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Open AccessFeature PaperArticle

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma

1
OncoRay–National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz- Zentrum Dresden-Rossendorf, 01307 Dresden, Germany
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Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology–OncoRay, 01307 Dresden, Germany
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German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany
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German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
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Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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National Center for Tumour Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
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Institute for Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, 01307 Dresden, Germany
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Institute for Legal Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, 01307 Dresden, Germany
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Department of Neurosurgery, Medical Faculty and University Hospital Carl Gustav Carus, 01307 Dresden, Germany
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Department of Particle Therapy, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 871; https://doi.org/10.3390/cancers12040871
Received: 9 March 2020 / Revised: 27 March 2020 / Accepted: 1 April 2020 / Published: 3 April 2020
(This article belongs to the Special Issue Patient-Derived Xenograft-Models in Cancer Research)
Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2+ cells (r = 0.49, p = 0.016) and nestin+ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers. View Full-Text
Keywords: patient-derived xenografts; preclinical models; cancer stem cell markers; glioblastoma; growth data patient-derived xenografts; preclinical models; cancer stem cell markers; glioblastoma; growth data
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Meneceur, S.; Linge, A.; Meinhardt, M.; Hering, S.; Löck, S.; Bütof, R.; Krex, D.; Schackert, G.; Temme, A.; Baumann, M.; Krause, M.; von Neubeck, C. Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma. Cancers 2020, 12, 871.

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