ArticleThe Journal of pharmacology and experimental therapeutics2011
Identification of chemosensitivity nodes for vinblastine through small interfering RNA high-throughput screens.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Mitochondrial dysfunction RAD51, and Ku80 proteolysis promote apoptotic effects of Dinaciclib in Bcl-xL silenced cells.Molecular carcinogenesis · 2018Article
- Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines.Molecular carcinogenesis · 2017Article
- Microtubule destabilising agents: far more than just antimitotic anticancer drugs.British journal of clinical pharmacology · 2017Review
- Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells.Cancer biology & therapy · 2015Article
- Inhibition of phosphatidylinositol 3-kinase/AKT signaling by NVP-BKM120 promotes ABT-737-induced toxicity in a caspase-dependent manner through mitochondrial dysfunction and DNA damage response in established and primary cultured glioblastoma cells.The Journal of pharmacology and experimental therapeutics · 2014Article
- Novel siRNA delivery strategy: a new "strand" in CNS translational medicine?Cellular and molecular life sciences : CMLS · 2014Review
- Survivin inhibitor YM-155 sensitizes tumor necrosis factor- related apoptosis-inducing ligand-resistant glioma cells to apoptosis through Mcl-1 downregulation and by engaging the mitochondrial death pathway.The Journal of pharmacology and experimental therapeutics · 2013Article
- YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context.Molecular cancer therapeutics · 2013Article
- Alkylation sensitivity screens reveal a conserved cross-species functionome.Molecular cancer research : MCR · 2012Article
- Phenotypic screening reveals topoisomerase I as a breast cancer stem cell therapeutic target.Oncotarget · 2012Article
- Identification of druggable targets for radiation mitigation using a small interfering RNA screening assay.Radiation research · 2012Article
- ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage, Bax activation, and mitochondrial dysfunction in an Akt-dependent context in malignant human glioma cell lines.The Journal of pharmacology and experimental therapeutics · 2012Article
- Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery.International journal of nanomedicineArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Discovering chemosensitivity pathways or nodes is an attractive strategy for formulating new drug combinations for cancer. Microtubules are among the most successful anticancer drug targets. Therefore, we implemented a small interfering RNA (siRNA) synthetic lethal screen targeting 5520 unique druggable genes to identify novel chemosensitivity nodes for vinblastine, a microtubule-destabilizing agent used clinically. We transiently transfected human glioblastoma cells with siRNAs for 48 h and then treated cells with a sublethal concentration of vinblastine. Forty-eight hours later, we analyzed cell viability and, using a series of statistical methods, identified 65 gene products that, when suppressed, sensitized glioblastoma cells to vinblastine. After completion of the secondary assays, we focused on one siRNA, B-cell lymphoma extra large (BCL-xL), because of its role in the intrinsic apoptosis signaling pathway as well as the availability of pharmacological inhibitors. We found that nontoxic concentrations of 4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide (ABT-263), an inhibitor of the BCL-2 family members (BCL-2, BCL-xL, and BCL-w), sensitized glioblastoma and non-small-cell lung cancer cells to vinblastine and induced apoptosis through the intrinsic cell death pathway. These results illustrate the usefulness of unbiased siRNA screens as a method for identifying potential novel anticancer therapeutic combinations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.