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dc.contributor.authorGounaris, Elias
dc.contributor.authorTung, Ching H.
dc.contributor.authorRestaino, Clifford
dc.contributor.authorMaehr, Rene
dc.contributor.authorKohler, Rainer H.
dc.contributor.authorJoyce, Johanna A.
dc.contributor.authorPlough, Hidde L.
dc.contributor.authorBarrett, Terrence A.
dc.contributor.authorWeissleder, Ralph
dc.contributor.authorKhazaie, Khashayarsha
dc.date.accessioned2010-11-01T17:00:15Z
dc.date.issued2008
dc.identifier.citationGounaris, Elias, Ching H. Tung, Clifford Restaino, René Maehr, Rainer Kohler, Johanna A. Joyce, Hidde L. Plough, Terrence A. Barrett, Ralph Weissleder, and Khashayarsha Khazaie. 2008. Live imaging of cysteine-cathepsin activity reveals dynamics of focal inflammation, angiogenesis, and polyp growth. PLoS ONE 3:e2916.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4515009
dc.description.abstractIt has been estimated that up to 30% of detectable polyps in patients regress spontaneously. One major challenge in the evaluation of effective therapy of cancer is the readout for tumor regression and favorable biological response to therapy. Inducible near infra-red (NIR) fluorescent probes were utilized to visualize intestinal polyps of mice hemizygous for a novel truncation of the Adenomatous Polyposis coli (APC) gene. Laser Scanning Confocal Microscopy in live mice allowed visualization of cathepsin activity in richly vascularized benign dysplastic lesions. Using biotinylated suicide inhibitors we quantified increased activities of the Cathepsin B & Z in the polyps. More than ¾ of the probe signal was localized in CD11b+Gr1+ myeloid derived suppressor cells (MDSC) and CD11b+F4/80+ macrophages infiltrating the lesions. Polyposis was attenuated through genetic ablation of cathepsin B, and suppressed by neutralization of TNFα in mice. In both cases, diminished probe signal was accounted for by loss of MDSC. Thus, in vivo NIR imaging of focal cathepsin activity reveals inflammatory reactions etiologically linked with cancer progression and is a suitable approach for monitoring response to therapy.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0002916en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488397/pdf/en_US
dash.licenseLAA
dc.subjectradiology and medical imagingen_US
dc.subjectimmunologyen_US
dc.subjectinnate immunityen_US
dc.subjectgastroenterology and hepatologyen_US
dc.subjectgastrointestinal cancersen_US
dc.titleLive Imaging of Cysteine-Cathepsin Activity Reveals Dynamics of Focal Inflammation, Angiogenesis, and Polyp Growthen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMaehr, Rene
dc.date.available2010-11-01T17:00:15Z
dc.identifier.doi10.1371/journal.pone.0002916*
dash.contributor.affiliatedKohler, Rainer
dash.contributor.affiliatedMaehr, Rene
dash.contributor.affiliatedWeissleder, Ralph


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