{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/106486"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/106486","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Targeting the receptor for advanced glycation end products with a quantitative multimodal imaging method for precision medicine","abstract":"The Receptor for Advanced Glycation End Products (RAGE) has been shown to contribute to a myriad of pathologies including nephropathy, Alzheimer’s disease, cardiomyopathy, and pulmonary, ocular, arterial, and atherosclerotic diseases. It has been shown that RAGE expression levels are high during development but markedly decreased in adult tissues; while on the other hand, RAGE expression in adult tissues is significantly augmented by increased levels of ligands named advanced-glycation end-products (AGEs), which are observed in pathological states including inflammation, diabetes, renal and heart failure, and cancer. Yet, the study of RAGE and its ligands in their relation to cancer progression are still in their early stages. Significantly, however, RAGE and its ligands have been shown to be both over expressed and critical to prostate cancer (PCa) development. Importantly, overexpression of RAGE and its ligand HMGB1 clinically has been shown to be associated with poor PCa patient survival, suggesting its promise as a molecular target for imaging and therapeutics. In this work, we developed and employed a nanoparticle-based imaging strategy of RAGE, first in a model of hind-limb ischemia (a widely-studied pathological model for RAGE signaling), and subsequently in PCa. Finally, we demonstrate the utility of this probe and the potential import RAGE and its ligands may play in disease, by using this RAGE-targeted imaging strategy to track the effects of dietary Advanced Glycation End Products on PCa progression. This strategy allows for the development of precision clinical assessment and treatment paradigms, while highlighting the import of this receptor.","abstract_html":"The Receptor for Advanced Glycation End Products (RAGE) has been shown to contribute to a myriad of pathologies including nephropathy, Alzheimer’s disease, cardiomyopathy, and pulmonary, ocular, arterial, and atherosclerotic diseases. It has been shown that RAGE expression levels are high during development but markedly decreased in adult tissues; while on the other hand, RAGE expression in adult tissues is significantly augmented by increased levels of ligands named advanced-glycation end-products (AGEs), which are observed in pathological states including inflammation, diabetes, renal and heart failure, and cancer. Yet, the study of RAGE and its ligands in their relation to cancer progression are still in their early stages. Significantly, however, RAGE and its ligands have been shown to be both over expressed and critical to prostate cancer (PCa) development. Importantly, overexpression of RAGE and its ligand HMGB1 clinically has been shown to be associated with poor PCa patient survival, suggesting its promise as a molecular target for imaging and therapeutics. In this work, we developed and employed a nanoparticle-based imaging strategy of RAGE, first in a model of hind-limb ischemia (a widely-studied pathological model for RAGE signaling), and subsequently in PCa. Finally, we demonstrate the utility of this probe and the potential import RAGE and its ligands may play in disease, by using this RAGE-targeted imaging strategy to track the effects of dietary Advanced Glycation End Products on PCa progression. This strategy allows for the development of precision clinical assessment and treatment paradigms, while highlighting the import of this receptor.","abstract_has_math":false,"creators":["Konopka, Christian James"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Dobrucki, Wawrzyniec L","Smith, Andrew M","Pan, Dipanjan","Kajdacsy-Balla, Andre"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-03-02T22:38:56Z","date_published":"2020-03-02T22:38:56Z","updated_at":"2026-07-22T22:24:47Z","subjects":["Molecular Imaging","Receptor For Advanced Glycation End Products","Prostate Cancer","Nanoparticles","PET-CT"],"languages":["en"],"rights":["Copyright 2019 Christian J. 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Yet, the study of RAGE and its ligands in their relation to cancer progression are still in their early stages. Significantly, however, RAGE and its ligands have been shown to be both over expressed and critical to prostate cancer (PCa) development. Importantly, overexpression of RAGE and its ligand HMGB1 clinically has been shown to be associated with poor PCa patient survival, suggesting its promise as a molecular target for imaging and therapeutics. In this work, we developed and employed a nanoparticle-based imaging strategy of RAGE, first in a model of hind-limb ischemia (a widely-studied pathological model for RAGE signaling), and subsequently in PCa. Finally, we demonstrate the utility of this probe and the potential import RAGE and its ligands may play in disease, by using this RAGE-targeted imaging strategy to track the effects of dietary Advanced Glycation End Products on PCa progression. This strategy allows for the development of precision clinical assessment and treatment paradigms, while highlighting the import of this receptor.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-12-01","The student, Christian Konopka, accepted the attached license on 2019-12-04 at 14:54.","The student, Christian Konopka, submitted this Dissertation for approval on 2019-12-04 at 15:02.","This Dissertation was approved for publication on 2019-12-06 at 08:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14695 on 2020-02-28 at 17:37:55","Made available in DSpace on 2020-03-02T22:38:56Z (GMT). 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In this work, we developed and employed a nanoparticle-based imaging strategy of RAGE, first in a model of hind-limb ischemia (a widely-studied pathological model for RAGE signaling), and subsequently in PCa. Finally, we demonstrate the utility of this probe and the potential import RAGE and its ligands may play in disease, by using this RAGE-targeted imaging strategy to track the effects of dietary Advanced Glycation End Products on PCa progression. This strategy allows for the development of precision clinical assessment and treatment paradigms, while highlighting the import of this receptor.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-12-01","The student, Christian Konopka, accepted the attached license on 2019-12-04 at 14:54.","The student, Christian Konopka, submitted this Dissertation for approval on 2019-12-04 at 15:02.","This Dissertation was approved for publication on 2019-12-06 at 08:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #14695 on 2020-02-28 at 17:37:55","Made available in DSpace on 2020-03-02T22:38:56Z (GMT). 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