dc.contributor.author |
Assi, Sara Ahmad, |
dc.date.accessioned |
2017-08-30T14:27:28Z |
dc.date.available |
2017-08-30T14:27:28Z |
dc.date.issued |
2016 |
dc.date.submitted |
2016 |
dc.identifier.other |
b18692953 |
dc.identifier.uri |
http://hdl.handle.net/10938/11030 |
dc.description |
Thesis. M.S. American University of Beirut. Department of Biology, 2016. T:6408 |
dc.description |
Advisor : Dr. Diana Jaalouk, Assistant Professor, Biology ; Committee members : Dr. Rabih Talhouk, Professor, Biology ; Dr. Ghanem Oweis, Associate Professor, Mechanical Engineering ; Dr. Rihab Nasr, Associate Professor, Anatomy, Cell Biology and Physiology. |
dc.description |
Includes bibliographical references (leaves 82-91) |
dc.description.abstract |
High Intensity Focused Ultrasound (HIFU) is an ex-corporeal medical device that was first introduced in the 1940s for the treatment of neurological disorders and has been subjected to several improvements since then. It is a non-invasive and non-ionizing therapeutic method that is now utilized to destroy a wide variety of tumors including breast cancer. At the focal point where the acoustic waves are intensified, cell death can result from cavitation and-or thermal ablation effects. However, the effects of sub-lethal HIFU exposure on cell function are not clearly understood. Previous work from our laboratory showed that sub-lethal HIFU exposure of MDA-MB-231 breast cancer cells in vitro results in significant alterations in transcript expression of a number of mechanosensitive genes, including Cav-1 gene which encodes for caveolin-1 protein. Moreover, there was enhanced cellular sensitivity to suboptimal cytotoxic doses of Paclitaxel and Doxil. Therefore, we hypothesized that sonoporation and-or caveolin-dependent endocytosis are among the mechanisms involved in this enhanced in vitro sensitivity of MDA-MB-231 cells post sub-lethal HIFU. For the purpose of this study, we utilized a commercial HIFU setup that operates at the fundamental resonance of 0.5MHz. To examine if sonoporation is implicated in the enhanced drug uptake post sub-lethal HIFU, we assessed the uptake of FITC-dextran by two methods: cell fixation followed by flow cytometry or laser confocal microscopic imaging and analysis. To determine if caveolin-dependent endocytosis is implicated as a mechanism of enhanced drug uptake, we pre-treated the cells with Genistein, a specific potent inhibitor of this pathway. Cellular viability was quantified using trypan blue vital stain exclusion assay. We found no significant change in FITC-dextran uptake in MDA-MB-231 cells post sub-lethal HIFU exposure at 30hr prior to the in vitro addition of agents by flow cytometry and laser confocal microscopy. Similarly, no significant change in FITC-dextran uptake was |
dc.format.extent |
1 online resource (xvi, 91 leaves) : illustrations (some color) |
dc.language.iso |
eng |
dc.relation.ispartof |
Theses, Dissertations, and Projects |
dc.subject.classification |
T:006408 |
dc.subject.lcsh |
Breast -- Cancer. |
dc.subject.lcsh |
High-intensity focused ultrasound. |
dc.subject.lcsh |
Epithelial cells. |
dc.subject.lcsh |
Mammary glands. |
dc.subject.lcsh |
Cell culture. |
dc.subject.lcsh |
Chemotherapy. |
dc.title |
Mechanisms implicated in the enhanced sensitivity of MDA-MB-231 breast cancer cells to anti-neoplastic agents post sub-lethal HIFU exposure - |
dc.type |
Thesis |
dc.contributor.department |
Faculty of Arts and Sciences. |
dc.contributor.department |
Department of Biology, |
dc.contributor.institution |
American University of Beirut. |