Evidence map›Paper›PMID 25395461›Full record

ArticleNeuro-oncology2015

Druggable targets in pediatric neurocutaneous melanocytosis: Molecular and drug sensitivity studies in xenograft and ex vivo tumor cell culture to identify agents for therapy.

Yibing Ruan, Anna Kovalchuk, Aarthi Jayanthan, Xueqing Lun, Yoji Nagashima, Olga Kovalchuk, James R Wright, Alfredo Pinto, Adam Kirton, Ronald Anderson and 1 more

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

Article in Neuro-oncology, 2015. 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
1.0field-weighted citation impact, top 25% 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
  2. Review
  3. Neurocutaneous melanocytosis (melanosis).Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020
    Article
  4. AN 11-Year-Old Boy with a Leptomeningeal Tumor.Brain pathology (Zurich, Switzerland) · 2017
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Lin28A/Neuro-oncology advances
    Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 2 countries.

Yibing RuanDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Anna KovalchukDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Aarthi JayanthanDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Xueqing LunDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Yoji NagashimaDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Olga KovalchukDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
James R WrightDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Alfredo PintoDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Adam KirtonDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Ronald AndersonDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Aru NarendranDivision of Pediatric Oncology, Alberta Children's Hospital and POETIC Laboratory for Preclinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada (Y.R., A.J., X.L., R.A., A.N.); Department of Biological Sciences, University of Lethbridge, Lethbridge, Canada (A.K., O.K.); Department of Pathology, Yokohama City University School of Medicine and Division of Diagnostic Pathology, Tokyo Women's Medical University Hospital, Tokyo, Japan (Y.N.); Department of Pathology and Laboratory Medicine, Alberta Children's Hospital and Calgary Laboratory Services, Calgary, Canada (J.R.W., A.P.); Department of Neurology, Alberta Children's Hospital, Calgary, Canada (A.K.).
Alberta Children's Hospital · CATokyo Women's Medical University Hospital · JPCalgary Laboratory Services · CAUniversity of Calgary · CAUniversity of Lethbridge · CAYokohama City University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeurocutaneous melanocytosis (NCM) is a rare congenital disorder that presents with pigmented cell lesions of the brain or leptomeninges in children with large or multiple congenital melanocytic nevi. Although the exact pathological processes involved are currently unclear, NCM appears to arise from an abnormal development of melanoblasts or melanocyte precursors. Currently, it has an extremely poor prognosis due to rapid disease progression and lack of effective treatment modalities.

methodsIn this study, we report on an experimental approach to examining NCM cells by establishing subcutaneous tumors in nude mice, which can be further expanded for conducting molecular and drug sensitivity experiments.

resultsAnalysis of the NRAS gene-coding sequences of an established NCM cell line (YP-MEL) and NCM patient cells revealed heterogeneity in NRAS Q61K that activated mutation and possibly consequential differential sensitivity to MEK inhibition. Gene expression studies were performed to compare the molecular profiles of NCM cells with normal skin fibroblasts. In vitro cytotoxicity screens of libraries of targeted small-molecule inhibitors revealed prospective agents for further evaluation.

conclusionsOur studies provide an experimental platform for the generation of NCM cells for preclinical studies and the production of molecular and in vitro data with which to identify druggable targets for the treatment.

Indexed as

AnimalsAntineoplastic AgentsChild, PreschoolGTP PhosphohydrolasesHeterograftsHumansMaleMelanosisMembrane ProteinsMiceMice, NudeMutationNeurocutaneous SyndromesSignal TransductionSmall Molecule LibrariesTranscriptomeAntineoplastic AgentsGTP PhosphohydrolasesMembrane ProteinsNRAS protein, humanSmall Molecule Librariesmolecular profilingneurocutaneous melanocytosistargeted therapy

Identifiers

PMID25395461
PMCPMC4483116
OpenAlexW2082213986

What OpenQuestion holds

Textmetadata
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.