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The intestinal transport properties and kinetics of camptothecin (CPT) through Caco-2 cell monolayers were characterized by determining concentration-, temperature-, and ATP-dependence as well as the effect of selected inhibitors. The absorptive permeability (Peff) of CPT was found to be concentration dependent and saturable (K(m) = 31.2 +/- 6.9 microM)(More)
Colorectal cancers (CRCs) that are sensitive to the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab or panitumumab almost always develop resistance within several months of initiating therapy. We report the emergence of polyclonal KRAS, NRAS, and BRAF mutations in CRC cells with acquired resistance to EGFR blockade. Regardless of the(More)
Molecular targeted drugs are clinically effective anti-cancer therapies. However, tumours treated with single agents usually develop resistance. Here we use colorectal cancer (CRC) as a model to study how the acquisition of resistance to EGFR-targeted therapies can be restrained. Pathway-oriented genetic screens reveal that CRC cells escape from EGFR(More)
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