Histone deacetylases expression in atypical teratoid rhabdoid tumors

Halpern, Abby L.; Hamm, Christopher A.; Bonaldo, Maria de Fátima; Tomita, Tadanori

doi:10.1007/s00381-012-1965-8

Cited by 12 publications

(7 citation statements)

References 25 publications

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“…Research approaches over the past years have focused on targeting deregulated pathways in RT [ 29 ]. Different signaling pathways (WNT, SHH, FGFR and many more) as well as epigenetic modifiers (HDAC, EZH2) have been described as being deregulated in these kind of tumors [ 12 , 13 , 14 , 30 , 31 ]. Several targeted compounds show promising preclinical results and some of them are tested in early clinical studies such as CDK4/6 inhibitors, EZH2 inhibitors and Aurora kinase inhibitors, with disappointing to discordant responses [ 29 , 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors

Kramer

Moreno

Frühwald

et al. 2017

IJMS

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Rhabdoid tumors (RT) are malignant neoplasms of early childhood. Despite intensive therapy, survival is poor and new treatment approaches are required. The only recurrent mutations in these tumors affect SMARCB1 and less commonly SMARCA4, both subunits of the chromatin remodeling complex SWItch/Sucrose Non-Fermentable (SWI/SNF). Loss of these two core subunits alters the function of the SWI/SNF complex, resulting in tumor development. We hypothesized that inhibition of aberrant SWI/SNF function by selective blockade of the BRD9 subunit of the SWI/SNF complex would reduce tumor cell proliferation. The cytotoxic and anti-proliferative effects of two specific chemical probes (I-BRD9 and BI-9564) which target the bromodomain of SWI/SNF protein BRD9 were evaluated in 5 RT cell lines. Combinatorial effects of I-BRD9 and cytotoxic drugs on cell proliferation were evaluated by cytotoxicity assays. Single compound treatment of RT cells with I-BRD9 and BI-9564 resulted in decreased cell proliferation, G1-arrest and apoptosis. Combined treatment of doxorubicin or carboplatin with I-BRD9 resulted in additive to synergistic inhibitory effects on cell proliferation. In contrast, the combination of I-BRD9 with vincristine demonstrated the antagonistic effects of these two compounds. We conclude that the BRD9 bromodomain is an attractive target for novel therapies in this cancer.

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Section: Discussionmentioning

confidence: 99%

BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors

Kramer

Moreno

Frühwald

et al. 2017

IJMS

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“…In ATRTs, HDAC1 is significantly differentially expressed (Sredni et al, 2013), and the chromatin remodeling and tumor suppressor gene SMARCB1 represses Cyclin D1 transcription by recruiting the HDAC1 complex to its promoter, resulting in cell cycle arrest (Tsikitis et al, 2005). A hallmark of malignant rhabdoid tumors is homozygous deletion or inactivation of SMARCB1.…”

Section: Epigenetic Basis Of Pediatric Brain Cancersmentioning

confidence: 99%

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

Perla

Fratini

Cardoso

et al. 2020

Front. Cell Dev. Biol.

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Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric high-grade gliomas (HGGs), and rhabdoid and atypical teratoid/rhabdoid tumors (ATRTs). We also discuss clinical perspectives for the use of HDACis in the treatment of pediatric brain tumors.

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“… 16 , 17 SREBP-1c also promotes fatty acid synthesis by activating several genes in the biosynthetic pathway. Insulin enhances SREBP-1c gene expression and its protein cleavage, therefore favoring its binding to sterol-response element 18 in the promoter of target genes. 19 PNPLA3 mRNA levels were increased in SREBP-1c transgenic mice with an expression pattern resembling that of fatty acid synthase (FAS).…”

Section: Introduction On Pnpla3: Origin and Tissue-specific Expressiomentioning

confidence: 99%

PNPLA3 expression and its impact on the liver: current perspectives

Bruschi

Tardelli

Claudel

et al. 2017

HMER

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A single-nucleotide polymorphism occurring in the sequence of the human patatin-like phospholipase domain-containing 3 gene (PNPLA3), known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C–related cirrhosis and hepatocellular carcinoma. The native gene encodes for a protein that has not yet a fully defined role in liver lipid metabolism and, according to recent observations, seems to be divergently regulated among distinct liver cells type, such as hepatic stellate cells. Therefore, the aim of this review is to collect the latest data regarding PNPLA3 expression in human liver and to analyze the impact of its genetic variant in human hepatic pathologies. Moreover, a description of the current biochemical and metabolic data pertaining to PNPLA3 function in both animal models and in vitro studies is summarized to allow a better understanding of the relevant pathophysiological role of this enzyme in the progression of hepatic diseases.

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Histone deacetylases expression in atypical teratoid rhabdoid tumors

Abstract: A class of HDACi specifically targeting HDAC1 may allow for the desired therapeutic benefits with fewer side effects for children with ATRT.

Cited by 12 publications

References 25 publications

BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors

BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

PNPLA3 expression and its impact on the liver: current perspectives

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