Evidence map›Paper›PMID 26136652›Full record

ArticleFrontiers in neuroscience2015

Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme.

Amanda Tivnan, Zaitun Zakaria, Caitrín O'Leary, Donat Kögel, Jenny L Pokorny, Jann N Sarkaria, Jochen H M Prehn

Open access · goldAbstract read
In one paragraph

Article in Frontiers in neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 2 pooled it
5.5field-weighted citation impact, top 3% 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

67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.

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  8. Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025
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7 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

7 authors at 2 institutions in 2 countries.

Amanda TivnanDepartment of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland Dublin, Ireland.
Zaitun ZakariaDepartment of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland Dublin, Ireland.
Caitrín O'LearyDepartment of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland Dublin, Ireland.
Donat KögelExperimental Neurosurgery, Neuroscience Center, Frankfurt University Hospital Frankfurt am Main, Germany.
Jenny L PokornyDepartment of Radiation Oncology, Mayo Clinic Rochester, MN, USA.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic Rochester, MN, USA.
Jochen H M PrehnDepartment of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland Dublin, Ireland.
Mayo Clinic in Arizona · USUniversity Hospital Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30-40% response rate, many fall into the range of 10-20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it's role in BBB active transport, highlights this member of the ABC transporter family as a target for improving drug responses in GBM. In this study we show that small molecule inhibitors and gene silencing of MRP1 had a significant effect on GBM cell response to temozolomide (150 μM), vincristine (100 nM), and etoposide (2 μM). Pre-treatment with Reversan (inhibitor of MRP1 and P-glycoprotein) led to a significantly improved response to cell death in the presence of all three chemotherapeutics, in both primary and recurrent GBM cells. The presence of MK571 (inhibitor of MRP1 and multidrug resistance protein 4 (MRP4) led to an enhanced effect of vincristine and etoposide in reducing cell viability over a 72 h period. Specific MRP1 inhibition led to a significant increase in vincristine and etoposide-induced cell death in all three cell lines assessed. Treatment with MK571, or specific MRP1 knockdown, did not have any effect on temozolomide drug response in these cells. These findings have significant implications in providing researchers an opportunity to improve currently used chemotherapeutics for the initial treatment of primary GBM, and improved treatment for recurrent GBM patients.

Indexed as

chemoresistanceglioblastomamultidrug resistance protein 1siRNA

Identifiers

PMID26136652
PMCPMC4468867
OpenAlexW1521631645

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.