Evidence map›Paper›PMID 26447477›Full record

ArticlePloS one2015

Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression.

Gloria Perazzoli, Jose Prados, Raul Ortiz, Octavio Caba, Laura Cabeza, Maria Berdasco, Beatriz Gónzalez, Consolación Melguizo

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 3 pooled it
7.4field-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

106 citing papers in PubMed, 3 syntheses or guidelines pooled it, 188 citations in OpenAlex.

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  20. Functional 3D Human Neuron-Glioblastoma Model Reveals Cellular Interactions Enabling Drug Safety Assessments.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article

46 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

8 authors at 4 institutions in 1 country.

Gloria PerazzoliInstitute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain.
Jose PradosInstitute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain.
Raul OrtizDepartment of Health Science, University of Jaén, Jaén, Spain.
Octavio CabaDepartment of Health Science, University of Jaén, Jaén, Spain.
Laura CabezaInstitute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain.
Maria BerdascoCancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain.
Beatriz GónzalezService of Medical Oncology, San Cecilio Hospital, Granada, Spain.
Consolación MelguizoInstitute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), SAS-Universidad de Granada, Granada, Spain.
Instituto de Investigación Biosanitaria de Granada · ESUniversidad de Jaén · ESInstitut d'Investigació Biomédica de Bellvitge · ESUniversidad de Granada · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe use of temozolomide (TMZ) has improved the prognosis for glioblastoma multiforme patients. However, TMZ resistance may be one of the main reasons why treatment fails. Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT) it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR) complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated.

methodsFour nervous system tumor cell lines were used to analyze the modulation of MGMT expression and MGMT promoter methylation by TMZ treatment. Furthermore, 5-aza-2'-deoxycytidine was used to demethylate the MGMT promoter and O(6)-benzylguanine to block GMT activity. In addition, MMR complex and P-glycoprotein expression were studied before and after TMZ exposure and correlated with MGMT expression. Finally, the effect of TMZ exposure on CD133 expression was analyzed.

resultsOur results showed two clearly differentiated groups of tumor cells characterized by low (A172 and LN229) and high (SF268 and SK-N-SH) basal MGMT expression. Interestingly, cell lines with no MGMT expression and low TMZ IC50 showed a high MMR complex expression, whereas cell lines with high MGMT expression and high TMZ IC50 did not express the MMR complex. In addition, modulation of MGMT expression in A172 and LN229 cell lines was accompanied by a significant increase in the TMZ IC50, whereas no differences were observed in SF268 and SK-N-SH cell lines. In contrast, P-glycoprotein and CD133 was found to be unrelated to TMZ resistance in these cell lines.

conclusionsThese results may be relevant in understanding the phenomenon of TMZ resistance, especially in glioblastoma multiforme patients laking MGMT expression, and may also aid in the design of new therapeutic strategies to improve the efficacy of TMZ in glioblastoma multiforme patients.

Indexed as

AC133 AntigenAntigens, CDAntineoplastic Agents, AlkylatingATP Binding Cassette Transporter, Subfamily B, Member 1AzacitidineCell Line, TumorDacarbazineDecitabineDNA MethylationDNA Modification MethylasesDNA Repair EnzymesDrug Resistance, NeoplasmEpigenesis, GeneticGene ExpressionGene Expression Regulation, NeoplasticGlioblastomaAC133 AntigenAntigens, CDAntineoplastic Agents, AlkylatingATP Binding Cassette Transporter, Subfamily B, Member 1AzacitidineDacarbazineDecitabineDNA Modification MethylasesDNA Repair EnzymesGlycoproteinsGuanineMGMT protein, humanO(6)-benzyl-8-oxoguaninePeptidesPROM1 protein, humanTemozolomideTumor Suppressor Proteins

Identifiers

PMID26447477
PMCPMC4598115
OpenAlexW2202848214

What OpenQuestion holds

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LicenceCC BY
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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.