment of NO<SUB>3</SUB>, Cl, Ca and Mg in groundwater of Subgroup II-2-2 is the result of substantial contamination from agrochemicals and manure. Thus, about 20.5% (Subgroups II-1 and II-2-2) of bedrock groundwater in South Korea records anthropogenic contamination. This study shows that the SOM approach can be successfully used to classify and characterize the groundwater in terms of hydrochemistry and quality on a regional scale.

Sol - Gel 방법을 이용한 FET 형 전해질 센서의 제작 및 특성

문수영,조병욱,김창수,고광락,손병기 ( S . Y . Moon,B . W . Cho,C . S . Kim,K . N . Koh,B . K . Sohn ) 한국센서학회 1998 센서학회지 Vol.7 No.4

PVC membrane, which has been used for membrane of electrolyte sensors, shortened sensor lifetime due to poor adhesion to sensor surface and exhibited difficulty in standardization and mass-production. To overcome these problems, the membrane solution was prepared with neutral carrier, matrix(TEOS:DEDMS=1:3), solvent(ethanol), and a catalyzer(HCl). The fabricated electrolyte sensors showed typical electrical characteristics of MISFET (metal-insulator-semiconductor field-effect transistor). The K-, Ca- and Na-ISFETs showed sensitivity of 53, 2b and 50 mV/decade in wide concentration range, respectively. The response time was about 90 seconds and the drift was 0.05mV/hour. These results suggest that the sol-gel method and the lift-off technique can be applied to formation of membranes and expected to improve mass-productivity, standardzation of the sensors.

Induction of proteinase 3-anti-neutrophil cytoplasmic autoantibodies by proteinase 3-homologous bacterial protease in mice

Kim, Y. C.,Choi, Y. S.,Alam, J.,Kim, Y. j.,Baek, K. J.,Koh, J.,Song, Y. W.,Chung, D. H.,Choi, Y. Springer Science + Business Media 2016 Immunologic research Vol.64 No.2

<P>Proteinase 3 (PR3) is the principal target of antineutrophil cytoplasmic autoantibodies (ANCA) associated with granulomatosis with polyangiitis. The aim of this study was to investigate whether bacterial PR3-homologous protease can induce autoantibodies to PR3 and ANCA-associated pathology in mice. Among the bacterial proteases that have greater than 30 % identity with PR3, a trypsin-like serine protease of Saccharomonospora viridis, a bacterium that causes hypersensitivity pneumonitis, was chosen. When the mice were immunized with the recombinant protease of S. viridis (SvPR), 75 % of NZBWF1 and 100 % of C57BL/6 mice developed high levels of autoantibodies to mouse PR3 (mPR3). The levels of antibodies to mPR3 had a strong positive correlation with those to SvPR. In addition, more than half of the mPR3-reactive sera (63 %) reacted to purified human PR3 (hPR3), and the levels of antibodies to hPR3 had a positive correlation with those to mPR3. The sera from the immunized mice strongly stained murine neutrophils in a C-ANCA pattern. Although granulomatous inflammation and signs of vasculitis were observed in several mice, they were attributable to the use of complete Freund's adjuvant in the immunization. Collectively, exposure to PR3-homologous bacterial protease could induce ANCA in mice, and this finding may provide a new insight into the triggering mechanisms for the production of PR3-ANCA.</P>

Involvement of the BLT₂ receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice

Kim, H J,Kim, D K,Kim, H,Koh, J Y,Kim, K M,Noh, M S,Lee, S,Kim, S,Park, S H,Kim, J J,Kim, S Y,Lee, C H Nature Publishing Group 2008 British journal of pharmacology Vol.154 No.5

Background and purpose:Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B<SUB>4</SUB> receptor BLT<SUB>2</SUB>. To confirm the involvement of the BLT<SUB>2</SUB> receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT<SUB>2</SUB> receptor agonists compound A (4′-{[pentanoyl (phenyl) amino]methyl}-1,1′-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid).Experimental approach:A video recording was used to determine whether the BLT<SUB>2</SUB> receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used.Key results:Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose–response curve for compound A showed peaks at around 0.005–0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT<SUB>1</SUB> receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT<SUB>2</SUB> receptor antagonist) on the BLT<SUB>2</SUB> agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT<SUB>2</SUB> receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice.Conclusions and implications:Our present results corroborate the hypothesis that the BLT<SUB>2</SUB> receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT<SUB>2</SUB> receptor antagonists.British Journal of Pharmacology (2008) 154, 1073–1078; doi:10.1038/bjp.2008.220; published online 9 June 2008