Evidence map›Paper›PMID 18952979›Full record

ArticleNeuro-oncology2009

Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts.

Gaspar J Kitange, Brett L Carlson, Mark A Schroeder, Patrick T Grogan, Jeff D Lamont, Paul A Decker, Wenting Wu, C David James, Jann N Sarkaria

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

228 citing papers in PubMed, 385 citations in OpenAlex.

  1. Magnetic Resonance Imaging of Iron Metabolism with T2* Mapping Predicts an Enhanced Clinical Response to Pharmacologic Ascorbate in Patients with GBM.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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  20. Biodegradable nanofibrous scaffolds enhance standard of care for glioblastoma via localized targeted therapy.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article

168 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

9 authors at 2 institutions in 1 country.

Gaspar J KitangeDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Brett L Carlson
Mark A Schroeder
Patrick T Grogan
Jeff D Lamont
Paul A Decker
Wenting Wu
C David James
Jann N Sarkaria
University of California, San Francisco · USMayo Clinic · US

Funding

Targeted MV-CEA as a Potent Antitumor Agent against GBMP50CA108961 · NCI · MAYO CLINIC ROCHESTER · PI O'NEILL, BRIAN PATRICK · 2004 to 2015
$22.5M
Epigenetic regulation of temozolomide responsiveness in glioblastomaR01CA127716 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2008 to 2012
$1.9M
NCI NIH HHS CA108961NCI NIH HHS CA127716NCI NIH HHS P50 CA108961NCI NIH HHS R01 CA127716
6 · The paper itself

Abstract

Temozolomide (TMZ)-based therapy is the standard of care for patients with glioblastoma multiforme (GBM), and resistance to this drug in GBM is modulated by the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Expression of MGMT is silenced by promoter methylation in approximately half of GBM tumors, and clinical studies have shown that elevated MGMT protein levels or lack of MGMT promoter methylation is associated with TMZ resistance in some, but not all, GBM tumors. In this study, the relationship between MGMT protein expression and tumor response to TMZ was evaluated in four GBM xenograft lines that had been established from patient specimens and maintained by serial subcutaneous passaging in nude mice. Three MGMT unmethylated tumors displayed elevated basal MGMT protein expression, but only two of these were resistant to TMZ therapy (tumors GBM43 and GBM44), while the other (GBM14) displayed a level of TMZ sensitivity that was similar in extent to that seen in a single MGMT hypermethylated line (GBM12). In tissue culture and animal studies, TMZ treatment resulted in robust and prolonged induction of MGMT expression in the resistant GBM43 and GBM44 xenograft lines, while MGMT induction was blunted and abbreviated in GBM14. Consistent with a functional significance of MGMT induction, treatment of GBM43 with a protracted low-dose TMZ regimen was significantly less effective than a shorter high-dose regimen, while survival for GBM14 was improved with the protracted dosing regimen. In conclusion, MGMT expression is dynamically regulated in some MGMT nonmethylated tumors, and in these tumors, protracted dosing regimens may not be effective.

Indexed as

AnimalsAntineoplastic Agents, AlkylatingBlotting, WesternCell Line, TumorDacarbazineDNA MethylationDNA Modification MethylasesDNA Repair EnzymesDrug Resistance, NeoplasmGene ExpressionGlioblastomaHumansMiceMice, NudePromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionAntineoplastic Agents, AlkylatingDacarbazineDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanTemozolomideTumor Suppressor Proteins

Identifiers

PMID18952979
PMCPMC2718972
OpenAlexW2158751879

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.