Urokinase Antisense Oligodeoxynucleotides as a Novel Therapeutic Agent for Malignant Glioma:In Vitroandin VivoStudies of Uptake, Effects and Toxicity
- Resource Type
- Article
- Authors
- Engelhard, Herbert; Narang, Carol; Homer, Ronald; Duncan, Holly
- Source
- Biochemical and Biophysical Research Communications; October 1996, Vol. 227 Issue: 2 p400-405, 6p
- Subject
- Language
- ISSN
- 0006291X; 10902104
Antisense therapy might offer an improved treatment for patients with malignant glioma. We studied the uptake and effects of urokinase antisense oligodeoxynucleotides on rat and human glioma cellsin vitroand the uptake and toxicity of these nucleotides in rat carcinomatosis and brain tumor models. Cultured glioma cells readily incorporated fluorescein isothiocyanate-conjugated oligonucleotides, as demonstrated by immunofluorescence microscopy and flow cytometry. Effects on urokinase expression as assessed by immunofluorescence microscopy varied according to cell line. Northern blot analysis showed decreases in urokinase expression with oligodeoxynucleotide treatment. Uptake into tumor cells was also demonstratedin vivo,with no detectable toxicity at concentrations exceeding expected therapeutic levels. These data are encouraging for the further study of antisense oligodeoxynucleotides as a new therapeutic modality for malignant glioma.