Linked Life Data

18376144

Source:http://linkedlifedata.com/resource/pubmed/id/18376144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-8-19
pubmed:abstractText
Melanoma differentiation associated gene-7/interleukin 24 (mda-7/IL-24) is a cytokine displaying selective apoptosis-inducing activity in tumors, including glioblastoma (GBM), without damaging normal cells. The present studies focused on defining whether an adenovirus expressing MDA-7/IL-24, Ad.mda-7, infused into pre-formed invasive primary human GBM tumors growing in athymic mouse brains altered tumor cell growth and animal survival, and whether Ad.mda-7 radiosensitized GBM cells and enhanced the survival benefit of irradiation. Ad.mda-7 directly radiosensitized glioma cells in vitro in a JNK1-3- and caspase 9-dependent fashion and demonstrated bystander-effect killing and radiosensitization of GBM cells when primary human astrocytes were infected with Ad.mda-7. Infusion of Ad.mda-7 into pre-formed glioma tumors caused a rapid decrease in proliferation and blood vessel density and an increase in cell killing. Irradiation of Ad.mda-7 infected tumors enhanced cell death. Cell killing correlated with pro-caspase 3 cleavage, enhanced phosphorylation of JNK1-3 and reduced phosphorylation of ERK1/2. Ad.mda-7 enhanced the survival of animals implanted with GBM6 and GBM12 tumors, and significantly increased the survival benefit of irradiation in animals bearing GBM12 tumors. Ad.mda-7 toxicity was evident against CD133+ and CD133- GBM cells; upon tumor re-growth approximately 70-100 days after virus infusion, the relative CD133+ level within the tumor was profoundly reduced with lower Ki67 reactivity and increased beta-galactosidase staining. Infusion of Ad.mda-7 into an immune competent rat brain did not cause normal tissue toxicity 1-4 weeks after infusion using T1 and T2 weighted MRI and H&E staining. Our data demonstrate that Ad.mda-7 prolongs the survival of animals bearing GBM tumors and does so through multiple mechanisms including direct tumor cell killing and selection for surviving cells that are more differentiated and potentially displaying a putatively senescent phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
917-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
MDA-7/IL-24 plus radiation enhance survival in animals with intracranial primary human GBM tumors.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298-0035, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural