TY - JOUR
T1 - Human glioblastoma biopsy spheroids xenografted into the nude rat brain show growth inhibition after stereotactic radiosurgery
AU - Thorsen, Frits
AU - Enger, Per Øyvind
AU - Wang, Jian
AU - Bjerkvig, Rolf
AU - Pedersen, Paal Henning
N1 - Funding Information:
Acknowledgements This work was supported by grants from The Norwegian Cancer Society, The Norwegian Research Council and fundings from Elekta Instrument AB (Stockholm, Sweden). The study has also been financially supported by the sixth EU Framework Programme (Integrated Project ‘Angio-targeting’; contract no 504743) in the area of ‘Life sciences, genomics and biotechnology for health.’
PY - 2007/3
Y1 - 2007/3
N2 - Background: The Gamma Knife is currently used to boost treatment of malignant gliomas. However, few experimental studies have focused on its radiobiological effects. In this work, the growth and invasiveness of human glioblastoma spheroids xenografted into nude rat brains were assessed after radiosurgery. Temporary in vitro as well as long-term in vivo radiation effects were studied. Methods: Glioblastoma biopsy spheroids were irradiated with 12 or 24 Gy. Short-term in vitro spheroid viability and tumour cell migration was determined by microscopic techniques. Pre-irradiated glioblastoma spheroids were implanted into brains of immunosuppressed rats. Long-term tumour development was assessed by magnetic resonance (MR) imaging, and animal survival was recorded. An immunohistochemical analysis was performed on the sectioned rat brains. Results: Both un-irradiated and irradiated spheroids remained viable during 2 months in culture, but a dose-dependent inhibition of tumour growth and migration was seen. MR imaging 4 weeks after implantation also showed a dose-dependent inhibition in tumour development. Median animal survival times were 25.5 days (control group), 43 days (12 Gy group) and 96 days (24 Gy group). The study of in vivo long-term radiation effects on the remaining viable tumour population showed no difference in Ki-67 labelling index and microvascular density before and after radiosurgery. Conclusions: A dose-dependent inhibition of tumour growth and invasion, as well as a dose-dependent increase in animal survival was observed. The model system described is well suited for assessing the radiobiological effects of Gamma Knife radiosurgery. The results indicate that radiosurgery of malignant gliomas might be effective in controlling tumour progression in selected glioblastoma patients.
AB - Background: The Gamma Knife is currently used to boost treatment of malignant gliomas. However, few experimental studies have focused on its radiobiological effects. In this work, the growth and invasiveness of human glioblastoma spheroids xenografted into nude rat brains were assessed after radiosurgery. Temporary in vitro as well as long-term in vivo radiation effects were studied. Methods: Glioblastoma biopsy spheroids were irradiated with 12 or 24 Gy. Short-term in vitro spheroid viability and tumour cell migration was determined by microscopic techniques. Pre-irradiated glioblastoma spheroids were implanted into brains of immunosuppressed rats. Long-term tumour development was assessed by magnetic resonance (MR) imaging, and animal survival was recorded. An immunohistochemical analysis was performed on the sectioned rat brains. Results: Both un-irradiated and irradiated spheroids remained viable during 2 months in culture, but a dose-dependent inhibition of tumour growth and migration was seen. MR imaging 4 weeks after implantation also showed a dose-dependent inhibition in tumour development. Median animal survival times were 25.5 days (control group), 43 days (12 Gy group) and 96 days (24 Gy group). The study of in vivo long-term radiation effects on the remaining viable tumour population showed no difference in Ki-67 labelling index and microvascular density before and after radiosurgery. Conclusions: A dose-dependent inhibition of tumour growth and invasion, as well as a dose-dependent increase in animal survival was observed. The model system described is well suited for assessing the radiobiological effects of Gamma Knife radiosurgery. The results indicate that radiosurgery of malignant gliomas might be effective in controlling tumour progression in selected glioblastoma patients.
KW - Glioma xenografts
KW - Ki-67 labelling index
KW - Magnetic resonance imaging
KW - Microvessel density
KW - Nude rats
KW - Radiosurgery
UR - http://www.scopus.com/inward/record.url?scp=33846979518&partnerID=8YFLogxK
U2 - 10.1007/s11060-006-9240-z
DO - 10.1007/s11060-006-9240-z
M3 - Article
C2 - 16955221
AN - SCOPUS:33846979518
SN - 0167-594X
VL - 82
SP - 1
EP - 10
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -