1. International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma
- Author
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John Caird, Stephanie Francis, Rachid Drissi, Chris Jones, Anahid Ehteda, Maria Vinci, Cynthia Hawkins, Jordan R. Hansford, Darach Crimmins, Alexander Plessier, Dannis G. van Vuurden, Tim Hassall, Danielle Upton, Bing Liu, David Castel, Jane Pears, Jane Cryan, Michael Farrell, Louise E. Ludlow, Esther Hulleman, Diana Carvalho, Michelle Monje, Chelsea Mayoh, Michaël H. Meel, Maria Tsoli, Jacques Grill, Andrea Carai, Maryam Fouladi, Maria Kirby, David S. Ziegler, Angela Mastronuzzi, Nicholas G. Gottardo, Han Shen, Laura Franshaw, Pediatric surgery, and CCA - Cancer biology and immunology
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Cell Survival ,Brain Stem Neoplasm ,Autopsy ,Histones ,Mice ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,Glioma ,Neurosphere ,Biopsy ,medicine ,Brainstem glioma ,Animals ,Brain Stem Neoplasms ,Humans ,Cells, Cultured ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,Neurology ,030220 oncology & carcinogenesis ,Mutation ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Purpose: Diffuse intrinsic pontine glioma is the most aggressive form of high grade glioma in children with no effective therapies. There have been no improvements in survival in part due poor understanding of underlying biology, and lack of representative in vitro and in vivo models. Recently, it has been found feasible to use both biopsy and autopsy tumors to generate cultures and xenograft models. Methods: To further model development, we evaluated the collective international experience from 8 collaborating centers to develop DIPG pre-clinical models from patient-derived autopsies and biopsies. Univariate and multivariate analysis was performed to determine key factors associated with the success of in vitro and in vivo PDX development. Results: In vitro cultures were successfully established from 57% of samples (84.2% of biopsies and 38.2% of autopsies). Samples transferred in DMEM media were more likely to establish successful culture than those transported in Hibernate A. In vitro cultures were more successful from biopsies (84.2%) compared with autopsies (38.2%) and as monolayer on laminin-coated plates than as neurospheres. Primary cultures successfully established from autopsy samples were more likely to engraft in animal models than cultures established from biopsies (86.7% vs. 47.4%). Collectively, tumor engraftment was more successful when DIPG samples were directly implanted in mice (68%), rather than after culturing (40.7%). Conclusion: This multi-center study provides valuable information on the success rate of establishing patient-derived pre-clinical models of DIPG. The results can lead to further optimization of DIPG model development and ultimately assist in the investigation of new therapies for this aggressive pediatric brain tumor.
- Published
- 2018