| Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometry. | |
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MedLine Citation:
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PMID: 16254255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Histone deacetylase (HDAC) inhibitors are a promising new class of anticancer drug. The aim of this study was to develop a versatile and sensitive technique for the pharmacodynamic (PD) assessment of HDAC inhibitor activity as monotherapy and in combination therapy. A multiparameter flow cytometric assay was developed initially in healthy donor lymphocytes and leukemia cell lines, and then tested in peripheral blood of solid tumor patients and in bone marrow aspirates of leukemia patients on phase I trials of the HDAC inhibitor MS-275. A technique was developed that allows highly sensitive single parameter determination of HDAC inhibitor activity in as little as 50 microl of whole blood. Multiparameter analysis enabled correlation on a single cell basis of protein acetylation with biologically relevant markers including cell lineage antigens, an apoptosis marker, and PD markers of other anti-cancer agents. The level of protein acetylation can be readily detected and quantified in peripheral blood or in bone marrow aspirates by flow cytometric analysis. The technique described has significant advantages for the PD assessment of HDAC inhibitors as monotherapy and as a component of combination therapy trials. |
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Authors:
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Eun Joo Chung; Sunmin Lee; Edward A Sausville; Qin Ryan; Judith E Karp; Ivana Gojo; William G Telford; Min-Jung Lee; Hye Sik Kong; Jane B Trepel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Annals of clinical and laboratory science Volume: 35 ISSN: 0091-7370 ISO Abbreviation: Ann. Clin. Lab. Sci. Publication Date: 2005 |
Date Detail:
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Created Date: 2005-10-28 Completed Date: 2006-02-14 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0410247 Medline TA: Ann Clin Lab Sci Country: United States |
Other Details:
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Languages: eng Pagination: 397-406 Citation Subset: IM |
Affiliation:
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Medical Oncology Clinical Research Unit, Bethesda, MD 20892, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Benzamides / pharmacology* Cells, Cultured Enzyme Inhibitors / pharmacology* Flow Cytometry / methods* Histone Deacetylase Inhibitors* Humans Pyridines / pharmacology* Tumor Markers, Biological / analysis |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Benzamides; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/N-(2-aminophenyl)-4-(N-(pyridin-3-ylmethoxycarbonyl)aminomethyl)benzamide; 0/Pyridines; 0/Tumor Markers, Biological |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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