Linked Life Data

12828859

Source:http://linkedlifedata.com/resource/pubmed/id/12828859

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-6-27
pubmed:abstractText
Inhibition of angiogenesis has been considered among the most promising approaches to treat highly vascularized solid tumors such as glioblastoma. In this study, we designed and validated a new in vitro assay system based on the implantation of tumor cells into organotypic brain slice cultures. We evaluated the effects of local production of three endogenous inhibitors of angiogenesis, angiostatin, endostatin, and interferon (IFN)-alpha(1), using stably transfected rat (9L) and human (GL15) glioblastoma cells on tumor vascularization and growth. Despite similar effectiveness of the three proteins in a classic in vitro endothelial cell migration assay, IFN-alpha(1) demonstrated the most potent antiangiogenic effect in organotypic brain slice cultures. In vivo, after intracerebral implantation of such genetically modified glioblastoma cells, IFN-alpha(1) caused a dramatic decrease in tumor volume revealed by magnetic resonance imaging and by postmortem histology. The mechanisms of this antitumor effect were most likely caused by the major antiangiogenic action of the cytokine, because IFN-alpha(1) expression provoked a pronounced decrease in blood vessel density, which was accompanied by extensive necrosis in the body mass of the tumors. The median survival time of rats implanted intracerebrally with IFN-alpha-expressing 9L cells tripled, and was still significantly increased when these constituted only 1% of transplanted tumor cells. A similar effect was seen when 50% of the transplanted cells were replaced by IFN-alpha-expressing bone marrow stromal cells. These data point to the local delivery of IFN-alpha(1) using cell vectors as a potent tool for the inhibition of tumor-induced angiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
883-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12828859-Angiogenesis Inhibitors, pubmed-meshheading:12828859-Angiostatins, pubmed-meshheading:12828859-Animals, pubmed-meshheading:12828859-Brain, pubmed-meshheading:12828859-Brain Neoplasms, pubmed-meshheading:12828859-Cells, Cultured, pubmed-meshheading:12828859-Collagen, pubmed-meshheading:12828859-Endostatins, pubmed-meshheading:12828859-Fluorescent Antibody Technique, pubmed-meshheading:12828859-Genetic Vectors, pubmed-meshheading:12828859-Glioblastoma, pubmed-meshheading:12828859-Humans, pubmed-meshheading:12828859-Interferon-alpha, pubmed-meshheading:12828859-Magnetic Resonance Imaging, pubmed-meshheading:12828859-Peptide Fragments, pubmed-meshheading:12828859-Plasminogen, pubmed-meshheading:12828859-Protein Engineering, pubmed-meshheading:12828859-Rats, pubmed-meshheading:12828859-Rats, Sprague-Dawley, pubmed-meshheading:12828859-Retroviridae, pubmed-meshheading:12828859-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Antiangiogenic therapy against experimental glioblastoma using genetically engineered cells producing interferon-alpha, angiostatin, or endostatin.
pubmed:affiliation
INSERM U 421, Neuroplasticity and Therapeutics, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't