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Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (Ph. D.)--Drexel University, 2007. / Includes abstract and vita. Includes bibliographical references (leaves 93-112).

Les chiffres mondiaux estiment l’incidence du cancer du sein, cancer féminin le plus fréquent, à 1.3 millions de cas par an, dont près d’un tiers a une issue fatale.La polarité est indispensable à l’organisation cellulaire, ses défauts peuvent mener au cancer. Notre projet est focalisé sur une protéine de la polarité, Lano, et son influence sur le cancer du sein et les CSC. L’Institut Paoli-Calmettes dispose d’environ 10000 échantillons de cancer du sein dont l’analyse montre que la perte de Lano est corrélée à des cancers du sein plus graves et à une augmentation des CSC. Nos résultats in vitro, sur des cellules de cancer du sein humain et in vivo montrent aussi que Lano est un régulateur du nombre de CSC. Les CSC sont une ces causes principales de rechute des patients. La suite de nos travaux pourrait déterminer si Lano est un facteur pronostique de la maladie ou une cible thérapeutique possible. / Breast cancer is the most common cancer in women. Worldwide figures estimate the incidence of breast cancer at 1.3 million cases per year, nearly one third of them has a fatal outcome.Our project focuses on the study of Lano, a polarity protein, in breast cancer and stem cells. The hospital “Institute Paoli-Calmettes” gathered 10,000 breast cancer samples whose analysis shows that the loss of Lano has a role in breast cancer and stem cells. Our in vitro results on human breast cancer cells and in vivo also show that Lano is a regulator of the number of cancer stem cells. Cancer stem cells are one of the major causes of relapse in patients. The rest of our work could determine if Lano could be a prognostic factor of the disease or a possible therapeutic target.

Orientadores: Marcelo Alvarenga, Cesar Cabello dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T14:34:16Z (GMT). No. of bitstreams: 1 Bianchessi_SusanaTrigo_M.pdf: 5977471 bytes, checksum: 691416790e0a9f01b1b82619e5b6e1f3 (MD5) Previous issue date: 2008 / Resumo: Introdução: A correta avaliação da extensão local do câncer de mama é necessária para a escolha do tratamento local entre cirurgia conservadora e mastectomia. Objetivo: Avaliar se a ressonância magnética (RM) é um bom preditor do tamanho tumoral, multifocalidade e multicentricidade. Sujeitos e Métodos: Vinte mulheres com carcinoma mamário unilateral e unifocal, agendadas para mastectomia, realizaram RM. As medidas dos três diâmetros tumorais foram realizadas em milímetros e outros focos de captação do contraste foram avaliados. O resultado anatomopatológico da peça de mastectomia incluiu os três diâmetros tumorais em milímetros (mm) e descrição de outros focos tumorais, quando presentes. Resultados: Os três diâmetros do tumor foram avaliados e os índices de concordância entre o AP e a RM foram de 95% para o diâmetro longitudinal e 85% para os diâmetros anteroposterior e transversal. A sensibilidade e a especificidade da RM no diagnóstico de doença multifocal foi de 78% e 82%, no diagnóstico de doença multicêntrica foi de 81% e 100% e sua acurácia foi de 80% e 85%. O Índice Kappa em relação a multifocalidade e a multicentricidade foi de 0,6 e 0,63, respectivamente. Conclusão: A RM pode ser usada como método complementar para auxiliar o planejamento cirúrgico / Abstract: Introduction: Predicting the extent of local breast cancer is essential for making the choice between breast-conservation treatment and mastectomy. Aim: To determine whether preoperative breast magnetic resonance (MR) could predict size of index tumor, multifocality and multicentricity. Patients and methods: Twenty women with unilateral end unifocal breast cancer scheduled for mastectomy underwent breast MR. Measurements in the three diameters were taken in millimeters (mm) and other foci of contrast uptake were evaluated. The anatomopathologic (AP) result of the mastectomy specimen included measurements in the three diameters of the index tumor, taken in millimeters, and other foci of tumor. Results: The concordance index was calculated for each diameter and was 95% for longitudinal diameter and 85% for antero-posterior and transversal diameters. The MR sensitivity and specificity for multifocal disease was 78% and 82% and for multicentric disease was 81% and 100%, respectively. The Kappa index was 0,6 for multifocality and 0.63 for multicentricity. Conclusion: MR can be used as a complementary method for surgical planning / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

Orientador: Jacks Jorge Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T16:42:54Z (GMT). No. of bitstreams: 1 SouzaLima_NathaliaCarolinede_M.pdf: 622004 bytes, checksum: 0c706eecc1567182559d2fa1ba1d3900 (MD5) Previous issue date: 2014 / Resumo: Exposição a hormônios sexuais no início da vida pode influenciar a susceptibilidade às doenças relacionadas às diferenças de sexo. A proporção 2D:4D tem sido considerada um marcador putativo de exposição e sensibilidade pré-natal a hormônios sexuais, assim como à expressão de genes relacionados ao câncer. Dessa maneira, essa dissertação propôs-se a investigar a proporção 2D:4D de mulheres com câncer de mama, mulheres com lesão benigna de mama e mulheres controle; e associar 2D:4D com diagnóstico histológico, receptores hormonais, expressão de HER-2 e estadiamento clínico tumoral. No total, 810 mulheres foram recrutadas e classificadas em três grupos: câncer de mama (CM); lesões benignas de mama (LBM); e controle (CON). Mulheres com histórico de injúria nos dedos indicador ou anelar foram excluídas. Todas as mulheres tiveram as palmas das mãos fotografadas utilizando câmera digital acoplada a uma estativa. As imagens foram transferidas para computador e analisadas utilizando o software Adobe Photoshop®, e a distância entre a depressão primária da superfície ventral e a ponta dos dedos indicador (2D) e anelar (4D) das mãos foram medidas duas vezes e registradas. Aos dados foram aplicados os testes de Coeficiente de Correlação Intraclasse, ANOVA, Teste t de Student e teste X². Os resultados mostraram que CM relatou amamentar mais (p=0,0043) e apresentou maior diferença entre as proporções digitais das mão direita e esquerda ( ?D-E ) em comparação ao CON (p=0,0320). Os grupos CM e CON relataram maior paridade em comparação ao grupo LBM (p=0,0157 e p=0,0439, respectivamente). Não houve relação entre 2D:4D e diagnóstico histológico, receptores hormonais, expressão de HER-2 ou estadiamento clínico tumoral. A análise da diferença entre 2D:4D das mãos direita e esquerda (?D-E) sugere que a exposição aos hormônios sexuais intra útero possa influenciar o desenvolvimento de câncer de mama em mulheres adultas / Abstract: Exposure to sex hormones in early life may influence susceptibility to diseases related to sex differences. The ratio 2D:4D has been considered a putative marker of prenatal exposure and sensitivity to sex hormones, as well as the expression of genes related to cancer. Thus, this dissertation aimed to investigate the ratio 2D:4D in breast cancer women, benign breast lesion women and healthy women, and to associate 2D:4D with histological diagnosis, hormone receptor status, HER- 2 expression and tumor clinical staging. Overall, 810 women were recruited and classified into three groups: breast cancer (BC), benign breast lesion (LBM) and control (CON). Subjects with history of injury in the index or ring finger were excluded. All women had their palms of the hands photographed, using a digital camera attached to a stand. The images were transferred to a computer and analyzed using Adobe Photoshop® software, and the distance between primary depression of the ventral surface and the tip of the index finger (2D) and ring finger (4D) were measured twice and recorded. Intraclass correlation coefficient, ANOVA, Student's t test, and X ² test were applied to the data. The results showed that CM reported more breastfeeding habits (p=0.0043) and showed higher ?R-L (p=0.0320) compared to CON. The CM and CON groups reported higher parity compared to LBM group (p=0.0157 and p=0.0439, respectively). Histological diagnosis, hormone receptor status, HER-2 expression, and tumor clinical staging were not associated to 2D:4D. The results of the difference between 2D:4D of the right and left hands (?R-L) suggests that exposure to prenatal sex hormones may influence the development of breast cancer in adult women / Mestrado / Estomatologia / Mestra em Estomatopatologia

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The epidermal growth factor receptor (EGFR) is a well-recognized proto-oncogene and mediator of cancer cell growth and proliferation. Emerging evidence suggests the paradoxical role of EGFR activation, unique to metastatic breast cancer cells. Previously studies elucidated the role of EGFR mediated activation of Signal Transducer and Activator of Transcription 1, STAT1, is required to induce apoptosis in cells with increased metastatic potential. In this current study, we evaluate the effects of cells with mutations leading to aberrations in phosphatidylinositol 3-kinase, PI3K/AKT/protein kinase B signaling. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) is a key regulator of the PI3K/Akt pathway and is one of the most commonly mutated genes in breast cancer patients. Utilizing human breast cancer cells, MDA-MB-468 and BT-20s, characterized by amplified protein levels of EGFR and mutations in the PI3K signaling, we demonstrate activation of EGFR with EGF leads to increased pSTAT1 expression. We further demonstrate biased EGFR signaling toward STAT1 activation by pharmacological inhibition of downstream kinase activity with MEK1/2 inhibitor, trametinib, and the AKT inhibitor, Uprosertib or in combination with the PI3Kα specific inhibitor Alpelisib, trade name, PIQRAY. Combination MEK and Akt signaling inhibition followed by EGF stimulation show marked increase in apoptotic activity and decreased cell viability. Moreover, we demonstrate changes in EGFR mediated apoptosis in murine breast cancer cell line derived from metastatic lung nodules, delineate from cells derived from the primary tumor. These finding support the notion of differential evolution of cancer cells as they metastasize to secondary organs. Furthermore, EGFR expression was observed to be vital in EGF mediated pSTAT1 in human breast cancer cell lines. To this end we explored alternative stimulators of pSTAT1 using interferon activation. Addition of INFγ led to robust pSTAT1 in cells that did not respond to EGF and levels of pSTAT1 were not attenuated with our combination treatment. Together, our findings demonstrate the differential role of EGFR expression and signaling in metastatic cells and tolerance for novel combination therapies for patients of late stage breast cancer.

In 2016, there were 250,000 new cases of invasive cancer and 60,000 of ductal carcinoma in situ. Mammograms are used to screen for cases of disease, but the literature shows that mammograms are highly dependent on patient characteristics and do not majorly impact mortality rates from invasive cancer. Additionally, they are prone to false-positives, false-negatives, and overdiagnosis in cases of in situ cancer, with overdiagnosis exposing patients to the side effects of treatment. Better screening tests are needed, and a potential solution can be to extend molecular screening methods often used in advanced stage 1 and higher cancers to stage 0 ductal carcinoma in situ cases. This new test would prevent overdiagnosis, be more accurate, and prevent unnecessary screening as well as be in line with the future of cancer care in the US.