Evidence map›Paper›PMID 25003660›Full record

ArticleBritish journal of cancer2014

Preferential potentiation of topoisomerase I poison cytotoxicity by PARP inhibition in S phase.

P Znojek, E Willmore, N J Curtin

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 47 citations in OpenAlex.

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  7. Antibody-Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients with Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

3 authors at 1 institution in 1 country.

P ZnojekNewcastle University, Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle upon Tyne NE2 4HH, UK.
E WillmoreNewcastle University, Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle upon Tyne NE2 4HH, UK.
N J CurtinNewcastle University, Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle upon Tyne NE2 4HH, UK.
Newcastle University · GB

Funding

Cancer Research UK C5201/A6710
6 · The paper itself

Abstract

backgroundTopoisomerase I (Topo I) poisons (e.g., camptothecin (CPT)), used to treat cancer, cause DNA breaks that are most cytotoxic during S phase. PARP-1 promotes DNA repair and PARP inhibitors (PARPi) sensitise cells to Topo I poisons. We aimed to determine whether chemosensitisation is also S phase specific using rucaparib, a potent PARPi in advanced clinical evaluation.

methodsThe impact of rucaparib, on CPT-induced cytotoxicity was measured in human colon cancer (LoVo) and leukaemic (K562) cells in asynchronous and cell cycle phase-separated cultures. Topoisomerase I and PARP levels and activity and the effect of rucaparib on DNA single-strand breaks (SSBs), double-strand breaks (DSBs) and collapsed replication fork induction and repair were determined in cell cycle phase-separated cells.

resultsThe cytotoxicity of CPT was greatest during S phase, partially attributable to high Topo I activity, and rucaparib preferentially sensitised S-phase cells. Rucaparib increased CPT-induced DNA SSBs in all phases of the cell cycle, and increased DSB and γH2AX foci in S and G2, with γH2AX foci being highest in S-phase cells. Repair of SSBs and DSBs was most rapid during S then G2 phases and was substantially hindered by rucaparib.

conclusionsRucaparib preferentially sensitises S-phase cells by increasing the frequency of collapsed replication forks.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsCamptothecinCell SurvivalDNA Breaks, Double-StrandedDNA RepairDNA Topoisomerases, Type IDrug Screening Assays, AntitumorDrug SynergismHumansIndolesK562 CellsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) PolymerasesS Phase Cell Cycle CheckpointsTopoisomerase I InhibitorsCamptothecinDNA Topoisomerases, Type IIndolesPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesrucaparibTOP1 protein, humanTopoisomerase I Inhibitors

Identifiers

PMID25003660
PMCPMC4183837
OpenAlexW1987714967

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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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.