ArticleMolecular cancer2013
Evaluation of p21 promoter for interleukin 12 radiation induced transcriptional targeting in a mouse tumor model.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Radiation-Responsive Promoters: Molecular Mechanisms, Screening Strategies, and Translational Applications as Radiation Biomarkers.Current issues in molecular biology · 2026Review
- Non-clinical evaluation of pmIL12 gene therapy for approval of the phase I clinical study.Scientific reports · 2024Article
- Tumor Radiosensitization by Gene Electrotransfer-Mediated Double Targeting of Tumor Vasculature.International journal of molecular sciences · 2023Article
- Non-Clinical In Vitro Evaluation of Antibiotic Resistance Gene-Free Plasmids Encoding Human or Murine IL-12 Intended for First-in-Human Clinical Study.Pharmaceutics · 2021Article
- Bioprofiling TS/A Murine Mammary Cancer for a Functional Precision Experimental Model.Cancers · 2019Review
- Identification of potential genes and pathways for response prediction of neoadjuvant chemoradiotherapy in patients with rectal cancer by systemic biological analysis.Oncology letters · 2019Article
- Article
- Intravital Monitoring of Vasculature After Targeted Gene Therapy Alone or Combined With Tumor Irradiation.Technology in cancer research & treatment · 2018Article
- Transgenic Mouse Models in Cancer Research.Frontiers in oncology · 2018Review
- Screening candidate microRNA-mRNA regulatory pairs for predicting the response to chemoradiotherapy in rectal cancer by a bioinformatics approach.Scientific reports · 2017Article
- Tumor radiosensitization by gene therapy against endoglin.Cancer gene therapy · 2016Article
- Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer.Cancer immunology, immunotherapy : CII · 2015Review
- Improved Specificity of Gene Electrotransfer to Skin Using pDNA Under the Control of Collagen Tissue-Specific Promoter.The Journal of membrane biology · 2015Article
- Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.Gene therapy · 2015Article
- IL-12 could induce monocytic tumor cells directional differentiation.Molecular and cellular biochemistry · 2015Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadiation induced transcriptional targeting is a gene therapy approach that takes advantage of the targeting abilities of radiotherapy by using radio inducible promoters to spatially and temporally limit the transgene expression. Cyclin dependent kinase inhibitor 1 (CDKN1A), also known as p21, is a crucial regulator of the cell cycle, mediating G1 phase arrest in response to a variety of stress stimuli, including DNA damaging agents like irradiation. The aim of the study was to evaluate the suitability of the p21 promoter for radiation induced transcriptional targeting with the objective to test the therapeutic effectiveness of the combined radio-gene therapy with p21 promoter driven therapeutic gene interleukin 12.
methodsTo test the inducibility of the p21 promoter, three reporter gene experimental models with green fluorescent protein (GFP) under the control of p21 promoter were established by gene electrotransfer of plasmid DNA: stably transfected cells, stably transfected tumors, and transiently transfected muscles. Induction of reporter gene expression after irradiation was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging using fluorescence stereomicroscope in vivo. The antitumor effect of the plasmid encoding the p21 promoter driven interleukin 12 after radio-gene therapy was determined by tumor growth delay assay and by quantification of intratumoral and serum levels of interleukin 12 protein and intratumoral concentrations of interleukin 12 mRNA.
resultsUsing the reporter gene experimental models, p21 promoter was proven to be inducible with radiation, the induction was not dose dependent, and it could be re-induced. Furthermore radio-gene therapy with interleukin 12 under control of the p21 promoter had a good antitumor therapeutic effect with the statistically relevant tumor growth delay, which was comparable to that of the same therapy using a constitutive promoter.
conclusionsIn this study p21 promoter was proven to be a suitable candidate for radiation induced transcriptional targeting. As a proof of principle the therapeutic value was demonstrated with the radio-inducible interleukin 12 plasmid providing a synergistic antitumor effect to radiotherapy alone, which makes this approach feasible for the combined treatment with radiotherapy.
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