Thesis (Ph. D.)--Marshall University, 2003. / Title from document title page. Document formatted into pages; contains xiii, 153 p. including illustrations. Includes abstract. Includes bibliographical references (p. 125-153).

Thesis (M.S.)--University of Delaware, 2007. / Principal faculty advisor: Mary Ann McLane, Dept. of Medical Technology. Includes bibliographical references.

Melanoma is the most aggressive skin cancer with high recurrence and low survival rate. In addition to genetic mechanisms, resistance also arises from phenotypic heterogeneity in which a proportion of cells, the so-called melanoma stem or initiating cells, survive therapy. Due to a lack of reliable markers, however, there is still debate about the existence of these cells in melanoma. Consistent with phenotypic heterogeneity, previous observations in our laboratory have demonstrated that cells in melanoma can reversibly segregate in vivo into different subpopulations with different properties, such as differentiation or increased invasive capacity (potentially attributed to the existence of de-differentiated stem-like cells). To characterise these cells, a dual reporter lentiviral system was engineered, expressing fluorescent proteins under cell stage/phenotype-specific promoters. The promoters for the transcription factors POU3F2 (Brn2) (to mark de-differentiated cells) and the microphthalmia-associated transcription factor (MITF) (to mark proliferating and differentiated cells) were chosen. Lentivirally-transduced cells were used to screen a library of kinase inhibitors for their potential to affect promoter activity in vitro. The RhoA/ROCK pathway, known to contribute to invasion and metastases, was identified to play a role in Brn2 promoter activity and exhibited differential effects on both the MITF and Brn2 promoters in 501mel and SKmel28 cell lines. Through investigation of other signalling pathways involved in melanoma metastasis, we also identified the co-activator Mastermind-like 1 (MAML1), previously reported to act in the Notch pathway, as an activator of the Brn2 promoter via the transcription factor TCF3, and the MITF promoter through the lymphoid-enhancer binding factor 1 (LEF1). The effects of MAML1 on Brn2 and MITF promoter activity were potentiated by β-catenin. These findings provide new opportunities for the identification of therapeutic targets to prevent metastases formation in melanoma.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 153-156). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 153-156). Also available on the Internet.

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

This thesis is concerned with developing and implementing a method for modelling and projecting cancer incidence data. The burden of cancer is an increasing problem for society and therefore, the ability to analyse and predict trends in large scale populations is vital. These predictions based on incidence and mortality data collected by cancer registries, can be used for estimation of current and future rates, which is helpful for public health planning. A large body of work already exists on the use of various modelling strategies, methods and fitting techniques. A multilevel method of preparing the data is proposed, fitted to historical data using regression modelling, to predict future rates of incidence for a given population. The proposed model starts with a model for the total incidence of the population, with each successive level stratifying the data into progressively more specific groupings, based on age. Each grouping is partitioned into subgroups, and each subgroup is expressed as a proportion of the parent group. Models are fitted to each of the proportional age-groups, and a combination of these models produces a model that predicts incidence for a specific age. A simple, efficient implementation of the modelling procedure is described, including key algorithms and measures of performance. The method is applied to data from populations that have very different melanoma incidence (the USA and Australia). The proportional structure reveals that the proportional age trends present in both populations are remarkably similar, indicating that there are links between causative factors in both populations. The method is applied fully to data from a variety of populations, and compared with results from existing models. The method is shown to be able to produce results that are reliable and stable, and are generally significantly more accurate than those of other models.

In the first part of the theses, I studied therapeutical effect of intratumoral application of various types of bacteria on melanoma B16-F10 bearing mice alone or in combination with another immunostimulatory compounds. Tumour size, metastasis and survival were monitored. The second part was focused on study of cytotoxic effect of neutrophils on melanoma cells and the role of neutrophil extracellular traps formation.

Transduction of melanoma cells with the aim to induce avidine expression on tumor cell surface was studied. Subsequently the method enabling quantification of binding of ligands to the cell surface was developed.

The aim of this thesis was to study the mechanisms of innate imunity involved in the degradation of tumor cells on which the ligands of phagocytic receptors were installed. For this purpose both in vivo experiments using immunodeficient mice, and in vitro experiments based on monitoring the levels of inflammatory cytokines produced in the tumor tissue and on measuring the level of myeloperoxidase released during neutrophil degranulation were performed.