Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis.
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...and are straightforward to apply in high-throughput screen...
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...This gives rise to a more stratified composition, with the rim of spheroids consisting of proliferating cells, followed by a layer of quiescent cells in the middle and necrotic cells in the center of the spheroid.(11) A similar cellular heterogeneity is present in nonvascularized tumor regions....
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...In addition, in suspension cultures, many tumor cell lines grow poorly in 3D as compact spheroids.(1,20) They form loose aggregates of cells only, an architecture that is significantly different from the in vivo tumor morphology....
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...A current limitation of the spheroid application in vitro is that numerous cancer cell lines do not form compact round spheroids in 3D.(1,20) For example, approximately half of the breast cancer cell lines tested in this study grew as aggregates of cells in 3D culture (Fig....
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...Because monolayer-based high-throughput (HT) systems have only a limited predictive value for the in vivo efficacy of antineoplastic compounds, the implementation of the spheroid model in the drug discovery process may improve the predicted activity of new cancer drugs in cell-based screening assays.(20) Several approaches have been developed to enable drug screening using spheroids: confocal microscopy to measure drug or antibody permeation into the spheroid,(20,21) electrochemical microscopy to measure the respiratory activity,(22) image cytometry to quantify lactate dehydrogenase activity as a marker for Roche Pharmaceutical Research Oncology, Penzberg, Germany....
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