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Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line.
Leonetti, C; Biroccio, A; Benassi, B; Stringaro, A; Stoppacciaro, A; Semple, S C; Zupi, G.
Afiliación
  • Leonetti C; Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, 00158 Rome, Italy. leonetti@ifo.it
Cancer Gene Ther ; 8(6): 459-68, 2001 Jun.
Article en En | MEDLINE | ID: mdl-11498766
Phosphorothioate c-myc antisense oligodeoxynucleotides [S]ODNs (free INX-6295) were encapsulated in a new liposome formulation and the antitumor activity was compared to the unencapsulated antisense in a human melanoma xenograft. The systemic administration of INX-6295 encapsulated in stabilized antisense lipid particles (SALP INX-6295) improved plasma AUC (area under the plasma concentration-time curve) and initial half-life of free INX-6295, resulting in a significant enhancement in tumor accumulation and improvement in tumor distribution of antisense oligodeoxynucleotides. Animals treated with SALP INX-6295 exhibited a prolonged reduction of c-myc expression, reduced tumor growth and increased mice survival. When administered in combination with cisplatin (DDP), SALP INX-6295 produced a complete tumor regression in approximately 30% of treated mice, which persisted for at least 60 days following the first cycle of treatment. Finally, the median survival of mice treated with DDP/SALP INX-6295 increased by 105% compared to 84% for animals treated with the combination DDP/free INX-6295. These data indicate that the biological activity and the therapeutic efficacy of c-myc antisense therapy may be improved when these agents are administered in lipid-based delivery systems.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genes myc / Oligonucleótidos Antisentido / Melanoma / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2001 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genes myc / Oligonucleótidos Antisentido / Melanoma / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2001 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido