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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-46231

Dedes, J. Acquired vorinostat resistance shows partial cross-resistance to "second-generation" HDAC inhibitors and correlates with loss of histone acetylation and apoptosis but not with altered HDAC and HAT activities. 2010, University of Zurich, Faculty of Medicine.

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Abstract

Histonedeacetylase(HDAC)inhibitors such as vorinostat (suberoylanilide hydroxamicacid), valproicacid,romidepsin (FK-228), and LBH589 comprise a relatively new class of potentanti canceragents. This study provides evidence for the potential of vorinostat to cause acquisition of multi drug resistance protein-independent resistance in HCT116 colon tumor cells. This acquired resistance is moderate(two-foldtothree-fold), is non-reversible, and correlates with the loss of responses typically seen with HDAC-inhibitors, that is the loss of acetylation of thehistones H2A, H2B, H3, and H4, the loss of the G2/M checkpoint activation, and the loss of caspase 3-dependent and caspase 7-dependent apoptosis. This acquired resistance also associates with cross-resistance to the hydroxamate-class(LBH589 and JNJ26481585)and to the aliphaticacid-class(valproicacid)HDAC inhibitors but not tothebenzamide-class(MGCD0103)and the cyclic peptide-class(romidepsin) HDAC inhibitors. The acquired HDAC inhibitor resistance described here.

Item Type:Dissertation
Referees:Fink D, Fedier A
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
DDC:610 Medicine & health
Language:German
Date:2010
Deposited On:18 Feb 2011 15:43
Last Modified:19 Oct 2013 09:23
Number of Pages:17
Additional Information:Acquired vorinostat resistance shows partial cross-resistance to "second-generation" HDAC inhibitors and correlates with loss of histone acetylation and apoptosis but not with altered HDAC and HAT activities / vorgelegt von Ioannis Dedes. - Zürich, 2009
Related URLs:http://opac.nebis.ch/F/?local_base=NEBIS&con_lng=GER&func=find-b&find_code=SYS&request=006217249

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