Evidence map›Paper›PMID 30701326›Full record

ArticleJournal of cancer research and clinical oncology2019

NRF2 orchestrates the redox regulation induced by radiation therapy, sustaining embryonal and alveolar rhabdomyosarcoma cells radioresistance.

Francesco Marampon, Silvia Codenotti, Francesca Megiorni, Andrea Del Fattore, Simona Camero, Giovanni Luca Gravina, Claudio Festuccia, Daniela Musio, Francesca De Felice, Valerio Nardone and 8 more

Open access · greenAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  5. The cross-talk between NRF2 and apoptosis in cancer.Medical molecular morphology · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. The botanical drug PBI-05204, a supercritical COFrontiers in pharmacology · 2022
    Article
  10. Review
  11. Article
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  15. Oncometabolites and the response to radiotherapy.Radiation oncology (London, England) · 2020
    Review
  16. Article
  17. Article
  18. Potential Applications of NRF2 Modulators in Cancer Therapy.Antioxidants (Basel, Switzerland) · 2020
    Review
  19. Article
  20. Article
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

18 authors at 9 institutions in 2 countries.

Francesco MaramponDepartment of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. f.marampon@gmail.com.ORCID http://orcid.org/0000-0002-0588-3039
Silvia CodenottiDivision of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Francesca MegiorniDepartment of Pediatrics, "Sapienza" University of Rome, Rome, Italy.
Andrea Del FattoreMulti-Factorial Disease and Complex Phenotype Research Area, Bambino Gesù Children's Hospital, IRCCS, Viale di San Paolo 15, 00146, Rome, Italy.
Simona CameroDepartment of Pediatrics, "Sapienza" University of Rome, Rome, Italy.
Giovanni Luca GravinaDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Claudio FestucciaDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100, L'Aquila, Italy.
Daniela MusioDepartment of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Francesca De FeliceDepartment of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Valerio NardoneUnit of Radiation Therapy, Ospedale del Mare, Naples, Italy.
Anna Natalizia SantoroAzienda Ospedaliera Universitaria Senese, Siena, Italy.
Carlo DominiciDepartment of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Alessandro FanzaniDivision of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Luigi PirtoliAzienda Ospedaliera Universitaria Senese, Siena, Italy.
Antonella FioravantiSbarro Health Research Organization, Temple University, Philadelphia, PA, USA.
Vincenzo TomboliniDepartment of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.
Sara CheleschiDepartment of Medicine, Surgery and Neuroscience, Rheumatology Unit, University of Siena, Policlinico Le Scotte, Siena, Italy.
Paolo TiniUnit of Radiation Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
Policlinico Umberto I · ITSapienza University of Rome · ITUniversity of Brescia · ITUniversity of L'Aquila · ITUniversity of Siena · ITAzienda Ospedaliera Universitaria Senese · ITBambino Gesù Children's Hospital · ITSbarro Health Research Organization · USTumour Institute of Tuscany · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTumor cells generally exhibit higher levels of reactive oxygen species (ROS), however, when stressed, tumor cells can undergo a process of 'Redox Resetting' to acquire a new redox balance with stronger antioxidant systems that enable cancer cells to become resistant to radiation therapy (RT). Here, we describe how RT affects the oxidant/antioxidant balance in human embryonal (RD) and alveolar (RH30) rhabdomyosarcoma (RMS) cell lines, investigating on the molecular mechanisms involved.

methodsRadiations were delivered using an x-6 MV photon linear accelerator and their effects were assessed by vitality and clonogenic assays. The expression of specific antioxidant-enzymes, such as Superoxide Dismutases (SODs), Catalase (CAT) and Glutathione Peroxidases 4 (GPx4), miRNAs (miR-22, -126, -210, -375, -146a, -34a) and the transcription factor NRF2 was analyzed by quantitative polymerase chain reaction (q-PCR) and western blotting. RNA interference experiments were performed to evaluate the role of NRF2.

resultsDoses of RT higher than 2 Gy significantly affected RMS clonogenic ability by increasing ROS production. RMS rapidly and efficiently brought back ROS levels by up-regulating the gene expression of antioxidant enzymes, miRNAs as well as of NRF2. Silencing of NRF2 restrained the RMS ability to counteract RT-induced ROS accumulation, antioxidant enzyme and miRNA expression and was able to increase the abundance of γ-H2AX, a biomarker of DNA damage, in RT-treated cells.

conclusionsTaken together, our data suggest the strategic role of oxidant/antioxidant balance in restraining the therapeutic efficiency of RT in RMS treatment and identify NRF2 as a new potential molecular target whose inhibition might represent a novel radiosensitizing therapeutic strategy for RMS clinical management.

Indexed as

AntioxidantsCell Line, TumorDose-Response Relationship, RadiationHumansMicroRNAsNF-E2-Related Factor 2Oxidation-ReductionRadiation ToleranceReactive Oxygen SpeciesRhabdomyosarcoma, AlveolarRhabdomyosarcoma, EmbryonalRNA, Small InterferingTransfectionUp-RegulationAntioxidantsMicroRNAsNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen SpeciesRNA, Small InterferingAnti-oxidantNRF2RadioresistanceRadiotherapyReactive oxygen speciesRhabdomyosarcoma

Identifiers

PMID30701326
PMCPMC11810283
OpenAlexW2914114049

What OpenQuestion holds

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Registered trials

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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.