ABC Transporters and Multidrug Resistance (Wiley Series in by Ahcene Boumendjel, Jean Boutonnat, Jacques Robert

By Ahcene Boumendjel, Jean Boutonnat, Jacques Robert

A entire overview of the most up-tp-date medical examine on ABC transporters and multidrug resistanceATP-binding cassette transporter genes (ABC transporters) are recognized to play an important position within the improvement of multidrug resistance (MDR). MDR is the facility of pathologic cells, similar to tumors, to resist chemical compounds designed to focus on and smash such cells. In MDR, sufferers who're on drugs finally strengthen resistance not to purely the drug they're taking, yet to a number of forms 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 ailments reminiscent of melanoma. in a single complete quantity, this ebook includes a selection of the most up-tp-date wisdom at the involvement of ABC transporters in drug shipping and resistance.This complete quantity presents an summary at the description of the constitution, the genome, basic tissue expression, physiological element, and mechanism of motion of the ABC protein. The specialist individuals discover the expression, detection, and implications of ABC proteins in hematological malignancies and stable 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. additionally, the publication deals crucial details at the organic and medical element of multidrug resistance.

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2007. Multiple molecular mechanisms for multidrug resistance transporters. Nature 446: 749–757. 6. Juliano RL and Ling V. 1976. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455: 152–162. 7. Gottesman MM and Ling V. 2006. The molecular basis of multidrug resistance in cancer: The early years of P-glycoprotein research. FEBS Lett 580: 998–1009. 8. Loo TW and Clarke DM. 2005. Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux.

These data were corroborated by studies of the association between phosphatidylinositol 3-kinase/AKT pathway and MDR of gastric cancer cells (170). It was shown that inhibition of P-AKT expression significantly upregulates p53 expression, and downregulates P-gp expression and ABCB1 transcription. 4. P-gp Importance in Immune Response Variable levels of P-gp expression have been reported in lymphocytes, ranging from 20% to 80% in B cells and from 30% to 100% in T cells. Thus, the link between P-gp expression and the function of lymphocytes remains controversial (171).

Other members of the p53 family (namely p63 and p73) can regulate the transcription of the ABCB1 gene, but a differential regulation can be observed. In fact, p63 and p73 regulate the majority of p53 target genes, but transient transfection assays demonstrated that p63 and p73 activated rather than repressed ABCB1 transcription. This upregulation is DNA binding-dependent but not through the HT site; p63 and p73 interact with the ABCB1 promoter via the alternate p63/p73 element, APE (37). The human ABCB1 gene promoter presents many regulating sequences that are bound by several different kinds of transcription factors.

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