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Marcais, Antoine,Blevins, Rory,Graumann, Johannes,Feytout, Amelie,Dharmalingam, Gopuraja,Carroll, Thomas,Amado, Inê,s F.,Bruno, Ludovica,Lee, Keunwook,Walzer, Thierry,Mann, Matthias,Freitas, Anto The Rockefeller University Press 2014 The Journal of experimental medicine Vol.211 No.11
<P>T cell receptor (TCR) signals can elicit full activation with acquisition of effector functions or a state of anergy. Here, we ask whether microRNAs affect the interpretation of TCR signaling. We find that Dicer-deficient CD4 T cells fail to correctly discriminate between activating and anergy-inducing stimuli and produce IL-2 in the absence of co-stimulation. Excess IL-2 production by Dicer-deficient CD4 T cells was sufficient to override anergy induction in WT T cells and to restore inducible Foxp3 expression in <I>Il2</I>-deficient CD4 T cells. Phosphorylation of Akt on S473 and of S6 ribosomal protein was increased and sustained in Dicer-deficient CD4 T cells, indicating elevated mTOR activity. The mTOR components Mtor and Rictor were posttranscriptionally deregulated, and the microRNAs Let-7 and miR-16 targeted the <I>Mtor</I> and <I>Rictor</I> mRNAs. Remarkably, returning Mtor and Rictor to normal levels by deleting one allele of <I>Mtor</I> and one allele of <I>Rictor</I> was sufficient to reduce Akt S473 phosphorylation and to reduce co-stimulation–independent IL-2 production in Dicer-deficient CD4 T cells. These results show that microRNAs regulate the expression of mTOR components in T cells, and that this regulation is critical for the modulation of mTOR activity. Hence, microRNAs contribute to the discrimination between T cell activation and anergy.</P>
Chang, Gee-Chen,Ahn, Myung-Ju,Wright, Elaine,Kim, Heung Tae,Kim, Joo-Hang,Kang, Jin Hyoung,Kim, Sang-We,Sherman, Steven,Walzer, Stefan Blackwell Pub. Asia 2011 Asia-Pacific journal of clinical oncology Vol.7 No.suppl2
<P>To indirectly compare real-life clinical effectiveness of bevacizumab + cisplatin-based therapy from the Safety of Avastin in Lung (SAiL) phase IV clinical trial with published evidence from the phase III clinical trial for pemetrexed + cisplatin among East Asian patients with non-squamous metastatic or recurrent non-small cell lung cancer (NSCLC).</P>
Ahn, Myung-Ju,Tsai, Chun-Ming,Hsia, Te-Chun,Wright, Elaine,Chang, John Wen-Cheng,Kim, Heung Tae,Kim, Joo-Hang,Kang, Jin Hyoung,Kim, Sang-We,Bae, Eun-Jin,Kang, Mijeong,Lister, Johanna,Walzer, Stefan Blackwell Pub. Asia 2011 Asia-Pacific journal of clinical oncology Vol.7 No.suppl2
<P>The aim of this analysis is to investigate the mean incremental costs and life expectancy associated with two first-line treatments for advanced non-squamous non-small cell lung cancer (NSCLC) in Korea and Taiwan; bevacizumab plus cisplatin and gemcitabine (BevCG) and cisplatin plus pemetrexed (CP).</P>