title: A reproducible brain tumour model established from human glioblastoma biopsies.
abstract: BACKGROUND
  Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates.
  
  
  METHODS
  In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features.
  
  
  RESULTS
  The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days +/- 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms.
  
  
  CONCLUSIONS
  In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.
authors.affiliation: Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway. jian.wang@biomed.uib.no
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Miletic
authors.forename: Per Ø
authors.initials: PØ
authors.lastname: Sakariassen
authors.forename: Peter C
authors.initials: PC
authors.lastname: Huszthy
authors.forename: Hege
authors.initials: H
authors.lastname: Jacobsen
authors.forename: Narve
authors.initials: N
authors.lastname: Brekkå
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Sverre
authors.initials: S
authors.lastname: Mørk
authors.forename: Martha
authors.initials: M
authors.lastname: Chekenya
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Per Ø
authors.initials: PØ
authors.lastname: Enger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001706:Biopsy; D001932:Brain Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000473:pathology; D051381:Rats; D011923:Rats, Nude; D015203:Reproducibility of Results; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D055815:Young Adult