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신규 백금착물 항암제 KBP31705-C127 , KBP30603-901 의 Clsplatn 및 Carboplatin 과의 약동력학적 동태 비교
정인숙(In Sook Jung),이주선(Ju Seon Lee),허수정(Soo Jung Huh),김진숙(Jin Sook Kim),진창배(Chang Bae Jin),김동현(Dong Hyun KIm),김명수(Myung Soo Kim),박경수(Kyung Su Park),손연수(Youn Soo Sohn),백형기(Hyoung Gee Back),조양하(Yang Ha C 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.4
The present study examined pharmacokinetic profiles of KBP31705-C127 and KBP30603-901, new platinum coordination complexes synthesized as anticancer candidates, in comparison with two well-known platinum-containing anticancer agents, cisplatin and carboplatin in rats. Under sodium pentobarbital anesthesia of male Sprague-Dawley rats, urinary bladder, and femoral artery and vein were catheterized for urine collection, blood sampling and drug injection, respectively. Following i.v, administration of cisplatin (2 ㎎/㎏), KBP31705-C127 (2 ㎎/㎏), carboplatin (20 ㎎/㎏) or KBP30603-901 (20 ㎎/㎏), blood samples were collected at 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 and 120 minutes. Urine samples were collected at 1-hr interval for 4 hr. Platinum concentrations in plasma and urine were measured using an inductively coupled plasmamass spectrometer. The plasma concentration-time curves were biphasic for all drugs during the time period studied. Compared with cisplatin, KBP31705-C127 showed similar decay patterns in the alpha- and beta-phases with slightly lower plasma concentrations. Urinary platinum excretion for cisplatin and KBP31705-C 127 was 56 and 52% of the administered dose in 4 hr, respectively. With regard to carboplatin and KBP30603-901, a similar decay pattern was also observed in the alpha-phase. The half life of KBP30603-901 in the beta-phase, however, was much longer than that of carboplatin, which was consistent with the urinary excretion results that 46 and 59% of the administered dose were excreted in the urine in 4hr, respectively. The results suggest that platinum coordination complexes are primarily excreted via the renal route and KBP30603-901 can elicit longer duration of action due to slower renal excretion compared to carboplatin.
Do, Sook Kyung,Choi, Sun Ha,Lee, Shin Yup,Choi, Jin Eun,Hong, Mi Jeong,Kang, Hyo-Gyoung,Lee, Won Kee,Lee, Eung Bae,Shin, Kyung Min,Jeong, Ji Yun,Lee, Yong Hoon,Seo, Hyewon,Yoo, Seung Soo,Lee, Jaehee,C Elsevier 2019 Gene Vol.703 No.-
<P><B>Abstract</B></P> <P>This study was conducted to explore whether polymorphisms of glucose transporter 3 (<I>GLUT3</I>) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in <I>GLUT3</I> were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, <I>GLUT3</I> rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04–2.53, <I>P</I> = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18–2.29, <I>P</I> = 0.003, under recessive model). When stratified by tumor histology, the association between the <I>GLUT3</I> rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (<I>P</I> = 0.40 for SCC and <I>P</I> = 0.04 for OS) and only in SCC for DFS (<I>P</I> = 0.03 for SCC and <I>P</I> = 0.08 for OS). When AC patients were stratified according to <I>EGFR</I> mutation status, the SNP was significantly associated with DFS in patients with <I>EGFR</I> mutant tumors (aHR = 2.47, 95% CI = 1.15–5.30, <I>P</I> = 0.02, under recessive model), but not in those with <I>EGFR</I> wild-type tumors. This study suggests that genetic variation in <I>GLUT3</I> may be useful in predicting survival of patients with early stage NSCLC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>GLUT3</I> variant was significantly associated with survival of NSCLC after surgery. </LI> <LI> The association was not limited to either squamous cell carcinoma or adenocarcinoma. </LI> <LI> The SNP may help identify patients at high risk of poor outcome in early stage NSCLC. </LI> </UL> </P>
Koo, Bo Kyung,Chae, Sehyun,Kim, Kristine M.,Kang, Min Jueng,Kim, Eunhee G.,Kwak, Soo Heon,Jung, Hye Seung,Cho, Young Min,Choi, Sung Hee,Park, Young Joo,Shin, Choong Ho,Jang, Hak C.,Shin, Chan Soo,Hwan American Diabetes Association 2014 Diabetes Vol.63 No.9
<P>Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: <I>1</I>) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and <I>2</I>) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (<I>P</I> < 0.01), which was also confirmed in the test cohort of children (<I>P</I> < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM.</P>
Hong, Mi Jeong,Lee, Shin Yup,Choi, Jin Eun,Kang, Hyo‐,Gyoung,Do, Sook Kyung,Lee, Jang Hyuck,Yoo, Seung Soo,Lee, Eung Bae,Seok, Yangki,Cho, Sukki,Jheon, Sanghoon,Lee, Jaehee,Cha, Seung Ick,Kim, C Wiley-Blackwells 2018 Thoracic cancer Vol.9 No.8
<P><B>Background</B></P><P>Genome‐wide association studies have indicated that most of the currently identified disease and trait‐associated single nucleotide polymorphisms (SNPs) are intronic or intergenic. RegulomeDB is a recently developed database that provides functional annotations for regulatory features of SNPs located in non‐coding regions. We evaluated the potential regulatory SNPs in the <I>EGFR</I> gene region using RegulomeDB and their associations with prognosis after surgery in non‐small cell lung cancer (NSCLC) patients.</P><P><B>Methods</B></P><P>A total of 698 patients with surgically resected NSCLC were enrolled and seven SNPs were selected based on the RegulomeDB database. All SNPs were genotyped using SEQUENOM MassARRAY iPLEX assay.</P><P><B>Results</B></P><P>Among the seven SNPs evaluated, rs9642391 (<I>EGFR</I> ivs19+2851C>G) was significantly associated with survival outcome (adjusted hazard ratio [HR] for overall survival = 0.70, 95% confidence interval [CI] 0.56–0.87, <I>P</I> = 0.001; adjusted HR for disease‐free survival = 0.82, 95% CI 0.70–0.97, <I>P</I> = 0.02; under a codominant model). According to RegulomeDB, rs9642391C>G, which is located in intron 19 of <I>EGFR</I>, was predicted to influence the expression of <I>GBAS</I> but not <I>EGFR</I>. As predicted, rs9642391C>G was associated with <I>GBAS</I> (<I>P</I> = 0.024) but not <I>EGFR</I> messenger RNA expression in tumor tissues.</P><P><B>Conclusion</B></P><P>In conclusion, our study provides evidence that rs9642391C>G in the intron of <I>EGFR</I> is associated with <I>GBAS</I> expression and survival outcomes of patients with surgically resected early‐stage NSCLC.</P>
High-Temperature Deformation Behavior of ELI Grade Ti-6Al-4V Alloy with Martensite Microstructure
Park, C.H.,Ko, Young Gun,Lee, Chong Soo,Park, Kyung Tae,Shin, Dong Hyuk,Lee, Ho Sung Scientific.Net 2007 Materials Science Forum Vol.551-552 No.-
<P>High-temperature deformation behavior and microstructural evolution process of ELI Ti-6Al-4V alloy having martensite microstructure were investigated with the variation of strain, strain rate and temperature. A series of hot compression tests was carried out isothermally for martensite microstructure at the true strain range of 0.6 to 1.4, strain rate range of 10-3 s-1 to 1 s-1 and temperature range of 700 oC to 950 oC. The processing maps for martensite microstructures were constructed on the basis of dynamic materials model (DMM). At the strain rate higher than 10-2 s-1 and the temperature lower than 750 oC regions of flow instability such as adiabatic shear band and micro-cracking were observed. Also, after imposing an effective strain of ≈ 1.4, deformed microstructure showed the significant kinking/bending behavior of lamellae resulting in the dynamic globularization associated with the fragmentation of beta-phase. The effects of strain, strain rate and temperature for dynamic globularization were discussed based on the microstructure and efficiency of power dissipation.</P>
Yi, Kyung Soo,Trivedi, Krutarth,Floresca, Herman C,Yuk, Hyungsang,Hu, Walter,Kim, Moon J American Chemical Society 2011 Nano letters Vol.11 No.12
<P>Quantum confinement of carriers has a substantial impact on nanoscale device operations. We present electrical transport analysis for lithographically fabricated sub-5 nm thick Si nanowire field-effect transistors and show that confinement-induced quantum oscillations prevail at 300 K. Our results discern the basis of recent observations of performance enhancement in ultrathin Si nanowire field-effect transistors and provide direct experimental evidence for theoretical predictions of enhanced carrier mobility in strongly confined nanowire devices.</P>