Evidence map›Paper›PMID 28874135›Full record

ArticleBMC cancer2017

Cytotoxicity of replication-competent adenoviruses powered by an exogenous regulatory region is not linearly correlated with the viral infectivity/gene expression or with the E1A-activating ability but is associated with the p53 genotypes.

Suguru Yamauchi, Boya Zhong, Kiyoko Kawamura, Shan Yang, Shuji Kubo, Masato Shingyoji, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Hideaki Shimada and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2017. 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
0.2field-weighted citation impact, top 33% 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, 3 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

12 authors at 6 institutions in 1 country.

Suguru YamauchiDivision of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
Boya ZhongDivision of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
Kiyoko KawamuraDivision of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
Shan YangDivision of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
Shuji KuboDepartment of Genetics, Hyogo College of Medicine, Nishinomiya, Japan.
Masato ShingyojiDivision of Respirology, Chiba Cancer Center, Chiba, Japan.
Ikuo SekineDepartment of Medical Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Yuji TadaDepartment of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Koichiro TatsumiDepartment of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hideaki ShimadaDepartment of Surgery, School of Medicine, Toho University, Tokyo, Japan.
Kenzo HiroshimaDepartment of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
Masatoshi TagawaDivision of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan. mtagawa@chiba-cc.jp.
Chiba Cancer Center · JPChiba University · JPHyogo Medical University · JPToho University · JPTokyo Women's Medical University · JPUniversity of Tsukuba · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundReplication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting.

methodsWe constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5' regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35). The cytotoxicity was examined by a colorimetric assay with human tumor cell lines, 4 kinds of pancreatic, 9 esophageal carcinoma and 5 mesothelioma. Ad infectivity and Ad-mediated gene expression were examined with replication-incompetent Ad5 and AdF35 which expressed the green fluorescence protein gene. Expression of cellular receptors for Ad5 and AdF35 was also examined with flow cytometry. A transcriptional activity of the regulatory sequences was investigated with a luciferase assay in the tumor cells. We then investigated a possible correlation between Ad-mediated cytotoxicity and the infectivity/gene expression, the transcriptional activity or the p53 genotype.

resultsWe found that the cytotoxicity was greater with AdF35 than with Ad5 vectors, but was not correlated with the Ad infectivity/gene expression irrespective of the fiber-knob region or the E1A-activating transcriptional activity. In contrast, replication-competent Ad produced greater cytotoxicity in p53 mutated than in wild-type esophageal carcinoma cells, suggesting a possible association between the cytotoxicity and the p53 genotype.

conclusionsSensitivity to Ad-mediated cytotoxic activity was linked with the p53 genotype but was not lineally correlated with the infectivity/gene expression or the E1A expression.

Indexed as

Gene ExpressionRegulatory Sequences, Nucleic AcidVirus ReplicationAdenoviridaeAdenovirus E1A ProteinsCell Line, TumorCytopathogenic Effect, ViralGenes, ReporterGenetic VectorsGenotypeHumansProtein BindingReceptors, VirusTranscriptional ActivationTransduction, GeneticTransgenesAdenovirus E1A Proteinsadenovirus receptorReceptors, VirusTumor Suppressor Protein p53BiomarkerInfectivityp53 genotypeReplication-competent adenovirusTranscriptional activity

Identifiers

PMID28874135
PMCPMC5584036
OpenAlexW2750670814

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Registered trials

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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.