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    Investigation of the Role of Tensile Forces in Cellular Response to Chemotherapeutic Agents

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    Schmitt_ku_0099M_15023_DATA_1.pdf (3.599Mb)
    Issue Date
    2016-12-31
    Author
    Schmitt, Sarah Beth
    Publisher
    University of Kansas
    Format
    68 pages
    Type
    Thesis
    Degree Level
    M.S.
    Discipline
    Bioengineering
    Rights
    Copyright held by the author.
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    Abstract
    Research using in vitro cell cultures are frequently conducted under static growth conditions. Cells growing in vivo, however, grow in a highly dynamic and interactive environment, where they receive cues in the form of mechanical stimuli from their surroundings. Lung cells, for example, are continually exposed in vivo to a cyclic tensile stretch during normal inhalation and exhalation. The absence of a mechanically representative environment could have important implications for research and development, particularly in the context of drug discovery. We hypothesize that tensile (mechanical) forces applied to two non-small cell lung cancer cell lines, bronchoalveolar H358 cells and alveolar A549 cells, play an important role in determining cellular response to chemotherapeutic agents. In order to investigate changes resulting from exposure to tensile stretch, we first looked at changes in proliferation and expression of a few cellular markers associated with epithelial-mesenchymal transition (EMT). Next, we looked at changes in cell cycle distribution and expression of a few cell-cycle checkpoint proteins. Finally, we studied the effect of a tensile force on the efficacy of three chemotherapeutic agents. We found that a tensile force significantly reduces cellular proliferation and causes significant shifts in cell cycle distribution. Mechanically active culture environments led to decreased efficacy of cisplatin and increased efficacy of Zactima. These results indicate that a mechanically active culture environment does impact cell survival and protein expression, and has important implications in the context of the discovery and screening of new antitumor drug therapies.
    URI
    http://hdl.handle.net/1808/25352
    Collections
    • Engineering Dissertations and Theses [1055]
    • Theses [3797]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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