Evidence map›Paper›PMID 30539410›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2019

Interfering with bromodomain epigenome readers as therapeutic option in mucoepidermoid carcinoma.

Renata L Markman, Liana P Webber, Carlos H V Nascimento Filho, Leonardo A Reis, Pablo A Vargas, Marcio A Lopes, Virgilio Zanella, Manoela D Martins, Cristiane H Squarize, Rogerio M Castilho

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Feeling the Heat. Mapping the Epigenetic Modifications of Histone during Burn Wound Healing.Journal of burn care & research : official publication of the American Burn Association · 2024
    Article
  4. Article
  5. Article
  6. Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2022
    Article
  7. Article
  8. The BET family in immunity and disease.Signal transduction and targeted therapy · 2021
    Review
  9. Non-coding RNAs underlying chemoresistance in gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2020
    Review
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

10 authors at 4 institutions in 2 countries.

Renata L MarkmanLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA.
Liana P WebberLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA.
Carlos H V Nascimento FilhoLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA.
Leonardo A ReisLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA.
Pablo A VargasDepartment of Oral Diagnosis, Piracicaba Dental School, State University of Campinas-UNICAMP, Piracicaba, Brazil.
Marcio A LopesDepartment of Oral Diagnosis, Piracicaba Dental School, State University of Campinas-UNICAMP, Piracicaba, Brazil.
Virgilio ZanellaDepartment of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul-UFRGS, Porto Alegre, RS, 90035-003, Brazil.
Manoela D MartinsDepartment of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul-UFRGS, Porto Alegre, RS, 90035-003, Brazil.
Cristiane H SquarizeLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA.
Rogerio M CastilhoLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N University Ave, Room 2029C, Ann Arbor, MI, 48109-1078, USA. rcastilh@umich.edu.ORCID http://orcid.org/0000-0001-5358-612X
Universidade Estadual de Campinas (UNICAMP) · BRUniversidade Federal do Rio Grande do Sul · BRUniversity of Michigan · USFaculdade de Medicina de São José do Rio Preto · BR

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
CAPES BEX / 88881.132606/2016-01 PDSENCI NIH HHS P30 CA046592School of Dentistry, University of Michigan N/A
6 · The paper itself

Abstract

purposeEmerging evidence indicates that bromodomains comprise a conserved class of epigenome readers involved in cancer development and inflammation. Bromodomains are associated with epigenetic modifications of gene transcription through interactions with lysine residues of histone tails. Particularly, the bromodomain and extra-terminal domain (BET) family member BRD4 has been found to be involved in the control over oncogenes, including c-MYC, and in the maintenance of downstream inflammatory processes. The objective of this study was to evaluate the effect of pharmacologically displacing BRD4 in mucoepidermoid carcinoma (MEC) cells.

methodsWe assessed the presence of BRD4 levels in a panel of human MEC tissue samples in conjunction with histological grading and clinical information. In vitro studies were carried out using human MEC-derived cell lines. The BET inhibitor iBET762 was administered to MEC cells to assess the impact of disrupted BRD4 signaling on colony forming capacities and cell cycle status. The activation of cellular senescence induced by iBET762 was determined by immunohistochemical staining for p16

resultsWe found that primary human MECs and MEC-derived cell lines are endowed with high BRD4 expression levels compared to those in normal salivary glands. We also found that, by displacing BRD4 from chromatin using the BET inhibitor iBET762, MEC cells lose their colony forming capacities and undergo G1 cell cycle arrest and senescence. Finally, we found that targeted displacement of BRD4 from chromatin results in depletion of cancer stem cells from the overall MEC cell populations.

conclusionsOur findings indicate that bromodomain-mediated gene regulation constitutes an epigenetic mechanism that is deregulated in MEC cells and that the use of BET inhibitors may serve as a feasible therapeutic strategy to manage MECs.

Indexed as

Epigenesis, GeneticMolecular Targeted TherapyAdolescentAdultAgedBenzodiazepinesBromodomain Containing ProteinsCarcinoma, MucoepidermoidCell Cycle ProteinsCell Line, TumorCellular SenescenceFemaleHistonesHumansMaleMiddle AgedBenzodiazepinesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsHistonesmolibresibNuclear ProteinsTranscription FactorsBRD4Cancer stem cellsEpi-drugEpigeneticiBET762Mucoepidermoid carcinoma

Identifiers

PMID30539410
PMCPMC12994356
OpenAlexW2904362207

What OpenQuestion holds

Textmetadata
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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.