<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Studying the origins of primary tumours and residual disease in breast cancer"^^ . "Breast cancer is the leading cause of death in women worldwide and these deaths are mostly attributed to metastasis and tumour recurrence following initially successful therapy. Metastasis refers to the development of invasive disease, wherein malignant cells dissociate from primary tumours, infiltrating other organs and tissues to give rise to secondary outgrowths. Previously, metastasis was thought to be initiated in advanced tumours, but breast cancer cellsh with metastatic potential have now been shown to disseminate very early from the primary site via largely unknown mechanisms. These early interactions of tumour cells with their cellular micro-environment and normal neighbours\r\nalso results in early tumour cell heterogeneity and must therefore be elucidated such that we can prevent metastatic spread in the patient situation and better treat the resulting heterogenous tumours. However, studying tumour initiation is not possible in patients because it happens on a cellular level not detectable by current technology. Tumour recurrence is another major cause of breast cancer related death and is believed to be caused by residual disease cells that survive initial therapy. These are a reservoir of refractory cells that can lay dormant for many years (sometimes decades) before resulting in relapse tumours. They are also difficult to obtain from human patients, since they are very few and cannot be detected easily, and thus their molecular mechanisms have not\r\nbeen fully explored.\r\nIn addition to the unavailability of human tissue, mouse models of breast cancer also fall short in helping us study early cancer initiation, because they allow oncogenic expression in all cells of the tissue instead of initiating cancer like in the human situation|one neoplastic\r\ntransformed cell proliferating unchecked in a normal epithelium. To address this issue, we used primary organoids from an inducible mouse model of breast cancer and lentivirally transduced single cells within these organoids to express oncogenes. We further optimized parameters for long term imaging using light sheet microscopy and developed big data analysis pipelines that lead us to discern that single transformed cells had a lower chance at establishing tumorigenic foci, when compared to clusters of cells. Thus, we postulate a proximity-controlled signalling that is imperative to tumour initiation within epithelial\r\ntissues using the first ever in vitro stochastic breast tumorigenesis model system. This new stochastic tumorigenesis system can be further used to identify the molecular interactions in the early breast cancer cells.\r\nOur group has already revealed distinct characteristics, such as dysregulated lipid metabolism, of the residual disease correlate obtained from an inducible mouse model.\r\nAs survival mechanisms invoked by residual cells remain largely unknown, we analysed the dynamic transcriptome of regressing tumours at important timepoints during the\r\nestablishment of residual disease. Key molecular players upregulated during regression {like c-Jun and BCL6 { were identified and the inflammatory arm of the Nf-kB cascade was\r\nfound to be dysregulated among others. Further validation of these molecular targets as potentially synthetic lethal interactors remains to be performed so that they can be used\r\nto limit the residual disease reservoir and eventually tumour recurrence."^^ . "2020" . . . . . . . "Ashna"^^ . "Alladin"^^ . "Ashna Alladin"^^ . . . . . . "Studying the origins of primary tumours and residual disease in breast cancer (PDF)"^^ . . . "Alladin_Thesis_Final2.pdf"^^ . . . "Studying the origins of primary tumours and residual disease in breast cancer (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #27419 \n\nStudying the origins of primary tumours and residual disease in breast cancer\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . .