Evidence map›Paper›PMID 34731160›Full record

ArticlePloS one2021

Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model.

Riccardo Serra, Tianna Zhao, Sakibul Huq, Noah Leviton Gorelick, Joshua Casaos, Arba Cecia, Antonella Mangraviti, Charles Eberhart, Renyuan Bai, Alessandro Olivi and 3 more

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

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  3. Article
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  6. Review
  7. Copper in Gynecological Diseases.International journal of molecular sciences · 2023
    Review
  8. Article
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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

13 authors at 2 institutions in 2 countries.

Riccardo SerraDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.ORCID 0000-0002-1975-393X
Tianna ZhaoDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Sakibul HuqDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Noah Leviton GorelickDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Joshua CasaosDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Arba CeciaDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Antonella MangravitiDepartment of Neurosurgery, School of Medicine - Catholic University of the Sacred Heart, Rome, Italy.
Charles EberhartDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Renyuan BaiDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Alessandro OliviDepartment of Neurosurgery, School of Medicine - Catholic University of the Sacred Heart, Rome, Italy.
Henry BremDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Eric M JacksonDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Betty TylerDepartment of Neurosurgery, Hunterian Neurosurgical Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Johns Hopkins University · USUniversità Cattolica del Sacro Cuore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMedulloblastoma (MB) is the most common brain malignancy in children, and is still responsible for significant mortality and morbidity. The aim of this study was to assess the safety and efficacy of Disulfiram (DSF), an FDA-approved inhibitor of Aldehyde-Dehydrogenase (ALDH), and Copper (Cu++) in human SSH-driven and Group 3 MB. The molecular mechanisms, effect on cancer-stem-cells (CSC) and DNA damage were investigated in xenograft models.

methodsThe cytotoxic and anti-CSC effects of DSF/Cu++ were evaluated with clonogenic assays, flow-cytometry, immunofluorescence, western-blotting. ONS76, UW228 (SHH-driven with Tp53m), D425med, D283 and D341 (Group 3) cell-lines were used. In vivo survival and nuclear protein localization protein-4 (NPL4), Ki67, Cleaved-Caspase-3, GFAP and NeuN expression were assessed in two Group 3 MB xenografts with immunohistochemistry and western-blotting.

resultsSignificant in vitro cytotoxicity was demonstrated at nanomolar concentrations. DSF/Cu++ induced cell-death through NPL4 accumulation in cell-nucleus and buildup of poly-ubiquitylated proteins. Flow-cytometry demonstrated a significant decrease in ALDH+, Nestin+ and CD133+ following treatment, anti-CSC effect was confirmed in vitro and in vivo. DSF/Cu++ prolonged survival, and increased nuclear NPL4 expression in vivo.

conclusionsOur data suggest that this combination may serve as a novel treatment, as monotherapy or in combination with existing therapies, for aggressive subtypes of pediatric MB.

Indexed as

Aldehyde DehydrogenaseAnimalsApoptosisBrain NeoplasmsCell CycleCell ProliferationCopperDisulfiramMedulloblastomaNeoplastic Stem CellsAldehyde DehydrogenaseCopperDisulfiram

Identifiers

PMID34731160
PMCPMC8565761
OpenAlexW3210823799

What OpenQuestion holds

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LicenceCC BY
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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.