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Temperature And Ph Imaging Using Chemical Exchange Saturation Transfer (Cest) Mri Contrast, Nevin Neil Campbell Mcvicar

Electronic Thesis and Dissertation Repository

Chemical exchange saturation transfer (CEST) is a novel mechanism used to generate contrast in magnetic resonance imaging (MRI). Recently, CEST contrast was proposed to noninvasively measure physiological parameters including temperature and pH. Tissue temperature and pH are known markers of pathological processes in many diseases including stroke and cancer. CEST contrast can be generated using endogenous proteins and peptides (endogenous CEST) or using exogenous paramagnetic lanthanide agents (PARACEST).

The general problem of optimizing applications of endogenous CEST and PARACEST contrast to measure temperature and pH is addressed in this thesis. Highlights of the thesis include a novel application of PARACEST …

Women's Stories Of Breast Cancer: Sharing Information Through Youtube Video Blogs, Jenna Kressler

Electronic Thesis and Dissertation Repository

Breast cancer is one of the most prevalent chronic diseases among North American women. Individuals need accessible and reliable health information for self-care and self-health promotion. Increasingly, individuals are contributing to and accessing information about cancer, using interactive online resources such as YouTube. The purpose of this research was to investigate the personal YouTube video blogs of women with breast cancer and their portrayed messages. This study used a narrative inquiry to examine the video blogs of four women with breast cancer. The women talked about having cancer as a transformative experience. Information about breast cancer from healthcare providers was …

The Role Of The Arginine Methyltransferase Carm1 In Global Transcriptional Regulation., Niamh Coughlan

Electronic Thesis and Dissertation Repository

Arginine methylation is a prevalent post-translational modification that is found on many nuclear and cytoplasmic proteins, and has been implicated in the regulation of gene expression. CARM1 is a member of the protein arginine methyltransferase (PRMT) family of proteins, and is a key protein responsible for arginine methylation of a subset of proteins involved in transcription. In this thesis I examine some of the mechanisms through which CARM1 contributes to global transcriptional regulation.

Using a ChIP-DSL approach, we show that the p/CIP/CARM1 complex is recruited to 204 proximal promoters following 17β-estradiol (E2) treatment in MCF-7 cells. Many of the target …

The Role Of Kim-1 Mediated Efferocytosis By Cancer Cells In Blocking The Immunogenicity Of Tumor Cell Death, Sahra Nathoo

Electronic Thesis and Dissertation Repository

The phagocytic clearance of apoptotic cells –efferocytosis- is essential for maintaining immune tissue homeostasis. Uncleared apoptotic cells can undergo secondary necrosis releasing endogenous danger signals such as high mobility group box protein 1 (HMGB1) into the extracellular milieu, triggering the innate immune system. Kidney Injury Molecule -1 (KIM-1) is a phosphatidylserine (PS) receptor that has been shown to confer on proximal tubular epithelial cells (PTECs) the ability to clear apoptotic cells during acute kidney injury. KIM-1 is overexpressed by various human tumours including renal clear cell carcinoma (RCC), though the impact of this on tumour progression is not known. Importantly, …

Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce

Electronic Thesis and Dissertation Repository

Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumour milieu, and may modulate resistance to TS-targeting drugs. We have previously shown that TS antisense molecules (oligodeoxynucleotides, ODNs, and small interfering siRNA, siRNA) sensitize tumour cells, both in vitro and in vivo, to TS targeting drugs. As both TS and TKs contribute to cellular …

Indoleamine 2,3-Dioxygenase Confers Resistance To Chemotherapy And Γ Radiation To Cancer Cells, Independent Of Direct Immune Involvement, Saman Maleki Vareki

Electronic Thesis and Dissertation Repository

Indoleamine 2,3-dioxygenase-1 (IDO) is an immunosuppressive molecule expressed by most human tumours. IDO levels correlate with poor prognosis in cancer patients and IDO inhibitors are under investigation to enhance endogenous anticancer immunosurveillance. Little is known regarding the immune-independent functions of IDO relevant to cancer therapy. In this thesis I show, for the first time, that IDO mediates human tumour cell resistance, in a cell-autonomous fashion, to single and combination treatment with a diverse group of chemotherapy drugs and g radiation. These drugs include a PARP inhibitor (olaparib), a DNA cross-linking agent (cisplatin), a folate antimetabolite (pemetrexed), a nucleoside analogue (gemcitabine), …