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dc.contributor.authorFaca, Vitor M
dc.contributor.authorSong, Kenneth S
dc.contributor.authorKrasnoselsky, Alexei L
dc.contributor.authorNewcomb, Lisa F
dc.contributor.authorPlentz, Ruben R
dc.contributor.authorRedston, Mark S
dc.contributor.authorPitteri, Sharon J
dc.contributor.authorPereira-Faca, Sandra R
dc.contributor.authorIreton, Renee C
dc.contributor.authorKatayama, Hiroyuki
dc.contributor.authorGlukhova, Veronika
dc.contributor.authorPhanstiel, Douglas
dc.contributor.authorBrenner, Dean E
dc.contributor.authorAnderson, Michelle A
dc.contributor.authorMisek, David
dc.contributor.authorScholler, Nathalie
dc.contributor.authorUrban, Nicole D
dc.contributor.authorBarnett, Matt J
dc.contributor.authorEdelstein, Cim
dc.contributor.authorGoodman, Gary E
dc.contributor.authorThornquist, Mark D
dc.contributor.authorMcIntosh, Martin W
dc.contributor.authorBardeesy, Nabeel
dc.contributor.authorHanash, Samir M
dc.contributor.authorWang, Hong
dc.contributor.authorZhang, Qing
dc.contributor.authorGurumurthy, Sushma
dc.contributor.authorDePinho, Ronald A.
dc.date.accessioned2011-04-17T04:49:39Z
dc.date.issued2008
dc.identifier.citationFaca, Vitor M., Kenneth S. Song, Hong Wang, Qing Zhang, Alexei L. Krasnoselsky, Lisa F. Newcomb, Ruben R. Plentz, et al. 2008. A mouse to human search for plasma proteome changes associated with pancreatic tumor development. PLoS Medicine 5(6): e123.en_US
dc.identifier.issn1549-1277en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4853388
dc.description.abstractBackground: The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings: Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions: Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pmed.0050123en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504036/pdf/en_US
dash.licenseLAA
dc.titleA Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Developmenten_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Medicineen_US
dash.depositing.authorGurumurthy, Sushma
dc.date.available2011-04-17T04:49:39Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pmed.0050123*
dash.authorsorderedfalse
dash.contributor.affiliatedGurumurthy, Sushma
dash.contributor.affiliatedDePinho, Ronald A.
dash.contributor.affiliatedZhang, Qing


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