Evidence map›Paper›PMID 34885051›Full record

ArticleCancers2021

GSK-3 Inhibition Is Cytotoxic in Glioma Stem Cells through Centrosome Destabilization and Enhances the Effect of Radiotherapy in Orthotopic Models.

Anke Brüning-Richardson, Gary C Shaw, Daniel Tams, Tim Brend, Hitesh Sanganee, Simon T Barry, Gregory Hamm, Richard J A Goodwin, John G Swales, Henry King and 10 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Anke Brüning-RichardsonLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.ORCID 0000-0002-9862-9805
Gary C ShawLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.ORCID 0000-0001-9344-4433
Daniel TamsLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Tim BrendLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.ORCID 0000-0001-9703-7042
Hitesh SanganeeDiscovery Sciences BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 8PA, UK.
Simon T BarryBioscience, Early Oncology, Oncology R&D, AstraZeneca, Cambridge CB2 8PA, UK.
Gregory HammImaging and Data Analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 8PA, UK.
Richard J A GoodwinImaging and Data Analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 8PA, UK.
John G SwalesImaging and Data Analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 8PA, UK.
Henry KingLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Lynette SteeleLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Ruth MortonLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Anastasia WidyadariLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Thomas A WardLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.ORCID 0000-0003-0937-4554
Filomena EstevesLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Marjorie BoissinotLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Georgia MavriaLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
Alastair DroopLeeds MRC Medical Bioinformatics Centre, University of Leeds, Leeds LS9 7TF, UK.
Sean E LawlerBrown University Cancer Center, Pathology & Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Susan C ShortLeeds Institute of Medical Research at St James's, University of Leeds, Leeds LS9 7TF, UK.
University of Leeds · GBAstraZeneca (United Kingdom) · GBBrown University · US

Funding

Cancer Research UK 28832Medical Research Council MR/K015214/1
6 · The paper itself

Abstract

backgroundPrevious data on glycogen synthase kinase 3 (GSK-3) inhibition in cancer models support a cytotoxic effect with selectivity for tumor cells compared to normal tissue but the effect of these inhibitors in glioma has not been widely studied. Here, we investigate their potential as cytotoxics in glioma.

methodsWe assessed the effect of pharmacologic GSK-3 inhibition on established (U87, U251) and patient-derived (GBM1, GBM4) glioblastoma (GBM) cell lines using cytotoxicity assays as well as undertaking a detailed investigation of the effect on cell cycle, mitosis, and centrosome biology. We also assessed drug uptake and efficacy of GSK-3 inhibition alone and in combination with radiation in xenograft models.

resultsUsing the selective GSK-3 inhibitor AZD2858, we demonstrated single agent cytotoxicity in two patient-derived glioma cell lines (GBM1, GBM4) and two established cell lines (U251 and U87) with IC

conclusionsThese data suggest that GSK-3 inhibition promotes cell death in glioma through disrupting centrosome function and promoting mitotic failure and that AZD2858 is an effective adjuvant to radiation at clinical doses.

Indexed as

centrosomecytotoxicityglioblastomaGSK-3radiation

Identifiers

PMID34885051
PMCPMC8657225
OpenAlexW3217190988

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.