Evidence map›Paper›PMID 23658244›Full record

ArticleScience translational medicine2013

Neural stem cell-mediated enzyme/prodrug therapy for glioma: preclinical studies.

Karen S Aboody, Joseph Najbauer, Marianne Z Metz, Massimo D'Apuzzo, Margarita Gutova, Alexander J Annala, Timothy W Synold, Larry A Couture, Suzette Blanchard, Rex A Moats and 9 more

Abstract read
In one paragraph

Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 1 pooled it
12.4field-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

144 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.

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84 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

19 authors at 3 institutions in 2 countries.

Karen S AboodyDepartment of Neurosciences, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA. kaboody@coh.org
Joseph Najbauer
Marianne Z Metz
Massimo D'Apuzzo
Margarita Gutova
Alexander J Annala
Timothy W Synold
Larry A Couture
Suzette Blanchard
Rex A Moats
Elizabeth Garcia
Soraya Aramburo
Valerie V Valenzuela
Richard T Frank
Michael E Barish
Christine E Brown
Seung U Kim
Behnam Badie
Jana Portnow
City Of Hope National Medical Center · USUniversity of British Columbia Hospital · CAUniversity of Southern California · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORSR44CA086768 · NCI · LAYTON BIOSCIENCE, INC. · PI MCGROGAN, MICHAEL P · 2001 to 2002
$858k
HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORSR43CA086768 · NCI · LAYTON BIOSCIENCE, INC. · PI ABOODY, KAREN S · 2000 to 2000
$100k
NCI NIH HHS P30 CA033572NCI NIH HHS R43 CA086768NCI NIH HHS R43 CA86768NCI NIH HHS R44 CA086768NCI NIH HHS R44 CA8678
6 · The paper itself

Abstract

High-grade gliomas are extremely difficult to treat because they are invasive and therefore not curable by surgical resection; the toxicity of current chemo- and radiation therapies limits the doses that can be used. Neural stem cells (NSCs) have inherent tumor-tropic properties that enable their use as delivery vehicles to target enzyme/prodrug therapy selectively to tumors. We used a cytosine deaminase (CD)-expressing clonal human NSC line, HB1.F3.CD, to home to gliomas in mice and locally convert the prodrug 5-fluorocytosine to the active chemotherapeutic 5-fluorouracil. In vitro studies confirmed that the NSCs have normal karyotype, tumor tropism, and CD expression, and are genetically and functionally stable. In vivo biodistribution studies demonstrated NSC retention of tumor tropism, even in mice pretreated with radiation or dexamethasone to mimic clinically relevant adjuvant therapies. We evaluated safety and toxicity after intracerebral administration of the NSCs in non-tumor-bearing and orthotopic glioma-bearing immunocompetent and immunodeficient mice. We detected no difference in toxicity associated with conversion of 5-fluorocytosine to 5-fluorouracil, no NSCs outside the brain, and no histological evidence of pathology or tumorigenesis attributable to the NSCs. The average tumor volume in mice that received HB1.F3.CD NSCs and 5-fluorocytosine was about one-third that of the average volume in control mice. On the basis of these results, we conclude that combination therapy with HB1.F3.CD NSCs and 5-fluorocytosine is safe, nontoxic, and effective in mice. These data have led to approval of a first-in-human study of an allogeneic NSC-mediated enzyme/prodrug-targeted cancer therapy in patients with recurrent high-grade glioma.

Indexed as

AnimalsCell LineCytosine DeaminaseFemaleFlow CytometryFlucytosineFluorouracilGliomaHumansMaleMiceMice, NudeNeural Stem CellsProdrugsCytosine DeaminaseFlucytosineFluorouracilProdrugs

Identifiers

PMID23658244
PMCPMC3864887
OpenAlexW2096338956

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.