UROKINASE ANTISENSE OLIGODEOXYNUCLEOTIDES AS A NOVEL THERAPEUTIC AGENT FOR MALIGNANT GLIOMA - IN-VITRO AND IN-VIVO STUDIES OF UPTAKE, EFFECTS AND TOXICITY

Antisense therapy might offer an improved treatment for patients with malignant glioma. We studied the uptake and effects of urokinase antis ense oligodeoxynucleotides on rat and human glioma cells ill vitro and the uptake and toxicity of these nucleotides in rat carcinomatosis an d brain tumor models, Cultured glioma cells readily incorporated fluor escein isothiocyanate-conjugated oligonucleotides, as demonstrated by immunofluorescence microscopy and flow cytometry. Effects on urokinase expression as assessed by immunofluorescence microscopy varied accord ing to cell line. Northern blot analysis showed decreases in urokinase expression with oligodeoxynucleotide treatment. Uptake into tumor cel ls was also demonstrated in vivo, with no detectable toxicity at conce ntrations exceeding expected therapeutic levels. These data are encour aging for the further study of antisense oligodeoxynucleotides as a ne w therapeutic modality for malignant glioma. (C) 1996 Academic Press, Inc.