Abstract
We evaluated the therapeutic efficacy and neurotoxicity of adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for experimental malignant brain tumors. The 5-FC sensitivity in 9 L cells infected by an adenovirus vector expressing CD (AdexCACD) was increased 1700-fold compared with control cells. Rats bearing 9 L brain tumors were treated with an intratumoral injection of AdexCACD followed by intraperitoneal administration of 5-FC. The rats demonstrated remarkable inhibition of tumor growth by magnetic resonance imaging, and 7 of 10 rats survived for >90 days. To evaluate the potential side-effects of the 5-FC/CD gene therapy, rats were treated with an intracerebral injection of AdexCACD into the right basal ganglia and with 5-FC. The magnetic resonance imaging showed a highly enhanced area on the gadollinium-enhanced T1-weighted image at 18 days postinjection. Pathologically, this corresponded to an area of necrosis with surrounding apoptotic cells. In addition, there was demyelination and gliosis with enlargement of the lateral ventricles. These results suggest that the 5-FC/CD gene therapy may provide an anticancer effect for malignant brain tumors in humans, but also show that there are neurotoxic effects on normal brain tissue.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ichikawa, T., Tamiya, T., Adachi, Y. et al. In vivo efficacy and toxicity of 5-fluorocytosine/cytosine deaminase gene therapy for malignant gliomas mediated by adenovirus. Cancer Gene Ther 7, 74–82 (2000). https://doi.org/10.1038/sj.cgt.7700086
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cgt.7700086
Keywords
This article is cited by
-
A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth
Stem Cell Research & Therapy (2020)
-
Dual-vector prodrug activator gene therapy using retroviral replicating vectors
Cancer Gene Therapy (2019)
-
Retargeted adenoviruses for radiation-guided gene delivery
Cancer Gene Therapy (2016)
-
Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma
Brain Tumor Pathology (2015)
-
Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma
Cancer Gene Therapy (2012)