Medicine and Health Sciences Commons^™

Elucidating Mechanisms Of Innate And Acquired Resistance To Pi3ka Inhibition In Head And Neck Squamous Cell Carcinoma, Kara M. Ruicci

Electronic Thesis and Dissertation Repository

The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signalling pathway is aberrantly activated in most head and neck squamous cell carcinomas (HNSCCs). PI3K signalling drives cellular proliferation, protein synthesis and cell survival. Although numerous targeted agents are available to inhibit PI3K signalling, results have been variable and factors influencing response to PI3K inhibition (e.g. genomic aberrations, pathway interconnectivity, acquired drug resistance) are not well defined. In this thesis, we employ a multifaceted approach to elucidate the molecular underpinnings of biomarkers of response and mediators of resistance to PI3K inhibition in HNSCC. We began by combining a large panel of HNSCC …

Impact Of Feeding Tube Status On Health Outcomes For Individuals With Oropharyngeal Cancer, Nedeljko Jovanovic

Electronic Thesis and Dissertation Repository

Abstract

This study investigated differences in outcomes related to health, swallowing, and quality of life (QoL) for individuals with oropharyngeal squamous cell carcinoma (OPSCC) receiving either radiotherapy (RT) alone, or concomitant chemoradiotherapy (CRT). Differences were assessed based on whether patients received a feeding tube (FT group) or not (NFT group). Measures including the Functional Oral Intake Scale (FOIS), Performance Status Scale for Head and Neck Cancer (PSS-HN), M.D. Anderson Dysphagia Inventory (MDADI), and weight were collected for 126 individuals at baseline, and at 3, 6, and 12 months post-treatment. Data were analyzed to identify potential prognostic differences between the groups, …

Oncoplastic Surgery: Is It Time To Change? From Innovation To Adoption Using Mentorship Program, Eman Khayat

Electronic Thesis and Dissertation Repository

Oncoplastic surgery is considered the standard of care for breast cancer therapy in numerous Western World countries, particularly in Europe. Despite the advancement of knowledge, Canada still lags in adoption of oncoplasty into the standard surgical practice. In our study, a mentorship program was used to introduce oncoplastic surgery to practicing breast surgeons at LHSC. The change in perception and adoption of oncoplastic surgery were evaluated using semi-structured interviews, before and after the intervention, by qualitative thematic analysis method. Mentorship program was validated as a superior method of learning new surgical techniques by practicing surgeons, demonstrating acceptance of different levels …

Acute Pharmacologic Modulation Of Glioblastoma Ph Monitored By Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Mohammed Albatany

Electronic Thesis and Dissertation Repository

The response of tumor intracellular pH (pH_i) to a pharmacological challenge could help identify aggressive cancer. In addition, tumor pH_i may influence cell proliferation, apoptosis, chemotherapy resistance, and thermosensitivity. Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is sensitive to cellular pH. More specifically, a CEST method called amine and amide concentration-independent detection (AACID) produces images weighted by intracellular pH (pH_i) and can be used to study pharmacologic pH modulation in tumours.

The overall goal of this thesis was to maximize the magnitude of intracellular tumour acidification using pharmacologic agents. Several …