Evidence map›Paper›PMID 25785590›Full record

ArticlePloS one2015

Molecular and in vivo characterization of cancer-propagating cells derived from MYCN-dependent medulloblastoma.

Zai Ahmad, Lukasz Jasnos, Veronica Gil, Louise Howell, Albert Hallsworth, Kevin Petrie, Tomoyuki Sawado, Louis Chesler

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. The Non-coding Side of Medulloblastoma.Frontiers in cell and developmental biology · 2020
    Review
  9. Article
  10. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
  11. Review
  12. Review
  13. Review
  14. 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

8 authors at 1 institution in 1 country.

Zai AhmadDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Lukasz JasnosDivision of Molecular Pathology, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Veronica GilDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Louise HowellDivision of Molecular Pathology, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Albert HallsworthDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Kevin PetrieDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Tomoyuki SawadoDivision of Molecular Pathology, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Louis CheslerDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Institute of Cancer Research · GB

Funding

Cancer Research UK 18339Cancer Research UK C34648/A12054
6 · The paper itself

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. While the pathways that are deregulated in MB remain to be fully characterized, amplification and/or overexpression of the MYCN gene, which is has a critical role in cerebellar development as a regulator of neural progenitor cell fate, has been identified in several MB subgroups. Phenotypically, aberrant expression of MYCN is associated with the large-cell/anaplastic MB variant, which accounts for 5-15% of cases and is associated with aggressive disease and poor clinical outcome. To better understand the role of MYCN in MB in vitro and in vivo and to aid the development of MYCN-targeted therapeutics we established tumor-derived neurosphere cell lines from the GTML (Glt1-tTA/TRE-MYCN-Luc) genetically engineered mouse model. A fraction of GTML neurospheres were found to be growth factor independent, expressed CD133 (a marker of neural stem cells), failed to differentiate upon MYCN withdrawal and were highly tumorigenic when orthotopically implanted into the cerebellum. Principal component analyzes using single cell RNA assay data suggested that the clinical candidate aurora-A kinase inhibitor MLN8237 converts GTML neurospheres to resemble non-MYCN expressors. Correlating with this, MLN8237 significantly extended the survival of mice bearing GTML MB allografts. In summary, our results demonstrate that MYCN plays a critical role in expansion and survival of aggressive MB-propagating cells, and establish GTML neurospheres as an important resource for the development of novel therapeutic strategies.

Indexed as

AllograftsAnimalsAntineoplastic AgentsAurora Kinase AAzepinesCell Line, TumorCerebellar NeoplasmsCerebellumFemaleGene ExpressionHumansMedulloblastomaMiceMice, TransgenicNeoplasm TransplantationNeoplastic Stem CellsAntineoplastic AgentsAurka protein, mouseAurora Kinase AAzepinesMLN 8237MYCN protein, mouseN-Myc Proto-Oncogene ProteinProtein Kinase InhibitorsProto-Oncogene ProteinsPyrimidines

Identifiers

PMID25785590
PMCPMC4365014
OpenAlexW2023750739

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.