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Statements

Subject Item
n2:RIV%2F00216224%3A14310%2F11%3A00050507%21RIV12-GA0-14310___
rdf:type
skos:Concept n9:Vysledek
dcterms: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.
dcterms: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.
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.
skos:notation
RIV/00216224:14310/11:00050507!RIV12-GA0-14310___
n9:predkladatel
n10:orjk%3A14310
n3:aktivita
n8:Z n8:P
n3:aktivity
P(GA301/09/0587), Z(MSM0021622430)
n3:cisloPeriodika
3
n3:dodaniDat
n15:2012
n3:domaciTvurceVysledku
n6:5512646
n3:druhVysledku
n11:J
n3:duvernostUdaju
n20:S
n3:entitaPredkladatele
n14:predkladatel
n3:idSjednocenehoVysledku
216593
n3:idVysledku
RIV/00216224:14310/11:00050507
n3:jazykVysledku
n13:eng
n3:klicovaSlova
myeloma; JAK2; STAT3; FGFR3
n3:klicoveSlovo
n4:JAK2 n4:STAT3 n4:myeloma n4:FGFR3
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[E8E44D96493C]
n3:nazevZdroje
Leukemia
n3:obor
n16:ED
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
16
n3:projekt
n18:GA301%2F09%2F0587
n3:rokUplatneniVysledku
n15:2011
n3:svazekPeriodika
25
n3:tvurceVysledku
Krejčí, Pavel Jove, R. Wu, J. Kowolik, C. Yen, Y. Wang, Y. Yu, H. Xin, H. Kretzner, L. Chen, L. Forman, S. Kujawski, M. Scuto, A. Popplewell, L. Wilcox, W. R.
n3:wos
000288159500017
n3:zamer
n17:MSM0021622430
s:issn
0887-6924
s:numberOfPages
13
n19:doi
10.1038/leu.2010.289
n7:organizacniJednotka
14310