RAF antisense oligonucleotide as a tumor radiosensitizer
نویسندگان
چکیده
منابع مشابه
Antisense Oligonucleotide Targeting of Raf-1
Purpose: We sought to identify determinants of growth response to the Raf-1-targeted antisense oligonucleotide (ASO; ISIS 5132) using a large panel of ovarian cancer cell lines. Experimental Design: First(ISIS 5132) and secondgeneration (ISIS 13650) anti-Raf 1 ASOs were compared with control oligonucleotides. Growth was assessed by cell counts; apoptosis was assessed by poly(ADP-ribose) polymer...
متن کاملAntisense oligonucleotide targeting of Raf-1: importance of raf-1 mRNA expression levels and raf-1-dependent signaling in determining growth response in ovarian cancer.
PURPOSE We sought to identify determinants of growth response to the Raf-1-targeted antisense oligonucleotide (ASO; ISIS 5132) using a large panel of ovarian cancer cell lines. EXPERIMENTAL DESIGN First-(ISIS 5132) and second-generation (ISIS 13650) anti-Raf 1 ASOs were compared with control oligonucleotides. Growth was assessed by cell counts; apoptosis was assessed by poly(ADP-ribose) polym...
متن کاملPharmacokinetics and metabolism in mice of a phosphorothioate oligonucleotide antisense inhibitor of C-raf-1 kinase expression.
The plasma and tissue disposition of CGP 69846A (ISIS 5132) was characterized in male CD-1 mice following iv bolus injections administered every other day for 28 days (total of 15 doses). The doses ranged from 0.8 mg/kg to 100 mg/kg. Urinary excretion of oligonucleotide was also monitored over a 24-hr period following single dose administration over the same dose range. Pharmacokinetic plasma p...
متن کاملPharmacokinetics and tissue distribution of a DNA-methyltransferase antisense (MT-AS) oligonucleotide and its catabolites in tumor-bearing nude mice.
The pharmacokinetics of a 20-mer phosphorothioate antisense oligodeoxynucleotide was investigated in nude mice bearing a s.c. human lung carcinoma. The oligodeoxynucleotide, referred to as DNA-methyltransferase antisense (MT-AS) was designed to bind to the mRNA that coded for DNA-methyltransferase, an enzyme that controls the extent of methylation of 5'-cytosine. MT-AS was administered at four ...
متن کاملA phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer.
Raf proteins play a central role in the mitogen-activated protein kinase signaling pathway and hence are involved in oncogenic transformation and tumor cell proliferation. ISIS 5132 is a 20-base antisense phosphorothioate oligodeoxyribonucleotide that specifically down-regulates c-raf expression. We report here an initial study of the safety and tolerability of an i.v. infusion of ISIS 5132 in ...
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ژورنال
عنوان ژورنال: Oncogene
سال: 2003
ISSN: 0950-9232,1476-5594
DOI: 10.1038/sj.onc.1206700