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

There is no abstract available for this dissertation. / Department of Educational Studies

Thesis (Ph. D.)--University of Adelaide, Dept. of Community Medicine, 1986? / Includes bibliographical references (v. 2, leaves [410]-464).

Thesis (M.S.)--University of Michigan, 1990. / eContent provider-neutral record in process. Description based on print version record.

Thesis (M.S.)--University of Michigan, 1990.

Breast cancer is the most feared and common female malignancy in the world. About one in ten women in South Africa will be diagnosed during her lifetime with this disease. The outcome of breast cancer treatment is dependent on early detection and swift subsequent management. A lack of research exists in South Africa about diagnostic and treatment delay factors. A situational analysis is currently underway to improve the breast cancer service in the country. Even less is known about the delays in rural health care. This study examined the delay during the diagnosis and treatment of breast lumps in the Theewaterskloof (TWK) sub district in the Western Cape. The results were compared to Worcester hospital, the secondary referral centre of this district. Three hundred and twenty (322) patients from Caledon hospital and surrounding clinics in the TWK and 322 randomly selected patients from Worcester hospital surgical clinic, who presented during 2007-2010, were retrospectively studied. The mean breast lump diagnostic period at TWK was 45 days versus 16 days at Worcester. Breast cancer diagnostic times were 38 days and 19 days respectively. More alarming was the difference in breast surgery delay of 173 days versus 16 days at TWK Worcester hospital respectively. These time periods were compared to the tertiary institutions in the Western Cape and with international guidelines. Cytological adequacy i.e. Fine Needle Aspiration (FNA) and core needle biopsy between the institutions are also reported. In conclusion it is suggested that regular training in FNA is required to improve the cytological adequacy at TWK. Long delay in surgical waiting periods can be addressed by referring TWK breast cancer patients to Worcester hospital after diagnosis.

A cirurgia de reconstrução de mama é uma ferramenta cirúrgica de importância ímpar para reparar os defeitos e assimetrias causadas pelos vários tipos de tratamentos cirúrgicos do Câncer de mama. Várias técnicas e táticas têm sido demosntradas e aplicadas nos últimos anos. Muitos são os estágios em que se encontram os pacientes e vários são os esquemas de abordagem terapêutica para diferentes estágios e tipos histológicos que se apresentam. Tratamentos quimioterápicos pré ou pós-operatório, tratamento radioterápico no pós-operatório quase imediato, mastectomias preventivas, setores amplos em diferentes quadrantes, quadrantectomias, todos estes são vários aspectos de tratamento de uma mesma patologia, porém com estágios e características histológicas e moleculares diferenciadas. Como alternativa cirúrgica para reconstrução de mama em câncer de mama, nos casos em que está indicada a quadrantectomia e/ou setor de mama, independentemente da localização na mama, é que propusemos uma técnica de uso de enxerto autólogo da mama contralateral para manter a forma e a simetria mamária associada a técnicas cirúrgicas de mamoplastias. Objetivo: O objetivo do presente estudo foi avaliar o uso de enxerto de mama contralateral associada a outras técnicas de cirurgia mamária já descritas por outros autores e acompanhar o resultado quanto à estética e simetria mamária no pós-operatório imediato e após o tratamento radioterápico. Comparar os resultados com as mamas do pré-operatório e avaliar a simetria e a estética no pós-operatório. Métodos: Foram incluídos neste estudo 42 pacientes com diferentes tratamentos, porém todas com indicação cirúrgica semelhantes: setor de mama ou quadrantectomia, seguidos de radioterapia. Todos os casos foram fotografados no pré-operatório e mais de 3 meses pós-tratamento radioterápico. Foi utilizada uma escala contínua para avaliar o grau de simetria mamária no pós-operatório de mais de 3 meses de radioterapia. A escalala de medição se baseou numa régua milimétrica de 0 a 10 cm. Foi solicitado a quatro especialistas na área para colocar uma marca na escala com relação à simetria e ao aspecto estético das mamas. As notas de cada paciente foram avaliadas estatisticamente. Resultados: Os resultados foram estatisticamente significativos para a avaliação estética e para a simetria mamária pós-cirurgia e radioterapia. Conclusão: Cocluímos que o enxerto autólogo de mama contralateral em cirurgia de reconstrução de mama é um procedimento que, quando utilizado com outras técnicas, traz um resultado estético e simétrico adequado, desta forma mostrando mais uma alternativa para cirurgia de reconstrução mamária. / Background: The Breast Reconstruction surgery is a surgical tool of unparalleled importance to repair the defects and asymmetries caused by various types of surgical breast cancer treatment. Various techniques and tactics has been demonstrated and applied in recent years. Many patients are at different stages of the disease and several are the sorts of therapeutic approaches for different stages and histologic types that feature. Neo adjuvant chemotherapy treatments or postoperative chemotherapy, radiotherapy in almost immediately after surgery, preventive mastectomies, removing large breast tissue in different quadrants, quadrantectomies. All these are various aspects of treatment of the same disease however to different stages and histological and molecular characteristics. As a surgical alternative to breast reconstruction in breast cancer, where it is indicated quadrantectomy and or wide resection of breast tissue in the same quadrant, regardless of location in the breast that I proposed a technique contralateral breast grafiting replacement to keep shape and breast symmetry. Objetive: The aim of this study was to evaluate the contralateral breast graft associated with other breast surgery techniques already described by other authors, and follow the aesthetic result in the immediate postoperative period and after three months of radiotherapy. Compare the results with those of preoperative breast, and evaluate the symmetry postoperatively and proper aesthetic result. Methods: The study included 42 patients. Each case with different proposals for treatment, but all with similar surgical indication, wide resection of the breast or quadrantectomy, followed by radiotherapy. All cases were photographed in their preoperative, “pre radiotherapy” and three months post radiotherapy. A continuous scale was used to assess the degree of mammary symmetry in these patients in the post operative period of three months after radiotherapy. The measurement was based on a rule millimeter scale from 0 to 10 cm. We were asked to four experts in the field to put a mark on the scale with respect to symmetry and aesthetic appearance of the breasts. The scores of each patient were evaluated statistically. Results: The results were statistically significant for the aesthetic evaluation of the breasts and also for evaluation of the symmetry of the breasts after surgery and radiotherapy. Conclusion: We concluded that autologous graft contralateral breast in breast reconstruction surgery is a procedure that when used with other techniques, brings an aesthetic and suitable symmetrical result thus showing an alternative to breast reconstruction surgery.

A cirurgia de reconstrução de mama é uma ferramenta cirúrgica de importância ímpar para reparar os defeitos e assimetrias causadas pelos vários tipos de tratamentos cirúrgicos do Câncer de mama. Várias técnicas e táticas têm sido demosntradas e aplicadas nos últimos anos. Muitos são os estágios em que se encontram os pacientes e vários são os esquemas de abordagem terapêutica para diferentes estágios e tipos histológicos que se apresentam. Tratamentos quimioterápicos pré ou pós-operatório, tratamento radioterápico no pós-operatório quase imediato, mastectomias preventivas, setores amplos em diferentes quadrantes, quadrantectomias, todos estes são vários aspectos de tratamento de uma mesma patologia, porém com estágios e características histológicas e moleculares diferenciadas. Como alternativa cirúrgica para reconstrução de mama em câncer de mama, nos casos em que está indicada a quadrantectomia e/ou setor de mama, independentemente da localização na mama, é que propusemos uma técnica de uso de enxerto autólogo da mama contralateral para manter a forma e a simetria mamária associada a técnicas cirúrgicas de mamoplastias. Objetivo: O objetivo do presente estudo foi avaliar o uso de enxerto de mama contralateral associada a outras técnicas de cirurgia mamária já descritas por outros autores e acompanhar o resultado quanto à estética e simetria mamária no pós-operatório imediato e após o tratamento radioterápico. Comparar os resultados com as mamas do pré-operatório e avaliar a simetria e a estética no pós-operatório. Métodos: Foram incluídos neste estudo 42 pacientes com diferentes tratamentos, porém todas com indicação cirúrgica semelhantes: setor de mama ou quadrantectomia, seguidos de radioterapia. Todos os casos foram fotografados no pré-operatório e mais de 3 meses pós-tratamento radioterápico. Foi utilizada uma escala contínua para avaliar o grau de simetria mamária no pós-operatório de mais de 3 meses de radioterapia. A escalala de medição se baseou numa régua milimétrica de 0 a 10 cm. Foi solicitado a quatro especialistas na área para colocar uma marca na escala com relação à simetria e ao aspecto estético das mamas. As notas de cada paciente foram avaliadas estatisticamente. Resultados: Os resultados foram estatisticamente significativos para a avaliação estética e para a simetria mamária pós-cirurgia e radioterapia. Conclusão: Cocluímos que o enxerto autólogo de mama contralateral em cirurgia de reconstrução de mama é um procedimento que, quando utilizado com outras técnicas, traz um resultado estético e simétrico adequado, desta forma mostrando mais uma alternativa para cirurgia de reconstrução mamária. / Background: The Breast Reconstruction surgery is a surgical tool of unparalleled importance to repair the defects and asymmetries caused by various types of surgical breast cancer treatment. Various techniques and tactics has been demonstrated and applied in recent years. Many patients are at different stages of the disease and several are the sorts of therapeutic approaches for different stages and histologic types that feature. Neo adjuvant chemotherapy treatments or postoperative chemotherapy, radiotherapy in almost immediately after surgery, preventive mastectomies, removing large breast tissue in different quadrants, quadrantectomies. All these are various aspects of treatment of the same disease however to different stages and histological and molecular characteristics. As a surgical alternative to breast reconstruction in breast cancer, where it is indicated quadrantectomy and or wide resection of breast tissue in the same quadrant, regardless of location in the breast that I proposed a technique contralateral breast grafiting replacement to keep shape and breast symmetry. Objetive: The aim of this study was to evaluate the contralateral breast graft associated with other breast surgery techniques already described by other authors, and follow the aesthetic result in the immediate postoperative period and after three months of radiotherapy. Compare the results with those of preoperative breast, and evaluate the symmetry postoperatively and proper aesthetic result. Methods: The study included 42 patients. Each case with different proposals for treatment, but all with similar surgical indication, wide resection of the breast or quadrantectomy, followed by radiotherapy. All cases were photographed in their preoperative, “pre radiotherapy” and three months post radiotherapy. A continuous scale was used to assess the degree of mammary symmetry in these patients in the post operative period of three months after radiotherapy. The measurement was based on a rule millimeter scale from 0 to 10 cm. We were asked to four experts in the field to put a mark on the scale with respect to symmetry and aesthetic appearance of the breasts. The scores of each patient were evaluated statistically. Results: The results were statistically significant for the aesthetic evaluation of the breasts and also for evaluation of the symmetry of the breasts after surgery and radiotherapy. Conclusion: We concluded that autologous graft contralateral breast in breast reconstruction surgery is a procedure that when used with other techniques, brings an aesthetic and suitable symmetrical result thus showing an alternative to breast reconstruction surgery.

M.Tech. / To determine whether a combination of real-time B-Mode ultrasound, Doppler Color flow and Power Doppler flow mapping would be reliable in differentiating benign from malignant breast nodules in an attempt to avoid unnecessary biopsies, where after ultrasound guidelines would be formulated. A quantitative cross-sectional comparative descriptive design in a study population which consisted of 62 women over the age of 35 years who came to Klerksdorp Radiology services for mammography. Both breast ultrasound imaging and mammography was used as a routine procedure as part of the workup for the classification of breast nodules, before histologic specimens were obtained. All nodules were classified according to the ultrasonographic BI-RADS lexicon and compared with the pathologic results. Of the 63 patients, 63 breast nodules were detected and confirmed by biopsy. Thirty seven (59%) nodules were found to be malignant and 26 (41%) were benign according to biopsy results. Mammography had 87% sensitivity and ultrasound 60% sensitivity in detecting malignancy. It is recommended that B-mode, Color Doppler flow and Power Doppler flow mapping be used in combination with mammography for screening as a gold standard.

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.