PMID- 23522913
OWN - NLM
STAT- MEDLINE
DCOM- 20130626
LR  - 20191210
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Linking)
VI  - 37
IP  - 6
DP  - 2013 Jun
TI  - Combined inhibition of the phosphoinosityl-3-kinase (PI3Kinase) P110delta subunit and 
      mitogen-extracellular activated protein kinase (MEKinase) shows synergistic 
      cytotoxicity against human acute myeloid leukemia progenitors.
PG  - 697-704
LID - S0145-2126(13)00078-7 [pii]
LID - 10.1016/j.leukres.2013.03.003 [doi]
AB  - Treatment of 32 acute myeloid leukemia (AML) blast samples showing activation of 
      the PI3K and RAS/RAF/MEK/ERK pathways with the PI3K p110delta isoform and MEKinase 
      selective inhibitors, PCN5603 and U0126 produced dose dependent progenitor kill 
      and inhibition of p-Akt Ser473 and p-Erk Tyr204 expression. Normal marrow or 
      blood progenitors were less sensitive to these inhibitors (median PCN5603 IC(5)(0)s 
      for AML and normal cells 1.5 and 5.8 muM and for U0126 9.6 and 25.8 muM, 
      respectively). U0126 synergized with PCN5603 for killing of both AML and normal 
      progenitors. However, the synergy was less for normal than for AML cells and the 
      median IC(5)(0) of each drug in the combination 7- to 10-fold higher than for AML 
      cells.
CI  - Crown Copyright (c) 2013. Published by Elsevier Ltd. All rights reserved.
FAU - Xing, Yan
AU  - Xing Y
AD  - Terry Fox Lab, British Columbia Cancer Agency, Vancouver, BC, Canada. 
      yxing@bccrc.ca
FAU - Hogge, Donna E
AU  - Hogge DE
LA  - eng
PT  - Journal Article
DEP - 20130321
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CD protein, human)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cells, Cultured
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - Drug Synergism
MH  - Enzyme Inhibitors/*administration & dosage
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/drug therapy/*pathology
MH  - MAP Kinase Kinase 1/*antagonists & inhibitors
MH  - MAP Kinase Kinase 2/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Neoplastic Stem Cells/*drug effects/pathology
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Young Adult
EDAT- 2013/03/26 06:00
MHDA- 2013/06/28 06:00
CRDT- 2013/03/26 06:00
PHST- 2012/10/09 00:00 [received]
PHST- 2013/02/26 00:00 [revised]
PHST- 2013/03/03 00:00 [accepted]
PHST- 2013/03/26 06:00 [entrez]
PHST- 2013/03/26 06:00 [pubmed]
PHST- 2013/06/28 06:00 [medline]
AID - S0145-2126(13)00078-7 [pii]
AID - 10.1016/j.leukres.2013.03.003 [doi]
PST - ppublish
SO  - Leuk Res. 2013 Jun;37(6):697-704. doi: 10.1016/j.leukres.2013.03.003. Epub 2013 
      Mar 21.