Evidence map›Paper›PMID 25427448›Full record

ArticleOncotarget2014

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.

Yimin Zhang, Sarah J Storr, Kerstie Johnson, Andrew R Green, Emad A Rakha, Ian O Ellis, David A L Morgan, Stewart G Martin

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 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.

Yimin ZhangAcademic Unit of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Sarah J StorrAcademic Unit of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Kerstie JohnsonClinical Oncology, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Andrew R GreenHistopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Emad A RakhaHistopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Ian O EllisHistopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
David A L MorganClinical Oncology, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Stewart G MartinAcademic Unit of Clinical Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, UK.
Nottingham University Hospitals NHS Trust · GBUniversity of Nottingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated breast cancers and metformin's ability to modulate Trx system expression and breast cancer radiosensitivity evaluated in vitro. AMPKα and pAMPKα(Thr172) expression was assessed using a discovery (n=166) and validation cohort (n=609). Metformin's role in regulating radioresponse, and Trx family expression, was examined via clonogenic assays and Western blots. Intracellular reactive oxygen species (ROS) levels, cell cycle progression and apoptosis were assessed by flow cytometry. High AMPKα expression associated with improved local recurrence-free (P=0.019), relapse-free (P=0.016) and breast cancer-specific survival (P=0.000065) and was, from multivariate analysis, an independent prognostic factor from the discovery cohort. From the validation cases AMPKα expression associated with relapse-free and breast cancer-specific survival in luminal breast cancers. Metformin substantially increased radiosensitivity, intracellular ROS levels and reduced Trx expression, in luminal breast cancer cells, but had little effect on basal phenotype cells. In conclusion, high AMPKα expression associates with improved prognosis, especially in luminal breast cancer. Metformin preferentially radiosensitises luminal breast cancer cells, potentially due to alterations to intracellular ROS levels via modulation of Trx family protein expression.

Indexed as

AMP-Activated Protein KinasesBasal Cell CarcinomaBreast NeoplasmsCell Line, TumorChemoradiotherapyCohort StudiesFemaleHumansMCF-7 CellsMetforminPrognosisSurvival AnalysisAMP-Activated Protein KinasesMetformin

Identifiers

PMID25427448
PMCPMC4350336
OpenAlexW1592486733

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.