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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
231

The Role of the p14ARF Tumour Suppressor in Promoting Apoptosis

Gallagher, Stuart John January 2008 (has links)
Doctor of Philosophy (PhD) / The incidence of melanoma has risen dramatically during the past three decades, yet there has been little improvement in effective treatments for this intractable and aggressive disease. Melanoma tumours are notoriously resistant to apoptosis, a cell suicide program that is activated by most cancer therapies. This thesis explores the role of the melanoma susceptibility gene product p14ARF in promoting cell cycle arrest and apoptosis, in order to resolve the impact of this tumour suppressor in melanomagenesis and melanoma susceptibility. The p14ARF tumour suppressor gene is mutated in almost half of all cancers, and germline mutations in p14ARF confer a greatly increased risk of developing melanoma. The primary function of p14ARF is to relay oncogenic signals to p53, a central regulator of cellular response to stress. There is conflicting evidence regarding the role of p14ARF in promoting apoptosis. Much of the current evidence is based on murine studies, which may not translate accurately to humans due to important differences in animal physiology and the primary sequence and functions of the mouse and human ARF proteins. Furthermore, results from previous studies are often compounded by supra-physiological expression of p14ARF, and are complicated by the fact that p14ARF shares its genomic sequence with the p16INK4a tumour suppressor gene. This study demonstrates that p14ARF expression in human cancer and primary cell lines promotes rapid p53-dependent cell cycle arrest, rather than apoptosis. As p14ARF expression did not induce apoptosis, we investigated if p14ARF could modulate the sensitivity of a cell to apoptosis induced by cytotoxic agents. Using a p14ARF-inducible U2OS osteosarcoma cell line model, we examined the impact of p14ARF expression on the apoptotic response of the cell to a panel of thirteen cytotoxic agents. p14ARF expression increased apoptosis caused by a sub-set of agents, including trichostatin A, sodium butyrate, DRB, Adriamycin and UVB radiation. p14ARF-mediated chemosensitivity was p53- and caspase-dependent, and involved the loss of mitochondrial potential. While loss of mitochondrial potential was dependent on p53, it was not blocked by caspase inhibition, demonstrating that caspases play a role downstream of mitochondrial depolarisation. Inhibition of individual components of the apoptotic program showed that p14ARF-mediated chemosensitivity was not strictly dependent on the pro-apoptotic Bax or Fas proteins. We also investigated whether p14ARF could sensitise melanoma to chemotherapeutics in vivo. We investigated the expression level of p14ARF, p16INK4a and MITFm and mutation status of B-RAF, N-RAS and PTEN in melanomas from 30 patients that had undergone isolated limb infusion - a palliative therapeutic strategy that results in much higher response rates than systemic treatment. Expression of p14ARF did not predict response to the drugs actinomycin D and melphalan . Instead, high expression of p16INK4a and presence of activating N-RAS mutation were independent predictors of response to high doses of these chemotherapeutic drugs. This work suggests that p14ARF analogues may be beneficial adjuncts in cancer therapy, but are unlikely to be effective as single agents. Additionally, p14ARF mimetics will only be effective in tumours with intact p53 signalling. Melanomas frequently carry functional p53, and may be susceptible to this mode of treatment providing the apoptotic pathway downstream of p53 is intact or can be restored.
232

Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma

Namkoong, Jin. January 2007 (has links)
Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Microbiology and Molecular Genetics." Includes bibliographical references (p. 66-75).
233

Quantitative analysis of melanoma transcripts : with emphasis on methodological and biological variation /

Farnebäck, Malin, January 2004 (has links) (PDF)
Diss. Linköping : Univ., 2004.
234

Body site of cutaneous malignant melanoma : primary tumor location in relation to phenotypic and prognostic factors /

Gillgren, Peter, January 2002 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.
235

Identifying molecular targets for cancer therapy /

Culp, W. David, January 2007 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 3 uppsatser.
236

Selection for the Xmrk oncogene in Xiphophorus cortezi

Fernandez, André A. January 2008 (has links)
Thesis (Ph.D.)--Ohio University, August, 2008. / Title from PDF t.p. Includes bibliographical references.
237

Melanoma and lifetime ultraviolet radiation exposure /

Solomon, Cam Charles. January 2004 (has links)
Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 68-74).
238

The role of osteopaths in the recognition of melanoma : attitudes, knowledge and practices in melanoma screening within the osteopathic community. A research project submitted in partial requirement for the degree of Master of Osteopathy, UNITEC Institute of Technology [i.e. Unitec New Zealand] /

Friedlander, Tim. January 2008 (has links)
Thesis (M.Ost.)--Unitec New Zealand, 2008. / Coda (electronic version) title-page has 2009 date. Includes bibliographical references (leaves 76-79).
239

Transdermal delivery of genistein as a chemoprotective drug for melanoma

Chadha, Gurkishan S. Parsons, Daniel L., Ramapuram, Jayachandra B., January 2009 (has links)
Thesis--Auburn University, 2009. / Abstract. Includes bibliographical references (p. 57-69).
240

Malignant melanoma prognostic factors /

Rampen, Franciscus Henricus Josephus, January 1982 (has links)
Thesis (doctoral)--Universiteit van Amsterdam.

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