Reference Detail

Ref Type

Journal Article

PMID

(26920892)

Authors

Muscat A, Popovski D, Jayasekara WS, Rossello FJ, Ferguson M, Marini KD, Alamgeer M, Algar EM, Downie P, Watkins DN, Cain JE, Ashley DM

Title

Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumor Growth Arrest and Multi-Lineage Differentiation of Malignant Rhabdoid Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	22	14	2016 Jul 15	3560-70	Clin Cancer Res

URL

Abstract Text

Malignant rhabdoid tumor (MRT) and atypical teratoid rhabdoid tumors (ATRT) are rare aggressive undifferentiated tumors primarily affecting the kidney and CNS of infants and young children. MRT are almost exclusively characterized by homozygous deletion or inactivation of the chromatin remodeling gene SMARCB1 SMARCB1 protein loss leads to direct impairment of chromatin remodeling and we have previously reported a role for this protein in histone acetylation. This provided the rationale for investigating the therapeutic potential of histone deactylase inhibitors (HDACi) in MRT.Whereas previously HDACis have been used at doses and schedules that induce cytotoxicity, in the current studies we have tested the hypothesis, both in vitro and in vivo, that sustained treatment of human MRT with low-dose HDACi can lead to sustained cell growth arrest and differentiation.Sustained low-dose panobinostat (LBH589) treatment led to changes in cellular morphology associated with a marked increase in the induction of neural, renal, and osteoblast differentiation pathways. Genome-wide transcriptional profiling highlighted differential gene expression supporting multilineage differentiation. Using mouse xenograft models, sustained low-dose LBH589 treatment caused tumor growth arrest associated with tumor calcification detectable by X-ray imaging. Histological analysis of LBH589-treated tumors revealed significant regions of ossification, confirmed by Alizarin Red staining. Immunohistochemical analysis showed increased TUJ1 and PAX2 staining suggestive of neuronal and renal differentiation, respectively.Low-dose HDACi treatment can terminally differentiate MRT tumor cells and reduce their ability to self-renew. The use of low-dose HDACi as a novel therapeutic approach warrants further investigation. Clin Cancer Res; 22(14); 3560-70. ©2016 AACR.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References