title: Tp53-gene transfer induces hypersensitivity to low doses of X-rays in glioblastoma cells: a strategy to convert a radio-resistant phenotype into a radiosensitive one.
abstract: Tp53 is frequently mutated or inactivated in glioblastomas. Due to the impairment of p53 activity, glioblastomas show a high degree of radioresistance. In an attempt to convert the radioresistant phenotype to a more radiosensitive one, we evaluated the efficacy of the combination of Adp53 gene transfer and X-ray irradiation. The combination of Adp53, at low multiplicity in order to mimic the low in vivo efficiency of virus-mediated gene delivery, with X-ray irradiation resulted in a marked decrease of glioblastoms cell survival. Interestingly, Adp53 was able to induce low dose (<2Gy) hypersensitivity. The data suggest the possibility for the development of new therapeutic strategies.
authors.affiliation: Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: D'Avenia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Porrello
authors.forename: Marco
authors.initials: M
authors.lastname: Berardo
authors.forename: Marco D'
authors.initials: MD
authors.lastname: Angelo
authors.forename: Silvia
authors.initials: S
authors.lastname: Soddu
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arcangeli
authors.forename: Ada
authors.initials: A
authors.lastname: Sacchi
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Orazi
mesh_terms: D000256:Adenoviridae; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D010641:Phenotype; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D014964:X-Ray Therapy