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    Studies of Breast Cancer Chemoprevention in Human High-Risk Primary Cells and Genetically Engineered Mouse Models

    Cover for Studies of Breast Cancer Chemoprevention in Human High-Risk Primary Cells and Genetically Engineered Mouse Models
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    View/Open: Alothman_georgetown_0076D_14015.pdf (7.1MB) Bookview

    Creator
    Alothman, Sahar J
    Advisor
    Furth, Priscilla A.
    Riggins, Rebecca B.
    ORCID
    0000-0003-4382-9065
    Abstract
    BRCA1 mutations have been associated with a 50-80% increased risk of developing breast cancer by the age of 70. Current recommendations for women carrying BRCA1 mutations include risk-reducing surgeries. Chemoprevention has been proposed as an option for these women. However, extensive research on the efficacy of these therapeutics is currently lacking due to the underrepresentation of women carrying BRCA1 mutations within clinical studies. Mouse models and primary cell culture of mammary epithelial cells serve as viable tools to study the efficacy of both estrogen-related hormonal and nonestrogen-related hormonal interventions in controlled settings. Here, studies using genetically engineered mouse models were employed to investigate the effectiveness of tamoxifen, raloxifene, letrozole, and efatutazone as chemopreventives strategies to reduce mammary cancers. Within mouse models, both estrogen-related hormonal and nonestrogen-related hormonal preventatives significantly reduced preneoplastic lesions but failed to eradicate disease. An in vitro system using high-risk for breast cancer human primary mammary epithelial cells was established to study estrogen-related hormonal response. Heterogeneity between samples was found with differences in estrogen-related hormonal response alluding to differences between response in women being conserved in vitro.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/1050904
    Date Published
    2018
    Subject
    BRCA1; Chemoprevention; Efatutazone; Genetically Engineered Mouse Model; High-Risk for Breast Cancer; human primary mammary epithelial cells; Biology; Biology;
    Type
    thesis
    Publisher
    Georgetown University
    Extent
    230 leaves
    Collections
    • Graduate Theses and Dissertations - Tumor Biology
    Metadata
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    Georgetown University Seal
    ©2009 - 2022 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility