http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement
Isaacs, Farren J.,Carr, Peter A.,Wang, Harris H.,Lajoie, Marc J.,Sterling, Bram,Kraal, Laurens,Tolonen, Andrew C.,Gianoulis, Tara A.,Goodman, Daniel B.,Reppas, Nikos B.,Emig, Christopher J.,Bang, Duhe American Association for the Advancement of Scienc 2011 Science Vol.333 No.6040
<P>We present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale. We used multiplex automated genome engineering (MAGE) to site-specifically replace all 314 TAG stop codons with synonymous TAA codons in parallel across 32 Escherichia coli strains. This approach allowed us to measure individual recombination frequencies, confirm viability for each modification, and identify associated phenotypes. We developed hierarchical conjugative assembly genome engineering (CAGE) to merge these sets of codon modifications into genomes with 80 precise changes, which demonstrate that these synonymous codon substitutions can be combined into higher-order strains without synthetic lethal effects. Our methods treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes.</P>
Charles S. Fuchs,Kei Muro,Jiri Tomasek,Eric Van Cutsem,조재용,오상철,Howard Safran,György Bodoky,Ian Chau,Yasuhiro Shimada,Salah-Eddin Al-Batran,Rodolfo Passalacqua,Atsushi Ohtsu,Michael Emig,David Ferry,Ku 대한위암학회 2017 Journal of gastric cancer Vol.17 No.2
The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Al-Batran, S.-E.,Van Cutsem, E.,Oh, S. C.,Bodoky, G.,Shimada, Y.,Hironaka, S.,Sugimoto, N.,Lipatov, O. N.,Kim, T.-Y.,Cunningham, D.,Rougier, P.,Muro, K.,Liepa, A. M.,Chandrawansa, K.,Emig, M.,Ohtsu, A Oxford University Press 2016 Annals of Oncology Vol.27 No.4
<P><B>Background</B></P><P>The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine–platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses.</P><P><B>Patients and methods</B></P><P>Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m<SUP>2</SUP>) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models.</P><P><B>Results</B></P><P>Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, <I>P</I> = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, <I>P</I> = 0.0508), deterioration by ≥1 PS level (HR = 0.802, <I>P</I> = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, <I>P</I> = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation.</P><P><B>Conclusion</B></P><P>In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration.</P><P><B>ClinicalTrials.gov</B></P><P>NCT01170663.</P>