Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 114-129). Available also in a digital version from Dissertation Abstracts.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Sydney, 2009. / Title from title screen (viewed February 10, 2009). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Molecular and Microbial Biosciences, Faculty of Science. Degree awarded 2009; thesis submitted 2008. Includes bibliographical references. Also available in print form.

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [68]-80).

Thesis (Ph.D.)--Brandeis University, 2010. / "UMI:3390479." MICROFILM COPY ALSO AVAILABLE IN THE UNIVERSITY ARCHIVES. Includes bibliographical references.

Introduction: Early growth response 1 (EGR1) is a zinc-finger transcription factor involved in the regulation of cell growth. It can act as either a tumour suppressor or a tumour promoter with a role in the induction of apoptosis in cancer cells by various pathways and is likely to play a role in colorectal cancer (CRC). EGR1 also appears to play a significant role in inflammatory pathways, therefore a possible role in Inflammatory Bowel Disease (IBD) is hypothesised. Patients with IBD have a greater risk of developing CRC, which is increased with duration of symptoms and severity of inflammation and dysplasia. The aim of this study is to determine whether EGR1 is differentially expressed in diseased colon tissue and to investigate novel EGR1-protein interactions in CRC cell lines. Methods: The relative EGR1 expression in CRC cell lines and in normal mucosa and tumours of colorectal cancer patients was determined by qRT-PCR. IBD patient samples were also examined for differential EGR1 expression levels by qRT-PCR, before and after stimulation with inflammatory mediators. Statistical analysis of the data was performed using ‘R’ statistical package, with the mixed-model ANOVA. Statistical significance was set at < 0.05. The genotype of three EGR1 variants was determined in the samples using PCR and sequencing, and the methylation status of regions of the EGR1 promoter was determined using bisulfite sequencing. A yeasttwo hybrid screen was conducted with EGR1 as bait, and screened against a SW480 CRC cell line library. Interesting novel interactions were investigated using immunocytochemistry and immunoprecipitation, as was the novel interaction between EGR1 and NOD2 and between EGR1 and components of the cytoskeleton. Results: Investigation into the relative EGR1 mRNA expression in CRC has shown that there is differential expression of EGR1 between matched normal mucosa and tumour. EGR1 expression is decreased in IBD patients compared with healthy controls. Induction of EGR1 by inflammatory stimuli also appears to be aberrant in these patients. The differential expression of EGR1 was not associated with aberrant methylation of a large region of the EGR1 promoter in either the CRC or IBD patients or with the genotype of EGR1 variants. EGR1 localises to both the cytoplasm and the nucleus in CRC cell lines and this study demonstrate interactions with the IBD susceptibility protein NOD2 and with components of the cyotskeleton. A yeast-two hybrid screen conducted with EGR1 as bait using a CRC cell line library has identified several other novel protein interactions of EGR1 in CRC cell lines. Conclusion: EGR1 is differentially expressed in both CRC and IBD, and in the case of IBD shows aberrant activity, suggesting that EGR1 may play a role in both colorectal diseases. EGR1 interacts with the IBD protein NOD2, and components of the cytoskeleton in CRC cells. Several novel protein interactions with EGR1 have been identified and warrant further study.

Microarray technology has revolutionized the field of molecular biology by offering an efficient and cost effective platform for the simultaneous quantification of thousands of genes or even entire genomes in a single experiment. Unlike southern blotting, which is restricted to the measurement of one gene at-a-time, microarrays offer biologists with the opportunity to carry out genome-wide experiments in order to help them gain a systems level understanding of cell regulation and control. The application of bioinformatics in the milieu of gene expression analysis has attracted a great deal of attention in the recent past due to specific algorithms and software solutions that attempt to illustrate complex multidimensional microarray data in a biologically coherent fashion so that it can be understood by the biologist. This has given rise to some exciting prospects for deciphering microarray data, by helping us refine our comprehension pertinent to the underlying physiological dynamics of disease. Although much progress is being made in the development of specialized bioinformatics software pipelines with the purpose of decoding large volumes of gene expression data in the context of systems biology, several loopholes exist. Perhaps most notable of these loopholes is the fact that there is an increasing demand for software solutions that specialize in automating the comparison of multiple gene expression profiles, derived from microarray experiments sharing a common biological theme. This is no doubt an important challenge, since common genes across different biological conditions having similar expression patterns are likely to be involved in the same biological process and hence, may share the same regulatory signatures. The potential benefits of this in refining our understanding of the physiology of disease are undeniable. The research presented in this thesis provides a systematic walkthrough of a series of software pipelines developed for the purpose of streamlining gene expression analysis in a systems biology context. Firstly, we present BiSAn, a software tool that deciphers expression data from the perspective of transcriptional regulation. Following this, we present Genome Interaction Analyzer (GIA), which analyzes microarray data in the integrative framework of transcription factor binding sites, protein-protein interactions and molecular pathways. The final contribution is a software pipeline called MicroPath, which analyzes multiple sets of gene expression profiles and attempts to extract common regulatory signatures that may be implicating the biological question.

Thesis (Ph. D.)--University of Missouri--Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves : 117-131). Also available on the Internet.

Os gliomas são tumores cerebrais intracraniais caracterizados pelo seu rápido crescimento e pela sua resistência à quimioterapia e radioterapia atuais. Assim, a procura por novos agentes terapêuticos com múltiplos mecanismos de ação têm identificado o ácido <font face=\"symbol\">g-linolênico (GLA), antiinflamatórios não esteroidais (AINEs) e compostos contendo rutênio como possíveis candidatos. Dessa forma, a principal proposta deste projeto foi entender melhor o mecanismo de ação dessas drogas sobre as células C6 de glioma de rato. Foram analisadas proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração através de RT-PCR e Western Blotting após tratamento in vitro e in vivo. Alterações da expressão de ciclina D1, E2F-1, pRb, p27, p21, p16, p65, c-myc, ERK1/2, nm23 e <font face=\"symbol\">b, MMP-2, Brevican GPI e Secretado, Tenascina-R, Tenascina-C, VEGF-A, Flt1, Flk1, Bax, PPAR<font face=\"symbol\">g, p53, COX-2, EP1, 2, 3 e 4, Ku70 e 80 foram encontradas. Em conclusão, o GLA e o complexo Rutênio-Ibuprofeno possuem múltiplos alvos que levam à inibição da proliferação celular. / Gliomas are intracranial tumors of cerebral origin characterized for its rapid growth and resistance to both conventional chemotherapy and radiotherapy. The search for new therapeutics agents with multiple mechanisms of action has identified <font face=\"symbol\">g-linolenic acid (GLA), nonsteroidal anti-inflammatory drugs (NSAIDs) and ruthenium containing compounds as possible candidates. The aim of this study was to better know the mechanism of action of these drugs on C6 rat glioma cells. Expression of proteins involved in control of the cell cycle, apoptosis, angiogenesis, invasion and migration was analyzed using RT-PCR and Western Blotting methods after treatment in vitro and in vivo. Alterations in cyclin D1, E2F-1, pRb, p27, p21, p16, p65, c-myc, ERK1/2, nm23 e <font face=\"symbol\">b, MMP-2, GPI and Secreted Brevican, Tenascin-R, Tenascin-C, VEGF-A, Flt1, Flk1, Bax, PPAR<font face=\"symbol\">g, p53, COX-2, EP1, 2, 3 and 4, Ku70 and 80 expression were observed. In conclusion, GLA and Ruthenium-Ibuprofen complex has multiple target wich translate into the inhibition of proliferation.

Os gliomas são tumores cerebrais intracraniais caracterizados pelo seu rápido crescimento e pela sua resistência à quimioterapia e radioterapia atuais. Assim, a procura por novos agentes terapêuticos com múltiplos mecanismos de ação têm identificado o ácido <font face=\"symbol\">g-linolênico (GLA), antiinflamatórios não esteroidais (AINEs) e compostos contendo rutênio como possíveis candidatos. Dessa forma, a principal proposta deste projeto foi entender melhor o mecanismo de ação dessas drogas sobre as células C6 de glioma de rato. Foram analisadas proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração através de RT-PCR e Western Blotting após tratamento in vitro e in vivo. Alterações da expressão de ciclina D1, E2F-1, pRb, p27, p21, p16, p65, c-myc, ERK1/2, nm23 e <font face=\"symbol\">b, MMP-2, Brevican GPI e Secretado, Tenascina-R, Tenascina-C, VEGF-A, Flt1, Flk1, Bax, PPAR<font face=\"symbol\">g, p53, COX-2, EP1, 2, 3 e 4, Ku70 e 80 foram encontradas. Em conclusão, o GLA e o complexo Rutênio-Ibuprofeno possuem múltiplos alvos que levam à inibição da proliferação celular. / Gliomas are intracranial tumors of cerebral origin characterized for its rapid growth and resistance to both conventional chemotherapy and radiotherapy. The search for new therapeutics agents with multiple mechanisms of action has identified <font face=\"symbol\">g-linolenic acid (GLA), nonsteroidal anti-inflammatory drugs (NSAIDs) and ruthenium containing compounds as possible candidates. The aim of this study was to better know the mechanism of action of these drugs on C6 rat glioma cells. Expression of proteins involved in control of the cell cycle, apoptosis, angiogenesis, invasion and migration was analyzed using RT-PCR and Western Blotting methods after treatment in vitro and in vivo. Alterations in cyclin D1, E2F-1, pRb, p27, p21, p16, p65, c-myc, ERK1/2, nm23 e <font face=\"symbol\">b, MMP-2, GPI and Secreted Brevican, Tenascin-R, Tenascin-C, VEGF-A, Flt1, Flk1, Bax, PPAR<font face=\"symbol\">g, p53, COX-2, EP1, 2, 3 and 4, Ku70 and 80 expression were observed. In conclusion, GLA and Ruthenium-Ibuprofen complex has multiple target wich translate into the inhibition of proliferation.