Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006. / Andrew Karellas, Ph.D., Committee Chair ; Ernest V. Garcia, Ph.D., Committee Member ; Xiaoping P. Hu, Ph.D., Committee Member ; John N. Oshinski, Committee Member.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 134-157).

No description available.

No description available.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 143-158). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 148-158). Available also in a digital version from Dissertation Abstracts.

Breast cancer is unanimously considered a highly heterogeneous disease due to its diverse molecular features. Breast tumor kinase (BRK), also known as protein tyrosine kinase 6 (PTK6), is a non-receptor tyrosine kinase that is highly expressed in over 80% of breast carcinomas. The role and mechanism of action of enzymatically activated BRK in breast pathology are unclear. The objectives of this project were to reveal the effect of BRK activation on cell migration, proliferation and tumorigenesis. We also aimed to determine the mechanism of action of BRK in the promotion of cell proliferation. We used BRK-negative cells (MCF10A, MDA-MB-231 and HEK293) to generate three sets of stable cell lines that stably expressed GFP alone, GFP-BRK-WT or GFP-BRK-Y447F (constitutively active) by retroviral infections. We also stably knocked down BRK from BRK-positive cells BT20 and SKBR3 by RNA interference using shRNAs against BRK. Western blotting, immunoprecipitation and qPCR studies were conducted to evaluate protein expression, protein-protein interaction and mRNA expression, respectively. Both sets of cell lines were used to determine the effect of BRK on cell proliferation (automated cell counter), cell migration (transwell and wound healing assay), transformation (colony formation assay) and tumor formation (mouse Xenograft assay). To investigate the mechanism of action of BRK, we validated downstream of tyrosine kinases 1 (Dok1), a tumor suppressor, as a BRK substrate. Deletion or site-directed mutagenesis was performed to map BRK-targeted tyrosines in Dok1 protein. Results obtained from this research project showed that stable expression of the constitutively active mutant of BRK (BRK-Y447F) in MDA-MB-231 cells led to a significant increase in the cell proliferation, migration rate and promoted colony formation and drastically enhanced tumor formation in athymic nude mice in comparison to control cells. Additionally, depletion of BRK abrogated the migration of BT20 and SKBR3 cells. Furthermore, we showed that BRK interacts with and phosphorylates Dok1, inducing Dok1 downregulation via a ubiquitin-proteasome-mediated mechanism. Together, our results show that the activation of BRK is essential for mammary gland tumorigenesis and suggest that targeting of Dok1 for degradation is a novel mechanism of action of BRK in the promotion of cell proliferation, migration and tumor formation.

This feminist postmodern praxis oriented research investigates the journey and discourses of women living with breast cancer. This study explores the ways in which discourses and health care practices are implicated in relations of power, and how these discourses and practices inter-relate and inform each other. Alternative possibilities for creating new discourses and practices for women living with breast cancer are also examined in the study. Seventeen women in various stages of being diagnosed and treated for breast cancer participated in two years of individual interviews, group discussions, and informal conversations with the researcher. Participants also read and responded to the emerging construction of the dissertation and contributed pieces of original writing that they had created over the course of their journey with breast cancer. This research uncovers and illuminates the ways in which participants interpret biomedical discourse and position themselves in biomedical and other discourses. It also fosters an understanding about the ways in which women's discourses, sense of agency, power, and identity are impacted as they traverse their journey with breast cancer. In fore-grounding women's discourses, the differences between a woman's personal illness story and her journey with breast cancer and the biomedical emphases on the disease diagnosis and treatment trajectory are highlighted. An examination of women's discourses also illuminates the various ways that women may be positioned by biomedical discourse, position themselves and others, and as well, resist and reposition themselves in relationships. These understandings direct our attention to the strengths and capacities of women and the manner in which they exercise personal and collective agency. This research is unique in it's emphases on illuminating women's discourses about living with breast cancer and on the professional, social, historical and institutional discourses that shape experiences for women. Highlighting a woman's journey with breast cancer, her own discourses, exercise of agency and development of transformative knowledge provides health care professionals with an insider's view. Knowledge of health care practices and relationships in the care of women with breast cancer are useful in envisioning ways of practicing to support and strengthen women's construction of a cogent illness journey and ability to participate in their care in meaningful ways. / Graduate

Carta al editor. / Revisión por pares