Global ETD Search

1	Better understanding of canine telomerase and its potential applications in canine oncology Liu, Yu January 2012 (has links) Telomerase, discovered in 1985, is considered a near-universal marker of malignancy and therefore has a potential use in cancer therapeutics and diagnostics. In this study, I used several approaches to gain a better understanding of telomerase and its potential applications in the canine context, for both cancer therapeutics and diagnosis. Having already developed an effective siRNA viral vector in vitro, the challenge still remained to deliver it efficiently in vivo. Thus, I initially investigated two possible approaches for in vivo delivery. First, I investigated a cell-based system for direct delivery to the tumours. Specifically I optimised a system for efficient gene-transfer to endothelial cells using a green fluorescent protein plasmid vector, and monitored systemic delivery by ex vivo imaging of dye-labelled cells in a canine xenograft tumour mouse model. In parallel, in vitro I investigated the gene transfer mediated by a novel dendrimer vector that can form nanoparticles with DNA and accumulate in tumour sites in vivo after i.v. administration. In order to utilize these delivery systems, I developed a DNA plasmid-based siRNA vector and tested its efficacy on canine tumour cells. To investigate telomerase as a cancer biomarker, I conducted a study that aimed to detect circulating telomerase reverse transcriptase (TERT) mRNA in serum taken from canine cancer patients. For this I developed several systems for effective RNA isolation from serum and used both conventional and quantitative PCR assays to detect TERT expression. Although for the first time I can confirm the existence of mRNA in serum of canine cancer patients, in this clinical study, I could only detect telomerase transcripts in a very small proportion of canine cancer patients. In a final pilot study to investigate anti-ageing technologies, I looked at the potential for drug-dependant telomerase induction rather than inhibition. For this I investigated the ability of three candidate drugs to induce TERT mRNA activation in canine embryonic fibroblasts. In this study, telomerase induction was measured using the quantitative PCR method that I had developed for serum detection. In summary, I have demonstrated that a cell-based delivery vehicle has a potential application in cancer therapy, but that more development is required before it can be applied clinically. I have also reported here that PPIG3 dendrimer-based gene transfer in vitro is low in canine cancer cells and thus require more optimisation and development before it can be utilised as an efficient systemic delivery vehicle. For the siRNA experiment, unfortunately, I did not observe any telomerase genesilencing in canine cancer cells using the plasmid-based siRNA expression vector, and therefore the gene sequence of cTR that we were targeting as well as the siRNA plasmid-vector that we used needs further validation in canine cells. I also suggest that TERT mRNA may not be a good serum biomarker for canine cancer diagnostics as I did not find TERT transcript in most of our serum samples from canine cancer patients, although circulating mRNA of a housekeeping gene was detected. Finally, in a pilot study, I have demonstrated that telomerase can be induced in normal canine somatic cells using small molecules. However, the long-term effects of telomerase induction on ageing must be determined in future studies. 572.8
2	Clients' Service Expectations and Practitioners' Treatment Recommendations in Veterinary Oncology Stoewen, Debbie Lynn 18 May 2012 (has links) Service provision in veterinary oncology in Ontario was examined using a mixed methods approach. First, an interview-based qualitative study explored the service expectations of oncology clients at a tertiary referral centre. Next, a survey-based quantitative study established an understanding of oncology service in primary care practice and investigated the treatment recommendations of practitioners for dogs diagnosed with cancer. The first study, which involved 30 individual and dyadic interviews, identified “uncertainty” (attributable to the unpredictable nature of cancer and its treatment) as an overarching psychological feature of clients’ experience. Consequently, “the communication of information” (both content and process) was the foremost service expectation. For clients, it enabled confidence in the service, the ability to make informed patient care decisions, and preparedness for the potential outcomes of those decisions; it also contributed to creating a humanistic environment, which enhanced client resiliency. Findings suggest that services can support client efforts to manage uncertainty through strategic design and delivery of service, and incorporate intentional communication strategies to support clients’ psychological fortitude in managing the cancer journey. The second study, a vignette-based survey of primary care practitioners across Ontario (N=1071) which investigated veterinarian decision-making in relation to oncology care, determined that 56% of practitioners recommended referral as their first choice of intervention, while 28% recommended palliative care, 13% in-clinic treatment, and 3% euthanasia. Recommendations were associated with patient, client and veterinarian factors. Specifically, referral and treatment were recommended for younger dogs, healthier dogs, and dogs with lymphoma versus osteosarcoma; for strongly bonded clients, and financially secure clients; and by veterinarians who graduated from a North American college, had experience with treating cancer, felt confident in the referral centre, and believed treatment was worthwhile, with variation in relation to practitioner gender and the type of medicine practiced. The human-animal bond appeared to be the primary factor associated with practitioners’ advocacy for quality of medical care for patients. Through a blend of qualitative and quantitative methodologies, this thesis contributes to the evidence upon which best practices may be built so as to enhance the quality of patient and client care in veterinary oncology. / Ontario Veterinary College Pet Trust Fund 049406 and 049854 client expectations treatment recommendations veterinary oncology practitioner service expectations qualitative research quantitative research thematic analysis vignette-based vignette-based inquiry full factorial experiment vignette-based research specialty oncology service primary care practice veterinary client logistic regression analysis uncertainty client uncertainty interview cancer cancer care canine cancer lymphoma osteosarcoma veterinary communication communication communication skills information content and process veterinary cancer care Ontario survey questionnaire referral euthanasia in-clinic treatment palliative care quality of care quality of medical care illness uncertainty service provision oncology epidemiology tertiary referral centre social epidemilogy veterinary epidemiology client well-being human-animal bond practitioner attitude best practice information preferences preparatory information cancer journey communication process continuity of care clinical decision making decision making practice variation adaptation

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Better understanding of canine telomerase and its potential applications in canine oncology

Clients' Service Expectations and Practitioners' Treatment Recommendations in Veterinary Oncology