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Breast Cancer
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2009 – 2010 One year study Validation and computer reconstruction of a 3D model of breast cancerDr V. Speirs & Dr D. Holliday |
Dr Speirs is a Reader in Cellular Pathology and part of the Breast Cancer Research Group at the Leeds Institute of Molecular Medicine, Leeds University.
Dr Holliday is a Research Fellow at the Leeds Institute of Molecular Medicine, Leeds University.
The pre-invasive form of breast cancer, ductal carcinoma in situ (DCIS) is a common pre-cursor to invasive carcinoma and occurs in up to 40% of patients. The biology of DCIS progression is poorly understood and cannot be accurately replicated in animal models[1].
Breast cancer is not easily replicated in animal models; besides the obvious species barrier, very few animal models are able to accurately replicate the pre-invasive form of breast cancer, DCIS. Animal experiments are used in the assessment of drug efficacy and metabolism, but they do not allow an understanding of the biology of the tumour, nor do they take into account the multiple human cell types involved in the progression of DCIS.
Previous work, funded by the DHT, has enabled the development of a novel in vitro model which replicates human DCIS[2]. This pilot study will further validate this model as a viable alternative to animal experiments.
To achieve this, the specific objectives are:
- To extend the culture time of the current model allowing complete formation of DCIS structures and surrounding basement membrane.
- To validate the model against human DCIS tissue to ensure that the pathology is comparable to that observed in vivo.
- To make the model suitable for computer generation of 3D models using resin embedding, ultra-thin sectioning and immunohistochemical staining.
The aim of this project is to further validate the in vitro model of DCIS as an alternative to in vivo experiments by comparing the model with paraffin embedded human breast tissue containing DCIS. State-of-the-art computer generated images of the models will be generated. This will be the first time that a human model of DCIS has been modelled using such sophisticated computer technology.
References
[1] Vargo-Gogola T &Rosen JM (2007). Modelling breast cancer: one size does not fit all. Nat Rev Cancer. 7(9):659-72. Review.
[2] Holliday DL, Brouilette KT, Markert A et al (2009). Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression. Breast Cancer Res 19;11(1):R3.