Evidence map›Paper›PMID 35179215›Full record

ArticleInternational journal of oncology2022

Targeting the TP53/MDM2 axis enhances radiation sensitivity in atypical teratoid rhabdoid tumors.

Irina Alimova, Dong Wang, Etienne Danis, Angela Pierce, Andrew Donson, Natalie Serkova, Krishna Madhavan, Senthilnath Lakshmanachetty, Ilango Balakrishnan, Nicholas K Foreman and 3 more

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

Article in International journal of oncology, 2022. 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
1.0field-weighted citation impact, top 28% 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, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
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 1 country.

Irina AlimovaDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Dong WangDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Etienne DanisDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Angela PierceDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Andrew DonsonDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Natalie SerkovaDepartment of Radiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Krishna MadhavanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Senthilnath LakshmanachettyDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Ilango BalakrishnanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nicholas K ForemanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Siddhartha MitraDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Sujatha VenkataramanDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Rajeev VibhakarDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Bruker 9.4T/ 20cm BioSpec MR Scanner for Colorado Animal Imaging Shared ResourcesS10OD023485 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2017 to 2017
$2.0M
Multi-Modal Optical/ microCT system for Colorado Animal Imaging ResourceS10OD027023 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2020 to 2020
$733k
NCI NIH HHS P30 CA046934NIH HHS S10 OD023485NIH HHS S10 OD027023
6 · The paper itself

Abstract

Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive pediatric brain tumor. Despite radiation, aggressive chemotherapy and autologous stem cell rescue, children usually have a poor survival time. In the present study, the role of TP53/MDM2 interaction in ATRT was investigated. A functional genomic screen identified the TP53/MDM2 axis as a therapeutic target in the central nervous system (CNS) ATRT. Gene expression analysis revealed that all ATRT sub‑groups expressed high levels of MDM2, which is a negative regulator of TP53. Using cell viability, colony formation and methylcellulose assays it was found that genetic MDM2 inhibition with short hairpin RNA or chemical MDM2 inhibition with small molecule inhibitors, Nutlin3 and idasanutlin (RG7388) decreased the growth of ATRT cell lines. Furthermore, idasanutlin significantly decreased the growth of intracranial orthotopic ATRT brain tumors, as evaluated using T2 MRI, and prolonged survival time relative to control animals. MRI of intracranial tumors showed that diffusion coefficient, an effective marker for successful treatment, significantly increased with idasanutlin treatment showing tumor necrosis/apoptosis. Immunohistochemistry revealed an increased number of caspase‑3‑positive cells in the idasanutlin treatment group, confirming the induction of apoptosis

Indexed as

Antineoplastic AgentsApoptosisCell Line, TumorCell ProliferationColoradoHumansProto-Oncogene Proteins c-mdm2Radiation ToleranceRhabdoid TumorTeratomaTumor Suppressor Protein p53Antineoplastic AgentsMDM2 protein, humanProto-Oncogene Proteins c-mdm2TP53 protein, humanTumor Suppressor Protein p53ATRTidasanutlinMDM2radiation sensitivitySMARCB1TP53

Identifiers

PMID35179215
PMCPMC8878716
OpenAlexW4212973634

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.