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dc.contributor.authorBlanchard, Helenen_US
dc.contributor.authorCutler, Samuelen_US
dc.contributor.authorDong, Lan-fengen_US
dc.contributor.authorIto, Koichien_US
dc.contributor.authorNeuzil, Jirien_US
dc.contributor.authorRalph, Stephenen_US
dc.contributor.authorScott, Stacyen_US
dc.date.accessioned2017-04-04T21:42:33Z
dc.date.available2017-04-04T21:42:33Z
dc.date.issued2011en_US
dc.date.modified2012-09-14T01:10:17Z
dc.identifier.issn15737209en_US
dc.identifier.doi10.1007/s10456-011-9213-5en_US
dc.identifier.urihttp://hdl.handle.net/10072/40730
dc.description.abstractCancer cells produce galectin-1 as a tumor promoting protein. Thiodigalactoside (TDG) as a non-metabolised small drug, is shown to suppress tumor growth by inhibiting multiple cancer enhancing activities of galectin-1, including immune cell dysregulation, angiogenesis and protection against oxidative stress. Thus, using B16F10 melanoma and 4T1 orthotopic breast cancer models, intratumoral injection of TDG significantly raised the levels of tumor-infiltrating CD8+ lymphocytes and reduced CD31+ endothelial cell content, reducing tumor growth. TDG treatment of tumors in Balb/c nude mice (defective in T cell immunity) reduced angiogenesis and slowed tumor growth by a third less than in immunocompetent mice. Knocking down galectin-1 expression (G1KD) in both cancer cell types significantly impeded tumor growth and the sensitivity of the G1KD tumors to TDG was severely reduced, highlighting a specific role for galectin-1. Endothelial cells were protected by galectin-1 from oxidative stress-induced apoptosis induced by H2O2, but TDG inhibited this antioxidant protective effect of galectin-1 and reduced tube forming activity in angiogenic assays. We show for the first time that the single agent, TDG, concurrently prevents many tumor promoting effects of galectin-1 on angiogenesis, immune dysregulation and protection against oxidative stress, providing a potent and novel small molecule as an anti-cancer drug.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.format.extent584232 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherSpringeren_US
dc.publisher.placeNetherlandsen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrom293en_US
dc.relation.ispartofpageto307en_US
dc.relation.ispartofissue3en_US
dc.relation.ispartofjournalAngiogenesisen_US
dc.relation.ispartofvolume14en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchCancer Therapy (excl. Chemotherapy and Radiation Therapy)en_US
dc.subject.fieldofresearchcode111204en_US
dc.titleThiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stressen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightCopyright 2011 Springer Netherlands. This is an electronic version of an article published in Apoptosis, 2011. Apoptosis is available online at: http://www.springerlink.com/ with the open URL of your article.en_US
gro.date.issued2011
gro.hasfulltextFull Text


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