Evidence map›Paper›PMID 22532440›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012

Innate immune agonist, dsRNA, induces apoptosis in ovarian cancer cells and enhances the potency of cytotoxic chemotherapeutics.

Danielle N Van, Charlotte F Roberts, James D Marion, Sandrine Lépine, Kuzhuvelil B Harikumar, Jessica Schreiter, Catherine I Dumur, Xianjun Fang, Sarah Spiegel, Jessica K Bell

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

  1. Trial
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  4. Targeted apoptotic immune modulator for the treatment of metastatic EGFR-positive solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  19. Overview on poly(ADP-ribose) immuno-biomedicine and future prospects.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2016
    Review
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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

10 authors at 2 institutions in 2 countries.

Danielle N VanDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
Charlotte F Roberts
James D Marion
Sandrine Lépine
Kuzhuvelil B Harikumar
Jessica Schreiter
Catherine I Dumur
Xianjun Fang
Sarah Spiegel
Jessica K Bell
Virginia Commonwealth University · USDiscovery Centre · CA

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0M
VCU Neuroscience Center Core GrantP30NS047463 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI POVLISHOCK, JOHN T · 2003 to 2013
$5.0M
SPHINGOSINE AS A MODULATOR OF CELLULAR PROLIFERATIONR01GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1990 to 2023
$3.8M
Sphingosine Kinases in Cancer Cell SignalingR01CA061774 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1994 to 2015
$3.8M
Sphingosine-1 phosphate phosphohydrolaseR37GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 2003 to 2012
$3.2M
Lysophospholipid in Neovascularization in Ovarian CancerR01CA102196 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FANG, XIANJUN · 2004 to 2010
$1.4M
Defining double-stranded RNA receptor induced apoptosis in ovarian cancer.F31CA144083 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SCHRAMM, DANIELLE NICOLE · 2009 to 2010
$65k
NCI NIH HHS CA102196NCI NIH HHS CA12282801NCI NIH HHS CA144083NCI NIH HHS CA61774NCI NIH HHS F31 CA144083NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA061774NCI NIH HHS R01 CA102196NIGMS NIH HHS GM043880NIGMS NIH HHS R01 GM043880NIGMS NIH HHS R37 GM043880NINDS NIH HHS 5P30NS047463-02NINDS NIH HHS P30 NS047463
6 · The paper itself

Abstract

Ovarian cancer is the most lethal gynecological cancer. Here we show that innate immune agonist, dsRNA, directly induces ovarian cancer cell death and identify biomarkers associated with responsiveness to this targeted treatment. Nuclear staining and MTT assays following dsRNA stimulation revealed two subpopulations, sensitive (OVCAR-3, CAOV-3; patient samples malignant 1 and 2) and resistant (DOV-13, SKOV-3). Microarray analysis identified 75 genes with differential expression that further delineated these two subpopulations. qPCR and immunoblot analyses showed increased dsRNA receptor expression after stimulation as compared to resistant and immortalized ovarian surface epithelial cells (e.g., 70-fold with malignant 2, 43-fold with OVCAR-3). Using agonists, antagonists, and shRNA-mediated knockdown of dsRNA receptors, we show that TLR3, RIG-I, and mda5 coordinated a caspase 8/9- and interferon-dependent cell death. In resistant cells, dsRNA receptor overexpression restored dsRNA sensitivity. When dsRNA was combined with carboplatin or paclitaxel, cell viability significantly decreased over individual treatments (1.5- to 7.5-fold). Isobologram analyses showed synergism in dsRNA combinations (CI=0.4-0.82) vs. an additive effect in carboplatin/paclitaxel treatment (CI=1.5-2). Our data identify a predictive marker, dsRNA receptor expression, to target dsRNA responsive populations and show that, in dsRNA-sensitive cells, dsRNA induces apoptosis and enhances the potency of cytotoxic chemotherapeutics.

Indexed as

ApoptosisBiomarkers, TumorCaspasesCell Line, TumorCisplatinDrug Resistance, NeoplasmDrug SynergismEnzyme ActivationFemaleHumansInterferon-betaNF-kappa BOvarian NeoplasmsPaclitaxelRNA, Double-StrandedRNA, MessengerBiomarkers, TumorCaspasesCisplatinInterferon-betaNF-kappa BPaclitaxelRNA, Double-StrandedRNA, Messenger

Identifiers

PMID22532440
PMCPMC3405273
OpenAlexW2151749514

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.