Dataset Information

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma.

ABSTRACT: 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.

SUBMITTER: Meneceur S

PROVIDER: S-EPMC7226316 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma.

Meneceur Sarah S Linge Annett A Meinhardt Matthias M Hering Sandra S Löck Steffen S Bütof Rebecca R Krex Dietmar D Schackert Gabriele G Temme Achim A Baumann Michael M Krause Mechthild M von Neubeck Cläre C

Cancers 20200403 4

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 axilla ...[more]

PMID: 32260145

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Project description:Patient-derived xenograft (PDX) models have been recognized as being more suitable for predicting therapeutic efficacy than cell-culture models. However, there are several limitations in applying PDX models in preclinical studies, including their availability-especially for cancers such as gastric cancer-that are not frequently encountered in Western countries. In addition, the differences in morphology between primary, PDX, and tumor cell line-derived xenograft (CDX) models have not been well established. In this study, we aimed to establish a series of gastric cancer PDXs and cell-lines from a relatively large number of gastric cancer patients. We also investigated the clinicopathological factors associated with the establishment of PDX and CDX models, and compared the histology between the primary tumor, PDX, and CDX that originated from the same patient. We engrafted 232 gastric cancer tissues into immune-deficient mice subcutaneously and successfully established 35 gastric cancer PDX models (15.1% success rate). Differentiated type adenocarcinomas (DAs, 19.4%) were more effectively established than poorly differentiated type adenocarcinomas (PDAs, 10.8%). For establishing CDXs, the success rate was less influenced by histological differentiation grade (DA vs. PDA, 12.1% vs. 9.8%). In addition, concordance of histological differentiation grade between primary tumors and PDXs was significant (p < 0.01), while concordance between primary tumors and CDXs was not. Among clinicopathological factors investigated, pathological nodal metastasis status (pN) was significantly associated with the success rate of PDX establishment. Although establishing cell lines from ascites fluid was more efficient (41.2%, 7/17) than resected tissues, it should be noted that all CDXs from ascites fluid had the PDA phenotype. In conclusion, we established 35 PDX and 32 CDX models from 249 gastric cancer patients; among them, 21 PDX/CDX models were established from the same patients. Our findings may provide helpful insights for establishing PDX and CDX models not only from gastric but from other cancer types, as well as select preclinical models for developing new therapeutics.

Dataset Information

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma.

Publications

Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma.

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