Evidence map›Paper›PMID 19351838›Full record

ArticleCancer research2009

Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors.

Hiroaki Wakimoto, Santosh Kesari, Christopher J Farrell, William T Curry, Cecile Zaupa, Manish Aghi, Toshihiko Kuroda, Anat Stemmer-Rachamimov, Khalid Shah, Ta-Chiang Liu and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers.

0numbers the graph read from it
0cells of the map it votes in
259citing papers in PubMed
13.8field-weighted citation impact, top 1% 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

259 citing papers in PubMed, 358 citations in OpenAlex.

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  6. Combinatorial treatment of glioblastoma with temozolomide (TMZ) plus 5-ethynyl-2'-deoxyuridine (EdU).Proceedings of the National Academy of Sciences of the United States of America · 2026
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199 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

15 authors at 3 institutions in 1 country.

Hiroaki WakimotoMolecular Neurosurgery Laboratory, Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA. hwakimoto@partners.org
Santosh Kesari
Christopher J Farrell
William T Curry
Cecile Zaupa
Manish Aghi
Toshihiko Kuroda
Anat Stemmer-Rachamimov
Khalid Shah
Ta-Chiang Liu
Deva S Jeyaretna
Jason Debasitis
Jan Pruszak
Robert L Martuza
Samuel D Rabkin
Harvard University Press · USDana-Farber Cancer Institute · USHarvard University · US

Funding

Vector Query and Therapy For TSC and NF2 LesionsP01NS024279 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI KWIATKOWSKI, DAVID J. · 1987 to 2012
$14.7M
GENETICALLY ENGINEERED VIRUSES FOR BRAIN TUMOR THERAPYR01NS032677 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MARTUZA, ROBERT L · 1994 to 2022
$9.0M
Role of Olig Genes in Human GliomagenesisK08CA124804 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KESARI, SANTOSH · 2007 to 2011
$704k
NCI NIH HHS K08 CA124804NINDS NIH HHS NS-032677NINDS NIH HHS P01 NS024279NINDS NIH HHS R01 NS032677
6 · The paper itself

Abstract

Glioblastoma, the most malignant type of primary brain tumor, is one of the solid cancers where cancer stem cells have been isolated, and studies have suggested resistance of those cells to chemotherapy and radiotherapy. Here, we report the establishment of CSC-enriched cultures derived from human glioblastoma specimens. They grew as neurospheres in serum-free medium with epidermal growth factor and fibroblast growth factor 2, varied in the level of CD133 expression and very efficiently formed highly invasive and/or vascular tumors upon intracerebral implantation into immunodeficient mice. As a novel therapeutic strategy for glioblastoma-derived cancer stem-like cells (GBM-SC), we have tested oncolytic herpes simplex virus (oHSV) vectors. We show that although ICP6 (UL39)-deleted mutants kill GBM-SCs as efficiently as wild-type HSV, the deletion of gamma34.5 significantly attenuated the vectors due to poor replication. However, this was significantly reversed by the additional deletion of alpha47. Infection with oHSV G47Delta (ICP6(-), gamma34.5(-), alpha47(-)) not only killed GBM-SCs but also inhibited their self-renewal as evidenced by the inability of viable cells to form secondary tumor spheres. Importantly, despite the highly invasive nature of the intracerebral tumors generated by GBM-SCs, intratumoral injection of G47Delta significantly prolonged survival. These results for the first time show the efficacy of oHSV against human GBM-SCs, and correlate this cytotoxic property with specific oHSV mutations. This is important for designing new oHSV vectors and clinical trials. Moreover, the new glioma models described in this study provide powerful tools for testing experimental therapeutics and studying invasion and angiogenesis.

Indexed as

AnimalsBrain NeoplasmsEmbryonic Stem CellsGlioblastomaHumansMiceMutationNeoplastic Stem CellsOncolytic VirotherapySimplexvirusTumor Cells, CulturedVirus ReplicationXenograft Model Antitumor Assays

Identifiers

PMID19351838
PMCPMC2785462
OpenAlexW2143308874

What OpenQuestion holds

Textmetadata
LicenceTDM
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.