CB5ED000d01 - Animal models of cancer Cells in culture as...

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Animal models of cancer
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Cells in culture as models for tumors • Uniform, well defined cell populations • Good quantitative endpoints for cell survival • Very useful model systems for some studies – Examine effects of proliferation, cell cycle phase, etc. – Examine effects of cellular environment – Examine mechanisms of action – Examine interactions between drugs and radiation and establish the mechanisms underlying such interactions – Provide insights into effects of sequence, time and dose on effects of single agent and combined modality treatments
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What can we learn from cell cultures ? Many things: Study biology of cells, how they grow, how they interact How they metabolize drugs How they respond to treatment with drugs and/or radiation How therapeutic agents interact Question: what happens to tumors and normal tissues in vivo ?
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Tumor cell lines in culture differ from tumor cells in vivo adapted to survive and grow in culture • altered proliferation • may have been cloned altered gene expression, enzyme activity • altered shape and motility • altered metabolism • altered differentiation • altered response to external signals
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The environment of cells in ordinary cell cultures differs from that of cells in vivo • Limited or no contact with similar cells • Limited or no contact with other cell types • Oxygen levels are high • Nutritional environment: artificial and limited • pH • Cytokines other external signals • Temperature, motion, growth surface, etc.
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Some culture systems are better models for tumors in vivo • Primary cell explants • Three dimensional cultures • Perfused cultures • Physiological growth surfaces • Co-cultures containing multiple cell types • Tissue and organ cultures None of these fully model tumors in vivo - they are all still models, with inherent limitations
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Spheroids: Sutherland et al .
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Human cells are sometimes needed • E.g. in studies of human cytokines, antibodies, or gene therapy • But: remember that cultures of human cells are also artificial model systems that do not fully model human tumors in vivo • Malignant cell lines are heavily selected • “Normal cells” are probably not normal if they grow well in culture, even if they have been cultured only for a limited period of time
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Animal tumor models are closer, but still have limitations as models for human patients
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This note was uploaded on 05/28/2010 for the course WE MOBI000000 taught by Professor Geertberx during the Spring '10 term at Ghent University.

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CB5ED000d01 - Animal models of cancer Cells in culture as...

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