Linked Life Data

16083344

Source:http://linkedlifedata.com/resource/pubmed/id/16083344

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-8-8
pubmed:abstractText
Histone deacetylases (HDACs) have recently emerged as an important target for therapeutic intervention in cancer and potentially other human diseases. By modulating the acetylation status of histones, histone deacetylase inhibitors (HDACIs) alter the transcription of genes involved in cell growth, maturation, survival and apoptosis, among other processes. Early clinical results suggest a potentially useful role for HDACIs in the treatment of certain forms of lymphoma (e.g., cutaneous T cell lymphoma) and acute leukaemia. An unresolved question is how HDACIs induce cell death in tumour cells. Recent studies suggest that acetylation of nonhistone proteins may play an important role in the biological effects of this class of compounds, and may explain lack of correlation between histone acetylation and induction of cell death by HDACIs in some circumstances. Recently, attention has focussed on the effects of HDACIs on disruption of co-repressor complexes, induction of oxidative injury, upregulation of the expression of death receptors, generation of lipid second messengers such as ceramide, interference with the function of chaperone proteins and modulation of the activity of NF-kappaB as critical determinants of lethality. Aside from providing critical insights into the mechanism of action of HDACIs in neoplastic disease, these findings may provide a foundation for the rational development of combination studies, involving HDACIs in combination with either conventional cytotoxic drugs as well as more novel targeted agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1744-7631
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
809-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Histone deacetylase inhibitors: insights into mechanisms of lethality.
pubmed:affiliation
Department of Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural