Antisense therapy of cancer.
Binding sites for the NF-kappa B transcription factor complex, composed of two subunits, p50 (NFKB1) and p65 (rel A), are present in many cell adhesion molecules, cytokines, and growth-factor receptors. Antisense techniques were used to establish the role of NF-kappa B in cell growth. Surprisingly, antisense phosphorothioate oligomers to the rel A subunit of NF-kappa B caused a pronounced block of cellular adhesion. Since adhesion plays an important role in diseases including cancer and inflammation, this chance observation was extended to various in vitro and in vivo models. Our results establish the in vivo efficacy of phosphorothioate oligomers.
Narayanan
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Division of Oncology, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA.
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D020572:Oncogene Proteins v-rel; D009857:Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000037:antagonists & inhibitors / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D020572:Oncogene Proteins v-rel; D015682:Retroviridae Proteins, Oncogenic