Evidence map›Paper›PMID 21567185›Full record

ArticleInvestigational new drugs2012

Effects of the novel DNA dependent protein kinase inhibitor, IC486241, on the DNA damage response to doxorubicin and cisplatin in breast cancer cells.

David Davidson, Jeremy Grenier, Veronica Martinez-Marignac, Lilian Amrein, May Shawi, Marc Tokars, Raquel Aloyz, Lawrence Panasci

Abstract read
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2012. 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
1.2field-weighted citation impact, top 23% 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, 26 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

8 authors at 2 institutions in 1 country.

David DavidsonMontreal Centre for Experimental Therapeutics in Cancer-Segal Cancer Center-Lady Davis Institute-Jewish General Hospital, McGill University, 3755, Côte Sainte Catherine Road, Montréal, Québec H3T 1E2, Canada.
Jeremy Grenier
Veronica Martinez-Marignac
Lilian Amrein
May Shawi
Marc Tokars
Raquel Aloyz
Lawrence Panasci
McGill University · CAJewish General Hospital · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

The purpose of this study was to determine the degree to which the novel DNA-PKcs inhibitor, IC486241 (ICC), synergizes the cytotoxicity of DNA damaging agents in 3 genetically diverse breast cancer cell lines. The sulforhodamine B (SRB) assay was employed as a primary screening method to determine the in-vitro cytotoxicity and the degree of synergy of ICC in combination with the topoisomerase II inhibitor, doxorubicin, or the DNA cross linking agent, cisplatin. Molecular mechanisms underlying drug toxicity were probed using immunostaining and flow cytometry, as well as, the alkaline comet assay to detect DNA damage. In this study, improved cytotoxicity and significant synergy were observed with both anticancer agents in the presence of nontoxic concentrations of ICC. Moreover, ICC decreased doxorubicin-induced DNA-PKcs autophosphorylation on Ser2056 and increased doxorubicin-induced DNA fragmentation. In conclusion, the novel DNA-PKcs inhibitor, ICC, synergistically sensitized 3 breast cancer cell lines to doxorubicin and cisplatin. Enhanced efficacy of doxorubicin was achieved by inhibiting non-homologous end joining resulting in increased accumulation of DNA damage.

Indexed as

DNA DamageAcridonesBreast NeoplasmsCell CycleCell Line, TumorCisplatinComet AssayDimethyl SulfoxideDNA, NeoplasmDoxorubicinDrug Screening Assays, AntitumorDrug SynergismFemaleFlow CytometryHumansInhibitory Concentration 50AcridonesCisplatinDimethyl SulfoxideDNA, NeoplasmDoxorubicinIC486241Protein Kinase InhibitorsQuinazolines

Identifiers

PMID21567185
OpenAlexW1981746443

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.