Evidence map›Paper›PMID 12923567›Full record

ArticleGene therapy2003

A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication.

H Fechner, X Wang, M Srour, U Siemetzki, H Seltmann, A P Sutter, H Scherübl, C C Zouboulis, R Schwaab, W Hillen and 2 more

Abstract read
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In one paragraph

Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Gene therapy for gastric cancer: is it promising?World journal of gastroenterology · 2006
    Review
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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

12 authors at 4 institutions in 2 countries.

H FechnerDepartment of Cardiology and Pneumology, University Medical Center Benjamin Franklin, Freie Universität, Berlin, Germany.
X Wang
M Srour
U Siemetzki
H Seltmann
A P Sutter
H Scherübl
C C Zouboulis
R Schwaab
W Hillen
H-P Schultheiss
W Poller
Freie Universität Berlin · DEUniversity of Bonn · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversity Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication. We show here that a tumor-selective E1B-deleted RRCA can be tightly regulated by use of doxycycline (dox)-controlled adenoviral E1A gene expression, which in turn determines vector replication. RRCA replication is switched on by addition and switched off by withdrawal of dox. The system results in efficient tumor cell killing after induction by dox, whereas cells are unaffected by the uninduced system. It was also employed for efficient external control of transgene expression from cotransfected replication-deficient adenovectors. Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy. The concept of external control of RRCAs may help to improve the safety of cancer gene therapy.

Indexed as

AdenoviridaeAdenovirus E1A ProteinsAdenovirus E1B ProteinsAnimalsDoxycyclineGene DeletionGenetic TherapyHumansMiceMice, NudeNeoplasmsProtein Synthesis InhibitorsTumor Cells, CulturedVirus ReplicationAdenovirus E1A ProteinsAdenovirus E1B ProteinsDoxycyclineProtein Synthesis Inhibitors

Identifiers

PMID12923567
OpenAlexW2123971341

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.