Evidence map›Paper›PMID 25236494›Full record

ArticleCancer gene therapy2014

Gene-directed enzyme prodrug therapy for localized chemotherapeutics in allograft and xenograft tumor models.

K H Carruthers, G Metzger, M J During, A Muravlev, C Wang, E Kocak

Abstract read
In one paragraph

Article in Cancer gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

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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

6 authors at 3 institutions in 2 countries.

K H CarruthersThe University of Toledo College of Medicine, Toledo, OH, USA.
G MetzgerThe Ohio State University Department of Plastic Surgery, Columbus, OH, USA.
M J DuringThe Ohio State University Department of Molecular Virology, Immunology and Medical Genetics, Columbus, OH, USA.
A MuravlevThe University of Auckland Department of Molecular Medicine and Pathology, Auckland, New Zealand.
C WangThe Ohio State University Department of Molecular Virology, Immunology and Medical Genetics, Columbus, OH, USA.
E Kocak1] The Ohio State University Department of Plastic Surgery, Columbus, OH, USA [2] Midwest Breast and Aesthetic Surgery, Dublin, OH, USA.
The Ohio State University · USUniversity of Auckland · NZUniversity of Toledo · US

Funding

University of Iowa Clinical and Translational Science Program (TL1)UL1RR025755 · NCRR · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2008 to 2011
$26.3M
The Ohio State University Center for clinical and Translational ScienceUL1TR001070 · NCATS · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA D · 2013 to 2017
$22.6M
CTSA: K12 COMPONENTKL2RR024130 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$19.3M
NCATS NIH HHS UL1 TR001070NCATS NIH HHS UL1TR001070NCRR NIH HHS KL2 K12 RR024130NCRR NIH HHS KL2 RR024130NCRR NIH HHS UL1 RR025755
6 · The paper itself

Abstract

Most chemotherapy regimens rely on systemic administration of drugs leading to a wide array of toxicities. Using viral-vector-mediated gene modification of muscle tissues, we have developed a method for gene-directed enzyme prodrug therapy that allows for localized drug administration. An inactive prodrug of geldanamycin was activated locally for inhibition of tumor growth without systemic toxicities. A recombinant adeno-associated virus (rAAV) was used to deliver β-galactosidase (LacZ) to the treatment group and green fluorescent protein to the control group. After 1 week, both groups received adenocarcinoma cells in the same location as the previous rAAV injection. The geldanamycin prodrug was administered 1 h later via intraperitoneal injection. Tumor growth was significantly suppressed in animals whose muscles were gene modified to express β-galactosidase compared with the control. Serum assay to access hepatotoxicity resulted in no significant differences between the animals treated with the inactive or activated form of geldanamycin, indicating minimal damage to non-target organs. Using gene-directed enzyme prodrug therapy, in combination with novel recombinant AAV vectors, we have developed a method for localized activation of chemotherapeutic agents that limits the toxicities seen with traditional systemic administration of these potent drugs.

Indexed as

Genes, Transgenic, SuicideAllograftsAnimalsAntibiotics, AntineoplasticBenzoquinonesCell ProliferationCysteine Proteinase InhibitorsDependovirusDisease Models, AnimalEnzymesGenetic TherapyGenetic VectorsHumansLactams, MacrocyclicLiver Function TestsMiceAntibiotics, AntineoplasticBenzoquinonesCysteine Proteinase InhibitorsEnzymesgeldanamycinLactams, MacrocyclicProdrugs

Identifiers

PMID25236494
PMCPMC4387004
OpenAlexW2060303774

What OpenQuestion holds

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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.