https://scholars.lib.ntu.edu.tw/handle/123456789/503595
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Yoon S. | en_US |
dc.contributor.author | KAI-WEN HUANG | en_US |
dc.contributor.author | Andrikakou P. | en_US |
dc.contributor.author | Vasconcelos D. | en_US |
dc.contributor.author | Swiderski P. | en_US |
dc.contributor.author | Reebye V. | en_US |
dc.contributor.author | Sodergren M. | en_US |
dc.contributor.author | Habib N. | en_US |
dc.contributor.author | Rossi J.J. | en_US |
dc.creator | Yoon S.;Kai-Wen Huang;Andrikakou P.;Vasconcelos D.;Swiderski P.;Reebye V.;Sodergren M.;Habib N.;Rossi J.J. | - |
dc.date.accessioned | 2020-06-19T02:26:59Z | - |
dc.date.available | 2020-06-19T02:26:59Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072279341&doi=10.1016%2fj.omtn.2019.08.017&partnerID=40&md5=96f05010beae5b5281284e7021697198 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/503595 | - |
dc.description.abstract | Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies; it preferentially metastasizes to the liver and is the main cause of death from this disease. In previous studies, small activating RNA against CCAAT/enhancer-binding protein-α (C/EBPα-saRNA) demonstrated efficacy of PDAC in a local subcutaneous tumor model. In this study, we focused on the efficacy of C/EBPα-saRNA in advanced stage PDAC. For targeted delivery, we selected a new anti-transferrin receptor aptamer (TR14), which demonstrated a high binding affinity to target proteins. The TR14 aptamer was internalized with clathrin-mediated endocytosis, distributed in early endosome, late endosome, and lysosome subcellularly. To investigate its anti-tumor effects to advanced PDAC, we conjugated C/EBPα-saRNA to TR14. Treatment of pancreatic cancer cells with the conjugates upregulated expression of C/EBPα and its downstream target p21, and inhibited cell proliferation. For in vivo assays, we established an advanced PDAC mouse model by engrafting luciferase reporter-PANC-1 cells directly into the livers of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After treatment of aptamer-C/EBPα conjugates, we observed significant reduction of tumor growth in this advanced PDAC mouse model. Combinational treatment of the conjugates with gemcitabine also demonstrated enhanced anti-tumor effects in advanced PDAC. This suggests that aptamer-C/EBPα conjugates could be used as an adjuvant, along with other conventional anti-cancer drugs in advanced PDAC. In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC. ? 2019 The Authors | - |
dc.publisher | Cell Press | - |
dc.relation.ispartof | Molecular Therapy - Nucleic Acids | - |
dc.subject | adjuvant; advanced PDAC; albumin affinity tag; anti-tumor effects; C/EBPα-saRNA; clathrin-mediated endocytosis; targeted delivery; transferrin receptor aptamer; truncation | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | aptamer; CCAAT enhancer binding protein alpha; clathrin; gemcitabine; protein p21; RNA; small activating RNA; tr14 aptamer; unclassified drug; advanced cancer; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer inhibition; controlled study; drug efficacy; endocytosis; endosome; female; human; human cell; in vitro study; in vivo study; lysosome; mouse; nonhuman; pancreas adenocarcinoma; priority journal; protein expression; upregulation | - |
dc.title | Targeted Delivery of C/EBPα-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1016/j.omtn.2019.08.017 | - |
dc.identifier.scopus | 2-s2.0-85072279341 | - |
dc.relation.pages | 142-154 | - |
dc.relation.journalvolume | 18 | - |
item.cerifentitytype | Publications | - |
item.openairetype | journal article | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
crisitem.author.dept | Surgery-NTUH | - |
crisitem.author.dept | Surgery | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.orcid | 0000-0001-6375-8714 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系 |
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