HDAC-class II specific inhibition involves HDAC proteasome-dependent degradation mediated by RANBP2.

Discovered for their ability to deacetylate histones and repress transcription, HDACs are a promising target for therapy of human diseases. The class II HDACs are mainly involved in developmental and differentiation processes, such as myogenesis. We report here that class I and class II HDAC inhibitors such as SAHA or the class II selective inhibitor MC1568 induce down-regulation of class II HDACs in human cells.

Clinical Governance and evidence-based laboratory medicine.

Background: Clinical Governance is described as "a framework through which the NHS organisations are accountable to continue to improve the quality of the service and safeguarding high standards of care by creating an environment in which excellence in clinical care would flourish"; it is aimed to ensure continuous improvement in the overall standard of clinical care, ensuring that clinical decisions are based on the most up-to-date evidence in terms of effectiveness.

Methods: If Clinical Governance is a framework through which NHS organisations are accountable to continuously improve the quality of their services and safeguarding high standards of care, Clinical Effectiveness is a vital part of Clinical Governance. Clinical Effectiveness is a term that refers to measuring and monitoring the quality of care, and comprises various activities, including: Evidence-Based Practice, Research and Development, Clinical Audit, Clinical Guidelines, Integrated Care Pathways, and Total Quality Management.

Acute myeloid leukemia: therapeutic impact of epigenetic drugs.

Acute myeloid leukemia (AML) is not a single disease but a group of malignancies in which the clonal expansion of various types of hematopoietic precursor cells in the bone marrow leads to perturbation of the delicate balance between self-renewal and differentiation that is characteristic of normal hematopoiesis. An increasing number of genetic aberrations, such as chromosomal translocations that alter the function of transcription regulatory factors, has been identified as the cause of AML and shown to act by deregulating gene programming at both the genetic and epigenetic level. While the genetic aberrations occurring in acute myeloid leukemia are fairly well understood, we have only recently become aware of the epigenetic deregulation associated with leukemia, in particular with myeloid leukemias.

Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides.

Chemical manipulations performed on aroyl-pyrrolyl-hydroxyamides (APHAs) led to (aryloxopropenyl)pyrrolyl hydroxamates 2a-w, and their inhibition against maize HDACs and their class I or class II HDAC selectivity were determined. In particular, from these studies some benzene meta-substituted compounds emerged as highly class II (IIa)-selective HDAC inhibitors, the most selective being the 3-chloro- and 3-fluoro-substituted compounds 2c (SI = 71.4) and2f (SI = 176.

Flavonoid quercetin sensitizes a CD95-resistant cell line to apoptosis by activating protein kinase Calpha.

We previously demonstrated that quercetin, a naturally occurring flavonoid with strong antioxidant properties, was able to enhance programmed cell death in HPB-acute lymphoblastic leukemia (ALL) cell line, derived from a human tymoma, when associated with the agonistic anti-CD95 monoclonal antibody. Here, we report that HPB-ALL cells are normally resistant to CD95-mediated apoptosis, and quercetin is able to sensitize this cell line through a mechanism independent of its antioxidant properties. In fact, other compounds structurally and functionally similar to quercetin, when associated with anti-CD95 antibody did not induce any CD95-mediated apoptosis, still maintaining their antioxidant capacity.