Wilson, Sandra Lee
Recently the traditional primary method of treatment for breast carcinoma — the Halsted radical mastectomy — has been challenged. It is felt by some people that other methods may be more appropriate for certain women. Quality of life and the patient's preferences are being considered in addition to the strictly medical aspects of the problem. One procedure that attempts to increase the quality of life for certain women is the selective biopsy. Women who are proven to have lymph node metastases at the biopsy are spared a mastectomy and treated by radiation since surgery cannot remove all of the cancer. A study was undertaken at the British Columbia Cancer Institute of selective biopsy patients diagnosed between 1955 and 1963 in order to assess the procedure in British Columbia. After studying survival for selective biopsy patients and others, it was concluded that the procedure should continue to be recommended. Since only 14% of the patients now referred to BCCI have had a selective biopsy, I decided to try to find a statistical method for assessing the probability of nodal metastases. The problem is one of statistical classification. The literature on the theory of several statistical models was reviewed. Two models were chosen for the problem: linear discriminant analysis and logistic regression. The classification procedure most often used is discriminant analysis. However, the linear discriminant model assumes a normal distribution and common covariance matrix for the vector of observations. Medical data is often non-normal and even discrete. The logistic probability model works well with such data. Both models were then used to study the selective biopsy problem. The patients of the BCCI study were used as a training set to estimate the parameters of the discriminant function and the logistic probability function. Then each estimated function was used to classify the patients as a measure of the goodness of fit of the models. The logistic regression correctly classified slightly more of the patients than the discriminant analysis did. Because of the iterative nature of the logistic regression, the execution time for the logistic regression was longer than for discriminant analysis, but not beyond practical limits. .The variables that were significant in the statistical analyses could be used to help the physician make a clinical assessment of the lymph nodes of a woman with breast carcinoma. The variables indicate areas where further research would be useful. / Science, Faculty of / Mathematics, Department of / Graduate
Brand, Juanita M.
There is no abstract available for this dissertation. / Department of Educational Studies
Investigation of the effects of [alpha]-TEA, 9-nitrocamptothecin and paclitaxel alone and in combination on 66cl-4-GFP murine mammary cancer cells in vitro and in vivoLatimer, Paul Brian, 1976- 14 June 2012 (has links)
Second only to lung cancer, breast is the leading type of cancer among women in the US. Despite all the medical advances over the past few decades, toxicity and increased resistance to standard drug therapy still remains a significant problem. The heterogeneic nature of all cancers has led to a shift in treatment approaches, in that more research is being carried out with combination treatments in the hope that a multidirectional targeting of cancer will be far more effective than the current single treatment options. Our goal was to gain a better understanding of the molecular mechanisms of a nonhydrolyzable ether analog of RRR-[alpha]-tocopherol, 2, 5, 7, 8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid (abbreviated [alpha] -TEA), and to investigate its efficacy when used in combination with known chemotherapeutics 9-nitro-camptothecin (9NC), and Paclitaxel (Taxol). The data presented here looks encouraging as it shows a clinically relevant delivery method using [alpha]-TEA and 9NC has the unique ability to reduce primary tumor burden as well as macro and micrometastatic lung and lymph node lesions in an aggressive syngeneic mouse mammary model, while displaying no obvious toxic side effects. The effect of combination treatments on tumor volume appears in part to be moderated by an increase in tumor cell apoptosis and a decrease in tumor cellular proliferation. Next, the intricate molecular mechanism of how [alpha]-TEA alone and in combination with 9NC is able to induce apoptosis in 66cl-4-GFP murine mammary cancer was investigated. The data suggest that the signaling pathway that ultimately leads to apoptosis is caspase dependent, is able to upregulate pro-death players while at the same time downregulate pro-survival proteins such as c-Flip and survivin. Finally, we investigated the efficacy of [alpha]-TEA used in an allograft mouse model following treatment with Taxol. Combination treatments were able to significantly reduce primary tumor burden, decrease lung and lymph node micrometastases, tumor cell proliferation, tumor blood vessel density as well as increase tumor cell apoptosis. Based on the results presented, we propose that [alpha]-TEA when used alone and in combination is an effective, non-toxic option for cancer treatment which warrants further investigation. / text
Fatigue, self-efficacy for physical activity, physical activity, and quality of life in women with breast cancerHaas, Barbara Kay 15 March 2011 (has links)
Not available / text
Mak, Wai-ming, Vivian
published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences
>Magister Scientiae - MSc / Breast cancer is responsible for a large portion of cancer-related deaths. Worldwide, incidence is increasing. Routinely-used treatments for breast cancer are invasive and are associated with a range of side-effects which may affect quality of life. Fucoidan, a marine bioactive compound, found primarily in brown seaweed, has various medicinal qualities. Among its bioactivities studied, it has potent anticancer activity. Despite numerous studies, the mechanism of action of fucoidan on cancer cells remains unclear. This project aims to shed light on the mechanism of action of fucoidan by studying its effect on the MCF7 breast cancer cell proteome. The IC50 obtained for fucoidan treated MCF7 cells was 0.2 mg/ml. Decrease in expression of XIAP and phosphorylation of ERK1/2 was observed, indicating a decrease in inhibition of apoptosis and increased sensitivity to apoptosis, respectively. Literature reports activation of several caspases, including caspase-3, in various cell lines after to fucoidan treatment. Taken together, with data from the current study it can be said that fucoidan treatment led to cell death by apoptosis. SILAC analysis identified over 2000 proteins with more than 1700 at 95% confidence. STRING analysis of enriched proteins revealed 19 cell death related proteins. However, SILAC results were ambiguous with regards to differential protein regulation and should be repeated with lower electrospray ionization flow rates, pairwise and single sample runs, and validation with Western blot analysis of various apoptosis related proteins and biochemical assays. / National Research Foundation
The efficacy of astragalus membranaceous tincture at maintaining the circulating leucocyte and absolute neutrophil counts of breast cancer patients undergoing chemotherapeutic treatmentMinnaar, Carrie-Anne 08 April 2010 (has links)
M. Tech. / AIM: To determine the efficacy of Astragalus membranaceous tincture at maintaining the circulating white blood cell count (WBC) and absolute neutrophil count (ANC) of breast cancer patients receiving chemotherapy. METHODS: This is an open-label study with an active control group. Both the study and control group consisted of fifteen participants. The participants in the study group each received ten millilitres of Astragalus membranaceous 1:2 tincture daily for the duration of their course of chemotherapy. RESULTS: The overall decrease in the WBC and ANC in the control was 4.9 and 3.13 parts per billion per litre, respectively. The study group showed an overall decrease of 2.7 and 1.9 parts per billion per litre, respectively. The average overall reduction in chemotherapy dose was 4.79 percent in the study group and 20.21 percent in the control. In all of the analyses p > 0.05. The small sample size, poor patient compliance and skewed distribution of the variables hindered the reliability of the results. CONCLUSION: The positive effects observed in the study group cannot be extrapolated to the entire population, however further research is strongly motivated.
Thesis (M.A.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at firstname.lastname@example.org. Thank you. / Although there are hereditary risk factors strongly associated with breast cancer, only a small percentage of breast tumors can be attributed to these. Instead, it is believed that 85-90% of breast cancers are primarily of environmental origin. Polycylic aryl hydrocarbons (PAHs) are environmental carcinogens derived from combustion including fossil fuels. PAHs bind to a cellular aryl hydrocarbon receptor (AhR) that mediates downstream events leading to cellular transformation. Previous work in our laboratory used the prototypical PAH 7,12-dimethylbenz[a]anthracene (DMBA) to form tumors in mouse mammary glands that had constitutive AhR activation, increased Wnt signaling, and strong induction of the CK2 subunit CK2α (Currier, Solomon et al. 2005). Wnt, an important developmental pathway, is implicated in several cancers (Dominguez, Sonenshein et al. 2009). CK2 is a highly promiscuous, constitutively active serine/threonine kinase that is over-expressed in every cancer that has been examined for its presence (Meggio and Pinna 2003). Data from the DMBA-induced mouse tumors demonstrated that these factors may be involved in carcinogen-induced breast cancer, but their role in tumor development is uncertain. The hypothesis underlying this project was that CK2 and the Wnt pathway would be involved in early changes in mouse mammary and liver tissues in animals exposed to DMBA. We used qPCR, Western blotting, and immunohistochemistry to look at changes in Wnt pathway components and known Wnt-dependent genes, and CK2 subunits in mammary and liver tissues one and two weeks after DMBA exposure. Liver tissue was analyzed along with mammary gland tissue because the liver is the site of DMBA metabolism. Our results showed no change in liver or mammary gland morphology at these time points. There was induction of the AhR gene targets cyp1a1 and cyp1b1 in liver tissue but not in mammary gland. Liver also had evidence of Wnt pathway activation. Mammary glands did not have a strong AhR response but did show Wnt induction at two weeks post-exposure, suggesting that DMBA was affecting the liver before the mammary glands. CK2α had an unexpected early decrease in protein expression at one week in liver, which at two weeks resolved to the same levels as control tissue. In mammary glands, CK2α expression levels were the same as control at one week and decreased at two weeks, again suggesting a slower response than liver. Interestingly, CK2β was markedly overexpressed in mammary glands at the two week time-point. These results suggest there is a role for both Wnt and CK2 in early DMBA-generated tissue changes. It is still unclear if these pathways are separately affected by DMBA or if one initiates the other. Further experimentation, possibly in cell culture using inhibitors and siRNA, are called for to better understand these findings. / 2031-01-01
Genome wide copy number and gene expression profiling using archived tissue for molecular marker studies in breast cancerIddawela, Mahesh Yasantha Bandara January 2011 (has links)
No description available.
Lee, Tian Yu
13 June 2019
Breast cancer is a complex heterogenous disease that consists of several different subtypes displaying distinct behaviors and responses to different treatments. It is the second leading cause of cancer death among women, and is the most commonly diagnosed cancer in women. Although recent developments have helped shed light into this disease, there is still much to investigate. One particular subtype of breast cancer, known as triple-negative breast cancer, remains the most aggressive, as this tumor type is of high histological grade and preferentially affects women with BRCA1 mutations and women who are younger than 40 years of age. Unlike other subtypes with better prognoses, triple-negative breast cancer still has no targeted therapy, and chemotherapy remains the primary systemic treatment. Recently, there has been an increase of interest in the SOXC family of high mobility group transcription factors and their roles in tumor development. Studies have revealed some of the effects that SOXC genes may have on various tumor types. However, further studies are still needed to elucidate the roles, functions, regulations, and mechanisms of these transcription factors. This study aims to focus on one particular gene in the SOXC family known as sex determining region Y-box 11. Recent studies have shown that sex determining region Y-box 11, also known as SOX11, is one of the factors required for maintaining the basal-like breast cancer phenotype and is also critical in regulating growth, migration, invasion, and expression of signature basal-like breast cancer genes. Emerging evidence also reveals that this transcription factor may have an impact on homologous recombination repair when DNA damage occurs, in triple-negative breast cancer. Using SOX11 overexpression and knockout cell models combined with basic science laboratory techniques and omics, the next generation of laboratory tools, this study seeks to explore the role and function of SOX11 in DNA damage in triple-negative breast cancer. The results of this study have confirmed the recent findings of the role of SOX11 in cell proliferation and growth in triple-negative breast cancer. It has also revealed that overexpression of SOX11 in triple-negative breast cancer cell lines leads to an increase in DNA damage, loss of BRCA1 function, and dysregulation in the cell cycle. High expression of SOX11 is also associated with worse prognostic outcomes in triple-negative breast cancer patients. Because overexpression of SOX11 resulted in a loss of BRCA1 function, there may be a potential role for SOX11 in inducing the BRCAness phenotype commonly seen in basal-like breast cancers. The results of this study strongly suggest that SOX11 is involved in defective DNA damage repair pathways. Further studies need to be conducted in order to evaluate SOX11 as an inducer of the BRCAness phenotype, which occurs when there is a homologous recombination repair defect and no germline BRCA1 mutation present. Because of this, SOX11 may also have the potential to act as a functional biomarker for therapies targeting DNA damage, as recent developments in identifying therapies that could potentially target homologous recombination repair defects have been promising.
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