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dc.contributor.authorO'SULLIVAN, JACINTHAen
dc.date.accessioned2017-05-25T11:29:58Z
dc.date.available2017-05-25T11:29:58Z
dc.date.created2016en
dc.date.issued2016en
dc.date.submitted2016en
dc.identifier.citationMurphy A.G, Casey R, Maguire A, Tosetto M, Butler C.T, Conroy E, Reynolds A.L, Sheahan K, O'Donoghue D, Gallagher W.M, Fennelly D, Kennedy B.N, O'Sullivan J, Preclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal cancer, Scientific Reports, 6, 2016en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/80228
dc.descriptionPUBLISHEDen
dc.descriptionCited By :2 Export Date: 3 April 2017en
dc.description.abstractColorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75 g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p < 0.001). In vitro, quininib reduced endothelial tubule formation (p < 0.001), cell migration was unaffected by quininib and cell survival was reduced by quininib (p < 0.001). Using ex vivo human CRC explants, quininib significantly reduced the secretions of IL-6, IL-8, VEGF, ENA-78, GRO-α, TNF, IL-1β and MCP-1 ex vivo (all values p < 0.01). Quininib is well tolerated in mice when administered at 50 mg/kg intraperitoneally every 3 days and significantly reduced tumour growth of HT-29-luc2 CRC tumour xenografts compared to vehicle control. In addition, quininib reduced the signal from a αvβ3 integrin fluorescence probe in tumours 10 days after treatment initiation, indicative of angiogenic inhibition. Furthermore, quininib reduced the expression of angiogenic genes in xenografted tumours. Collectively, these findings support further development of quininib as a novel therapeutic agent for CRC.en
dc.description.sponsorshipAdrian Murphy was funded by a Newman Fellowship from the University College Dublin Newman Foundation to conduct this work. This work was also funded by a Science Foundation Ireland TIDA grant 11/TIDA/B1966.en
dc.relation.ispartofseriesScientific Reportsen
dc.relation.ispartofseries6en
dc.rightsYen
dc.subjectColorectal cancer (CRC)en
dc.subject.lcshColorectal cancer (CRC)en
dc.titlePreclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal canceren
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/osullij4en
dc.identifier.rssinternalid156571en
dc.identifier.doihttp://dx.doi.org/10.1038/srep34523en
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber11/TIDA/B1966en
dc.identifier.rssurihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84991738304&doi=10.1038%2fsrep34523&partnerID=40&md5=22e2c9e3072301d6de01d426c59fbcd0en


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