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- Matuszewski, Damian J., et al.
(författare)
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Image-Based Detection of Patient-Specific Drug-Induced Cell-Cycle Effects in Glioblastoma
- 2018
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Ingår i: SLAS Discovery. - : Elsevier BV. - 2472-5560 .- 2472-5552. ; 23:10, s. 1030-1039
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Tidskriftsartikel (refereegranskat)abstract
- Image-based analysis is an increasingly important tool to characterize the effect of drugs in large-scale chemical screens. Herein, we present image and data analysis methods to investigate population cell-cycle dynamics in patient-derived brain tumor cells. Images of glioblastoma cells grown in multiwell plates were used to extract per-cell descriptors, including nuclear DNA content. We reduced the DNA content data from per-cell descriptors to per-well frequency distributions, which were used to identify compounds affecting cell-cycle phase distribution. We analyzed cells from 15 patient cases representing multiple subtypes of glioblastoma and searched for clusters of cell-cycle phase distributions characterizing similarities in response to 249 compounds at 11 doses. We show that this approach applied in a blind analysis with unlabeled substances identified drugs that are commonly used for treating solid tumors as well as other compounds that are well known for inducing cell-cycle arrest. Redistribution of nuclear DNA content signals is thus a robust metric of cell-cycle arrest in patient-derived glioblastoma cells.
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