|Title:||Examining the Role of Microparticles in Mediating Multidrug Resistance in Cancer|
|Authors:||Gong, Joyce Huai Xin|
|Publisher:||University of Sydney.|
Discipline of Pathology.
School of Medical Sciences.
|Abstract:||Multi-drug resistance (MDR) is a major obstacle for successful cancer treatment. MDR occurs when cancer cells become resistant to numerous chemotherapeutic drugs following treatment by a single agent. Its emergence is largely attributed to the overexpression of P-glycoprotein (P-gp), a transporter which effluxes multiple drugs from cells, leaving a sub-lethal intracellular concentration. Despite investigation into P-gp inhibitors, their efficacy is questionable. Therefore, another avenue to address the MDR phenotype needed to be explored. One such direction includes submicron vesicles called microparticles (MPs). MPs are vesicles 0.1-1 μm in diameter that are released by membrane budding and carry components from the parent cell to mediate intercellular communication. In this study, we show that MPs mediate the intercellular transfer of P-gp and its associated nucleic acids from donor drug-resistant cells to recipient drug-sensitive cells, disseminating the MDR phenotype. As a parallel pathway for resistance, MPs also sequester chemotherapeutic drugs, reducing the concentration available at the target site. In addition to drug resistance, MPs also promote metastasis, providing a link between the two phenotypes. Therefore, in investigating the role of MPs in cancer, this study aims to reveal a novel intervention pathway that has the potential to regulate multiple aspects of cancer progression.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|GONG Joyce - Final thesis.pdf||Thesis||11.41 MB||Adobe PDF|
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