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- W3012594994 endingPage "756" @default.
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- W3012594994 abstract "Central nervous system atypical teratoid/rhabdoid tumors (ATRTs) are rare and aggressive tumors with a very poor prognosis. Current treatments for ATRT include resection of the tumor, followed by systemic chemotherapy and radiation therapy, which have toxic side effects for young children. Gene expression analyses of human ATRTs and normal brain samples indicate that ATRTs have aberrant expression of epigenetic markers including class I histone deacetylases (HDAC’s) and lysine demethylase (LSD1). Here, we investigate the effect of a small molecule epigenetic modulator known as Domatinostat (4SC-202), which inhibits both class I HDAC’s and Lysine Demethylase (LSD1), on ATRT cell survival and single cell heterogeneity. Our findings suggest that 4SC-202 is both cytotoxic and cytostatic to ATRT in 2D and 3D scaffold cell culture models and may target cancer stem cells. Single-cell RNA sequencing data from ATRT-06 spheroids treated with 4SC-202 have a reduced population of cells overexpressing stem cell-related genes, including SOX2. Flow cytometry and immunofluorescence on 3D ATRT-06 scaffold models support these results suggesting that 4SC-202 reduces expression of cancer stem cell markers SOX2, CD133, and FOXM1. Drug-induced changes to the systems biology landscape are also explored by multi-omics enrichment analyses. In summary, our data indicate that 4SC-202 has both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and is an important potential cancer therapeutic to be investigated in vivo." @default.
- W3012594994 created "2020-03-27" @default.
- W3012594994 creator A5003549657 @default.
- W3012594994 creator A5005279080 @default.
- W3012594994 creator A5006934425 @default.
- W3012594994 creator A5016763648 @default.
- W3012594994 creator A5020015400 @default.
- W3012594994 creator A5026125815 @default.
- W3012594994 creator A5048065612 @default.
- W3012594994 creator A5056934029 @default.
- W3012594994 creator A5078377293 @default.
- W3012594994 creator A5084015923 @default.
- W3012594994 date "2020-03-23" @default.
- W3012594994 modified "2023-10-16" @default.
- W3012594994 title "Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid" @default.
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