Evidence map›Paper›PMID 22074700›Full record

ArticleLeukemia research2012

LBH-589 (panobinostat) potentiates fludarabine anti-leukemic activity through a JNK- and XIAP-dependent mechanism.

Roberto Rosato, Stefanie Hock, Paul Dent, Yun Dai, Steven Grant

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Roberto RosatoDivision of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University and the Massey Cancer Center, Richmond, VA 23298, USA.
Stefanie Hock
Paul Dent
Yun Dai
Steven Grant
Virginia Commonwealth University · US

Funding

SPORE in LymphomaP50CA130805 · NCI · UNIVERSITY OF ROCHESTER · PI FISHER, RICHARD I · 2008 to 2012
$11.7M
P4 -TARGETING MULTIPLE MYELOMA BY COMBINING CDK INHIBITORS AND BCL-2 ANTAGONISTSP50CA142509 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KWAK, LARRY W · 2010 to 2014
$11.1M
SIGNALING PATHWAYS REGULATING EPITHELIAL CELL SURVIVALR01DK052825 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 1999 to 2013
$3.3M
NF-kappaB Inhibitors and Differentiation-Inducers in LeukemiaR01CA093738 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2002 to 2011
$2.4M
Checkpoint Abrogation and MEK 1/2 Inhibition in MyelomaR01CA100866 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2003 to 2013
$2.2M
OSU-03012 therapy for glioblastomaR01CA141703 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 2010 to 2014
$1.5M
Lapatinib and Obatoclax combination therapyR01CA150214 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 2010 to 2014
$1.5M
Proteasome/HDAC Inhibition in Leukemia/MDS; Phase I Trial and Correlative StudiesRC2CA148431 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2009 to 2010
$1.2M
Phase I Trial of Bortezomib and Romidepsin in CLL and Small Cell LymphomaR21CA137823 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2009 to 2010
$537k
Flavopiridol / Bortezomib in Myeloma / B-Cell NeoplasmsR21CA110953 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2004 to 2008
$483k
NCI NIH HHS CA100866NCI NIH HHS CA130805NCI NIH HHS CA142509NCI NIH HHS CA93738NCI NIH HHS P50 CA130805NCI NIH HHS P50 CA142509NCI NIH HHS R01 CA093738NCI NIH HHS R01 CA100866NCI NIH HHS R01 CA141703NCI NIH HHS R01 CA150214NCI NIH HHS R21 CA110953NCI NIH HHS R21 CA137823NCI NIH HHS RC2 CA148431NIDDK NIH HHS R01 DK052825
6 · The paper itself

Abstract

Effects of the HDAC inhibitor LBH-589 (panobinostat) on fludarabine lethality toward acute myeloid leukemia (AML) cells were examined in vitro and in vivo. LBH-589 pretreatment sensitized U937, HL-60, and primary leukemia cells to fludarabine while blocking NF-κB activation accompanied by XIAP down-regulation and JNK activation. Pharmacologic or genetic JNK inhibition significantly attenuated LBH-589/fludarabine lethality, whereas XIAP over-expression diminished JNK activation and apoptosis. Combined in vivo treatment abrogated leukemia growth in a U937 xenograft murine model and substantially increased animal survival. These studies highlight the interplay between NF-κB activation, XIAP down-regulation, and JNK activation in anti-leukemic synergism between fludarabine and LBH-589.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBlotting, WesternCell Line, TumorDown-RegulationDrug SynergismElectrophoretic Mobility Shift AssayEnzyme ActivationEnzyme-Linked Immunosorbent AssayHumansHydroxamic AcidsIndolesLeukemiaMAP Kinase Kinase 4MicefludarabineHydroxamic AcidsIndolesMAP Kinase Kinase 4NF-kappa BPanobinostatVidarabineX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID22074700
PMCPMC3288169
OpenAlexW2128617722

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.