Linked Life Data

11339897

Source:http://linkedlifedata.com/resource/pubmed/id/11339897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2001-5-7
pubmed:abstractText
Malignant gliomas are the most common primary brain tumors in adults and, with few exceptions, have a dismal prognosis despite the therapeutic use of surgery, radiation therapy, and chemotherapy. Because CNS gliomas rarely metastasize, they represent an attractive target for gene therapy through local gene delivery. Here we report on the use of two different fusogenic membrane glycoproteins (FMGs), the measles virus proteins F and H (MV-F and MV-H) and a mutated form of the retroviral envelope protein of the gibbon ape leukemia virus (GALV.fus), as a novel class of therapeutic transgenes in gliomas. Transfection of U87 and U118 cells with MV-F and MV-H cDNA or GALV.fus cDNA led in 48 hr to massive syncytial formation followed by cell death. FMG-mediated cytotoxicity in the U87 and U118 cell lines was superior to the cytotoxicity caused by transfection with HSV-tk cDNA followed by ganciclovir (GCV) treatment at all time points. At high-density cell seeding, addition of tumor cells transfected with MV-F and H killed at least 1 log more cells than by HSV-tk + GCV treatment, indicating higher bystander effect. Similar results were obtained with GALV.fus. The mechanism of syncytial death in cultured glioma cell lines was predominantly apoptotic. Transfection of U87 cells with F + H or GALV.fus expression constructs completely suppressed their tumorigenicity. Treatment of established U87 xenografts in nude mice with a combination of F and H adenoviruses at 1:1 ratio led to complete tumor regression, significantly higher antitumor effect, and prolongation of survival as compared with control animals treated with a GFP adenovirus. In summary, the viral fusogenic membrane glycoproteins (GALV and the MV-F + MV-H combination) are potent therapeutic transgenes with potential utility in the gene therapy of gliomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
811-21
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11339897-Animals, pubmed-meshheading:11339897-Apoptosis, pubmed-meshheading:11339897-Brain Neoplasms, pubmed-meshheading:11339897-Cell Fusion, pubmed-meshheading:11339897-Ganciclovir, pubmed-meshheading:11339897-Gene Therapy, pubmed-meshheading:11339897-Genetic Vectors, pubmed-meshheading:11339897-Giant Cells, pubmed-meshheading:11339897-Glioma, pubmed-meshheading:11339897-Hemagglutinins, Viral, pubmed-meshheading:11339897-Humans, pubmed-meshheading:11339897-Lentivirus, pubmed-meshheading:11339897-Leukemia Virus, Gibbon Ape, pubmed-meshheading:11339897-Measles virus, pubmed-meshheading:11339897-Membrane Glycoproteins, pubmed-meshheading:11339897-Mice, pubmed-meshheading:11339897-Mice, Inbred BALB C, pubmed-meshheading:11339897-Mice, Nude, pubmed-meshheading:11339897-Mutation, pubmed-meshheading:11339897-Neoplasm Transplantation, pubmed-meshheading:11339897-Thymidine Kinase, pubmed-meshheading:11339897-Transgenes, pubmed-meshheading:11339897-Tumor Cells, Cultured, pubmed-meshheading:11339897-Viral Fusion Proteins
pubmed:year
2001
pubmed:articleTitle
Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas.
pubmed:affiliation
Medical Oncology and Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA. galanis.evanthia@mayo.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't