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      • <i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

        Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

        <P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

      • Effects of dextrorotatory morphinans on brain Na<sup>+</sup> channels expressed in Xenopus oocytes

        Lee, J.H.,Shin, E.J.,Jeong, S.M.,Lee, B.H.,Yoon, I.S.,Lee, J.H.,Choi, S.H.,Kim, Y.H.,Pyo, M.K.,Lee, S.M.,Chae, J.S.,Rhim, H.,Oh, J.W.,Kim, H.C.,Nah, S.Y. North-Holland ; Elsevier Science Ltd 2007 european journal of pharmacology Vol.564 No.1

        We previously demonstrated that dextromethorphan (DM; 3-methoxy-17-methylmorphinan) analogs have neuroprotective effects. Here, we investigated the effects of DM, three of its analogs (DF, 3-methyl-17-methylmorphinan; AM, 3-allyloxy-17-methoxymorphian; and CM, 3-cyclopropyl-17-methoxymorphinan) and one of its metabolites (HM; 3-methoxymorphinan), on Na<SUP>+</SUP> channel activity. We used the two-microelectrode voltage-clamp technique to test the effects of DM, DF, AM, CM and HM on Na<SUP>+</SUP> currents (I<SUB>Na</SUB>) in Xenopus oocytes expressing cRNAs encoding rat brain Nav1.2 α and β1 or β2 subunits. In oocytes expressing Na<SUP>+</SUP> channels, DM, DF, AM and CM, but not HM, induced tonic and use-dependent inhibitions of peak I<SUB>Na</SUB> following low- and high-frequency stimulations. The order of potency for the inhibition of peak I<SUB>Na</SUB> was AM-CM > DM=DF. The DM, DF, AM and CM-induced tonic inhibitions of peak I<SUB>Na</SUB> were voltage-dependent, dose-dependent and reversible. The IC<SUB>50</SUB> values for DM, DF, AM and CM were 116.7+/-14.9, 175.8+/-16.9, 38.6+/-15.5, and 42.5+/-8.5 μM, respectively. DM and its analogs did not affect the steady-state activation and inactivation voltages. AM and CM, but not DM and DF, inhibited the plateau I<SUB>Na</SUB> more effectively than the peak I<SUB>Na</SUB> in oocytes expressing inactivation-deficient I1485Q-F1486Q-M1487Q (IFMQ3) mutant channels; the IC<SUB>50</SUB> values for AM and CM in this system were 8.4+/-1.3 and 8.7+/-1.3 μM, respectively, for the plateau I<SUB>Na</SUB> and 43.7+/-5.9 and 32.6+/-7.8 μM, respectively, for the peak I<SUB>Na</SUB>. These results collectively indicate that DM and its analogs could be novel Na<SUP>+</SUP> channel blockers acting on the resting and open states of brain Na<SUP>+</SUP> channels.

      • Phase I/II study of S-1 combined with weekly docetaxel in patients with metastatic gastric carcinoma

        Park, S R,Kim, H K,Kim, C G,Choi, I J,Lee, J S,Lee, J H,Ryu, K W,Kim, Y-W,Bae, J-M,Kim, N K Cancer Research UK 2008 The British journal of cancer Vol.98 No.8

        We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1–14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30–45 mg m<SUP>−2</SUP> b.i.d.) and docetaxel (25–40 mg m<SUP>−2</SUP>); MTD was 45 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel and RD was 40 mg m<SUP>−2</SUP> b.i.d. S-1/35 mg m<SUP>−2</SUP> docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8–79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9–8.1) and 13.7 months (95% CI: 9.9–17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.British Journal of Cancer (2008) 98, 1305–1311. doi:10.1038/sj.bjc.6604312 www.bjcancer.com Published online 25 March 2008

      • KCI등재

        LIGA-like 공정을 이용한 마이크로 부품 복제용 Ni과 Ni-W 금형 제조 및 특성

        황완식,박준식,강영철,조진우,박순섭,이인규,강성군,Hwang, W.S.,Park, J.S.,Kang, Y.C.,Cho, J.W.,Park, S.S.,Lee, I.G.,Kang, S.G. 한국재료학회 2003 한국재료학회지 Vol.13 No.1

        Electroplated Ni and Ni-W micro-molds using LIGA-like process for replication of micro-components such as microfluidic parts and micro optical parts have been investigated. In general, it is hard to produce micro-parts using conventional mechanical processes. Micro-mold formed by LIGA-like process could fabricate micro-parts with high aspect ratio. In this paper, fabrication and properties of electroplated Ni molds with varying applied current types as well as those of Ni-W molds were investigated. Ni molds fabricated under pulse-reverse current showed the highest hardness value of about 160 Hv. Ni-W molds showed the hardness of about 500 Hv which was much harder than that of Ni electroplated molds. The above results suggested that high quality micro-molds could be fabricated by using Ni electroplating of pulse-reverse type for core molds and sequential Ni-W alloys coating.

      • SCISCIESCOPUS

        SHRIMP U-Pb dating and geochemistry of the Cretaceous plutonic rocks in the Korean Peninsula: A new tectonic model of the Cretaceous Korean Peninsula

        Kim, S.W.,Kwon, S.,Park, S.I.,Lee, C.,Cho, D.L.,Lee, H.J.,Ko, K.,Kim, S.J. Universitetsforlaget ; Elsevier Science Ltd 2016 Lithos Vol.262 No.-

        <P>The Cretaceous tectonomagmatism of the Korean Peninsula was examined based on geochemical and geochronological data of the Cretaceous plutonic rocks, along with distribution of volcano-sedimentary nonmarine N- to NE-trending fault bounded sedimentary basins. We conducted sensitive high-resolution ion microprobe (SHRIMP) zircon U-Pb ages and whole-rock geochemical compositions of 21 Cretaceous plutonic rocks, together with previously published data, from the central to southern Korean Peninsula. Four age groups of plutonic rocks were identified: Group I (ca. 119-106 Ma) in the northern to central area, Group II (ca. 99-87 Ma) in the central southern area, Group III (ca. 85-82 Ma) in the central to southern area, and Group IV (ca. 76-67 Ma) in the southernmost area. These results indicate a sporadic trenchward-younging trend of the Cretaceous magmatism in the Korean Peninsula. The Group I, II, and III rocks are dominated by high-K calc-alkaline I-type rocks with rift-related A-type granitoids. In contrast, the Group IV rocks are high-K calc-alkaline I-type plutonic rocks with no A-type rocks. The geochemical signatures of the entire groups indicated LREEs (light rare earth elements) enrichments and negative Nb, Ta, and Ti anomalies, indicating normal arc magmatism. A new tectonic model of the Cretaceous Korean Peninsula was proposed based on temporal and spatial distribution of the Cretaceous plutons represented by four age groups; 1) magmatic quiescence throughout the Korean Peninsula from ca. 160 to 120 Ma, 2) intrusions of the I- and A-type granitoids in the northern and central Korean Peninsula (Group I plutonic rocks from ca. 120 to 100 Ma) resulted from the partial melting of the lower continental crust due to the rollback of the Izanagi plate expressed as the conversion from flat-lying subduction to normal subduction. The Gyeongsang nonmarine sedimentary rift basin in the Korean Peninsula and adakite magmatism preserved in the present-day Japanese Islands supported the slab rollback followed by steepening of the Izanagi plate with an injection of upwelling of the hot asthenosphere into the mantle wedge. 3) Alternating shallow (from similar to 100 to 85 Ma) to steep (from similar to 85 to 65 Ma) subduction resulted in the migration of the normal arc magmatism in the southern Korean Peninsula, expressed as the intruded I- and A-type (Group III) and I-type granitoids (Group IV), respectively. The tectonomagmatism of, the Korean Peninsula showed the unique style of evolution, different from those of South China and Japanese Islands. (C) 2016 Elsevier B.V. All rights reserved.</P>

      • Identification of thioredoxin domain-containing protein 17 from big-belly seahorse <i>Hippocampus abdominalis</i>: Molecular insights, immune responses, and functional characterization

        Liyanage, D.S.,Omeka, W.K.M.,Yang, Hyerim,Godahewa, G.I.,Kwon, Hyukjae,Nam, Bo-Hye,Lee, Jehee Elsevier 2019 Fish & shellfish immunology Vol.86 No.-

        <P><B>Abstract</B></P> <P>Thioredoxin domain-containing protein 17 (TXNDC17) is a small protein (∼14 kDa) involved in maintaining cellular redox homeostasis via a thiol-disulfide reductase activity. In this study, TXNDC17 was identified and characterized from <I>Hippocampus abdominalis</I>. The open reading frame (ORF) consisted of 369 bp and 123 amino acids. Similar to the other thioredoxins, TXNDC17 contained a conserved WCXXC functional motif. The highest spatial mRNA expressions of <I>HaTXNDC17</I> were observed in the muscle, brain, and intestine. Interestingly, the mRNA expression of <I>HaTXNDC17</I> in blood showed significant upregulation at 48 h against all the pathogen associated molecular patterns (PAMPs) and bacteria. Further, <I>HaTXNDC17</I> transcripts in the trunk kidney were significantly upregulated at 24–48 h by bacterial endotoxin lipopolysaccharides (LPS), viral mimic polyinosinic: polycytidylic acid (poly I:C), and gram-negative bacteria (<I>Edwardsiella tarda</I>). The DPPH assay showed that the radical scavenging activity varies in a concentration-dependent manner. The insulin reduction assay demonstrated a significant logarithmic relationship with the concentration of rHaTXNDC17. Moreover, FHM cells treated with recombinant HaTXNDC17 significantly enhanced cellular viability under oxidative stress. Together, these results show that HaTXNDC17 function is important for maintaining cellular redox homeostasis and that it is also involved in the immune mechanism in seahorses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Big-belly seahorse thioredoxin domain containing protein 17 maintain redox homeostasis. </LI> <LI> TXNDC17 is ubiquitously found in cytosol and extracellular space. </LI> <LI> Thiol active CXXC conserved motif consists in HaTXNDC17. </LI> <LI> Spatial and temporal mRNA expression was evaluated. </LI> <LI> Radical scavenging ability, antioxidant activity and cellular viability were measured. </LI> </UL> </P>

      • KCI우수등재

        1×1 ㎟ 대면적 녹색 LED의 전기 광학적 특성 분석

        장이운(L. W. Jang),조동섭(D. S. Jo),전주원(J. W. Jeon),안태영(Tae-Young Ahn),박민주(M. J. Park),안병준(B. J. Ahn),송정훈(J. H. Song),곽준섭(J. S. Kwak),김진수(Jin-Soo Kim),이인환(I. -H. Lee),안행근(H. K. Ahn) 한국진공학회(ASCT) 2011 Applied Science and Convergence Technology Vol.20 No.4

        본 논문은 InGaN/GaN 다중양자우물 구조를 가지는 녹색 발광다이오드의 활성층 내 인듐(In) 조성비와 piezoelectric field에 대한 전계 흡수 현상을 연구하였다. 활성층 내 결정학적 성질과 In 조성비는 double crystal X-ray diffraction 측정으로 분석하였으며, 1×1 ㎟ 대면적 칩을 제작하여 발광특성을 조사하였다. 또한, 활성층 내 piezoelectric field는 electro-reflectance spectroscopy로부터 측정한 compensation voltage를 이용해 계산하였고, 인가전압에 따른 photocurrent의 변화를 측정함으로써 녹색 발광 소자의 전기 광학적 특성을 분석하였다. We investigated the effects of piezoelectric field on the electro-absorption characteristics in InGaN/GaN multiple-quantum well (MQW) green light emitting diodes (LED). Double crystal X-ray diffraction measurement was performed to study the crystalline property and indium (In) composition in the MQW active layer. To measure the electro-luminescence and electro-reflectance (ER) spectroscopy, we fabricated the 1×1 ㎟ large-area green LED chip. The piezoelectric field inside the LED structure was evaluated from the Vcomp in active layer by the ER spectra. Finally, we analyzed the electro-absorption characteristics of the green LED by using the photo-current spectroscopy.

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