Evidence map›Paper›PMID 23115158›Full record

ArticleNeuro-oncology2013

Overexpression of isocitrate dehydrogenase mutant proteins renders glioma cells more sensitive to radiation.

Sichen Li, Arthur P Chou, Weidong Chen, Ruihuan Chen, Yuzhong Deng, Heidi S Phillips, Julia Selfridge, Mira Zurayk, Jerry J Lou, Richard G Everson and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% 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

99 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.

  1. Pooled it
  2. Article
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  5. Article
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  7. Article
  8. Review
  9. Article
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  11. Cancers · 2023
    Review
  12. Article
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  16. Article
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39 more citing papers are in PubMed but not listed here.

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

15 authors at 1 institution in 1 country.

Sichen LiDepartment of Neurology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California 90095, USA.
Arthur P Chou
Weidong Chen
Ruihuan Chen
Yuzhong Deng
Heidi S Phillips
Julia Selfridge
Mira Zurayk
Jerry J Lou
Richard G Everson
Kuan-Chung Wu
Kym F Faull
Timothy Cloughesy
Linda M Liau
Albert Lai
University of California, Los Angeles · US

Funding

UCLA Neurosurgery Research Training and Education ProgramR25NS079198 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LIAU, LINDA M · 2012 to 2021
$1.2M
Genome-wide promoter methylation profiling of gliomaK08CA124479 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LAI, ALBERT · 2008 to 2012
$790k
NCI NIH HHS K08CA124479NINDS NIH HHS R25 NS079198
6 · The paper itself

Abstract

Mutations in isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) are found in a subset of gliomas. Among the many phenotypic differences between mutant and wild-type IDH1/2 gliomas, the most salient is that IDH1/2 mutant glioma patients demonstrate markedly improved survival compared with IDH1/2 wild-type glioma patients. To address the mechanism underlying the superior clinical outcome of IDH1/2 mutant glioma patients, we investigated whether overexpression of the IDH1(R132H) protein could affect response to therapy in the context of an isogenic glioma cell background. Stable clonal U87MG and U373MG cell lines overexpressing IDH1(WT) and IDH1(R132H) were generated, as well as U87MG cell lines overexpressing IDH2(WT) and IDH2(R172K). In vitro experiments were conducted to characterize baseline growth and migration and response to radiation and temozolomide. In addition, reactive oxygen species (ROS) levels were measured under various conditions. U87MG-IDH1(R132H) cells, U373MG-IDH1(R132H) cells, and U87MG-IDH2(R172K) cells demonstrated increased sensitivity to radiation but not to temozolomide. Radiosensitization of U87MG-IDH1(R132H) cells was accompanied by increased apoptosis and accentuated ROS generation, and this effect was abrogated by the presence of the ROS scavenger N-acetyl-cysteine. Interestingly, U87MG-IDH1(R132H) cells also displayed decreased growth at higher cell density and in soft agar, as well as decreased migration. Overexpression of IDH1(R132H) and IDH2(R172K) mutant protein in glioblastoma cells resulted in increased radiation sensitivity and altered ROS metabolism and suppression of growth and migration in vitro. These findings provide insight into possible mechanisms contributing to the improved outcomes observed in patients with IDH1/2 mutant gliomas.

Indexed as

Antineoplastic Agents, AlkylatingApoptosisBlotting, WesternBrain NeoplasmsCell AdhesionCell MovementCell ProliferationDacarbazineElectromagnetic RadiationFlow CytometryFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticGliomaHumansIsocitrate DehydrogenaseMutant ProteinsAntineoplastic Agents, AlkylatingDacarbazineIDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseMutant ProteinsReactive Oxygen SpeciesTemozolomide

Identifiers

PMID23115158
PMCPMC3534418
OpenAlexW2148339251

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.