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Title: | MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer | Authors: | Passadouro, Marta Lima, Maria C. Pedroso de Faneca, Henrique |
Keywords: | pancreatic cancer gene therapy; anti-microRNAs oligonucleotides; delivery nanosystems; albumin-associated lipoplexes | Issue Date: | 2014 | Publisher: | Dove Medical Press | Project: | PTDC/SAU-BMA/114482/2009 PEst-C/SAU/LA0001/2013–2014 SFRH/BD/46903/2008 |
Serial title, monograph or event: | International Journal of Nanomedicine | Volume: | 9 | Abstract: | Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin-1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/-) (4/1) nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. | URI: | https://hdl.handle.net/10316/109459 | ISSN: | 1178-2013 | DOI: | 10.2147/IJN.S64456 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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MicroRNA-modulation-combined-with-sunitinib-as-a-novel-therapeutic-strategy-for-pancreatic-cancerInternational-Journal-of-Nanomedicine.pdf | 1.84 MB | Adobe PDF | View/Open |
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