Evidence map›Paper›PMID 23645448›Full record

ArticleInvestigational new drugs2013

Bortezomib overcomes MGMT-related resistance of glioblastoma cell lines to temozolomide in a schedule-dependent manner.

Panagiotis J Vlachostergios, Eleana Hatzidaki, Christina D Befani, Panagiotis Liakos, Christos N Papandreou

Abstract read
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

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  13. The Clinical Significance of OFrontiers in neurology · 2018
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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

5 authors at 1 institution in 1 country.

Panagiotis J VlachostergiosDepartment of Medical Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41110, Larissa, Greece, pvlacho@med.uth.gr.
Eleana Hatzidaki
Christina D Befani
Panagiotis Liakos
Christos N Papandreou
University of Thessaly · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Development of drug resistance after standard chemotherapy for glioblastoma multiforme (GBM) with temozolomide (TMZ) is associated with poor prognosis of GBM patients and is at least partially mediated by a direct DNA repair pathway involving O6-methylguanine methyltransferase (MGMT). This enzyme is under post-translational control by a multisubunit proteolytic cellular machinery, the 26S proteasome. Inhibition of the proteasome by bortezomib (BZ), a boronic acid dipeptide already in clinical use for the treatment of myeloma, has been demonstrated to induce growth arrest and apoptosis in GBM cells. In this study we investigated the effect of sequential treatment with BZ and TMZ on cell proliferation-viability and apoptosis of the human T98G and U87 GBM cell lines. We also tested for an effect of treatment on MGMT expression and important upstream regulators of the latter, including nuclear factor kappa B (NFκB), p44/42 mitogen-activated protein kinase (MAPK), p53, signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor 1α (HIF-1α). The sequence of drug administration for maximal cytotoxicity favored BZ prior to TMZ in T98G cells while the opposite was the case for U87 cells. Maximal efficacy was associated with downregulation of MGMT, reduced IκBα-mediated proteasome-dependent nuclear accumulation of NFκB, attenuation of p44/42 MAPK, AKT and STAT3 activation, and stabilization of p53 and inactive HIF-1α. Collectively, these results suggest that proteasome inhibition by BZ overcomes MGMT-mediated GBM chemoresistance, with scheduling of administration being critical for obtaining the maximal tumoricidal effect of combination with TMZ.

Indexed as

Antineoplastic AgentsBoronic AcidsBortezomibCell Line, TumorDacarbazineDrug Resistance, NeoplasmHumansHypoxia-Inducible Factor 1, alpha SubunitMitogen-Activated Protein KinasesNF-kappa BO(6)-Methylguanine-DNA MethyltransferaseProto-Oncogene Proteins c-aktPyrazinesSTAT3 Transcription FactorTemozolomideTumor Suppressor Protein p53Antineoplastic AgentsBoronic AcidsBortezomibDacarbazineHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMitogen-Activated Protein KinasesNF-kappa BO(6)-Methylguanine-DNA MethyltransferaseProto-Oncogene Proteins c-aktPyrazinesSTAT3 protein, humanSTAT3 Transcription FactorTemozolomideTumor Suppressor Protein p53

Identifiers

PMID23645448
OpenAlexW2012909561

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.