PMID- 23721513
OWN - NLM
STAT- MEDLINE
DCOM- 20141006
LR  - 20220408
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 55
IP  - 2
DP  - 2014 Feb
TI  - Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 
      effectively blocks proliferation and induces cell death in diffuse large B-cell 
      lymphoma.
PG  - 425-34
LID - 10.3109/10428194.2013.806800 [doi]
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive lymphoma, 
      with a great demand for novel treatments for relapsing and refractory disease. 
      Constitutive activation of the phosphatidyl-inositol-3-kinase 
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is often 
      detected in this lymphoma. Inhibition of this signaling cascade with the 
      pan-class I PI3K inhibitor NVP-BKM120 decreased cell proliferation and increased 
      apoptotic cell death. DLBCL proliferation was further decreased if 
      NVP-BKM120-induced autophagy was blocked. Treatment with NVP-BKM120 was 
      associated with an increase of the pro-apoptotic BH3-only proteins Puma and Bim 
      and down-regulation of the anti-apoptotic Bcl-xL and Mcl-1. Translation of Bcl-xL 
      and Mcl-1 is facilitated by cap-dependent mRNA translation, a process that was 
      partially inhibited by NVP-BKM120. Overall, we demonstrated here the potential of 
      NVP-BKM120 for the treatment of DLBCL.
FAU - Zang, Chuanbing
AU  - Zang C
AD  - Department of Oncology and Hematology.
FAU - Eucker, Jan
AU  - Eucker J
FAU - Liu, Hongyu
AU  - Liu H
FAU - Coordes, Annekatrin
AU  - Coordes A
FAU - Lenarz, Minoo
AU  - Lenarz M
FAU - Possinger, Kurt
AU  - Possinger K
FAU - Scholz, Christian Wilfried
AU  - Scholz CW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130725
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Aminopyridines)
RN  - 0 (MCL1 protein, human)
RN  - 0 (Morpholines)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (NVP-BKM120)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Aminopyridines/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/drug effects
MH  - Blotting, Western
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Cell Survival/drug effects
MH  - Class I Phosphatidylinositol 3-Kinases/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Humans
MH  - Lymphoma, Large B-Cell, Diffuse/metabolism/pathology
MH  - Morpholines/*pharmacology
MH  - Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism
MH  - Protein Biosynthesis/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Cells, Cultured
MH  - bcl-X Protein/genetics/metabolism
EDAT- 2013/06/01 06:00
MHDA- 2014/10/07 06:00
CRDT- 2013/06/01 06:00
PHST- 2013/06/01 06:00 [entrez]
PHST- 2013/06/01 06:00 [pubmed]
PHST- 2014/10/07 06:00 [medline]
AID - 10.3109/10428194.2013.806800 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2014 Feb;55(2):425-34. doi: 10.3109/10428194.2013.806800. Epub 
      2013 Jul 25.