Evidence map›Paper›PMID 26138445›Full record

ArticleCell death and differentiation2016

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact.

O Fornara, J Bartek, A Rahbar, J Odeberg, Z Khan, I Peredo, P Hamerlik, J Bartek, G Stragliotto, N Landázuri and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
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  4. Does human cytomegalovirus provide a novel therapeutic target for patients with glioblastoma?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
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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

11 authors at 3 institutions in 3 countries.

O FornaraKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
J BartekKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
A RahbarKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
J OdebergKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
Z KhanKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
I PeredoKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
P HamerlikDanish Cancer Society Research Center, Copenhagen, Denmark.
J BartekDanish Cancer Society Research Center, Copenhagen, Denmark.
G StragliottoDepartment of Neurology and Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
N LandázuriKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
C Söderberg-NauclérKarolinska Institute, Department of Medicine, Center for Molecular Medicine, Cell and Molecular Immunology, Microbial Pathogenesis Unit, Stockholm, Sweden.
Karolinska University Hospital · SEDanish Cancer Society · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor.

Indexed as

AdultAgedBrain NeoplasmsCell Transformation, NeoplasticCytomegalovirusDisease-Free SurvivalFemaleGlioblastomaHumansKaplan-Meier EstimateMaleMiddle AgedNeoplastic Stem CellsPhenotypePrimary Cell CulturePrognosis

Identifiers

PMID26138445
PMCPMC4716305
OpenAlexW1545617022

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.