No description available.

Thesis (Ph. D.)--University of Rhode Island, 2003. / Typescript. Includes bibliographical references (leaves 167-178).

Thesis (M. Phil.)--University of Hong Kong, 1995. / Includes bibliographical references (leaf 155-198).

Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 97-114). Available also in a digital version from Dissertation Abstracts.

No description available.

Understanding the role of deregulated biological pathways in cancer samples has the potential to improve cancer treatment, making it more effective by selecting treatments that reverse the biological cause of the cancer. One of the challenges with pathway analysis is identifying a deregulated pathway in a given sample. This project develops the Universal Probability of Expression Code (UPC), a profile of a single deregulated biological path- way, and projects it into a cancer cell to determine if it is present. One of the benefits of this method is that rather than use information from a single over-expressed gene, it pro- vides a profile of multiple genes, which has been shown by Sjoblom et al. (2006) and Wood et al. (2007) to be more effective. The UPC uses a novel normalization and summarization approach to characterize a deregulated pathway using only data from the array (Mixture model-based analysis of expression arrays, MMAX), making it applicable to all microarray platforms, unlike other methods. When compared to both Affymetrix's PMA calls (Hubbell, Liu, and Mei 2002) and Barcoding (Zilliox and Irizarry 2007), it performs comparably.

No description available.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves : 172-189). Also available on the Internet.

No abstract provided. / Thesis / Doctor of Philosophy (PhD) / Scope and contents: Seven adenoviruses, including oncogenic and nononcogenic serotypes from human and simian hosts, were utilized to investigate their effects upon the chromosomes of human and Syrian hamster cells. Human cells support adenovirus multiplication while hamster cells do not support replication of infectious adenovirus. The chromosome damage induced by adenoviruses in abortive infection of hamster cells was compared with respect to the effect of virus dose upon the incidence and the types of chromosome aberrations. The effect of different adenoviruses upon the amount and types of chromosome damage was also examined. The effect of adenovirus infection upon DNA synthesis of human and hamster cells was examined, and the relevance of adenovirus-induced chromosome aberrations to the etiology of human cancers is discussed.

O câncer de cervical é causado por uma infecção persistente por algum dos tipos oncogênicos de Papilomavírus Humano (HPV) e continua a ser um problema de saúde pública, especialmente nos países em desenvolvimento. Por Peptide Phage Display, foram selecionadas sequências de peptídeos com afinidade de ligação a linhagens celulares ou a tumores associados ao HPV. Dentre elas, foi possível identificar sequências contidas em moléculas importantes para a progressão de tumores, como a -manosidase e triptase, enzimas que desempenham um papel importante na progressão tumoral. Para caracterizar o efeito da inibição de -manosidase II na terapia de tumores cervicais em camundongos, utilizamos a droga Swainsonina (SW), previamente descrita como inibidor desta enzima. Nós testamos o efeito desta droga tratando animais inoculados com células tumorais que expressam os oncogenes E6 e E7 de HPV16. Observamos que os animais tratados com Swainsonina apresentaram crescimento tumoral significativamente mais rápido do que os animais controle. Investigando os mecanismos por trás desse efeito, descobrimos que embora SW module parcialmente os macrófagos associados aos tumores, o tratamento induz o acúmulo de células com fenótipo mieloderivado supressor no baço dos animais, potencializando o efeito tolerogênico dos tumores sobre o sistema imune. Sendo assim, sugerimos cautela no uso deste fármaco para a terapia de pacientes com tumores HPV&#43. Outro braço do trabalho foi avaliar o papel da triptase, que é produzida por mastócitos, no infiltrado inflamatório. Para isto padronizamos um modelo de co-cultura de esferóides tumorais da linhagem TC-1 com a linhagem de mastócitos murinos PT18. Através deste modelo pudemos observar que a linhagem tumoral consegue induzir a desgranulação dos mastócitos independentemente de anticorpos. Além disso, quando em co-cultura, a linhagem tumoral parece estar aumentando a meia-vida dos mastócitos e estimulando a proliferação destes. Em experimentos in vivo observamos que tumores induzidos com as células PT18 e TC-1 cresceram mais rapidamente do que tumores induzidos apenas com TC-1. Através da imunofenotipagem dos tumores ficou evidenciado um aumento de células CD31+ e no infiltrado inflamatório total de tumores induzidos com o co-cultivo. Justificando o fato destes crescerem mais rapidamente, sugerindo que os mastócitos podem ter efeitos tanto proliferativos quanto no processo de angiogênese tumoral. / Cervical cancer is caused by a persistent infection by some of the oncogenic types of Human Papillomavirus (HPV) and continues to be a public health problem, especially in developing countries. By Peptide Phage Display peptide sequences were selected with binding affinity to cell lines or to HPV-associated tumors. Among them, it was possible to identify sequences contained in molecules important for the progression of tumors, such as -mannosidase and tryptase, enzymes that play an important role in tumor progression. To characterize the effect of -mannosidase II inhibition on cervical tumor therapy in mice, we used the drug Swainsonina (SW), previously described as an inhibitor of this enzyme. We tested the effect of this drug by treating animals inoculated with tumor cells expressing HPV16 E6 and E7 oncogenes. We observed that Swainsonine treated animals had significantly faster tumor growth than control animals. Investigating the mechanisms behind this effect, we found that although SW partially modulates tumor-associated macrophages, the treatment induces the accumulation of cells with suppressive myeloderivative phenotype in the animals spleens, enhancing the tolerogenic effect of tumors on the immune system. Therefore, we suggest caution in the use of this drug for the therapy of patients with HPV&#43 tumors. Another arm of the study was to evaluate the role of tryptase, which is produced by mast cells, in the inflammatory infiltrate. For this we standardized a co-culture model of tumor spheroids of the TC-1 lineage with the murine mast cell line PT18. Through this model we could observe that the tumoral lineage can induce mast cell degranulation independently of antibodies. In addition, when co-cultured, the tumoral lineage appears to be increasing the half-life of mast cells and stimulating the proliferation of these. In in vivo experiments we observed that tumors induced with PT18 and TC-1 cells grew faster than tumors induced only with TC-1. Tumor immunophenotyping revealed an increase in CD31&#43 cells and in the total inflammatory infiltrate of tumors induced with co-culture. Justifying the fact that they grow faster, suggesting that mast cells can have both proliferative effects and the process of tumor angiogenesis.