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Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.
MedLine Citation:
PMID:  21193455     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background and objectives Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate of patients with HCC is manifested by an aggressive and metastatic phenotype, as well as a poor response to common therapeutic strategies. The purpose of this study was to evaluate the efficacy of nanoliposomal C6-ceramide as an antineoplastic agent in an in vivo model of human HCC. Methods The growth-arresting and pro-apoptotic properties of nanoliposomal C6-ceramide were first evaluated in vitro in human SK-HEP-1 cells by assessing cellular viability, caspase 3/7 activity, annexin-V expression, DNA fragmentation, cell cycle distribution and AKT phosphorylation. SK-HEP-1 cells were then engrafted subcutaneously into athymic nude mice and nanoliposomal C6-ceramide was administered by tail vein injection. Tumour size was monitored over time, followed by excision of tumours to evaluate tumour vascularisation, proliferation, apoptosis and cellular signalling. Results Nanoliposomal C6-ceramide, but not ghost (no ceramide) nanoliposomes, induced apoptotic cell death of SK-HEP-1 cells in vitro, concomitant with an accumulation of cells in the G(2) phase of the cell cycle and decreased phosphorylation of AKT. Systemic administration of nanoliposomal C6-ceramide to mice engrafted with SK-HEP-1 tumours reduced tumour vascularisation and proliferation, induced tumour cell apoptosis, decreased phosphorylation of AKT and ultimately blocked tumour growth. Conclusions These studies show that nanoliposomal ceramide is an efficacious antineoplastic agent for the treatment of in vitro and in vivo models of human HCC.
Authors:
Hephzibah Rani S Tagaram; Nicole A Divittore; Brian M Barth; James M Kaiser; Diego Avella; Eric T Kimchi; Yixing Jiang; Harriet C Isom; Mark Kester; Kevin F Staveley-O'Carroll
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-30
Journal Detail:
Title:  Gut     Volume:  -     ISSN:  1468-3288     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
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