Evidence map›Paper›PMID 29089623›Full record

ArticleScientific reports2017

Enzalutamide inhibits testosterone-induced growth of human prostate cancer xenografts in zebrafish and can induce bradycardia.

Nicole Melong, Shelby Steele, Morgan MacDonald, Alice Holly, Colin C Collins, Amina Zoubeidi, Jason N Berman, Graham Dellaire

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 24% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 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 1 institution in 1 country.

Nicole MelongDepartment of Pediatrics, IWK Health Centre, Halifax, Canada.
Shelby SteeleDepartment of Pediatrics, Dalhousie University, Halifax, Canada.
Morgan MacDonaldDepartment of Urology, Dalhousie University, Halifax, Canada.
Alice HollyDepartment of Pathology, Dalhousie University, Halifax, Canada.
Colin C CollinsVancouver Prostate Centre, Vancouver, Canada.
Amina ZoubeidiVancouver Prostate Centre, Vancouver, Canada.
Jason N BermanDepartment of Pediatrics, IWK Health Centre, Halifax, Canada. Jason.Berman@iwk.nshealth.ca.
Graham DellaireDepartment of Pathology, Dalhousie University, Halifax, Canada. dellaire@dal.ca.ORCID 0000-0002-3466-6316
Dalhousie University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The zebrafish has become a popular human tumour xenograft model, particularly for solid tumours including prostate cancer (PCa). To date PCa xenotransplantation studies in zebrafish have not been performed in the presence of testosterone, even when employing androgen-dependent cell models, such as the LNCaP cell line. Thus, with the goal of more faithfully modelling the hormonal milieu in which PCa develops in humans, we sought to determine the effects of exogenous testosterone on the growth of LNCaP, or androgen-independent C4-2 cells xenografted into zebrafish embryos. Testosterone significantly increased engrafted LNCaP proliferation compared to control xenografts, which could be inhibited by co-administration of the anti-androgen receptor drug, enzalutamide. By contrast, C4-2 cell growth was not affected by either testosterone or enzalutamide. Enzalutamide also induced bradycardia and death in zebrafish embryos in a dose-dependent manner and strongly synergized with the potassium-channel blocking agent, terfenadine, known to induce long QT syndrome and cardiac arrhythmia. Together, these data not only indicate that testosterone administration should be considered in all PCa xenograft studies in zebrafish but also highlights the unique opportunity of this preclinical platform to simultaneously evaluate efficacy and toxicity of novel therapies and/or protective agents towards developing safer and more effective PCa treatments.

Indexed as

AnimalsAntineoplastic AgentsBenzamidesBradycardiaCell Line, TumorCell ProliferationDisease Models, AnimalDrug-Related Side Effects and Adverse ReactionsDrug SynergismEmbryo, NonmammalianHumansMaleNitrilesPhenylthiohydantoinProstatic NeoplasmsReceptors, AndrogenAntineoplastic AgentsBenzamidesenzalutamideNitrilesPhenylthiohydantoinReceptors, AndrogenTerfenadineTestosterone

Identifiers

PMID29089623
PMCPMC5665934
OpenAlexW2766016514

What OpenQuestion holds

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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.