Linked Life Data

17308048

Source:http://linkedlifedata.com/resource/pubmed/id/17308048

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-19
pubmed:abstractText
A major limitation of adenovirus type 5-mediated cancer gene therapy is the inefficient infection of many cancer cells. Previously, we showed that treatment with low doses of the histone deacetylase inhibitor FK228 (FR901228, depsipeptide) increased coxsackie adenovirus receptor (CAR) levels, histone H3 acetylation, and adenovirus infection efficiencies as measured by viral transgene expression in cancer cell lines but not in cultured normal cells. To evaluate FK228 in vivo, the effects of FK228 therapy in athymic mice bearing LOX IMVI or UACC-62 human melanoma xenografts were examined. Groups of mice were treated with FK228 using several dosing schedules and the differences between treated and control animals were determined. In mice with LOX IMVI xenografts (n = 6), maximum CAR induction was observed 24 h following a single FK228 dose of 3.6 mg/kg with a 13.6 +/- 4.3-fold (mean +/- SD) increase in human CAR mRNA as determined by semiquantitative reverse transcription-PCR analysis. By comparison, mouse CAR levels in liver, kidney, and lung from the same animals showed little to no change. Maximum CAR protein induction of 9.2 +/- 4.8-fold was achieved with these treatment conditions and was associated with increased histone H3 acetylation. Adenovirus carrying a green fluorescent protein (GFP) transgene (2 x 10(9) viral particles) was injected into the xenografts and GFP mRNA levels were determined. A 7.4 +/- 5.2-fold increase in GFP mRNA was found 24 h following adenovirus injection into optimally FK228-treated mice (n = 10). A 4-fold increase in GFP protein-positive cells was found following FK228 treatment. These studies suggest that FK228 treatment prior to adenovirus infection could increase the efficiency of adenovirus gene therapy in xenograft model systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
496-505
pubmed:dateRevised
2011-7-1
pubmed:meshHeading
pubmed-meshheading:17308048-Acetylation, pubmed-meshheading:17308048-Adenoviridae Infections, pubmed-meshheading:17308048-Adenoviruses, Human, pubmed-meshheading:17308048-Animals, pubmed-meshheading:17308048-Antibiotics, Antineoplastic, pubmed-meshheading:17308048-Blotting, Western, pubmed-meshheading:17308048-Depsipeptides, pubmed-meshheading:17308048-Female, pubmed-meshheading:17308048-Green Fluorescent Proteins, pubmed-meshheading:17308048-Histone Deacetylase Inhibitors, pubmed-meshheading:17308048-Histones, pubmed-meshheading:17308048-Humans, pubmed-meshheading:17308048-Melanoma, pubmed-meshheading:17308048-Mice, pubmed-meshheading:17308048-Mice, Nude, pubmed-meshheading:17308048-RNA, Messenger, pubmed-meshheading:17308048-RNA, Viral, pubmed-meshheading:17308048-Receptors, Virus, pubmed-meshheading:17308048-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17308048-Skin Neoplasms, pubmed-meshheading:17308048-Transgenes
pubmed:year
2007
pubmed:articleTitle
The histone deacetylase inhibitor FK228 given prior to adenovirus infection can boost infection in melanoma xenograft model systems.
pubmed:affiliation
Experimental Therapeutics Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Building 10, Room 13N240, MSC 1903, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural