Thesis (M.Sc. in Microbiology) -- Mahidol University, 1976.

The aim of this thesis is to evaluate the role of the extracellular environment in regulating breast cancer cell morphological and invasive characteristics. In vitro experiments of breast cancer cell lines in three dimensional matrices, which afford control over variables of interest while maintaining physiological relevance, were utilized for this purpose. We evaluated the sensitivity of cell morphology to the dimensionality, biochemistry, and mechanical properties of the extracellular environment as well as the reciprocal effects cells display when remodeling the extracellular environment during invasion. Chapter 1 introduces background material on breast cancer development, classification systems, and in vitro methods of research. Chapter 2 describes protocols for cell care and experiments used in these studies. In chapter 3, we explore the role of fibrillar collagen I environments in breast cancer cell invasion. This was motivated by previous research that has associated high breast tissue density with breast cancer risk and poor prognosis as well as tissue stiffness with cancer cell aggressiveness. Breast cancer cells were found to regain an invasive phenotype in sterically constrained environments when the extracellular matrix included a fibrillar component. In chapter 4, the relationship between cell morphology and invasive behavior in various dimensional contexts was assessed. Anecdotal evidence has shown stellate morphology may be associated with epithelial to mesenchymal transition and invasive capacity in cancer cells. Differences in the dimensionality and biochemistry of the environment resulted in changes to cell aggregate morphology. Although morphology did not predict invasive capacity as measured by spheroid invasion in collagen I, invasion was found to correlate with cancer-related gene expression profiling, suggesting the ability of cancer cells to utilize more than one mode of invasion. Chapter 5 explores to what degree the presence of invasive cells can give rise to invasive behavior from noninvasive cells. Segregation of cell subtypes during co-culture spheroid formation was found to be altered in the presence of BME. When implanted into collagen gels, invasive cell lines that generate structural changes to the extracellular matrix on their own were able to confer invasive behavior to otherwise noninvasive cell lines in some cases. Chapter 6 summarizes these findings and suggests further studies. Appendix 1 lists useful abbreviations. In Appendices 2 and 3, codes for ImageJ and Matlab-based analyses are recorded. Through this work, we see how cell morphology and invasive capacity are influenced by the extracellular environment. Cells that can interact with components of the extracellular matrix through matrix-specific integrins show a range of capacities for remodeling the extracellular environment, which in turn plays a role in invasive capacity. We anticipate that enhanced understanding of the role of the extracellular environment in regulating cell morphology and invasive behavior will lead to advances in the study of cell locomotion as well as in cancer research, diagnosis, and treatment.

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Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [132]-134).

Thesis (doctoral)--University of Lund, 1981. / "From the Departments of Infectious Diseases and Clinical Bacteriology, University of Lund, General Hospital, Malmö, Sweden." "The English text revised by L. James Brown." Bibliography: p. 29-33.

abstract: Dopamine (DA) is a neurotransmitter involved in attention, goal oriented behavior, movement, reward learning, and short term and working memory. For the past four decades, mathematical and computational modeling approaches have been useful in DA research, and although every modeling approach has limitations, a model is an efficient way to generate and explore hypotheses. This work develops a model of DA dynamics in a representative, single DA neuron by integrating previous experimental, theoretical and computational research. The model consists of three compartments: the cytosol, the vesicles, and the extracellular space and forms the basis of a new mathematical paradigm for examining the dynamics of DA synthesis, storage, release and reuptake. The model can be driven by action potentials generated by any model of excitable membrane potential or even from experimentally induced depolarization voltage recordings. Here the model is forced by a previously published model of the excitable membrane of a mesencephalic DA neuron in order to study the biochemical processes involved in extracellular DA production. After demonstrating that the model exhibits realistic dynamics resembling those observed experimentally, the model is used to examine the functional changes in presynaptic mechanisms due to application of cocaine. Sensitivity analysis and numerical studies that focus on various possible mechanisms for the inhibition of DAT by cocaine provide insight for the complex interactions involved in DA dynamics. In particular, comparing numerical results for a mixed inhibition mechanism to those for competitive, non-competitive and uncompetitive inhibition mechanisms reveals many behavioral similarities for these different types of inhibition that depend on inhibition parameters and levels of cocaine. Placing experimental results within this context of mixed inhibition provides a possible explanation for the conflicting views of uptake inhibition mechanisms found in experimental neuroscience literature. / Dissertation/Thesis / Ph.D. Applied Mathematics for the Life and Social Sciences 2012