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A reproducible brain tumour model established from human glioblastoma biopsies

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 xenogr...

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Autores principales: Wang, Jian, Miletic, Hrvoje, Sakariassen, Per Ø, Huszthy, Peter C, Jacobsen, Hege, Brekkå, Narve, Li, Xingang, Zhao, Peng, Mørk, Sverre, Chekenya, Martha, Bjerkvig, Rolf, Enger, Per Ø
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810304/
https://www.ncbi.nlm.nih.gov/pubmed/20040089
http://dx.doi.org/10.1186/1471-2407-9-465
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author Wang, Jian
Miletic, Hrvoje
Sakariassen, Per Ø
Huszthy, Peter C
Jacobsen, Hege
Brekkå, Narve
Li, Xingang
Zhao, Peng
Mørk, Sverre
Chekenya, Martha
Bjerkvig, Rolf
Enger, Per Ø
author_facet Wang, Jian
Miletic, Hrvoje
Sakariassen, Per Ø
Huszthy, Peter C
Jacobsen, Hege
Brekkå, Narve
Li, Xingang
Zhao, Peng
Mørk, Sverre
Chekenya, Martha
Bjerkvig, Rolf
Enger, Per Ø
author_sort Wang, Jian
collection PubMed
description 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.
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spelling pubmed-28103042010-01-23 A reproducible brain tumour model established from human glioblastoma biopsies Wang, Jian Miletic, Hrvoje Sakariassen, Per Ø Huszthy, Peter C Jacobsen, Hege Brekkå, Narve Li, Xingang Zhao, Peng Mørk, Sverre Chekenya, Martha Bjerkvig, Rolf Enger, Per Ø BMC Cancer Research Article 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. BioMed Central 2009-12-29 /pmc/articles/PMC2810304/ /pubmed/20040089 http://dx.doi.org/10.1186/1471-2407-9-465 Text en Copyright ©2009 Wang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Jian
Miletic, Hrvoje
Sakariassen, Per Ø
Huszthy, Peter C
Jacobsen, Hege
Brekkå, Narve
Li, Xingang
Zhao, Peng
Mørk, Sverre
Chekenya, Martha
Bjerkvig, Rolf
Enger, Per Ø
A reproducible brain tumour model established from human glioblastoma biopsies
title A reproducible brain tumour model established from human glioblastoma biopsies
title_full A reproducible brain tumour model established from human glioblastoma biopsies
title_fullStr A reproducible brain tumour model established from human glioblastoma biopsies
title_full_unstemmed A reproducible brain tumour model established from human glioblastoma biopsies
title_short A reproducible brain tumour model established from human glioblastoma biopsies
title_sort reproducible brain tumour model established from human glioblastoma biopsies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810304/
https://www.ncbi.nlm.nih.gov/pubmed/20040089
http://dx.doi.org/10.1186/1471-2407-9-465
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