Evidence map›Paper›PMID 24526307›Full record

ArticleNeuro-oncology2014

Ependymoma stem cells are highly sensitive to temozolomide in vitro and in orthotopic models.

Daniela Meco, Tiziana Servidei, Giuseppe Lamorte, Elena Binda, Vincenzo Arena, Riccardo Riccardi

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2014. 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
1.2field-weighted citation impact, top 21% 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, 26 citations in OpenAlex.

  1. Modeling pediatric brain tumors with human stem cells.Frontiers in cellular neuroscience · 2026
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  13. Remarkable efficacy of temozolomide for relapsed spinal myxopapillary ependymoma with multiple recurrence and cerebrospinal dissemination: a case report and literature review.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2018
    Review
  14. Article
  15. Glioma: experimental models and reality.Acta neuropathologica · 2017
    Review
  16. Article
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

6 authors at 2 institutions in 2 countries.

Daniela MecoDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Tiziana ServideiDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Giuseppe LamorteDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Elena BindaDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Vincenzo ArenaDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Riccardo RiccardiDepartment of Pediatric Oncology, Catholic University, Rome, Italy (D.M., T.S., R.R.); Istituto CSS - Mendel Laboratory, Rome, Italy (G.L.); Department of Biotechnology and Biosciences, Building U3, University of Milan Bicocca, Milan, Italy (E.B.); Institute of Pathology, Catholic University, Rome, Italy (V.A.).
Catholic University of America · USUniversity of Milano-Bicocca · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpendymoma management remains challenging because of the inherent chemoresistance of this tumor. To determine whether ependymoma stem cells (SCs) might contribute to therapy resistance, we investigated the sensitivity of ependymoma SCs to temozolomide and etoposide.

methodsThe efficacies of the two DNA damaging agents were explored in two ependymoma SC lines in vitro and in vivo models.

resultsEpendymoma SC lines were highly sensitive to temozolomide and etoposide in vitro, but only temozolomide impaired tumor-initiation properties. Consistently, temozolomide but not etoposide showed significant antitumoral activity on ependymoma SC-driven subcutaneous and orthotopic xenografts by reducing the mitotic fraction. In vitro temozolomide at the EC50 (10 µM) induced accumulation of cells in the G2/M phase that was unexpectedly accompanied by downregulation of p27 and p21 without modulation of full-length p53 (FLp53). Differentiation-committed ependymoma SCs acquired resistance to temozolomide. Inhibition of proliferation was partly due to apoptosis, that occurred earlier in differentiated cells as compared to neurospheres. The activation of apoptosis correlated with an increase in p53β/γ isoforms without modulation of FLp53 under both serum-free and differentiation-promoting media. Incubation of cells in both conditions with temozolomide resulted in increased glioneuronal differentiation exhibiting elevated glial fibrillary acidic protein, galactosylceramidase, and βIII-tubulin expression compared to untreated controls. O(6)-methylguanine DNA methyltransferase (MGMT) transcript levels were very low in SCs, and were increased by treatment and, epigenetically, by differentiation through MGMT promoter unmethylation.

conclusionEpendymoma growth might be impaired by temozolomide through preferential depletion of a less differentiated, more tumorigenic, MGMT-negative cell population with stem-like properties.

Indexed as

AnimalsAntineoplastic Agents, AlkylatingDacarbazineDisease Models, AnimalDNA Modification MethylasesDrug Resistance, NeoplasmEpendymomaGlioblastomaMice, NudeO(6)-Methylguanine-DNA MethyltransferaseStem CellsTemozolomideTumor Cells, CulturedTumor Suppressor Protein p53Xenograft Model Antitumor AssaysAntineoplastic Agents, AlkylatingDacarbazineDNA Modification MethylasesO(6)-Methylguanine-DNA MethyltransferaseTemozolomideTumor Suppressor Protein p53differentiationependymoma stem cellsMGMTorthotopic modelstemozolomide

Identifiers

PMID24526307
PMCPMC4096174
OpenAlexW2164289577

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.