Over the past few years, the histone deacetylase (HDAC) inhibitors have occupied an important place in the effort to develop novel, but less toxic, anticancer therapy. HDAC inhibitors block HDACs, which are the enzymes responsible for histone deacetylation, and therefore they modulate gene expression. The cellular effects of HDAC inhibitors include growth arrest and the induction of differentia...

Histone deacetylases (HDAC) modify the architecture of chromatin, leading to decreased gene expression, an effect that is reversed by HDAC inhibition. The balance between deacetylation and acetylation is central to many biological events including the regulation of cell proliferation and cancer but also the differentiation of immune T cells. The effects of HDAC inhibition on the interaction bet...

Waldenström macroglobulinemia (WM) cells present with increased expression of microRNA-206 (miRNA-206) and reduced expression of miRNA-9*. Predicted miRNA-206- and -9*-targeted genes include histone deacetylases (HDACs) and histone acetyl transferases (HATs), indicating that these miRNAs may play a role in regulating histone acetylation. We were able to demonstrate that primary WM cells are cha...

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms ...

Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity we...

We are writing to clarify the interpretation of results contained within a paper by Giles et al.1 In their abstract, the authors state, “The [complete remission] CR rate was significantly higher for the laromustine/[high-dose cytarabine] HDAC group (35% vs 19%, P .005). However, the 30-day mortality rate and median progression-free survival were significantly worse in this group compared with H...

ヒストン脱アセチル化酵素（HDAC）阻害剤は皮膚T細胞リンパ腫の有効な治療法であるが，単剤では獲得耐性が必発であり，適切な併用療法の開発が求められている．我々は皮膚T細胞リンパ腫の細胞株のキノーム解析により，少数のキナーゼ活性がHDAC阻害剤の刺激により共通して亢進することを明らかにした．同定された分子群の中で，臨床使用可能な薬剤が存在するプロゲステロン受容体に着目して，HDAC阻害剤の併用療法のターゲットとなりうるか検討した．プロゲステロン受容体拮抗薬であるmifepristoneを用いて，romidepsinによる抗腫瘍効果の増強効果についてin vitroで検討したところ，mifepristoneはromidepsinによる細胞増殖抑制効果やアポトーシス誘導効果を増強させた．プロゲステロン受容体はHDAC阻害剤の併用療法のターゲットとなりうる．

PURPOSE Corneal myofibroblasts differentiated from activated corneal stromal cells are the major cellular sources of extracellular matrix synthesis for the repair of corneal injury. In this study, the effects of histone deacetylase (HDAC) inhibitors on the activation, proliferation, migration and senescence of corneal stromal cells were evaluated. METHODS Primary human and mouse corneal strom...

Histone deacetylase (HDAC) inhibitors reactivate tumor suppressor gene transcription; induce cancer cell differentiation, growth arrest, and programmed cell death; and are among the most promising new classes of anticancer drugs. Myc oncoproteins can block cell differentiation and promote cell proliferation and malignant transformation, in some cases by modulating target gene transcription. Her...

Histone deacetylases (HDAC's) became increasingly important targets for therapy of various diseases, resulting in a pressing need to develop HDAC class- and isoform-selective inhibitors. Class IIa deacetylases possess only minimal deacetylase activity against acetylated histones, but have several other client proteins as substrates through which they participate in epigenetic regulation. Herein...