Linked Life Data

19509253

Source:http://linkedlifedata.com/resource/pubmed/id/19509253

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-6-11
pubmed:abstractText
Vorinostat (suberoylanilide hydroxamic acid), a histone deacetylase inhibitor, is currently undergoing clinical evaluation as therapy for cancer. We investigated the effects of vorinostat on tumor cell radiosensitivity in a breast cancer brain metastasis model using MDA-MB-231-BR cells. In vitro radiosensitivity was evaluated using clonogenic assay. Cell cycle distribution and apoptosis was measured using flow cytometry. DNA damage and repair was evaluated using gammaH2AX. Mitotic catastrophe was measured by immunostaining. Growth delay and intracranial xenograft models were used to evaluate the in vivo tumor radiosensitivity. Cells exposed to vorinostat for 16 hours before and maintained in the medium after irradiation had an increase in radiosensitivity with a dose enhancement factor of 1.57. gammaH2AX, as an indicator of double-strand breaks, had significantly more foci per cell in the vorinostat plus irradiation group. Mitotic catastrophe, measured at 72 hours, was significantly increased in cells receiving vorinostat plus irradiation. Irradiation of s.c. MDA-MB-231-BR tumors in mice treated with vorinostat resulted in an increase in radiation-induced tumor growth delay. Most importantly, animals with intracranial tumor implants lived the longest after combination treatment. These results indicate that vorinostat enhances tumor cell radiosensitivity in vitro and in vivo. There was a greater than additive improvement in survival in our intracranial model. Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1538-8514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1589-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19509253-Acetylation, pubmed-meshheading:19509253-Animals, pubmed-meshheading:19509253-Apoptosis, pubmed-meshheading:19509253-Brain Neoplasms, pubmed-meshheading:19509253-Breast Neoplasms, pubmed-meshheading:19509253-Cell Cycle, pubmed-meshheading:19509253-Cell Line, Tumor, pubmed-meshheading:19509253-Cell Proliferation, pubmed-meshheading:19509253-Combined Modality Therapy, pubmed-meshheading:19509253-Enzyme Inhibitors, pubmed-meshheading:19509253-Female, pubmed-meshheading:19509253-Histone Deacetylase Inhibitors, pubmed-meshheading:19509253-Histone Deacetylases, pubmed-meshheading:19509253-Histones, pubmed-meshheading:19509253-Humans, pubmed-meshheading:19509253-Hydroxamic Acids, pubmed-meshheading:19509253-Immunoblotting, pubmed-meshheading:19509253-Kaplan-Meier Estimate, pubmed-meshheading:19509253-Mammary Neoplasms, Experimental, pubmed-meshheading:19509253-Mice, pubmed-meshheading:19509253-Mice, Nude, pubmed-meshheading:19509253-Mitotic Index, pubmed-meshheading:19509253-Tumor Burden, pubmed-meshheading:19509253-Xenograft Model Antitumor Assays
pubmed:year
2009
pubmed:articleTitle
Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts.
pubmed:affiliation
Radiation Oncology Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural