Evidence map›Paper›PMID 32101575›Full record

ArticlePloS one2020

Revealing the epigenetic effect of temozolomide on glioblastoma cell lines in therapeutic conditions.

Agnieszka Belter, Jakub Barciszewski, Anna-Maria Barciszewska

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

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  16. Drug resistance in glioblastoma: are persisters the key to therapy?Cancer drug resistance (Alhambra, Calif.) · 2020
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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

3 authors at 2 institutions in 1 country.

Agnieszka BelterInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Jakub BarciszewskiInstitute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Anna-Maria BarciszewskaIntraoperative Imaging Unit, Chair and Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.ORCID 0000-0002-7179-1474
Institute of Bioorganic Chemistry, Polish Academy of Sciences · PLHeliodor Swiecicki Clinical Hospital · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Temozolomide (TMZ) is a drug of choice in glioblastoma treatment. Its therapeutic applications expand also beyond high grade gliomas. However, a significant number of recurrences and resistance to the drug is observed. The key factor in each chemotherapy is to achieve the therapeutic doses of a drug at the pathologic site. Nonetheless, the rate of temozolomide penetration from blood to cerebrospinal fluid is only 20-30%, and even smaller into brain intestinum. That makes a challenge for the therapeutic regimens to obtain effective drug concentrations with minimal toxicity and minor side effects. The aim of our research was to explore a novel epigenetic mechanism of temozolomide action in therapeutic conditions. We analyzed the epigenetic effects of TMZ influence on different glioblastoma cell lines in therapeutically achieved TMZ concentrations through total changes of the level of 5-methylcytosine in DNA, the main epigenetic marker. That was done with classical approach of radioactive nucleotide post-labelling and separation on thin-layer chromatography. In the range of therapeutically achieved temozolomide concentrations we observed total DNA hypomethylation. The significant hypermethylating effect was visible after reaching TMZ concentrations of 10-50 μM (depending on the cell line). Longer exposure time promoted DNA hypomethylation. The demethylated state of the glioblastoma cell lines was overcome by repeated TMZ applications, where dose-dependent increase in DNA 5-methylcytosine contents was observed. Those effects were not seen in non-cancerous cell line. The increase of DNA methylation resulting in global gene silencing and consecutive down regulation of gene expression after TMZ treatment may explain better glioblastoma patients' survival.

Indexed as

5-MethylcytosineBrain NeoplasmsCell Line, TumorDNA MethylationDNA Modification MethylasesDrug Resistance, NeoplasmEpigenesis, GeneticEpigenomicsGene Expression Regulation, NeoplasticGlioblastomaGliomaHumansNeoplasm Recurrence, LocalTemozolomide5-MethylcytosineDNA Modification MethylasesTemozolomide

Identifiers

PMID32101575
PMCPMC7043761
OpenAlexW3008820509

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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.