Evidence map›Paper›PMID 22086234›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012

Modification of the early gene enhancer-promoter improves the oncolytic potency of adenovirus 11.

Han Hsi Wong, Guozhong Jiang, Rathi Gangeswaran, Pengju Wang, Jiwei Wang, Ming Yuan, Hexiao Wang, Vipul Bhakta, Heike Müller, Nicholas R Lemoine and 1 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Han Hsi WongCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Guozhong Jiang
Rathi Gangeswaran
Pengju Wang
Jiwei Wang
Ming Yuan
Hexiao Wang
Vipul Bhakta
Heike Müller
Nicholas R Lemoine
Yaohe Wang
Queen Mary University of London · GBZhengzhou University · CN

Funding

Cancer Research UK 12008Cancer Research UK A6251Cancer Research UK A6253Cancer Research UK C633-A6253/A6251Medical Research Council G0701383Medical Research Council G0701383(85070)
6 · The paper itself

Abstract

Oncolytic adenoviruses based on serotype 5 (Ad5) have several shortcomings, including the downregulation of its receptor in cancer cells, high prevalence of neutralizing antibodies and hepatotoxicity. Another adenoviral serotype, Ad11, could overcome these obstacles. Here, we show that human cancer cell lines express higher levels of the Ad11 receptor CD46, resulting in much better infectivity than Ad5. Surprisingly, only 36% (9/25) of the cell lines were more sensitive to Ad11- than to Ad5-mediated cytotoxicity. Investigations revealed that it was the transcription of Ad11 E1A, not CD46 expression or virus infectivity, which determined the cell's sensitivity to Ad11 killing. Ad11 E1A mRNA levels have an effect on viral DNA replication, structural protein synthesis and infectious particle production. To test the hypothesis that increased E1A transcription would lead to improved Ad11 replication in Ad5-sensitive (but Ad11-less sensitive) cells, two Ad11 mutants (Ad11-Ad5-P and Ad11-Ad5-EP) were constructed where either the E1A promoter or enhancer-promoter, respectively, was replaced by that of Ad5. Ad11-Ad5-EP demonstrated increased E1A mRNA levels and replication, together with enhanced oncolytic potency in vitro and in vivo. This effect was found in both the Ad5-sensitive and Ad11-sensitive cancer cells, broadening the range of tumors that could be effectively killed by Ad11-Ad5-EP.

Indexed as

Enhancer Elements, GeneticPromoter Regions, GeneticAdenoviridaeAdenovirus E1A ProteinsAnimalsCapsid ProteinsCell Line, TumorCytopathogenic Effect, ViralDesmoglein 2Genetic VectorsHumansMembrane Cofactor ProteinMiceMice, Inbred BALB CMice, NudeNeoplasmsAdenovirus E1A ProteinsCapsid ProteinsDesmoglein 2hexon capsid protein, AdenovirusMembrane Cofactor Protein

Identifiers

PMID22086234
PMCPMC3272483
OpenAlexW1966367001

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.