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The combination of adenoviral HSV TK gene
therapy and radiation is effective in athymic mouse glioblastoma xenografts
without increasing toxic side effects
Nestler U, Wakimoto H, Siller-Lopez F, Aguilar LK, Chakravarti A, Muzikansky
A, Stemmer-Rachamimov A, Chiocca EA, Aguilar-Cordova E, Hochberg FH
Molecular Neuro-Oncology Laboratory, Department of Radiation
Oncology, Massachusetts General Hospital East, Charlestown, MA, USA.
ulf.nestler@neuro.med.uni-giessen.de
Object. In mouse models of prostate and breast cancer therapeutic effects
are enhanced when adenoviral HSV TK gene therapy is combined with ionizing
radiation.
In the present study, we adopted this approach for the treatment of human
glioblastoma xenografts in an athymic mouse model and assessed treatment results
as well as toxic side effects.
Methods. About 72 nude mice received intracerebral inoculations of 2 x
10(5) U87deltaEGFR cells.
On day 7 after tumor implantation the study population was randomized into six
treatment arms:
(1) intratumoral buffer inoculation on day 7,
(2) intratumoral adenoviral vector injection (2 x 10(9) vp) on day 7,
(3) single dose radiation (2.1 Gy) on day 9,
(4) adenoviral injection + radiation,
(5) adenoviral injection + ganciclovir (GCV) (20 microg/g twice daily from day 8
to 17),
(6) adenoviral injection + GCV + radiation.
On day 21 half of the animals were sacrificed for histological evaluation of the
brain tumors, the other half was assessed for survival.
Results. This study showed significantly prolonged median survival
time of 5 days for the GCV treated groups.
The addition of radiation decreased the frequency of neurological symptoms and
delayed the onset of deficits without altering the expression of thymidine
kinase in the tumor cells.
Conclusions. We conclude that adenoviral HSV TK gene therapy in
combination with adjuvant radiotherapy does not generate increased toxic side
effects in glioblastoma treatment.
The prolonged survival time of animals receiving gene therapy and the reduced
occurrence of neurological symptoms in irradiated mice constitute promising
features of the combined treatment.
PMID: 15072465 [PubMed]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15072465
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