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Full-Text Articles in Medicine and Health Sciences

Phase Ii Clinical Trial Of Concurrent Neoadjuvant Chemotherapy With Radiotherapy In Locally Advanced Breast Cancer, Muriel Brackstone Dec 2015

Phase Ii Clinical Trial Of Concurrent Neoadjuvant Chemotherapy With Radiotherapy In Locally Advanced Breast Cancer, Muriel Brackstone

Electronic Thesis and Dissertation Repository

Locally advanced breast cancer (LABC) represents 15% of all non-metastatic breast cancers, with an overall poor prognosis, despite current guidelines that recommend neoadjuvant chemotherapy followed by surgery and adjuvant radiation. Therefore, a novel treatment paradigm using concurrent neoadjuvant chemoradiotherapy was proposed. A clinical trial was designed, where 32 LABC patients were treated with q3 weekly 5-fluorouracil, epirubicin and cyclophosphamide for three cycles, followed by weekly docetaxel for 9 weeks with concurrent regional radiation (45+5.4Gy) for the first 6 weeks. Patients subsequently underwent modified radical mastectomies. Pathological complete responses (pCR) and 3 year overall survival rates were compared to a matched …


Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman Sep 2015

Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman

Electronic Thesis and Dissertation Repository

Breast cancer (BC) patient management has been transformed over the last two decades due to the development and application of genome-wide technologies. The vast amounts of data generated by these assays, however, create new challenges for accurate and comprehensive analysis and interpretation. This thesis describes novel methods for fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (aCGH), and next generation DNA- and RNA-sequencing, to improve upon current approaches used for these technologies. An ab initio algorithm was implemented to identify genomic intervals of single copy and highly divergent repetitive sequences that were applied to FISH and aCGH probe design. FISH …


Development Of A Small Animal Conformal Irradiator With Dual Energy X-Ray Computed Tomography Imaging For Kilovoltage Dosimetry, Michael D. Jensen Aug 2015

Development Of A Small Animal Conformal Irradiator With Dual Energy X-Ray Computed Tomography Imaging For Kilovoltage Dosimetry, Michael D. Jensen

Electronic Thesis and Dissertation Repository

External beam radiotherapy has become technically sophisticated with image guided radiation therapy (IGRT) and intensity modulated radiation therapy (IMRT). These technologies allow for precise delivery of radiation to geometric targets in cancer patients. However, many questions remain on how to best define targets based on biological information, such as functional imaging, and how to combine radiation with other cancer therapies. To help answer these questions, small animal preclinical studies are needed to generate data to inform clinical trials. However, the precise radiation delivery capabilities of IGRT and IMRT have not been available in the preclinical labs. To enable translational experiments …


Design Of Novel Sensors And Instruments For Minimally Invasive Lung Tumour Localization Via Palpation, Anish Srinivasan Naidu Jul 2015

Design Of Novel Sensors And Instruments For Minimally Invasive Lung Tumour Localization Via Palpation, Anish Srinivasan Naidu

Electronic Thesis and Dissertation Repository

Minimally Invasive Thoracoscopic Surgery (MITS) has become the treatment of choice for lung cancer. However, MITS prevents the surgeons from using manual palpation, thereby often making it challenging to reliably locate the tumours for resection. This thesis presents the design, analysis and validation of novel tactile sensors, a novel miniature force sensor, a robotic instrument, and a wireless hand-held instrument to address this limitation. The low-cost, disposable tactile sensors have been shown to easily detect a 5 mm tumour located 10 mm deep in soft tissue. The force sensor can measure six degrees of freedom forces and torques with temperature …


Kiss1r Signaling Promotes Breast Cancer Drug Resistance, Alexandra J. Blake Jun 2015

Kiss1r Signaling Promotes Breast Cancer Drug Resistance, Alexandra J. Blake

Electronic Thesis and Dissertation Repository

Kisspeptins signal via the G-protein coupled receptor, KISS1R, and act as metastasis suppressors in numerous cancers. In estrogen receptor (ERα)-negative breast cancer cells, however, KISS1R signaling promotes cell invasion by activating the epidermal growth factor receptor (EGFR). Unfortunately, clinical success of anti-EGFR therapeutics has been limited, as patients often develop drug resistance. Recently, another receptor tyrosine kinase, AXL, has been shown to promote breast cancer drug resistance. We hypothesize that KISS1R promotes EGFR expression and induces breast cancer drug resistance. We demonstrated that KISS1R increases EGFR transcription, by increasing SP-1 binding to the EGFR promoter, as demonstrated by chromatin immunoprecipitation …


Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke Jun 2015

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H2S-specific probes, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism …