By Ahcène Boumendjel, Jean Boutonnat, Jacques Robert
A finished overview of the most up-tp-date clinical learn on ABC transporters and multidrug resistance
ATP-binding cassette transporter genes (ABC transporters) are identified to play an important position within the improvement of multidrug resistance (MDR). MDR is the power of pathologic cells, resembling tumors, to resist chemical compounds designed to focus on and break such cells. In MDR, sufferers who're on drugs finally advance resistance not to purely the drug they're taking, yet to numerous types of drugs.
ABC Transporters and Multidrug Resistance deals an important source for pharmaceutical researchers who're operating to find medicines to counteract multidrug resistance in illnesses resembling melanoma. in a single entire quantity, this publication incorporates a choice of the most up-tp-date wisdom at the involvement of ABC transporters in drug delivery and resistance.
This complete quantity presents an summary at the description of the constitution, the genome, common tissue expression, physiological element, and mechanism of motion of the ABC protein. The professional individuals discover the expression, detection, and implications of ABC proteins in hematological malignancies and reliable tumors and ABC proteins and pathogenic microorganisms. This quantity additionally explains MDR modulation via inhibition of ABC transporters and the layout of inhibitors and mechanism of motion. moreover, the publication deals crucial info at the organic and scientific point of multidrug resistance.
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Extra info for ABC Transporters and Multidrug Resistance
J Biol Chem 265: 506–514. 18. Mickley LA, Spengler BA, Knutsen TA, Biedler JL, and Fojo T. 1997. Gene rearrangement: A novel mechanism for MDR-1 gene activation. J Clin Invest 99: 1947–1957. 19. Huff LM, Lee J-S, Robey RW, and Fojo T. 2006. Characterization of gene rearrangement leading to activation of MDR-1. J Biol Chem 281: 36501–36509. 20. Van Groenigen M, Valentijn LJ, and Baas F. 1993. Identiﬁcation of a functional initiator sequence in the human MDR1 promoter. Biochim Biophys Acta 1172: 138–146.
In cells transfected with the ABCB1 gene, P-gp was detected in vesicles located around the periphery of the nuclei (130), suggesting a mitochondrial pattern, while Gong et al. (131) have shown that 30 THE P-GLYCOPROTEIN 170 accumulation of daunorubicin occurred in mitochondria-like organelles in K562-resistant cells. In addition, Munteanu et al. (132), then Solazzo et al. 5) hepatocarcinoma cells, and in ABCB1transfected (PNA1)NIH/3T3 cells. The two groups have studied P-gp expression in whole cells by confocal microscopy and in puriﬁed isolated mitochondria by western blot.
49) did not observe differences in transcellular transport and intracellular accumulation between cells with polymorphic variants (G2277T/A and C3435T) and cells expressing the wild-type genotype. Furthermore, the C3435T polymorphism in exon 26 may affect the function of P-gp by inﬂuencing its expression level, thus modifying cancer prognosis in breast cancer (due to chemotherapy resistance) (50, 51). It may be one of the risk factors for susceptibility in upper aerodigestive tract cancers, which are associated with tobacco use and alcohol consumption (52).