ArticleGene therapy2002
Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy.
Article in Gene therapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 51 citations in OpenAlex.
- Non-viral nitric oxide-based gene therapy improves perfusion and liposomal doxorubicin sonopermeation in neuroblastoma models.Theranostics · 2023Article
- NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.Redox biology · 2015Review
- Evaluation of p21 promoter for interleukin 12 radiation induced transcriptional targeting in a mouse tumor model.Molecular cancer · 2013Article
- Is Nitric Oxide (NO) the Last Word in Radiosensitization? A Review.Translational oncology · 2012Article
- Improvement and induction property of radiation-responsive promoter through DNA shuffling of 5'-flanking regions of the human p21 gene.Journal of bioscience and bioengineering · 2010Article
- Activator protein 2alpha suppresses intestinal tumorigenesis in the Apc(min) mouse.Cancer letters · 2009Article
- The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitizes hypoxic tumour cells to radiation.Gene therapy · 2008Article
- p21((WAF1))-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy.Gene therapy · 2007Article
- Cancer gene therapy: combination with radiation therapy and the role of bystander cell killing in the anti-tumor effect.Pathology oncology research : POR · 2006Article
- Evaluation of a synthetic CArG promoter for nitric oxide synthase gene therapy of cancer.Gene therapy · 2005Article
- Transcriptional Targeting in Cancer Gene Therapy.Journal of biomedicine & biotechnology · 2003Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO(*)) has many characteristics including cytotoxicity, radiosensitization and anti-angiogenesis, which make it an attractive molecule for use in cancer therapy. We have investigated the use of iNOS gene transfer, driven by both a constitutive (CMV) and X-ray inducible (WAF1) promoter, for generating high concentrations of NO(*) within tumour cells. We have combined this treatment with radiation to exploit the radiosensitizing properties of this molecule. Transfection of murine RIF-1 tumour cells in vitro with the iNOS constructs resulted in increased iNOS protein levels. Under hypoxic conditions cells were radiosensitized by delivery of both constructs so that these treatments effectively eliminated the radioresistance observed under hypoxic conditions. In vivo transfer of the CMV/iNOS construct by direct tumour injection resulted in a delay (4.2 days) in tumour growth compared with untreated controls. This was equivalent to the effect of 20 Gy X-rays alone. Combination of CMV/iNOS gene transfer with 20 Gy X-rays resulted in a dramatic 19.8 day growth delay compared with controls. Tumours treated with the CMV/iNOS showed large areas of necrosis and abundant apoptosis. We believe that iNOS gene transfer has the potential to be a highly effective treatment in combination with radiotherapy.
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