About: The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival.     Goto   Sponge   NotDistinct   Permalink

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Description
  • IL-6 and downstream JAK-dependent signaling pathways have critical roles in the pathophysiology of multiple myeloma (MM). We investigated the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK signal transduction and its biological consequences on the human myeloma-derived cell lines U266 and Kms. 11. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. These biological responses to AZD1480 are associated with concomitant inhibition of phosphorylation of JAK2, STAT3 and MAPK signaling proteins. In addition, there is inhibition of expression of STAT3 target genes, particularly Cyclin D2. Examination of a wider variety of myeloma cells (RPMI 8226, OPM-2, NCI-H929, Kms. 18, MM1. S and IM-9), as well as primary myeloma cells, showed that AZD1480 has broad efficacy. In contrast, viability of normal peripheral blood (PB) mononuclear cells and CD138(+) cells derived from healthy controls was not significantly inhibited.
  • IL-6 and downstream JAK-dependent signaling pathways have critical roles in the pathophysiology of multiple myeloma (MM). We investigated the effects of a novel small-molecule JAK inhibitor (AZD1480) on IL-6/JAK signal transduction and its biological consequences on the human myeloma-derived cell lines U266 and Kms. 11. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. These biological responses to AZD1480 are associated with concomitant inhibition of phosphorylation of JAK2, STAT3 and MAPK signaling proteins. In addition, there is inhibition of expression of STAT3 target genes, particularly Cyclin D2. Examination of a wider variety of myeloma cells (RPMI 8226, OPM-2, NCI-H929, Kms. 18, MM1. S and IM-9), as well as primary myeloma cells, showed that AZD1480 has broad efficacy. In contrast, viability of normal peripheral blood (PB) mononuclear cells and CD138(+) cells derived from healthy controls was not significantly inhibited. (en)
Title
  • The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival.
  • The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival. (en)
skos:prefLabel
  • The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival.
  • The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting insuppression of human myeloma cell growth and survival. (en)
skos:notation
  • RIV/00216224:14310/11:00050507!RIV12-GA0-14310___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GA301/09/0587), Z(MSM0021622430)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 216593
http://linked.open...ai/riv/idVysledku
  • RIV/00216224:14310/11:00050507
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • myeloma; JAK2; STAT3; FGFR3 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [E8E44D96493C]
http://linked.open...i/riv/nazevZdroje
  • Leukemia
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 25
http://linked.open...iv/tvurceVysledku
  • Chen, L.
  • Krejčí, Pavel
  • Wang, Y.
  • Forman, S.
  • Jove, R.
  • Kowolik, C.
  • Kretzner, L.
  • Kujawski, M.
  • Popplewell, L.
  • Scuto, A.
  • Wilcox, W. R.
  • Wu, J.
  • Xin, H.
  • Yen, Y.
  • Yu, H.
http://linked.open...ain/vavai/riv/wos
  • 000288159500017
http://linked.open...n/vavai/riv/zamer
issn
  • 0887-6924
number of pages
http://bibframe.org/vocab/doi
  • 10.1038/leu.2010.289
http://localhost/t...ganizacniJednotka
  • 14310
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