By Toshihisa Ishikawa, John Schuetz
ABC Transporters and Cancer offers priceless info at the intriguing and fast-moving box of melanoma examine. the following, remarkable and unique experiences are provided on quite a few themes. This quantity covers ABC transporters and melanoma, and is acceptable for researchers and scholars alike.
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Additional info for ABC Transporters and Cancer
2011). Yang et al. (2010) showed that brain-to-plasma ratio of tandutinib in Abcb1a/1b-deficient mice was increased by 2- to 3-fold and that in Abcb1a/1b;Abcg2-deficient mice by 13-fold compared to the WT strain, whereas remained unchanged in Abcg2-deficient mice. 3-fold) but not in the absence of Abcg2. , 2012). 7-fold) compared to WT mice. , 2012). , 2014). 2 Drugs only affected by Abcb1a in their brain accumulation For a few other drugs, Abcb1a seems to be the only contributor to brain efflux at the BBB.
Interestingly, there is a large overlap in the substrate specificities of these ABC transporters; therefore, the absence or decreased activity of one of these transporters is often compensated by one or more other members (Table 1). , 2009). Figure 1 Generalized overview of tissue expression of the human ATP-binding cassette (ABC) transporters ABCB1 (P-GP), ABCG2 (BCRP), and ABCC2 (MRP2). 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.
ABCB1, ABCC2, and ABCG2 are the most extensively studied apical ABC transporters in relation to chemotherapeutic drug disposition. They are localized at the apical membranes of intestinal and renal proximal tubule epithelial cells and at the bile canalicular membranes of the hepatocytes, where they efflux their substrates into intestinal lumen or feces, urine, and bile to protect the organism (Fig. , 2009). They are also expressed at the apical membranes of blood–brain, blood–testis, and blood–placenta barriers, where they extrude endogenous or exogenous substrates, including drugs, carcinogens, and toxins, into the main circulation in order to protect those tissue sanctuaries (Fig.