title: Human glioblastoma biopsy spheroids xenografted into the nude rat brain show growth inhibition after stereotactic radiosurgery.
abstract: 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.
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway. frits.thorsen@biomed.uib.no
authors.forename: Frits
authors.initials: F
authors.lastname: Thorsen
authors.forename: Per Øyvind
authors.initials: PØ
authors.lastname: Enger
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Paal-Henning
authors.initials: PH
authors.lastname: Pedersen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation / Q000473:pathology; D016634:Radiosurgery / Q000295:instrumentation*; D011879:Radiotherapy Dosage; D051381:Rats; D011923:Rats, Nude; D018874:Spheroids, Cellular / Q000637:transplantation; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays