<i>S100A9</i> and <i>EGFR</i> gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy

Kim, W. T.,Kim, J.,Yan, C.,Jeong, P.,Choi, S. Y.,Lee, O. J.,Chae, Y. B.,Yun, S. J.,Lee, S. C.,Kim, W. J. Oxford University Press 2014 Annals of Oncology Vol.25 No.5

<P>In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.</P>

Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs

Chae, S.Y.,Jin, C.H.,Shin, J.H.,Son, S.,Kim, T.H.,Lee, S.,Youn, Y.S.,Byun, Y.,Lee, M.S.,Lee, K.C. Elsevier Science Publishers 2010 Journal of controlled release Vol.142 No.2

Alterations in the physicochemical characteristics of peptide drugs can transform their biological and pharmaceutical features. In the present study, we explored the potentials of lithocholic acid (LCA)-modified exendin-4 derivatives as novel long-acting GLP-1 receptor agonists. Exendin-4 was modified with lithocholic acid at two lysine residues to produce three derivatives that were obtained by reverse-phase HPLC separation, namely, Lys<SUP>12</SUP>-LCA-exendin-4 (LCA-M2), Lys<SUP>27</SUP>-LCA-exendin-4 (LCA-M1), and Lys<SUP>12,27</SUP>-LCA-exendin-4 (LCA-Di)). The biological, pharmacological, and physicochemical characteristics of these three exendin-4 analogues were then investigated. Although slight reductions in the GLP-1 receptor binding capacity and insulinotropic activity of exendin-4 were observed after derivatization, the mono-LCA substitutions, especially LCA-M1, well-preserved antidiabetic activity in type 2 diabetic mice when administered subcutaneously or intraperitoneally. Furthermore, the pharmacokinetic characteristics were dramatically enhanced, that is, absorption was delayed and elimination half-life was increased (1.6+/-0.4 and 9.7+/-1.4h by exendin-4 and LCA-M1, respectively). The enhanced long-acting characteristics of the derivative was found to be due to albumin binding and nanoparticle formation, and these were verified by the restoration of normoglycemia in type 2 diabetic mice after single injection (>24h, >10nmol/kg, s.c.) and daily injections (15nmol/kg/day) maintained normoglycemia for the 4-week administration period. Furthermore, antidiabetic potentials, such as, glucose clearance kinetics and percentage areas occupied by pancreatic β-cells were also enhanced by long-term LCA-M1 administration. The present study demonstrates that the derivatization of exendin-4 with LCA offers a possible means of producing a long-acting GLP-1 receptor agonist.

Sphingosine-1-phosphate is involved in inflammatory reactions in patients with Graves’ orbitopathy

Seo, Y.,Chae, M. K.,Han, S. A.,Lee, E. J.,Lee, J. H.,Yoon, J. S. Birkha@user 2017 Inflammation research Vol.66 No.6

<P>S1P has an important role in the pathological inflammatory process of GO, which is mediated through the SphK1-S1P- S1P receptor pathway. SphK1 inhibitors and S1P receptors or antagonists could be potential approaches for controlling the inflammatory process of GO.</P>

Oxide-free Sb₂S₃ sensitized solar cells fabricated by spin and heat-treatment of Sb(III)(thioacetamide)₂Cl₃

You, M.S.,Lim, C.S.,Kwon, D.H.,Heo, J.H.,Im, S.H.,Chae, K.J. Elsevier Science 2015 ORGANIC ELECTRONICS Vol.21 No.-

Pure Sb<SUB>2</SUB>S<SUB>3</SUB> without oxide impurities was formed by thermal decomposition of Sb(thioacetamide: TA)<SUB>2</SUB>Cl<SUB>3</SUB> precursor. From the analysis of thermal properties of Sb(TA)<SUB>2</SUB>Cl<SUB>3</SUB>, we developed a spin-coating and heat-treatment process to form pure Sb<SUB>2</SUB>S<SUB>3</SUB> thin-films with controllable thickness due to the formation of insoluble Sb<SUB>2</SUB>S<SUB>3</SUB> by heat-treatment. Through the spin-coating and heat-treatment process, we could fabricate oxide-free Sb<SUB>2</SUB>S<SUB>3</SUB> planar type sensitized solar cell with 8.12mA/cm<SUP>2</SUP> of short circuit current density (J<SUB>sc</SUB>), 0.616V of open circuit voltage (V<SUB>oc</SUB>), 45.9% of fill factor (F.F), and overall power conversion efficiency (η) of 2.3% at 1 sun condition.

Heat, heat waves, and out-of-hospital cardiac arrest

Kang, S.H.,Oh, I.Y.,Heo, J.,Lee, H.,Kim, J.,Lim, W.H.,Cho, Y.,Choi, E.K.,Yi, S.M.,Sang, D.S.,Kim, H.,Youn, T.J.,Chae, I.H.,Oh, S. Elsevier/North-Holland Biomedical Press 2016 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.221 No.-

<P>Objective: Cardiac arrest is one of the common presentations of cardiovascular disorders and a leading cause of death. There are limited data on the relationship between out-of-hospital cardiac arrest (OHCA) and ambient temperatures, specifically extreme heat. This study investigated how heat and heat waves affect the occurrence of OHCA. Methods: Seven major cities in Korea with more than 1 million residents were included in this study. A heat wave was defined as a daily mean temperature above the 98th percentile of the yearly distribution for at least two consecutive days. Results: A total of 50,318 OHCAs of presumed cardiac origin were identified from the nationwide emergency medical service database between 2006 and 2013. Ambient temperature and OHCA had a J-shaped relationship with a trough at 28 degrees C. Heat waves were shown to be associated with a 14-% increase in the risk of OHCA. Adverse effects were apparent from the beginning of each heat wave period and slightly increased during its continuation. Excess OHCA events during heat waves occurred between 3 PM and 5 PM. Subgroup analysis showed that those 65 years or older were significantly more susceptible to heat waves. Conclusions: Ambient temperature and OHCA had a J-shaped relationship. The risk of OHCA was significantly increased with heat waves. Excess OHCA events primarily occurred during the afternoon when the temperature was high. We found that the elderly were more susceptible to the deleterious effects of heat waves. (C) 2016 Elsevier Ireland Ltd. All rights reserved.</P>

Syntheses of PCDTBT containing tetrafluorobenzene as electron-withdrawing group with deep HOMO energy level and applications for photovoltaics

Kim, J.,Kim, N.H.,Song, S.,Park, S.Y.,Chae, S.,Bae, E.,Kim, I.,Kim, H.J.,Kim, J.Y.,Suh, H. IPC Science and Technology Press 2016 Polymer Vol.102 No.-

Conjugated polymers using tetrafluorophenylene unit were synthesized and deployed for photovoltaics. The tetrafluorophenylene unit which has the strong electron-withdrawing ability, was utilized for the copolymers of push-pull type with low bandgaps for organic solar cells. 9H-Carbazole as electron-rich unit and di-2-thienyl-2,1,3-benzothiadiazole (DTBT) or tetrafluorophenylene unit as electron-deficient unit were utilized for the syntheses of donor-acceptor (D-A) types of conjugated polymers with different ratios of tetrafluorophenylene unit (PCDTBTF-1, PCDTBTF-3 and PCDTBTF-10). By introduction of tetrafluorophenylene unit in the backbone of PCDTBT, the energy level of the highest occupied molecular orbital (HOMO) and the bandgap were decreased as compared to those of PCDTBT. The higher amount of tetrafluorophenylene unit, the lower energy levels of the HOMO of the polymers were observed. The device of PCDTBTF-1:PC<SUB>71</SUB>BM (1:1) with additive of diphenyl ether (DPE) showed an open-circuit voltage (V<SUB>OC</SUB>) of 0.82 V, a short circuit current (J<SUB>SC</SUB>) of 9.66 mA/cm<SUP>2</SUP>, and a fill factor (FF) of 0.44, which yields PCE of 3.44%.

왕겨에 의한 신령버섯균사체 액체배양액의 생쥐 항복수암성 증가

Young S. Kim(김영숙),Wook J. Jang(장욱진),Md. A. Rakib(라키브),Jung M. Kwon(권정민),Chae R. Ahn(안채린),So Y. Kim(김소영),Yong U. Cho(조용운),Young K. Ha(하영권),Jeong O. Kim(김정옥),Yeong L. Ha(하영래) 한국생명과학회 2010 생명과학회지 Vol.20 No.9

왕겨가 Agaricus blazei Murill (AB: 신령버섯)균사체 액체배양 추출물의 항암성을 증가시키는지에 관한 연구를 수행하였다. AB균사체를 대두박을 기본으로 한 액체배지에 다양한 조건으로 배양하여, β-glucan 함량, Brix, 균사체를 측정하여 적정 생육조건을 선정하고, 이들의 열수추출물의 S-180 cell로 유도한 mouse 복수암에 대한 항암성을 조사하였다. AB균사체는 25℃에서 5일간 배양하였을 때 최적 생육을 나타내었고, 이 배양물이 다른 조건에서 배양한 배양물보다 우수한 항암성을 나타내었다. AB균사체의 생육 및 항암성은 변온배양에 따른 효과는 없었다. 따라서 이 최적배양조건(25℃, 5일 배양)에서 AB균사체를 1% 왕겨분말이 함유된 액체배지에 배양하고, 이의 열수 추출물의 항암성을 검증하였다. 1% 왕겨가 함유된 액체배지에서 배양한 열수추출물의 항암성은 왕겨가 함유되지 않은 배지의 열수추출물보다 항암성이 유의성 있게 증가되었다(p<0.05). 왕겨의 첨가는 AB균사체의 생육을 오히려 촉진시켰다. 이 결과는 왕겨가 AB균사체 뿐 만 아니라 다른 버섯균사체 액체배양물의 항암성 증진을 위한 원료로 활용될 수 있을 것임을 의미한다. The effects of rice hull (RH) powder on the anticarcinogenic activity of submerged-liquid cultures of Agaricus blazei Murill (AB) were assessed for mouse ascites cancers induced by mouse Sarcoma S-180 (S-180) cancer cells. Optimal growth of AB mycelia in the basal liquid culture medium, containing soybean meal, was achieved by culturing at 25℃ for 5 days, when evaluated by β-glucan content, Brix, and mycelial weight, relative to other culture conditions. Hot-water extract (HWE) of the submergedliquid culture of AB mycelia grown at 25℃ for 5 days exhibited a stronger anticarcinogenic activity, relative to HWE from other culture conditions. No such effects were obtained from AB mycelial cultures by alternative temperature-controlling cultures. Both cytotoxicity for S-180 cells and anticarcinogenic potentials for mouse ascites cancer of the HWE from AB mycelia grown in the basal medium containing 1% RH powder for 5 days at 25℃ were significantly (p<0.05) enhanced, relative to HWE from the AB mycelia culture of the basal medium without RH powder. These results indicate that HWE of submerged-liquid culture of AB mycelia, incubated in media containing 1% RH powder at 25℃ for 5 days, enhanced anticarcinogenic activity against S-180 cell-induced mouse ascites cancer, and suggest that RH powder is an excellent ingredient for the improvement of the anticarcinogenic potentials of the submerged-liquid culture of mushroom mycelia.

Psoriasin (S100A7), an antimicrobial peptide, is increased in human middle ear cholesteatoma

Kim, K. H.,Cho, J. G.,Song, J. J.,Woo, J. S.,Lee, H. M.,Jung, H. H.,Hwang, S. J.,Chae, S. Informa Healthcare 2009 Acta oto-laryngologica Vol.129 No.10

Bottom-gate poly-Si thin-film transistors by nickel silicide seed-induced lateral crystallization with self-aligned lightly doped layer

Lee, S.K.,Seok, K.H.,Chae, H.J.,Lee, Y.H.,Han, J.S.,Jo, H.A.,Joo, S.K. Pergamon Press ; Elsevier Science Ltd 2017 Solid-state electronics Vol.129 No.-

We report a novel method to reduce source and drain (S/D) resistances, and to form a lightly doped layer (LDL) of bottom-gate polycrystalline silicon (poly-Si) thin-film transistors (TFTs). For application in driving TFTs, which operate under high drain voltage condition, poly-Si TFTs are needed in order to attain reliability against hot-carriers as well as high field-effect mobility (μ<SUB>FE</SUB>). With an additional doping on the p<SUP>+</SUP> Si layer, sheet resistance on S/D was reduced by 37.5% and an LDL was introduced between the channel and drain. These results contributed to not only a lower leakage current and gate-induced drain leakage, but also high immunity of kink-effect and hot-carrier stress. Furthermore, the measured electrical characteristics exhibited a steep subthreshold slope of 190mV/dec and high μ<SUB>FE</SUB> of 263cm<SUP>2</SUP>/Vs.

Conjugated polymers containing pyrimidine with electron withdrawing substituents for organic photovoltaics with high open-circuit voltage

Kim, J.,Lee, J.,Chae, S.,Shim, J.Y.,Lee, D.Y.,Kim, I.,Kim, H.J.,Park, S.H.,Suh, H. IPC Science and Technology Press 2016 Polymer Vol.83 No.-

Polymers using 6-(2-thienyl)-4H-thieno[3,2-b]indole (TTI) with high planarity were synthesized and utilized for the photovoltaics. Push-pull types of conjugated polymers (PTTICN, PTTICNR and PTTIFR) containing TTI as electron pushing unit and 2-pyriminecarbonitrile or 2-fluoropyrimidine as electron pulling unit were synthesized. We designed pyrimidine derivatives with strong electron-withdrawing group (C?N or fluorine) for the generation of strong electron pulling property. By the combination with the electron pushing unit, the pyrimidines with strong electron pulling units will provide low highest occupied molecular orbital (HOMO) energy levels for higher open-circuit voltages (V<SUB>OC</SUB>). For the syntheses of the polymers, the electron pushing and the electron pulling units were combined by Stille coupling reaction with Pd(0)-catalyst. The polymers of PTTICN and PTTICNR with CN unit show higher V<SUB>OC</SUB> than the polymer with fluorine unit. The device comprising PTTICNR and PCBM (1:4) with diiodooctane (DIO) additive showed a V<SUB>OC</SUB> of 0.82 V, a J<SUB>SC</SUB> of 6.38 mA/cm<SUP>2</SUP>, and a fill factor (FF) of 0.53, giving a power conversion efficiency of 2.81%.