ArticleGene therapy1999
Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection.
Article in Gene therapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 73 citations in OpenAlex.
- Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial.BMC medicine · 2014Trial
- G2/M checkpoint regulation and apoptosis facilitate the nuclear egress of parvoviral capsids.Frontiers in cell and developmental biology · 2022Article
- HOPXAmerican journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage.Scientific reports · 2021Article
- Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib.Oncology reports · 2015Article
- Stochastic model-assisted development of efficient low-dose viral transduction in microfluidics.Biophysical journal · 2013Article
- Avoiding cytotoxicity of transposases by dose-controlled mRNA delivery.Nucleic acids research · 2011Article
- Air-assisted intranasal instillation enhances adenoviral delivery to the olfactory epithelium and respiratory tract.Gene therapy · 2011Article
- Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells.Cancer gene therapy · 2010Article
- Widespread phosphorylation of histone H2AX by species C adenovirus infection requires viral DNA replication.Journal of virology · 2009Article
- Oncolytic virus therapy for pancreatic cancer using the adenovirus library displaying random peptides on the fiber knob.Gene therapy · 2009Article
- Targeting inhibition of K-ras enhances Ad.mda-7-induced growth suppression and apoptosis in mutant K-ras colorectal cancer cells.Oncogene · 2007Article
- Reversible inactivation of the transcriptional function of P53 protein by farnesylation.BMC biotechnology · 2006Article
- Prevention of posterior capsule opacification by the induction of therapeutic apoptosis of residual lens cells.Gene therapy · 2006Article
- Inhibition of NF-kappaB enhances the cytotoxicity of virus-directed enzyme prodrug therapy and oncolytic adenovirus cancer gene therapy.Gene therapy · 2005Article
- Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways.Cancer gene therapy · 2005Article
- Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system.Journal of virology · 2003Article
- Adenoviral transduction of tumor cells induces apoptosis in co-cultured T lymphocytes.Gene therapy · 2002Article
- Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16.Journal of virology · 2002Article
- Role of integrin alphaVbeta3 in the production of recombinant adenoviruses in HEK-293 cells.Gene therapy · 2002Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication-deficient adenoviruses are among the most widely used vectors in gene therapy and are also becoming increasingly popular as analytical tools in basic research. However, significant toxicity of these vectors in vivo has been reported. Here, we show that in an in vitro setting, first generation adenoviruses lead to growth retardation, prolongation of the G2/M phase and induction of apoptosis if applied at a high multiplicity of infection (MOI). These findings were obtained in p53-deficient hepatocytes, derived from knock-out mice (A2 cells) and in several tumor cell lines containing wild-type (wt) or mutant p53. Apoptosis induction was correlated with increased levels of p53 and bax proteins and it was stronger in cells containing wt p53 as compared with cells lacking functional p53. Apoptosis was highly dependent on the MOI used with marked effects starting at an MOI twice as high as needed for 100% gene transfer. Expression of the adenoviral E4 ORF6 gene as well as adenoviral replication were detected in all cell lines infected with first generation adenovirus. Apoptosis could be considerably reduced but not abrogated by UV inactivation of adenovirus, which indicates proapoptotic effects caused by the infection event as well as by residual adenoviral gene expression or adenoviral replication. First generation adenoviruses apparently display proapoptotic activity if used at higher MOIs, which may be of relevance when these vectors are used as analytical or gene therapeutic tools.
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