Evidence map›Paper›PMID 32087559›Full record

ArticleTranslational oncology2020

Lipid Peroxidation Plays an Important Role in Chemotherapeutic Effects of Temozolomide and the Development of Therapy Resistance in Human Glioblastoma.

Wei Wu, Yang Wu, Karoline Mayer, Charlotte von Rosenstiel, Johannes Schecker, Sandra Baur, Sylvia Würstle, Friederike Liesche-Starnecker, Jens Gempt, Jürgen Schlegel

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

Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.

  1. Pooled it
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  4. Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026
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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

10 authors at 2 institutions in 1 country.

Wei WuDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Yang WuDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Karoline MayerDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Charlotte von RosenstielDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Johannes ScheckerDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Sandra BaurDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Sylvia WürstleDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Friederike Liesche-StarneckerDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Jens GemptDepartment of Neurosurgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany.
Jürgen SchlegelDepartment of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str.22, 81675 München, Germany. Electronic address: schlegel@tum.de.
Klinikum rechts der Isar · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is the most malignant primary brain tumor. Relapse occurs regularly, and the clinical behavior seems to be due to a therapy-resistant subpopulation of glioma-initiating cells that belong to the group of cancer stem cells. Aldehyde dehydrogenase (ALDH) has been identified as a marker for this cell population, and we have shown previously that ALDH1A3-positive GBM cells are more resistant against temozolomide (TMZ) treatment. However, it is still unclear how ALDH expression mediates chemoresistance. MATERIALS AND

methodsALDH1A3 expression was analyzed in 112 specimens from primary and secondary surgical resections of 56 patients with GBM (WHO grade IV). All patients received combined adjuvant radiochemotherapy. For experimental analysis, CRISPR-Cas9-induced knockout cells from three established GBM cell lines (LN229, U87MG, T98G) and two glioma stem-like cell lines were investigated after TMZ treatment.

resultsALDH1A3 knockout cells were more sensitive to TMZ, and oxidative stress seemed to be the molecular process where ALDH1A3 exerts its role in resistance against TMZ. Oxidative stress led to lipid peroxidation, yielding active aldehydes that were detoxified by ALDH enzymatic activity. During the metabolic process, autophagy was induced leading to downregulation of the enzyme, but ALDH1A3 is upregulated to even higher expression levels after finishing the TMZ therapy in vitro. Recurrent GBMs show significantly higher ALDH1A3 expression than the respective samples from the primary tumor, and patients suffering from GBM with high ALDH1A3 expression showed a shorter median survival time (12 months vs 21 months, P < .05).

conclusionOxidative stress is an important and clinically relevant component of TMZ-induced therapeutic effects. Cytotoxicity seems to be mediated by aldehydes resulting from lipid peroxidation, and ALDH1A3 is able to reduce the number of toxic aldehydes. Therefore, we present a molecular explanation of the role of ALDH1A3 in therapeutic resistance of human GBM cells.

Identifiers

PMID32087559
PMCPMC7033364
OpenAlexW3007849461

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.