Evidence map›Paper›PMID 17916749›Full record

ArticleBlood2008

Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells.

Saskia A G M Cillessen, John C Reed, Kate Welsh, Clemencia Pinilla, Richard Houghten, Erik Hooijberg, José Deurhof, Kitty C M Castricum, Pim Kortman, Corine J Hess and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 35 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Saskia A G M CillessenDepartment of Clinical Pathology, VU University Medical Center, Amsterdam, the Netherlands.
John C Reed
Kate Welsh
Clemencia Pinilla
Richard Houghten
Erik Hooijberg
José Deurhof
Kitty C M Castricum
Pim Kortman
Corine J Hess
Gert J Ossenkoppele
Chris J L M Meijer
Joost J Oudejans
Amsterdam UMC Location VUmc · NLSanford Burnham Prebys Medical Discovery Institute · USTorrey Pines Institute For Molecular Studies · US

Funding

Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
Small Molecule Antagonists of IAPs Based on Mimicking SMACU19CA113318 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI HUANG, ZIEWIE · 2005 to 2009
$5.7M
NCI NIH HHS CA -113318NCI NIH HHS P01 CA-081534NCI NIH HHS P01 CA081534
6 · The paper itself

Abstract

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.

Indexed as

Aniline CompoundsAntineoplastic Agents, PhytogenicApoptosisB-LymphocytesCaspase 3Caspase 7Caspase 9Drug Resistance, NeoplasmEtoposideHumansLymphoma, Large B-Cell, DiffusePalatine TonsilPhenylurea CompoundsTumor Cells, CulturedX-Linked Inhibitor of Apoptosis ProteinAniline CompoundsAntineoplastic Agents, PhytogenicCaspase 3Caspase 7Caspase 9EtoposideN-(6-((anilinocarbonyl)amino)-5-((anilinocarbonyl)((1-(4-cyclohexylbutyl)pyrrolidin-2-yl)methyl)amino)hexyl)-N-methyl-N'-phenylureaPhenylurea CompoundsXIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID17916749
PMCPMC2200818
OpenAlexW1992423562

What OpenQuestion holds

Textmetadata
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.