Georgetown University LogoGeorgetown University Library LogoDigitalGeorgetown Home
    • Login
    View Item 
    •   DigitalGeorgetown Home
    • Georgetown University Institutional Repository
    • Georgetown University Medical Center
    • Lombardi Comprehensive Cancer Center
    • Program of Tumor Biology
    • Graduate Theses and Dissertations - Tumor Biology
    • View Item
    •   DigitalGeorgetown Home
    • Georgetown University Institutional Repository
    • Georgetown University Medical Center
    • Lombardi Comprehensive Cancer Center
    • Program of Tumor Biology
    • Graduate Theses and Dissertations - Tumor Biology
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Distinct Response of Circulating microRNAs to the Treatment of Pancreatic Cancer

    Cover for Distinct Response of Circulating microRNAs to the Treatment of Pancreatic Cancer
    View/Open
    View/Open: Peran_georgetown_0076D_12741.pdf (2.8MB) Bookview

    Creator
    Peran, Ivana
    Advisor
    Wellstein, Anton
    Abstract
    An early detection and monitoring of pancreatic adenocarcinoma has been very challenging, which makes it one of the deadliest cancers today. This has stimulated research to explore new therapeutic strategies and new ways of following treatment response. We believe that miRNAs play an important role in cancer, and circulating miRNAs from peripheral blood could not only be used as early diagnostic biomarkers, but their expression profile could give us a valuable clue about response to therapy.
     
    We focus on targeting tumor-stroma interaction in a pancreatic cancer xenograft mouse model, with two small molecule inhibitors: (1) a fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, PD173074; and (2) an anaplastic lymphoma kinase receptor (ALK) kinase inhibitor, TAE684. Both drugs reduced COLO357PL pancreatic cancer cell proliferation and disruption of endothelial cell monolayer by cancer cells in vitro. In vivo, initial treatment with both drugs reduced mitosis and angiogenesis similarly. First, we identified serum miRNA expression changes as a response to the tumor presence. Furthermore, we describe a distinctive set of circulating miRNAs that corresponds to each initial treatment before necrotic changes took place and influenced miRNA expression pattern. More importantly, in our study we distinguish between drug effect on the tumor versus host, based on the miRNA expression changes in tumor tissue and the circulation. Finally, we show a connection between successful treatment of pancreatic cancer xenografts and the circulating miRNA expression pattern.
     
    The approach of determining circulating miRNA expression levels and patterns upon the initial treatment could be of immense importance for pancreatic cancer patients in finding the effective drug (combination) treatment and might be a model to expand to other cancers and treatment evaluations.
     
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/710048
    Date Published
    2014
    Subject
    ALK; FGFR; miRNA; pancreatic cancer; treatment response; Oncology; Cytology; Molecular biology; Oncology; Cellular biology; Molecular biology;
    Type
    thesis
    Embargo Lift Date
    2015-08-21
    Publisher
    Georgetown University
    Extent
    134 leaves
    Collections
    • Graduate Theses and Dissertations - Tumor Biology
    Metadata
    Show full item record

    Related items

    Showing items related by title, author, creator and subject.

    • Cover for A multi-faceted approach to the detection and treatment of pancreatic
      cancer

      A multi-faceted approach to the detection and treatment of pancreatic cancer 

      LaConti, Joseph James. (Georgetown University, 2010)
    Related Items in Google Scholar

    Georgetown University Seal
    ©2009 - 2023 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility
     

     

    Browse

    All of DigitalGeorgetownCommunities & CollectionsCreatorsTitlesBy Creation DateThis CollectionCreatorsTitlesBy Creation Date

    My Account

    Login

    Statistics

    View Usage Statistics

    Georgetown University Seal
    ©2009 - 2023 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility