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Treatment
> Gene
Therapy / Stem
Cells
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Cancer Lett. 2006 Dec 28; [Epub ahead of
print]
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Abstract |
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Genetically engineered neural stem
cells migrate and suppress glioma cell growth at distant intracranial
sites
Shaoyi Li a,b,
Yun Gaoa,c, Tsutomu Tokuyamaa,
Junkoh Yamamotoa, Naoki Yokotaa,
Seiji Yamamotod, Susumu Terakawad,
Masatoshi Kitagawac and Hiroki Nambaa,*
aDepartment of Neurosurgery, Hamamatsu University School
of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. bDepartment
of Neurosurgery, Second Affiliated Hospital of China Medical
University, Shenyang, China. cDepartment of Biochemistry,
Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu
431-3192, Japan. dPhoton Medical Research Center, Hamamatsu
University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192,
Japan. *Corresponding author. Email: hnamba@hama-med.ac.jp; Tel.: +81
53 435 2281; fax: +81 53 435 2282. Received 22 August 2006;
revised 30 October 2006; accepted 22 November 2006.
Available online 28 December 2006.
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Our previous study demonstrated successful
treatment of an established rat brain tumor through the bystander
effect by intra-tumoral injection of neural stem cells transduced with
herpes simplex virus-thymidine kinase gene (NSCtk) followed by
systemic ganciclovir (GCV) administration (NSCtk therapy).
Since glioma has a strong tendency to
infiltrate into surrounding brain tissue and that is one of the main
causes of local treatment failure, we, in the present study, injected
NSCtk cells at distant sites of rat brain tumors and evaluated
migratory potential of NSCtk toward the tumor and anti-tumor effects
of the NSCtk therapy of this experimental setting.
NSCtk cells were intracranially implanted
either at 2 mm medial in the ipsilateral hemisphere or at the
mirror point in the contralateral hemisphere to the C6 rat glioma cell
implantation.
Active migration of NSCtk cells toward C6
cells was observed even when NSCtk cells were implanted in the
contralateral hemisphere.
When GCV was systemically administered,
growth of intracranial tumor was markedly inhibited and the survival
was significantly prolonged through the bystander effect by NSCtk
cells migrated from distant injection sites of the tumor.
The results of the present study suggest
that NSCtk therapy is still effective in the area far from the NSCtk
injection site and, therefore, suitable for treatment of malignant
gliomas that deeply infiltrate and widely disseminate in the brain.
Keywords: Herpes simplex virus
thymidine kinase; Ganciclovir; Bystander effect; Glioma; Neural stem
cell; Migration
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Copyright © 2006 Elsevier Ireland Ltd
All rights reserved
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.JPG)
Abstract
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