Adenoviral vector-mediated gene transfer:: timing of wild-type p53 gene expression in vivo and effect of tumor transduction on survival in a rat glioma brachytherapy model

被引:10
作者
Bampoe, J
Glen, J
Hubbard, SL
Salhia, B
Shannon, P
Rutka, J
Bernstein, M
机构
[1] Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada
[2] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada
[3] Univ Toronto, Div Neuropathol, Toronto, ON, Canada
关键词
rat brain tumor model; p53 gene therapy; radiation enhancement; survival times;
D O I
10.1023/A:1006476608036
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. This study sought to investigate modification of the radiation response in a rat 9L brain tumor model in vivo by the wild-type p53 gene (wtp53). Determination of the timing and dose of radiation therapy required the assessment of the duration of the effect of wtp53 expression on 9L tumors after in vivo transfection. Methods. Anesthetized male F-344 rats each were stereotactically inoculated with 4 x 10(4) 9L gliosarcoma cells through a skull screw into the cerebrum in the right frontal region. Twelve-day-old tumors were inoculated through the screw with recombinant adenoviral vectors under isoflurane anaesthesia: control rats with Ad5/RSV/GL2 (carrying the luciferase gene), and study rats with Ad5CMV-p53 (carrying the wtp53 gene). Brain tumors removed at specific times after transfection were measured, homogenized, and lysed and wtp53 expression determined by Western blot analysis. Four groups of nine rats were, subsequently, implanted with iodine-125 seeds 15 days post-tumor inoculation to give a minimum tumor dose of 40 or 60 Gy. Results. We demonstrated transfer of wtp53 into rat 9L tumors in vivo using the Ad5CMV-p53 vector. The expression of wtp53 was demonstrated to be maximum between days 1 and 3 post-vector inoculation. Tumors expressing wtp53 were smaller than controls transfected with Ad5/RSV/GL2 but this difference was not statistically significant. Radiation made a significant difference to the survival of tumor-bearing rats. Moreover, wtp53 expression conferred a significant additional survival advantage. Conclusion. The expression of wtp53 significantly improves the survival of irradiated tumor-bearing rats in our model.
引用
收藏
页码:27 / 39
页数:13
相关论文
共 60 条
[1]   PATTERNS OF RECURRENCE OF MALIGNANT ASTROCYTOMA FOLLOWING STEREOTAXIC INTERSTITIAL BRACHYTHERAPY WITH I-125 IMPLANTS [J].
AGBI, CB ;
BERNSTEIN, M ;
LAPERRIERE, N ;
LEUNG, P ;
LUMLEY, M .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1992, 23 (02) :321-326
[2]   NEGATIVE EFFECTS OF WILD-TYPE P53 AND S-MYC ON CELLULAR GROWTH AND TUMORIGENICITY OF GLIOMA-CELLS - IMPLICATION OF THE TUMOR-SUPPRESSOR GENES FOR GENE-THERAPY [J].
ASAI, A ;
MIYAGI, Y ;
SUGIYAMA, A ;
GAMANUMA, M ;
ILHONG, S ;
TAKAMOTO, S ;
NOMURA, K ;
MATSUTANI, M ;
TAKAKURA, K ;
KUCHINO, Y .
JOURNAL OF NEURO-ONCOLOGY, 1994, 19 (03) :259-268
[3]   ADENOVIRUS-MEDIATED P53 GENE DELIVERY INHIBITS 9L GLIOMA GROWTH IN RATS [J].
BADIE, B ;
DRAZAN, KE ;
KRAMAR, MH ;
SHAKED, A ;
BLACK, KL .
NEUROLOGICAL RESEARCH, 1995, 17 (03) :209-216
[4]   Adenovirus-mediated p53 gene delivery potentiates the radiation-induced growth inhibition of experimental brain tumors [J].
Badie, B ;
Kramar, MH ;
Lau, R ;
Boothman, DA ;
Economou, JS ;
Black, KL .
JOURNAL OF NEURO-ONCOLOGY, 1998, 37 (03) :217-222
[5]   Effect of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model: Implications for brain tumor therapy [J].
Bampoe, J ;
Glen, J ;
Mackenzie, I ;
Porter, P ;
Bernstein, M .
NEUROSURGERY, 1997, 41 (06) :1374-1383
[6]   Advances in radiotherapy of brain tumors: radiobiology versus reality [J].
Bampoe, J ;
Bernstein, M .
JOURNAL OF CLINICAL NEUROSCIENCE, 1998, 5 (01) :5-14
[7]  
BARKER M, 1975, J NATL CANCER I, V54, P851
[8]  
BARKER M, 1973, CANCER RES, V33, P976
[9]   REGROWTH PATTERNS OF GLIOBLASTOMA-MULTIFORME RELATED TO PLANNING OF INTERSTITIAL BRACHYTHERAPY RADIATION-FIELDS [J].
BASHIR, R ;
HOCHBERG, F ;
OOT, R .
NEUROSURGERY, 1988, 23 (01) :27-30
[10]   A MEDICAL-RESEARCH-COUNCIL TRIAL OF 2 RADIOTHERAPY DOSES IN THE TREATMENT OF GRADE-3 AND GRADE-4 ASTROCYTOMA [J].
BLEEHEN, NM ;
STENNING, SP .
BRITISH JOURNAL OF CANCER, 1991, 64 (04) :769-774