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

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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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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
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	P Z
http://linked.open...avai/riv/aktivity	P(GA301/09/0587), Z(MSM0021622430)
http://linked.open...iv/cisloPeriodika	3
http://linked.open...vai/riv/dodaniDat	2012
http://linked.open...aciTvurceVysledku	Krejčí, Pavel
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Masarykova univerzita / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	216593
http://linked.open...ai/riv/idVysledku	RIV/00216224:14310/11:00050507
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	myeloma; JAK2; STAT3; FGFR3 (en)
http://linked.open.../riv/klicoveSlovo	myeloma STAT3 FGFR3 JAK2
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	ED
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	16 (xsd:int)
http://linked.open...vavai/riv/projekt	Novel pathways of FGFR3 signaling in achondroplasia
http://linked.open...UplatneniVysledku	2011
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	Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
issn	0887-6924
number of pages	13 (xsd:int)
http://bibframe.org/vocab/doi	10.1038/leu.2010.289
http://localhost/t...ganizacniJednotka	14310

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