By Toshihisa Ishikawa, John Schuetz
ABC Transporters and Cancer offers priceless details at the fascinating and fast-moving box of melanoma examine. the following, remarkable and unique experiences are provided on numerous subject matters. This quantity covers ABC transporters and melanoma, and is appropriate for researchers and scholars alike.
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Extra info for ABC Transporters and Cancer
Purple bold lines indicate the functionally relevant locations of one or more of these transporters. Black arrows indicate the direction of transport of substrates at all expression sites. Wide arrows indicate net body excretion of the substrates of these transporters. For lactating breast, only the expression of ABCG2 has been demonstrated. For testis, the situation in humans is depicted, where ABCB1, ABCG2, and ABCC2 are expressed at the blood–testis barrier. This figure was modified from van Herwaarden and Schinkel (2006) and Vlaming et al.
2012). There were differences in the ABCG2-overexpressing cell lines (Saos-2 or MDCKII cells), type of transport assay (cellular accumulation or transepithelial transport), and specific inhibitors (none or Ko143) used. Based on our own experience, we consider transepithelial transport assays, complemented with the use of relatively “specific” inhibitors, as one of the more sensitive in vitro probes for testing hydrophobic ABC transporter substrates. Conflicting findings were also reported by Shibayama et al.
2012). Yang et al. (2010) showed that oral availability of tandutinib was also increased in both the single and the combination knockout mice of Abcb1a/1b and Abcg2 compared to WT mice, indicating that both of these transporters limit the oral uptake of this drug. For a few TKIs, the individual contributions of Abcb1a/1b and/or Abcg2 in restricting the oral availability were not clear due to the study design, although their combined effects were apparent. For example, plasma exposures of erlotinib and dabrafenib were increased significantly in Abcb1a/1b;Abcg2 combination knockout compared to WT mice; however, the impact of either of these transporters alone was not studied using single-knockout mice.