Applying Tissue Slice Culture in Cancer Research—Insights from Preclinical Proton Radiotherapy
Open Access
- 16 June 2020
- Vol. 12 (6), 1589
- https://doi.org/10.3390/cancers12061589
Abstract
A challenge in cancer research is the definition of reproducible, reliable, and practical models, which reflect the effects of complex treatment modalities and the heterogeneous response of patients. Proton beam radiotherapy (PBRT), relative to conventional photon-based radiotherapy, offers the potential for iso-effective tumor control, while protecting the normal tissue surrounding the tumor. However, the effects of PBRT on the tumor microenvironment and the interplay with newly developed chemo- and immunotherapeutic approaches are still open for investigation. This work evaluated thin-cut tumor slice cultures (TSC) of head and neck cancer and organotypic brain slice cultures (OBSC) of adult mice brain, regarding their relevance for translational radiooncology research. TSC and OBSC were treated with PBRT and investigated for cell survival with a lactate dehydrogenase (LDH) assay, DNA repair via the DNA double strand break marker γH2AX, as well as histology with regards to morphology. Adult OBSC failed to be an appropriate model for radiobiological research questions. However, histological analysis of TSC showed DNA damage and tumor morphological results, comparable to known in vivo and in vitro data, making them a promising model to study novel treatment approaches in patient-derived xenografts or primary tumor material.Keywords
Funding Information
- Horizon 2020 (730983)
This publication has 69 references indexed in Scilit:
- Proton beam irradiation stimulates migration and invasion of human U87 malignant glioma cellsJournal of Radiation Research, 2013
- Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine ModelInternational Journal of Molecular Sciences, 2013
- Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatmentsNeuro-Oncology, 2013
- Biological Effects of Proton Radiation: What We Know and Don't KnowRadiation Research, 2013
- Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer researchCancer Letters, 2012
- Organotypic Brain Slice Cultures of Adult Transgenic P301S Mice—A Model for Tauopathy StudiesPLOS ONE, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Radiation-induced brain injury: A reviewFrontiers in Oncology, 2012
- Characterization of Cortical Neuronal and Glial Alterations during Culture of Organotypic Whole Brain Slices from Neonatal and Mature MicePLOS ONE, 2011
- Preclinical model of organotypic culture for pharmacodynamic profiling of human tumorsProceedings of the National Academy of Sciences of the United States of America, 2010