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No description available.

Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2022 / Background Breast cancer is known to be a heterogeneous disease that demands patient centered care. Establishing the clinicopathological characteristics of breast cancer patients is a vital step in an effort to individualize their treatment. Aim The aim is to evaluate the clinicopathologic features of the different subtypes of breast cancer when classified according to immunohistochemistry markers in women attending Pietersburg hospital. Methods A retrospective review of medical records of women treated at Pietersburg hospital between 2010 and 2011 was done. Data collection was extracted on a customized data collection sheet. Chi square was used to determine association between clinicopathologic features and molecular subtypes. Analysis of variants was used to assess association between molecular types and age. Results The mean age of the population was 55.3 years (+/-14 standard deviation). The majority of patients were in stage III (46.9%) and IV (33.5%). The ER, PR, HER2/neu positive rate was 50.6%, 30% and 14,3 % respectively with a negative rate of 13,4%, 19,5% and 23,4% respectively. ER, PR and HER2/neu was unknown in 18%, 19, 5% and 23,4% respectively. The most common molecular subtype was luminal A (53,6%) followed by triple negative (27.2%), HER2/neu (11, 4%) and luminal B (7. 9%).There was no association between the subtypes and tumour stage (p=0.578).The rate of distant metastasis was similar across the subtypes being 37,9%,35%, 32,4% and 31,9% in HER2/neu, luminal B ,luminal A and TNBC, respectively. All four molecular subtypes had high rate of axillary lymph node involvement (p=0.886) Luminal A had the least percentage of high grade tumours with TNBC having the highest. Five-year overall survival for the cohort was 25, 6% with luminal A and B having a better 5 year overall survival of 27,2% and 25% respectively, whereas HER2/neu and TNBC had lower 5 year OS of 24% and 23,3%. Conclusion The findings of this study suggest that luminal A subtype is the most predominant and the majority might benefit from hormonal therapy. However, some patients could not be classified due to missing IHC marker test results. The outcome across all four subtypes is poor and more effort should be put towards improving the diagnosis and treatment individualization and follow-up in these patients.

<p>Breast cancer is the most common cancer among Canadian women with one in nine women expected to develop breast cancer in their lifetime. Until recently these breast tumors were thought to be a homogeneous cell population. Recent studies have shown that breast tumors contain a rare cell type termed breast tumor initiating cells (TICs) or cancer stem cells (CSCs) with the ability to elicit new tumor growth and metastases. These TICs exist apex of a tumor cell hierarchy and give rise to more TICs and non-tumorigenic cells. Traditionally, drugs were developed to target the highly proliferative cells population resulting in a decrease in tumor volume. However, these therapies spare the TICs, which results in tumor relapse demonstrating the need for new drugs that target the TICs. Because in cancer, mutated protein kinases are the controllers of cell proliferation, invasion and metastasis, they have become a target for drug development. Inhibition of these kinases could lead to the identification of compounds that selectively target breast TICs. Using mammary tumors from cancer prone mice propagated as non-adherent tumorspheres (TMS), which contain a high fraction of breast TICs and the same conditions to propagate the non-transformed mouse mammary epithelial stem and progenitor cells (MESC), as non-adherent mammospheres (MMS) a 240-kinase inhibitor library was screened using an AlamarBlue proliferation assay. Twenty percent of the compounds resulted in 75% decrease in proliferation of TMS derived cells and some of which were TMS-selective. Sunitinib, a multi-targeted kinase inhibitor, was one of the selective compounds identified and when administered to mice with subcutaneous mammary tumors resulted in tumor shrinkage. This was accompanied by an increase in apoptotic cells, decrease in proliferating cells and tumor vasculature, and a change in tumor morphology and composition. These findings show the efficacy of Sunitinib in shrinking mouse mammary tumors and suggest a potential use of Sunitinib for treatment of breast cancer.</p> / Master of Science (MSc)

Activated protein tyrosine kinases, which have been implicated in the genesis of a number of human cancers, rely on a variety of protein-protein interactions to transmit their proliferative signals within the cell. These interactions are often mediated by Src homology 2 and 3 (SH2 and SH3) domains. A class of proteins which are mainly composed of such domains, termed adaptor proteins, has been identified. The Growth factor receptor bound proteins Grb2 and Grb7 are SH2 domain adaptor proteins which have been shown to associate directly or in complex with many tyrosine kinases, including the c-ErbB-2/Neu receptor tyrosine kinase. While overexpression of either protein alone in rat fibroblasts is not transforming, human breast cancer cell lines exhibit Grb2 and Grb7 gene amplification, and mRNA and protein overexpression. The role of Grb2 in polyomavirus middle T antigen-mediated mammary tumorigenesis has been examined utilizing gene targeting and transgenic approaches. Initial characterization of the progeny of matings involving Grb2+/mice and MMTV/middle T transgenic mice indicated that delayed tumor kinetics may be the result of Grb2 dosage differences between mT+;Grb2+/-and mT+;Grb2+/+ animals. Transgenic animals expressing a dominant negative version of Grb2 in the mammary epithelium have been generated to explore an alternate method for disrupting signaling from middle T antigen. The role of Grb2 and Grb7 in Neu-mediated mammary tumorigenesis is also being examined. Both MMTV/Grb2 and MMTV/Grb7 transgenic mice that express the transgene in the mammary epithelium have been identified by ribonuclease protection analysis. Matings involving these strains and MMTV/neu mice should aid in determining the effects of overexpressing Grb2 or Grb7 on Neu-mediated mammary tumorigenesis. / Thesis / Master of Science (MS)

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No description available.

Optical character recognition (OCR) has been a topic of interest for many years. It is defined as the process of digitizing a document image into a sequence of characters. Despite decades of intense research, OCR systems with capabilities to that of human still remains an open challenge. In this work there is presented a design and implementation of such system, which is capable of detecting texts in graphical user interfaces.

O objetivo do estudo foi avaliar a importância da expressão das proteínas topoisomerase II alfa (topo II) e HER-2 como fatores preditvos da resposta à quimioterapia neoadjuvante e prognóstico em pacientes com câncer de mama nos estádio clínico II e III. Pacientes e métodos: 99 pacientes receberam quimioterapia neoadjuvante com docetaxel (75mg /m²) e epirrubicina (50 mg/m²) em infusão endovenosa no dia 1 a cada 3 semanas após terem sido submetidas a biópsia incisional. Foi complementado tratamento sistêmico com quimioterapia adjuvante com CMF ou FEC de acordo com o estado axilar avaliada após a cirurgia definitiva e/ou hormonioterapia de acordo com a avaliacãodos receptores hormonais. Avaliamos a taxa de resposta ao tratamento neoadjuvante e a influência da topo II alfa e do HER-2 na taxa de resposta à quimioterapia neoadjuvante bem comona sobrevida livre de doença e sobrevida global. Também foram avaliadas a expressão dos receptores hormonais. Resultados: a taxa de resposta clínica objetiva foi de 80,8 % com 9,1 % de resposta patológica completa. A expressão da topo II alfa nao apresentou significância nas taxas de resposta ou na sobrevida das pacietnes e nao houve correlação entre a expressão desta proteína e de HER-2. A superexpressão da proteína HER-2 foi associada com uma redução significante nas taxas de sobrevida livre de doença e sobrevida global (p= 0,04 e p= 0,004, respectivamente). Conclusão: a expressão da topo II alfa não demonstrou, em nosso estudo, ser fator preditivo ou prognóstico nas pácientes submetidas a quimioterapia neoadjuvante com docetaxel e epirrubicina. / The objective of this study is to evaluate the importance of the expression of the proteins topoisomerase II alpha (topo II) and HER-2 as predictive factors to response to neoadjuvant chemotherapy and the prognosis of patients diagnosed with clinical stage II and stage III breast cancer. Patients and methods: 99 patients have received neoadjuvant chemotherapy with docetaxel (75mg /m²) and epirrubicine (50 mg/m²) through intravenous infusion on D1 q3 weeks, after submitted to pathologic specimen harvest. Systemic treatment was then complemented with CMF or FEC according to the status of axilla involvement after surgical staging and/or hormone therapy according tohormone receptor status. We evaluated the response rate to neoadjuvant treatment and the influence of topo II alpha and HER-2 expression on the response rate and disease free survival and overall survival. The expression of hormone receptors was also evaluated. Results: Objective clinical response was 78,8%, with 8,2% of complete pathological response.Topo II alpha expression did not correlate to response to chemotherapy or survival and there was no correlation between topo II alpha expression and HER-2 expression. Superexpression of HER-2 protein was associated to a significant reduction in disease free survival and overall survival (p=0,04 and p=0,004, respectively). Conclusion: topo II alpha expression did not demonstrate, in our study, to be a predictive nor prognostic factor to the patientssubmitted to neoadjuvant with docetaxel and epirrubicin.