Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

<P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

Toward high efficiency organic photovoltaic devices with enhanced thermal stability utilizing P3HT-b-P3PHT block copolymer additives

Zhu, M.,Kim, H.,Jang, Y.,Park, S.,Ryu, D.,Kim, K.,Tang, P.,Qiu, F.,Kim, D.,Peng, J. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.47

<P>Organic photovoltaics (OPVs) have drawn an extensive amount of attention due to their low cost, processibility and flexibility. However, a cell based on a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) has a limited power conversion efficiency (PCE) due to the short exciton diffusion length of similar to 10 nm. We address this issue by designing a series of all-conjugated diblock copolymers, poly(3-hexylthiophene)-b-poly(3-(6-diethylphosphonatohexyl) thiophene) (P3HT-b-P3PHT), intended for use as additives to improve the performance of P3HT:PC61BM-based photovoltaic devices. The PCE of the devices improved from 3.30% to 4.03% with the addition of P3HT-b-P3PHT (3 : 1). The thermal stability of devices with P3HT-b-P3PHT additives improved significantly relative to that of the P3HT:PC61BM reference device, where the devices including a copolymer with a higher P3PHT content exhibited a better thermal stability. It was found that the fill factor (FF) could be regulated by simply varying the block ratio of P3HT-b-P3PHT and played a crucial role in improving both the PCE and the thermal stability. The P3HT-b-P3PHT diffused at the P3HT:PC61BM interface, improved the miscibility between P3HT and PC61BM, optimized the nanoscale morphology of the photoactive layer, and reduced the active layer roughness, all of which improved the FF and thus contributed to an improvement in device performance.</P>

Unveiling the synergistic effect of polysulfide additive and MnO2 hollow spheres in evolving a stable cyclic performance in Li-S batteries

Ahad, S.,Ragupathy, P.,Ryu, S.,Lee, H. W.,Kim, D. unknown 2017 Chemical Communications Vol. No.

<P>Herein, we demonstrate a synergistic approach involving polar-based oxide and polysulfide additives for effectively suppressing polysulfide dissolution during cycling. The MnO2 hollow spheres not only provide physical confinement for the polysulfide species but also enable strong chemical interactions between polysulfide species and oxides, while the added polysulfide furnishes a mass buffering effect and compensates for the capacity losses due to partial cathode dissolution during discharge. The capacity retentions of S/KB, S/KB/LiPS, S/KB/MnO2, and S/KB/MnO2/LiPS composite cathodes are 31%, 45%, 59%, and 91% respectively. The remarkable capacity retention of the S/KB/LiPS/MnO2 composite electrode is mainly attributed to the synergistic effect between MnO2 and polysulfide additives.</P>

Seismic stratigraphy and structural analysis of the western South Korea Plateau (WSKP), East Sea

Cukur, D.,Kim, S.P.,Horozal, S.,Ryu, B.J.,Kim, G.Y.,Kong, G.S. Pergamon Press 2015 Quaternary international Vol.384 No.-

The western South Korea Plateau (WSKP), situated on the southwestern part of East Sea, is characterized by rifted continental fragments that were formed in the early phase of back-arc opening. In this work, we analyze multi-channel seismic reflection profiles from the WSKP to document the structural and stratigraphic framework of the area. We also present fault-derived stretching (beta) factors related to the continental rifting along two regional seismic profiles. Our data reveal several graben and half graben subbasins, up to 1300 m thick, bound by N-S trending normal faults. We show that, on the basis of constructed isopach maps, tectonic activity was the main controlling factor on the sedimentation through much of the plateau history. The seismic data reveal that the sedimentation history of the WSKP is characterized by four main phases (Phase 1 to Phase 4; P1-P4) separated by regional unconformities. Rapid extension and subsidence took place at an early stage of P1 leading to the graben and half-graben openings. Volcanic activity was widespread at early times and ~700 m thick succession of lacustrine and fluvial sediments was deposited. Following P2 (early mid Miocene - latest Miocene), dramatic extension and subsidence changed the lacustrine environment into marine, enabling to the deposition of thick marine sediments (~750 m) over the subbasins. Extension ceased during P3 (latest Miocene - early Pliocene) and less pronounced subsidence continued. At this time, the sedimentation was uniform over the area and included the cyclic succession of hemipelagic deposits and turbidites which were probably expressed by climatic forcing. P3 was interrupted by regional compression, when normal fault movement was reversed and gentle anticlines formed as a result of inversion. The latter was accompanied by widespread uplift and erosion along the western margin of the plateau, and substantial erosion took place on the crests of the folds. The uplift also shifted the main depocenters of the plateau which were ultimately filled by thick mass-transport deposits during the following phase of P4 (early Pliocene - Holocene). Subsidence has been dominant in the area since the beginning of P4, which was locally interspersed by inversion along the reactivated normal faults. Total upper-crust (βf) and whole-crust extension (βc) estimates in the WSKP show similarities, suggesting that the observed rift structure in WSKP has resulted from uniform pure-shear stretching.

P2Y receptor regulation of sodium transport in human mammary epithelial cells

Lee, S.Y.,Palmer, M.L.,Maniak, P.J.,Jang, S.H.,Ryu, P.D.,O Grady, S.M. AMERICAN PHYSIOLOGICAL SOCIETY 2007 American journal of physiology. Cell physiology Vol.293 No.5

Impaired expression of Toll-like receptor 2 in nontuberculous mycobacterial lung disease.

Ryu, Y J,Kim, E J,Lee, S-H,Kim, S Y,Suh, G Y,Chung, M P,Kim, H,Kwon, O J,Koh, W-J Published jointly by the Society and Munksgaard 2007 The European respiratory journal Vol.30 No.4

<P>The aims of the present study were to investigate the expression of Toll-like receptor (TLR)2 on the peripheral blood monocytes of patients with nontuberculous mycobacterial (NTM) lung disease and healthy controls, and to assess the responses of these monocytes to TLR2 agonists such as Mycobacterium avium and lipoteichoic acid (LTA). Reverse transcriptase-PCR was used to analyse TLR2 mRNA expression in peripheral blood monocytes from 17 NTM patients and 10 healthy controls. mRNA and protein secretion levels were also determined for the cytokines interleukin (IL)-12 p40 and tumour necrosis factor (TNF)-alpha. Expression of TLR2 mRNA by peripheral blood monocytes after stimulation with M. avium or LTA was lower in NTM patients than in healthy controls. IL-12 p40 and TNF-alpha mRNA and cytokine secretion levels were also lower in patients than in healthy controls. Treatment with anti-TLR antibody decreased M. avium- and LTA-induced IL-12 p40 and TNF-alpha production in healthy controls, but not in NTM patients. The present results suggest that the downregulation of Toll-like receptor 2 and the resulting decreased production of interleukin-12 p40 and tumour necrosis factor-alpha following Mycobacterium avium or lipoteichoic acid stimulation may contribute to host susceptibility to nontuberculous mycobacterial lung disease.</P>

Analysis of Si wafer coated by spin-on-glass for laser ablation ICP-MS

Ryu, W. K.,Kim, J. S.,Lee, J. S.,Lim, H. B.,Jun, P. K. Royal Society of Chemistry 2007 Journal of analytical atomic spectrometry Vol.22 No.6

<P>A method involving laser ablation sector type inductively coupled plasma mass spectrometry (LA-ICP-MS) was developed for the direct determination of metal impurities in the spin-on-glass (SOG) layer on a silicon wafer surface. For a reference wafer, the preparation procedure for the SOG layer was re-designed and optimized in a sequence of spiking of known amounts of metal contaminants in SOG chemical (Model: P-MSQ, 5.5% silicon dioxide in polypylene and glycol–dimethyl ether), spin-coating, and baking. Optimization of the procedure affected the contamination levels of metals which were determined by a solution scanning sampling followed by a sector type ICP-MS analysis. For homogeneity study, 74 sectors of the SOG layer were individually scanned using a laboratory-made automatic scanner with a scanning solution. The average contamination levels of each sector were obtained in the range of 10<SUP>10</SUP>–10<SUP>12</SUP> atoms cm<SUP>−2</SUP> under optimized conditions. SEM images of craters for LA, each produced by one laser shot (266 nm, 9 mJ per pulse), showed that the depths of the craters were larger than the thickness of the SOG layer, 2350 Å, and the diameter increased with the power and decreased with de-focused beam diameter. Limits of detection of LA-ICP-MS were estimated at ∼10<SUP>9</SUP> atoms cm<SUP>−2</SUP> on the Si wafer surface, depending on the element.</P> <P>Graphic Abstract</P><P>A laser ablation-ICP-MS method was developed for direct determination of metal impurities in the SOG layer on a silicon wafer surface and preparation of a reference wafer. The detection limit was ∼10<SUP>9</SUP> atoms cm<SUP>−2</SUP>. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=b618184h'> </P>

Spin-induced band modifications of graphene through intercalation of magnetic iron atoms

Sung, S. J.,Yang, J. W.,Lee, P. R.,Kim, J. G.,Ryu, M. T.,Park, H. M.,Lee, G.,Hwang, C. C.,Kim, K. S.,Kim, J. S. Royal Society of Chemistry 2014 Nanoscale Vol.6 No.7

Intercalation of magnetic iron atoms through graphene formed on the SiC(0001) surface is found to induce significant changes in the electronic properties of graphene due mainly to the Fe-induced asymmetries in charge as well as spin distribution. From our synchrotron-based photoelectron spectroscopy data together with ab initio calculations, we observe that the Fe-induced charge asymmetry results in the formation of a quasi-free-standing bilayer graphene while the spin asymmetry drives multiple spin-split bands. We find that Fe adatoms are best intercalated upon annealing at 600 degrees C, exhibiting split linear p-bands, characteristic of a bilayer graphene, but much diffused. Subsequent changes in the C 1s, Si 2p, and Fe 3p core levels are consistently described in terms of Fe-intercalation. Our calculations together with a spin-dependent tight binding model ascribe the diffuse nature of the pi-bands to the multiple spin-split bands originated from the spin-injected carbon atoms residing only in the lower graphene layer.

Characteristics of Ferroelectric in the Au/Sr$_{0.25}$Ba$_{0.75}$Nb$_2$O$_6$/Si Structure by C-V Measurement

M. K. Ryu,M. S. Jang,J. P. Kim,J. P. Kim,S. H. Lee 한국물리학회 2003 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.42 No.IV

Ferroelectric Sr0:25Ba0:75Nb2O6 (SBN) thin lms were successfully grown on p-type (100) Si and (111) Pt substrates by the rf magnetron sputtering method. The crystallinity of the lms was conrmed using x-ray diraction pattern. The capacitance-voltage (C-V) characteristic of Au/SBN/Si capacitor post-annealed at 750 C has a hysteresis curve with a clockwise rotation and the memory window at the hysteresis loop is 1.3 V when the gate voltage was 6 V.

산란사료 내 석회석에 대한 고막조개 패분의 부분 대체 급여가 산란후기의 난 생산성 및 난각질에 미치는 영향

박태순,유선종,김성권,안병기,강창원,ark T. S.P,Ryu S. J.,Kim S. K.,Ahn B. K.,Kang C. W. 한국가금학회 2004 韓國家禽學會誌 Vol.31 No.3

본 실험은 산란계의 칼슘 공급원으로서 국내산 고막조개패분(GAS)을 석회석과 대체하여 산란후기의 난각질에 미치는 영향을 조사하고, 부존 원료의 사료 자원화 가능성을 시험하기 위한 목적으로 수행하였다. 54주령 Hy-Line Brown Variety 산란계 암탉 200수를 공시하였고, Ca 3.6% 수준의 실험사료(Control)에 유사한 입자도의 GAS를 1%, 2% 및 3% 수준으로 석회석과 대체하여 첨가한 실험사료(GAS 1%, GAS 2% 및 GAS 3%)를 6주간 급여하였다. In vitro 용해도는 석회석에 비해 GAS에서 유의하게 낮은 것으로 나타났다(P < 0.05). 사료섭취량 및 난 생산성에서는 처리간에 통계적인 유의성이 있는 차이는 발견되지 않았다. GAS의 대체 수준이 증가함에 따라 주별 난각 강도 및 난각 두께가 증가하는 경향을 나타내었고, 전체 실험기간의 평균 난각 강도 및 두께의 결과에서는 처리간에 유의한 차이가 인정되었다(P < 0.05). 경골 파쇄 강도에서는 처리간에 큰 차이가 없었으나, 경골 내 회분 함량은 GAS 3% 급여구가 대조구에 비해 유의하게 높은 수치를 나타내었다. 혈청 내 Ca 및 P의 농도는 처리간에 큰 차이를 보이지 않았다. 본 실험의 결과로부터 산란사료내 석회석을 국내산 고막조개 패분으로 대체 급여를 통해 산란후기 난각질의 긍정적인 개선 효과를 기대할 수 있으며, 산란계 사료에서 Ca 공급원으로서 부존 자원의 효율적인 활용이 가능한 것으로 판단되었다. This experiment was conducted to examine the dietary effects of local granular ark shell(GAS) replacing limestone on egg shell quality in aged hens. A total of 200 Hy-Line Brown layers of 54-weeks-old were allotted into four treatments with five replications each. They were fed control(limestone only) 1% GAS, 2% GAS and 3% GAS diets for 6 weeks. GAS was substituted for coarse-type limestone at 0, 1, 2 or 3% of diet on weight basis. Particle sizes of limestone and GAS were within the ranges of 2~4 mm in diameters. In vitro HCl solubility of GAS was significantly lower(6.27 vs. 7.90%) compared to that of limestone(p < 0.05). The dietary treatment did not affect feed intake and egg production rate of the birds. Egg shell strength and thickness tended to be improved for birds fed the diets containing higher levels of GAS. The average egg shell strength and thickness of 2 or 3% GAS groups were significantly greater than those of the control (P < 0.05). The Tibial ash content of birds from 3% GAS group increased significantly as compared to that of the control. Tibial breaking strength, however, was not affected by the dietary treatment. Serum Ca and P contents of the birds were also not different among the dietary treatments. In conclusion, locally prepared GAS can be used as a calcium source in aged layer diet.