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|Title: ||Tumour Microenvironment, Cancer Stem Cells and Radiation Response in Oropharyngeal Cancer|
|Authors: ||Zhang, Xiao Mei|
|Issue Date: ||29-Sep-2015|
|Publisher: ||University of Sydney|
Sydney Medical School
|Abstract: ||The incidence of Human papillomavirus (HPV) induced oropharyngeal squamous cell carcinoma (OSCC) is rising. HPV-positive OSCC is associated with a favourable prognosis, the mechanism is not fully understood and could be related to intrinsic radiosensitivity of the HPV-positive OSCC. The aim of this candidature was to study the influence of tumour microenvironment on radiosensitivity by examine HIF-1α in OSCC and by using in vitro 3D tumour models.
The main finding of the HIF-1α study was the HPV status remains the strongest prognostic factor in OSCC. Hypoxia might be an important factor in HPV-negative cancer. In consistent with clinical observations, in vitro studies revealed HPV-positive OSCC cells were more sensitive to radiation than were HPV-negative OSCC cells. Radiosensitivity of HPV-positive OSCC was related to G1/S cell cycle regulation, increased cyclin D1 expression and apoptosis; associated with p16/CDK/Rb pathways. HPV-negative OSCC cells displayed a radiation-induced G2 arrest indicating the activation of DNA repair mechanism. Radiation induced cyclin D1 expression indicated that responsible for HPV-positive OSCC radiosensitivity.
The results from this candidature emphasize the important roles of HPV and microenvironment on cancer cell response to radiation. The results provided a biological basis for using different strategies when treating HPV-positive and HPV-negative OSCC.|
|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)|
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|ZHANG Xiao Mei - Final Thesis.pdf||Thesis||7.59 MB||Adobe PDF|
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