Abstract
Patients with malignant gliomas continue to have very poor prognosis even after surgical resection, radiation and chemotherapy. Because these tumors often have alterations in the p53 tumor suppressor gene, which plays a key role in the cellular response to DNA damaging agents, we investigated the role of p53 gene therapy in conjunction with ionizing radiation in a rat brain tumor model. Exposure of cultured rat 9L gliosarcoma cells, which contain a mutant p53 gene, to a recombinant adenovirus-vector bearing the wild-type p53 gene (Adp53), induced apoptosis within 24 hours. Although ionizing radiation had no additional effect on apoptosis within this time frame, it caused G1 arrest in non-apoptotic cells after Adp53 therapy. In contrast, wild-type 9L cells demonstrated little G1 arrest after X-irradiation. When animals bearing brain tumors were irradiated after intratumoral Adp53 injections, more than 85% reduction in tumor size was noted. Moreover, the group of rats receiving both radiation and Adp53 therapy had a significant increase in survival as compared to animals receiving either therapy alone. These results support the use of p53 gene therapy as an adjunct to radiation in treatment of malignant brain tumors.
Citations
Mar 20, 1999·Current Opinion in Pediatrics·J B Rubin, M W Kieran
May 26, 1999·The Journal of Pathology·C A Schmitt, S W Lowe
May 18, 1999·Current Opinion in Oncology·A Weyerbrock, E H Oldfield
Feb 5, 2000·Journal of Neurosurgery·S LalF F Lang
Nov 4, 2000·Expert Opinion on Investigational Drugs·N Gupta
Feb 26, 2000·Carcinogenesis·S W Lowe, A W Lin
Jul 24, 2002·Journal of Neurosurgery·Seung-Ki KimHyun Jib Kim
Jan 9, 2007·Journal of Neuro-oncology·Aaron J ClarkWilliam C Broaddus
Dec 2, 1999·Radiation Oncology Investigations·S J ChmuraR R Weichselbaum
Mar 17, 2000·Neurosurgery·J N BruceA T Parsa
Jun 6, 2000·Journal of Neurosurgery·K AsaokaH Abe
Mar 16, 2002·Cancer Gene Therapy·Tatsuya AbeJames P Basilion
Oct 30, 2007·The Journal of Gene Medicine·Sander IdemaClemens M F Dirven
Nov 5, 1999·Neurosurgery·F F LangP J Tofilon
Dec 10, 1999·Journal of Neurosurgery·W C BroaddusH L Fillmore
Jul 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frederick F LangW K Alfred Yung
Oct 27, 2004·Expert Opinion on Biological Therapy·Svend O FreytagMyung Chung
May 28, 2014·Brain Pathology·Stacey L ThomasSandra A Rempel
Apr 2, 2021·Frontiers in Molecular Neuroscience·Kaushik BanerjeeMaria G Castro
Jul 13, 2021·JCO Precision Oncology·Omeed MoavenMitesh J Borad
Aug 28, 2021·Brain Sciences·Alice Giotta Lucifero, Sabino Luzzi