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Local oestrogen biosynthesis within the breast can be highly variable, in vitro aromatase activity both in breast cancers and mammary adipose tissue displaying over a 40-fold range between the highest and lowest levels. Evidence is presented to show that: (i) transcriptional activity may influence oestrogen biosynthesis within breast cancers in that both(More)
The aromatase enzyme complex is responsible for the conversion of C19 androgens to oestrogens. Aromatase expression in oestrogen-responsive breast cancers may be an important mechanism of autocrine regulation in tumour growth. To evaluate whether aromatase cytochrome P450 (P450arom) transcript levels within breast tumours were correlated to the enzyme(More)
Resistance to targeted cancer therapies such as trastuzumab is a frequent clinical problem not solely because of insufficient expression of HER2 receptor but also because of the overriding activation states of cell signaling pathways. Systems biology approaches lend themselves to rapid in silico testing of factors, which may confer resistance to targeted(More)
The extracellular matrix glycoprotein tenascin-C (TN) is overexpressed in the stroma of malignant ovarian tumours particularly at the interface between epithelia and stroma leading to suggestions that it may be involved in the process of invasion (Wilson et al (1996) Br J Cancer 74: 999-1004). To define regulation of TN further and investigate its function(More)
The majority of ovarian cancer patients are treated with platinum-based chemotherapy, but the emergence of resistance to such chemotherapy severely limits its overall effectiveness. We have shown that development of resistance to this treatment can modify cell signaling responses in a model system wherein cisplatin treatment has altered cell responsiveness(More)
Activation of gonadotropin-releasing hormone (GnRH) receptors inhibits proliferation of transformed cells derived from reproductive tissues and in transfected cell lines. Hence, GnRH receptors represent a therapeutic target for direct action of GnRH analogues on certain proliferating cells. However, more cell biological data are required to develop this(More)
High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing(More)
BACKGROUND Resistance to trastuzumab is a clinical problem, partly due to overriding activation of MAPK/PI3K signalling. Sprouty-family proteins are negative regulators of MAPK/PI3K signalling, but their role in HER2-therapy resistance is unknown. PATIENTS AND METHODS Associations between Sprouty gene expression and clinicopathological features were(More)
Growth inhibition observed following administration of an LHRH agonist to a clonal variant of the MCF-7 breast cancer cell line is accompanied by an accumulation of cells in the GO/Gi phase of the cell cycle. LHRH is a hypothalamic hormone which stimulates the release of gonadotrophins from the pituitary (Fraser & Baird, 1987). Recently, synthetic analogues(More)
PURPOSE The aim of this study was to investigate the antitumor effects of HER2-directed combination therapy in ovarian cancer xenograft models to evaluate their potential. The combinations of trastuzumab and pertuzumab, and trastuzumab and aromatase inhibitor therapy were investigated. EXPERIMENTAL DESIGN The effects of trastuzumab, pertuzumab, and(More)