Linked Life Data

11479223

Source:http://linkedlifedata.com/resource/pubmed/id/11479223

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2001-7-31
pubmed:abstractText
Adenoviral chimeric tumor suppressor 1 (CTS1) gene transfer was evaluated as a novel approach of somatic gene therapy for malignant glioma. CTS1 is an artificial p53-based gene designed to resist various pathways of p53 inactivation. Here, we report that an adenovirus encoding CTS1 (Ad-CTS1) induces growth arrest and loss of viability in all glioma cell lines examined, in the absence of specific cell cycle changes. In contrast, an adenovirus encoding wild-type p53 (Ad-p53) does not consistently induce apoptosis in the same cell lines. Electron microscopic analysis of Ad-CTS1-infected glioma cells reveals complex cytoplasmic pathology and delayed apoptotic changes. Ad-CTS1 induces prominent activation of various p53 target genes, including p21 and MDM-2, but has no relevant effects on BCL-2 family protein expression. Although Ad-CTS1 strongly enhances CD95 expression at the cell surface, endogenous CD95/CD95 ligand interactions do not mediate CTS1-induced cell death. This is because Ad-CTS1 promotes neither caspase activation nor mitochondrial cytochrome c release and because the caspase inhibitors, z-val-Ala-DL-Asp-fluoromethylketone (zVAD)-fmk or z-Ile-Glu-Thr-Asp- fluoromethylketone (z-IETD)-fmk, do not block CTS1-induced cell death. Ad-CTS1 synergizes with radiotherapy and CD95 ligand in killing glioma cells. In summary, Ad-CTS1 induces an unusual type of cell death that appears to be independent of BCL-2 family proteins, cytochrome c release, and caspases. CTS1 gene transfer is a promising strategy of somatic gene therapy for malignant glioma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5833-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11479223-Adenoviruses, Human, pubmed-meshheading:11479223-Antigens, CD95, pubmed-meshheading:11479223-Antineoplastic Agents, pubmed-meshheading:11479223-Caspases, pubmed-meshheading:11479223-Cell Division, pubmed-meshheading:11479223-Cell Survival, pubmed-meshheading:11479223-Combined Modality Therapy, pubmed-meshheading:11479223-Cytochrome c Group, pubmed-meshheading:11479223-Fas Ligand Protein, pubmed-meshheading:11479223-Gene Therapy, pubmed-meshheading:11479223-Genes, p53, pubmed-meshheading:11479223-Glioma, pubmed-meshheading:11479223-Humans, pubmed-meshheading:11479223-Membrane Glycoproteins, pubmed-meshheading:11479223-Mitochondria, pubmed-meshheading:11479223-Mutation, pubmed-meshheading:11479223-Recombinant Fusion Proteins, pubmed-meshheading:11479223-Transfection, pubmed-meshheading:11479223-Tumor Cells, Cultured, pubmed-meshheading:11479223-Tumor Suppressor Protein p53
pubmed:year
2001
pubmed:articleTitle
Chimeric tumor suppressor 1, a p53-derived chimeric tumor suppressor gene, kills p53 mutant and p53 wild-type glioma cells in synergy with irradiation and CD95 ligand.
pubmed:affiliation
Laboratory of Molecular Neuro-Oncology, Department of Neurology, Institute of Pathology, University of Tübingen Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't