Evidence map›Paper›PMID 33838899›Full record

ArticleJournal of pediatric surgery2021

Combining inhibitors of Brd4 and cyclin-dependent kinase can decrease tumor growth in neuroblastoma with MYCN amplification.

Lauren Wood, Min Huang, Jasmine Zeki, Miao Gong, Jordan Taylor, Hiroyuki Shimada, Bill Chiu

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

Article in Journal of pediatric surgery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021
    Review
  7. 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

7 authors at 2 institutions in 1 country.

Lauren WoodDepartment of Surgery, Stanford University, Stanford, CA, USA.
Min HuangDepartment of Pediatrics, Stanford University, Stanford, USA.
Jasmine ZekiDepartment of Surgery, Stanford University, Stanford, CA, USA.
Miao GongDepartment of Surgery, Stanford University, Stanford, CA, USA.
Jordan TaylorDepartment of Surgery, Stanford University, Stanford, CA, USA.
Hiroyuki ShimadaDepartment of Pathology, Stanford University, Stanford, CA, USA.
Bill ChiuDepartment of Surgery, Stanford University, Stanford, CA, USA. Electronic address: bhsc@stanford.edu.
Stanford University · USStanford Medicine · US

Funding

Focal Sustained Release Chemotherapy-Loaded Biomaterials at Tumor SitesR01NS094218 · NINDS · TUFTS UNIVERSITY MEDFORD · PI CHIU, BILL, KAPLAN, DAVID L. · 2017 to 2021
$1.7M
NINDS NIH HHS R01 NS094218
6 · The paper itself

Abstract

introductionHigh-risk neuroblastoma is a deadly disease; poor prognosticators are MYCN-amplification and TERT-overexpression. We hypothesized that Gene Set Enrichment Analysis (GSEA) could identify pathways associated with MYCN-amplification and that inhibition of these pathways could decrease tumor growth.

methodsWe analyzed the Neuroblastoma-Kocak dataset (GSE45547, n = 649) and identified pathways associated with MYCN-amplification. Inhibitors were selected from upregulated gene sets for in vitro cytotoxicity testing using ST16-patient-derived primary neuroblastoma cells and in vivo testing using orthotopic ST16-patient-derived xenografts (PDX) in mice. Tumor volume was measured with ultrasound and tumor sections examined after H&E staining.

resultsGSEA identified significantly overexpressed gene sets in MYCN-amplified tumors including MYC targets, cell cycle mitotic genes, TERT associated genes, loss of RB1 gene sets, and E2Fs targets. Several genes were potential Bromodomain-containing protein 4 (Brd4) targets, making Brd4 inhibitors - JQ1, AZD5153 - and cyclin-dependent kinase (Brd4's binding partner) inhibitors - dinaciclib - potential therapeutic agents. JQ1 and dinaciclib were synergistic in inducing cytotoxicity in vitro. Dinaciclib-AZD5153 in vivo decreased tumor size compared to control, and increased tumor lymphocyte infiltration and necrosis on histology.

conclusionsGSEA is a powerful approach to identify upregulated genes and potential therapeutic targets. Dinaciclib-AZD5153 combination therapy can be effective against MYCN-amplified and TERT-overexpressing neuroblastoma tumors.

Indexed as

Cyclin-Dependent KinasesNeuroblastomaAnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceN-Myc Proto-Oncogene ProteinNuclear ProteinsTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsCyclin-Dependent KinasesMYCN protein, humanN-Myc Proto-Oncogene ProteinNuclear ProteinsTranscription FactorsBromodomain inhibitionCyclin-dependent kinase inhibitionMYCNNeuroblastomaTERT

Identifiers

PMID33838899
PMCPMC8225564
OpenAlexW3140848551

What OpenQuestion holds

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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.