PURPOSE: The overexpression of @entity517 associated with uncontrolled cell proliferation is a frequent genetic event in @entity342 -refractory prostatic @entity5 . The purpose of this study was to evaluate the bioavailability and efficacy of a novel antisense phosphorodiamidate morpholino oligomer directed against @entity517 , @entity69205 , in PC-3 @entity342 -independent @entity1 @entity263 xenograft @entity19 model and its safety in a Phase I @entity1 clinical study. EXPERIMENTAL DESIGN: @entity69205 administration in athymic @entity19 bearing s.c. PC-3 xenografts was carried out to determine the bioavailability, tolerance, antitumor activity, and histological changes induced by targeted inhibition of @entity517 expression using a specific morpholine antisense oligomer. The Phase I safety study involved a single center, open label, dose-escalating design in healthy volunteers after i.v. administration of @entity69205 . RESULTS: The data reveal that @entity69205 targets and inhibits @entity517 translation in a sequence-specific manner and causes significant growth inhibition and apoptosis in @entity263 cells and in s.c. @entity5 xenografts. A 75-80% reduction in @entity5 burden was observed in @entity69205 -treated animals compared with the scrambled oligomer and saline control groups. Histologically, @entity5 grown in the athymic @entity19 treated with @entity69205 were less cellular and vascular than those in control @entity19 and showed an increased level of cellular degeneration, cytoplasmic vacuoles, and hyperchromatic nuclei. Phase I safety trials in @entity1 via i.v. route of administration showed no @entity137 or serious adverse events. CONCLUSIONS: The present study demonstrates that inhibition of @entity517 expression by antisense phosphorodiamidate morpholino oligomer is a promising new and safe therapeutic strategy for @entity263 .

Efficacy of antisense morpholino oligomer targeted to XXXX in @entity263 xenograft @entity19 model and a Phase I safety study in @entity1 .

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'neoplasia'] @entity69205 :: ('MESH:C554718', 'Chemical') :: ['AVI-4126'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity517 :: ('4609', 'Gene') :: ['c-myc', 'c-Myc'] @entity342 :: ('CHEBI:50113', 'Chemical') :: ['androgen']
@entity517 :: (4609,Gene) :: ['c-myc']
