Data/hora: 13/06/2024 00:35:21

Provedor de dados: 	17	
País: 	United Kingdom	
Título: 	A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1	
Autores: 	Shi-He Liu; Donald Rao; John Nemunaitis; Neil Senzer; David Dawson; Marie-Claude Gingras; Zhaohui Wang; Richard Gibbs; Michael Norman; Nancy Templeton; Francesco DeMayo; Kelly Stehling; William Fisher; Charles Brunicardi.	
Data: 	2011-06-21	
Ano: 	2011	
Palavras-chave: 	Cancer; Genetics &amp; Genomics.	
Resumo: 	Bi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA&amp;#x3c;sup&amp;#x3e;mousePDX-1&amp;#x3c;/sup&amp;#x3e; or shRNA&amp;#x3c;sup&amp;#x3e;mousePDX-1&amp;#x3c;/sup&amp;#x3e; lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of shRNA&amp;#x3c;sup&amp;#x3e;mousePDX-1&amp;#x3c;/sup&amp;#x3e; lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of pancreatic neoplasia. Moreover, three cycles of the bi-shRNA&amp;#x3c;sup&amp;#x3e;humanPDX-1&amp;#x3c;/sup&amp;#x3e; lipoplexes resulted in near complete ablation of tumor volume and considerably improved survival in a human PANC-1 implanted SCID-mouse model. Human pancreatic neoplasia specimens also stained strongly for PDX-1 expression. Together, these data support the clinical development of a novel therapeutic strategy using systemic bi-shRNA&amp;#x3c;sup&amp;#x3e;PDX-1&amp;#x3c;/sup&amp;#x3e; lipoplexes against pancreatic neoplasia.	
Tipo: 	Manuscript	
Identificador: 	http://precedings.nature.com/documents/6047/version/1

oai:nature.com:10101/npre.2011.6047.1

http://hdl.handle.net/10101/npre.2011.6047.1	
Fonte: 	Nature Precedings	
Fonte: 	Creative Commons Attribution 3.0 License