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01-08-2013 | Original Paper

Epigenetic modification after inhibition of IGF-1R signaling in human central nervous system atypical teratoid rhabdoid tumor (AT/RT)

Authors: Kyu-Won Shim, Guifa Xi, Barbara-Mania Farnell, Dong-Seok Kim, Takao Tsurubuchi, Tadanori Tomita, C. Shekhar Mayanil

Published in: Child's Nervous System | Issue 8/2013

Abstract

Objective

This study investigated epigenetic modifications in human central nervous system atypical teratoid rhabdoid tumors (AT/RTs), in response to inhibition of insulin-like growth factor receptor 1 (IGF-1R).

Materials and methods

Tumor tissue was obtained from two pediatric patients, tissue was dissociated, and primary cultures were established. Cultured cells were treated with picropodophyllin (PPP; 0, 1, and 2 μM for 48 h), a selective IGF-1R inhibitor. Histone acetylation and methylation patterns (H3K9ac, H3K18ac, H3K4me3, H3K27me3) and levels of histone deacetylases (HDACs; HDAC1, HDAC3, and SirT1) and histone acetyl transferases (GCN5 and p300) were examined. H3K9ac and H3K18ac decreased in response to treatment with PPP. HDAC levels showed a biphasic response, increasing with 1 μM PPP, but then decreasing with 2 μM PPP.

Conclusion

Inhibition of IGF-1R modified epigenetic status in AT/RT. Determining the mechanisms behind these modifications will guide the development of novel therapeutic targets for this malignant embryonal cancer.

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Title: Epigenetic modification after inhibition of IGF-1R signaling in human central nervous system atypical teratoid rhabdoid tumor (AT/RT)
Authors: Kyu-Won Shim
Guifa Xi
Barbara-Mania Farnell
Dong-Seok Kim
Takao Tsurubuchi
Tadanori Tomita
C. Shekhar Mayanil
Publication date: 01-08-2013
Publisher: Springer Berlin Heidelberg
Published in: Child's Nervous System / Issue 8/2013
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI: https://doi.org/10.1007/s00381-013-2087-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Epigenetic modification after inhibition of IGF-1R signaling in human central nervous system atypical teratoid rhabdoid tumor (AT/RT)

Abstract

Objective

Materials and methods

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Materials and methods

Conclusion

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