TY - JOUR
T1 - Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma
AU - Cirielli, Corrado
AU - Inyaku, Kyosuke
AU - Capogrossi, Maurizio C.
AU - Yuan, Xuan
AU - Williams, Jeffery A.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV:p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.
AB - Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV:p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.
KW - Adenoviral gene transfer
KW - Apoptosis
KW - Experimental malignant gliomas
KW - p53
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U2 - 10.1023/A:1006289505801
DO - 10.1023/A:1006289505801
M3 - Article
C2 - 10533721
AN - SCOPUS:0032855038
SN - 0167-594X
VL - 43
SP - 99
EP - 108
JO - Journal of neuro-oncology
JF - Journal of neuro-oncology
IS - 2
ER -