By Ahcene Boumendjel, Jean Boutonnat, Jacques Robert
A entire evaluation of the most up-tp-date clinical examine on ABC transporters and multidrug resistanceATP-binding cassette transporter genes (ABC transporters) are recognized to play a vital function within the improvement of multidrug resistance (MDR). MDR is the power of pathologic cells, reminiscent of tumors, to resist chemical compounds designed to focus on and ruin such cells. In MDR, sufferers who're on drugs ultimately strengthen resistance not to purely the drug they're taking, yet to numerous types of drugs.ABC Transporters and Multidrug Resistance bargains a vital source for pharmaceutical researchers who're operating to find medications to counteract multidrug resistance in illnesses reminiscent of melanoma. in a single complete quantity, this ebook incorporates a number of the most up-tp-date wisdom at the involvement of ABC transporters in drug delivery and resistance.This finished quantity offers an summary at the description of the constitution, the genome, general tissue expression, physiological point, and mechanism of motion of the ABC protein. The specialist participants 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. moreover, the publication bargains crucial details at the organic and medical element of multidrug resistance.
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Extra info for ABC Transporters and Multidrug Resistance (Wiley Series in Drug Discovery and Development)
Today, several therapeutic assays have been conducted using retroviral ABCB1 gene transfer to convert drugsensitive hematopoietic cells into drug-resistant cells, in order to protect normal cells from intensive cancer chemotherapy (106). The aim of this approach is to combine high-dose chemotherapy with transplantation of ABCB1-transduced hematopoietic stem cells; clinical benefits are under investigation. A recent study (107) also reported expression and function of P-gp in human fetal neural stem/progenitor cells, hNSPCs.
35. Zhan M, Yu D, Lang A, Li L, and Pollock RE. 2001. Wild type p53 sensitizes soft tissue sarcoma cells to doxorubicin by down-regulating multidrug resistance-1 expression. Cancer 92: 1556–1566. 36. Zhan M, Yu D, Liu J, Glazer RI, Hannay J, and Pollock RE. 2005. Transcriptional repression of protein kinase C alpha via Sp1 by wild type p53 is involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation. J Biol Chem 280: 4825–4833. 38 THE P-GLYCOPROTEIN 170 37. Johnson RA, Shepard EM, and Scotto KW.
An induction of P-gp by chemotherapeutic agents has been suggested, although the mechanism of this induction remains unclear (12). Upon exposure to both endogenous and exogenous stresses (metabolic modifications, hypoxia, chemotherapy), cancer cells are committed to adaptation. Enhancement of ABCB1 expression constitutes one part of the response. 2. Cellular Localization of P-gp Numerous studies have suggested a different intracellular localization of cytotoxic drugs between sensitive and MDR cells (116–120).
ABC Transporters and Multidrug Resistance (Wiley Series in Drug Discovery and Development) by Ahcene Boumendjel, Jean Boutonnat, Jacques Robert