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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
461

Diggin in, moving on : the experiences of breast cancer dragon boat paddlers

Shermak, Sheryl Lee 05 1900 (has links)
It is commonly believed that breast cancer dragon boating benefits survivors in a range of psychosocial areas, but there have been few empirical studies to investigate such relationships. An interpretive description design and a critical health promotion approach were used to explore the psychosocial experiences of women who breast cancer dragon boat. In-depth interviews with six participants were analyzed. Themes that arose from the data are: (1) moving past isolation — networks of like-minded support, (2) taking control,(3) journey into adventure, (4) affirmative outlook, (5) confronting painful experience, (6) rebuilding identity, (7) and spiritual engagement. The findings illustrate that dragon boating provides breast cancer survivors with a significant venue for change and the opportunity to move beyond traumatic elements of cancer.
462

Y-box binding protein-1 (YB-1) is essential for the growth and survival of HER-2 over-expressing breast cancer cells

Lee, Cathy 05 1900 (has links)
The human epidermal growth factor receptor (HER-2) is over-expressed in 20-30% of breast carcinomas and is a prognostic marker for poor patient outcome. We previously identified the transcription/translation factor Y-box binding protein-1 (YB-1) to be a novel substrate of AKT which binds to epidermal growth factor receptor (EGFR) and HER-2 promoters once phosphorylated (Wu J et al. 2006). YB-1 is over-expressed in approximately 40% of breast cancers; its expression is strongly correlated with HER-2 and is associated with poor patient survival. In order to gain a deeper understanding of the functional role of YB-1 in HER-2 over-expressing breast cancer, we silenced the expression of this factor in BT474-m1 and MDA-MB-453 cells. The loss of YB-1 inhibited the growth of BT474-m1 and MDA-MB-453 cells in monolayer and/or in soft agar. Consistent with this, we found a decrease in the expression of YB-1 responsive gene egfr and/or her-2 in BT474-m1 and MDA-MB-453 cells, which could begin to explain how growth is promoted by this factor. Furthermore, loss of YB-1 expression induced apoptosis in BT474-m1 cells. Beyond its role in tumor growth, YB-1 is also strongly linked to drug resistance. We therefore addressed whether it could play a part in Herceptin sensitivity. Herceptin is currently being used to treat patients with HER-2 positive breast cancer; however, only 30% of the patients respond to the therapy and many of them develop resistance within the first year of treatment. Therefore, it is of utmost importance to understand the biology of HER-2 over-expressing breast cancer to develop novel therapies that can benefit more patients. First we established that Herceptin inhibited BT474-m1 cell growth in anchorage-independent conditions whereas MDA-MB-453 cells were resistant to this treatment. We subsequently demonstrated that knock-down of YB-1 increased sensitivity of BT474-m1 cells to Herceptin while MDA-MB-453 cells failed to respond to the combination treatment. The mechanism for Herceptin resistance in MDA-MB-453 cells still remains elusive and requires further investigation. Thus far, we conclude that YB-1 is needed for the growth and survival of HER-2 positive BT474-m1 and MDA-MB-453 breast cancer cells by inducing members of the HER family.
463

Y-box binding protein-1 (YB-1) is a bio-marker of aggressiveness in breast cancer and is a potential target for therapeutic intervention

Habibi, Golareh 11 1900 (has links)
Early detection is one of the most important factors for successful treatment of cancer. Currently, scientists are searching for molecular markers that can help identify and predict outcome and chance of recurrence in patients. In this study, we demonstratet he potential impact of Y-Box binding protein-1 (YB-1) as a marker of aggressiveness and cancer recurrence in breast malignancies by screening one of the largest tissue microarrays in North America. YB-1 is an oncogenic transcription/translation factor, which is over-expressed in the majority of malignancies, including breast cancer. In the cohort of 4049 primary breast tumours, we show that YB-1 is a strong marker of aggressiveness, poor survival and cancer recurrence in all subtypes of human breast cancer with a particularly high frequency of expression in the ER negative basal-like and HER-2 breast cancer subtypes. This suggests that targeting YB-1 may provide a new avenue for therapeutic intervention in these breast cancers that are currently challenging to treat. Cox regression multivariate analysis indicates that YB-1 is second only to nodal status as a strong independent prognostic marker for poor outcome and relapse compared to established clinico-pathological biomarkers, including tumour size, age, grade, ER and HER-2 status. This finding suggests that YB-1 has great potential to be in a priority list of biomarkers for identifying the patients with a higher risk of relapse and poor outcome. Subsequently, we find an association between YB-1 and urokinase Plasminogen Activator (uPA) expression in the basal-like subtype. We then show that YB-1 is involved in the regulation of uPA expression. More importantly, silencing YB-1 or uPA results in a significant reduction in cancer cell invasion. As there are no commercially available YB-linibitors we examine the efficacy of BMS-536924, a small molecule inhibitor for activated IGF-1R/IR on SUM149 cells. We demonstrate that activated IGF-1R is associated with poor survival in primary breast tumours and, that BMS-536924 reduces uPA expression through inhibition YB-1 in SUM149 cells. We therefore conclude that YB-1 is a bio-marker for poor survival and relapse. We also indicate that YB-1 has potential use as a molecular marker in a clinical setting. Inhibiting YB-1 may provide an ideal opportunity for targeted therapy in breast cancer.
464

Identification and Validation of Candidate Breast Cancer Biomarkers: A Mass Spectrometric Approach

Kulasingam, Vathany 17 April 2012 (has links)
One of the best ways to diagnose breast cancer early or to predict therapeutic response is to use serum biomarkers. Unfortunately, for breast cancer, we do not have effective serological biomarkers. We hypothesized that novel candidate tumor markers for breast cancer may be secreted or shed proteins that can be detected in tissue culture supernatants of human breast cancer cell lines. A two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) strategy was utilized to identify and compare levels of extracellular and membrane-bound proteins in the conditioned media. Proteomic analysis of the media identified in excess of 600, 500 and 700 proteins in MCF-10A, BT474 and MDA-MB-468, respectively. We successfully identified the internal control proteins, kallikreins 5, 6 and 10 (ranging in concentration from 2-50 µg/L), as validated by ELISA and confidently identified HER-2/neu in BT474 cells. Sub-cellular localization was determined based on Genome Ontology (GO) for the 1,139 proteins, of which 34% were classified as extracellular and membrane-bound. Tissue specificity, functional classifications and label-free quantification were performed. The levels of eleven promising molecules were measured in biological samples to determine its discriminatory ability for control versus cases. This screen yielded activated leukocyte cell adhesion molecule (ALCAM) as a promising candidate. The levels of ALCAM, in addition to the classical breast cancer tumor markers carbohydrate antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) were examined in 300 serum samples by quantitative ELISA. All three biomarkers effectively separated cancer from non-cancer groups. ALCAM, with area under the curve (AUC) of 0.78 [95% CI: 0.73, 0.84] outperformed CA15-3 (AUC= 0.70 [95% CI: 0.64, 0.76]) and CEA (AUC= 0.63 [95% CI: 0.56, 0.70]). The incremental values of AUC for ALCAM over that for CA15-3 were statistically significant (Delong test, p <0.05). Serum ALCAM appears to be a new biomarker for breast cancer and may have value for disease diagnosis.
465

ADENOSINE AS AN ENVIRONMENTAL STRESSOR AFFECTING HSP27 AND CXCR4 IN EPITHELIAL CELLS

Tufts, Julia 19 December 2011 (has links)
Solid tumours are a hostile tissue environment in which the cells are exposed to many stresses including hypoxia. One consequence of hypoxic conditions is an increase in extracellular levels of the purine nucleoside adenosine, which enhances tumour cell migration. This is achieved in part through an increase in the levels of the chemokine receptor CXCR4, which along with its ligand CXCL12, is a key player in breast cancer metastasis. The cellular response to stress is mediated by a family of proteins known as heat-shock proteins (HSPs). The small heat shock protein 27 (HSP27) has been implicated in changes in cancer cell migration. I have therefore studied the regulation of HSP27 in human breast cancer cells by conditions that normally exist in the stressful tumor environment. My project specifically aimed to establish whether changes in HSP27 are linked to hypoxia, adenosine levels and alterations in the CXCL12-CXCR4 migratory pathway.
466

"SOME WOMEN ARE JUST SO MUCH BETTER THAN ME:" GOVERNMENTALITY ENACTED THROUGH THE BREAST CANCER SOCIAL MOVEMENT

Fredericks, Erin 08 March 2013 (has links)
Breast cancer social movements have, in many ways, succeeded in increasing the visibility of the disease in North America, yet researchers understand little about the effects of this visibility; there is little information about how women with breast cancer navigate breast cancer discourse. Feminist relational autonomy helps us to understand that women's degree of autonomy in making treatment decisions regarding their breast cancer is affected by their understanding of the disease and available options. I draw on the results of multiple qualitative interviews and online discussion group posts from 12 women with breast cancer in Nova Scotia, Canada, to examine the interconnections between breast cancer discourse and approaches to decision-making. Many representations of the best ways to “do” breast cancer cross the boundaries of allopathic and homeopathic medicine, popular self-help literature, and support services approaches to care, making them extremely pervasive in women’s lives. An idealised subject position that portrays women with breast cancer as strong, positive survivors/thrivers connects to a context in which certain identities are more likely to be accepted than others. Constraining the identities worthy of social recognition, breast cancer discourse is taken up in ways that limit the actions participants could imagine and justify, and encourage self-governance and discipline of others.
467

A Comparative Study of the Anti-Breast Cancer and Immunomodulatory Effects of [6]-, [8]-, and [10]-Gingerol

Bernard, Megan M 16 July 2013 (has links)
[6]-Gingerol, [8]-gingerol, and [10]-gingerol are phytochemical extracts from ginger that are thought to contribute to its health-benefitting properties. The objectives of this investigation were to explore and compare the in vitro anti-proliferative and cytotoxic effects of [6]-, [8]-, and [10]-gingerol on human and mouse mammary carcinoma cells, as well as their ability to inhibit T cell proliferation. [8]-Gingerol and [10]-gingerol induced mammary carcinoma cell death that did not require ROS production or caspase activation. All three gingerols inhibited the proliferation of mammary carcinoma cells and T cells, and the production of IFN-? by T cells. The production of IL-2 and the expression of early T cell activation markers, CD25 and CD69, were significantly decreased by [8]- and [10]-gingerol. The results demonstrated that [10]-gingerol was the most potent, followed by [8]-gingerol, then [6]-gingerol. Consequently, [8]- and [10]-gingerol warrant further investigation for the treatment of breast cancer and the control of inflammation.
468

Combined Effects of N-3 Polyunsaturated Fatty Acids and 1alpha, 25-dihydroxyvitamin D on Breast Cancer Cell Growth

Broadfield, Lindsay 23 August 2013 (has links)
Omega-3 polyunsaturated fatty acids (PUFA) and vitamin D both have anti-cancer effects through common and unique pathways. The hypothesis of this thesis is that the combination of n-3 PUFA with 1,25(OH)2D3 will inhibit breast cancer cell growth in an additive or synergistic manner. A 3X3 factorial design was used to test the combinations of five PUFA treatments (α-linoleic acid (ALA, 18:3n3), eicosapentaenoic acid (EPA, 20:5n3) and docosahexaenoic acid (DHA, 22:6n3), γ-linolenic acid (GLA, 18:3n6) and arachidonic acid (AA, 20:4n6)) with 1,25(OH)2D3 on MCF-7, MDA-MB-231, and MCF-10A cell growth, and determine any potential synergism in combination treatments. MCF-7 and MCF-10A cells responded to PUFA and 1,25(OH)2D3 treatments, but combinations provided no potential synergism. MDA-MB-231 growth was not affected by 1,25(OH)2D3, while combinations treatments involving ALA, EPA, GLA, and AA caused potentially synergistic growth inhibition. This thesis presents the novel observation that PUFA are sensitizing MDA-MB-231 cells to 1,25(OH)2D3 treatment.
469

Characterizing ErbB2-induced mammary tumourigenesis

Oliver, Joseph James 18 September 2007 (has links)
Approximately 30% of human breast cancers demonstrate overexpression of the receptor tyrosine kinase ErbB2/HER2/Neu, with these cases correlating with recurrence and poor prognosis. While therapy targeting ErbB2 has met with some success, particularly in early-stage breast cancers, transformation and progression towards a later-stage metastatic phenotype is likely sustained by aberrant signaling from additional players, for instance that downstream of integrins. In fact, treatment with integrin-blocking antibodies and ß1-integrin ablation leads to reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo. Moreover, ErbB2 has recently been found to interact with the ß4-integrin subunit to promote tumour formation and progression, as deletion of the ß4-integrin signaling domain led to suppression of mammary tumour onset and invasive growth, coupled with decreases in ErbB2-dependent signaling. ErbB2 may interact with integrin subunits by direct binding or via the intracellular kinases Src and focal adhesion kinase (FAK), both known to be activated downstream of ErbB2 and integrins and having well-established roles in cell adhesion, migration, and invasion. Using an inducible model of ErbB2 activation, we have demonstrated that controlled ErbB2 activation in human mammary epithelial cells leads to phosphorylation of Src Tyr215 and FAK Tyr861, consistent with a recently published clinical study examining phosphorylated forms of Src and FAK in ErbB2-positive human breast tumour samples. We have also confirmed that ErbB2 activation increases the capacity of cells for survival: Normally, MCF10A human mammary epithelial cells cultured in three-dimensional, laminin-rich extracellular matrix gel form mammary acini-like spheroids with hollow lumen surrounded by a single layer of polarized epithelial cells. However, ErbB2 activation prevents luminal clearance and induces luminal filling in acini formed in three-dimensional culture, and leads to activation of Akt, a known survival signal. Taken together these data indicate a potential role for ErbB2 at the apex of cell survival signaling via Src, FAK, and Akt, contributing to luminal cell survival in three-dimensional culture. We have thus confirmed Src, FAK, and Akt as potential players in early onset of breast cancer, and targeting these signaling players concurrently with ErbB2 may prove effective, especially in early stage breast cancers. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2007-08-31 16:25:59.917
470

Molecular Stress Signaling in Breast Epithelial Cells

Antonova, Lilia 15 January 2008 (has links)
ABSTRACT Breast cancer is a complex disease, whose etiology is not well understood. A number of factors have been found to contribute to its development. Psychological stress has been recognized as such a factor in epidemiological studies, but few molecular mechanisms have been proposed to explain its association to breast cancer risk. This work addresses the lack of knowledge in the area of stress and breast cancer with the use of molecular and epidemiological techniques. Molecular experiments allowed the identification of a link between stress signaling and intracellular signaling pathways known to be affected in breast cancer development. Namely, the stress hormone hydrocortisone (cortisol) was found to down-regulate the Breast Cancer Susceptibility Gene 1 (BRCA1). Further study allowed identification of some of the mechanisms involved. Binding of the transcription factors GABPa/b and USF2 at specific sites of the BRCA1 promoter (the RIBS and UP sites) was shown to be negatively affected by hydrocortisone. In addition, a novel hormone-independent function of the receptor for hydrocortisone, the glucocorticoid receptor, was identified in the context of BRCA1 regulation. GR was determined to act as a positive regulator of BRCA1 in the absence of hydrocortisone through the RIBS and UP sites. Taken altogether these results represent a novel molecular mechanism linking stress signaling to breast cancer development. The second objective of this work was to design an epidemiological study which would determine whether stress-susceptible individuals are at higher risk of developing breast cancer. This study would be the first of its kind in the case of breast cancer and would allow the development of a genetic method of measuring stress exposure which can be used in future studies. The study was designed to look at glucocorticoid receptor iii polymorphisms known to produce phenotypic differences in GR activity in a population of women with incident breast cancer and population-based controls. In conclusion, the present work suggests an integrative model of the effect of stress on breast cancer development which incorporates genetic predisposition to the effects of stress and downstream changes in the expression and activity of the Breast Cancer Susceptibility Gene 1. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2008-01-02 23:42:20.89 / Canadian Breast Cancer Foundation-Ontario Chapter Canadian Institute of Health Research

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