ArticleCancer gene therapy2006
Modification of the p53 transgene of a replication-competent adenovirus prevents mdm2- and E1b-55kD-mediated degradation of p53.
Article in Cancer gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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.
Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Evaluation of a Novel Oncolytic Adenovirus SilencingInternational journal of molecular sciences · 2022Article
- Strategies for Advanced Oncolytic Virotherapy: Current Technology Innovations and Clinical Approaches.Pharmaceutics · 2022Review
- Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy.Molecular therapy oncolytics · 2017Review
- Negative regulation-resistant p53 variant enhances oncolytic adenoviral gene therapy.Human gene therapy · 2012Article
- Selectivity and efficiency of late transgene expression by transcriptionally targeted oncolytic adenoviruses are dependent on the transgene insertion strategy.Human gene therapy · 2011Article
- Armed replicating adenoviruses for cancer virotherapy.Cancer gene therapy · 2009Review
- The mitochondrial p53 pathway.Biochimica et biophysica acta · 2009Review
- Mitochondrially targeted wild-type p53 induces apoptosis in a solid human tumor xenograft model.Cell cycle (Georgetown, Tex.) · 2008Article
- Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded.Nature reviews. Microbiology · 2008Review
- Mitochondrially targeted wild-type p53 suppresses growth of mutant p53 lymphomas in vivo.Oncogene · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Clinical efficacy of adenovirus-mediated cancer gene therapy has been limited thus far. To improve its oncolytic effect, a replication-competent adenoviral vector was previously constructed to express high levels of p53 at a late time point in the viral life cycle. p53 expression from this vector improved tumor cell killing and viral spread in vitro. However, p53 function is antagonized by cellular mdm2 and adenoviral E1b-55kD, both of which are known to bind to and inactivate p53. Therefore, a new vector (Adp53W23S) that expresses a modified p53 transgene, which does not bind to E1b-55kd and mdm2, was constructed. The modified p53 protein was demonstrated to have a substantially prolonged half-life, and its localization was predominantly nuclear. Viral replication was unaffected by expression of the modified p53 and cancer cell killing was improved in vitro. However, in a xenograft model, efficacy was not significantly different from control virus. In conclusion, expression of a degradation-resistant p53 transgene late in the life cycle of a replication-competent adenovirus improves p53 stability and cancer cell killing in vitro. However, other factors, such as the adenoviral E1b-19kD and E1a proteins, which oppose p53 function, and limitations to viral spread need to be addressed to further improve in vivo efficacy.
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Registered trials
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.