By Ahcène Boumendjel, Jean Boutonnat, Jacques Robert
A entire overview of the most up-tp-date medical study on ABC transporters and multidrug resistance
ATP-binding cassette transporter genes (ABC transporters) are recognized to play a very important function within the improvement of multidrug resistance (MDR). MDR is the facility of pathologic cells, reminiscent of tumors, to resist chemical substances designed to focus on and smash such cells. In MDR, sufferers who're on medicine finally improve resistance not to purely the drug they're taking, yet to a number of varieties of drugs.
ABC Transporters and Multidrug Resistance deals a necessary source for pharmaceutical researchers who're operating to find medicines to counteract multidrug resistance in ailments similar to melanoma. in a single complete quantity, this e-book features a choice 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, general tissue expression, physiological point, and mechanism of motion of the ABC protein. The professional participants discover the expression, detection, and implications of ABC proteins in hematological malignancies and good 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. furthermore, the booklet deals crucial info at the organic and scientific element of multidrug resistance.
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Additional info for ABC Transporters and Multidrug Resistance
Data suggested that P-gp was functionally expressed in cultured hNSPCs and was downregulated during differentiation, indicating that ABCB1 expression might be important in maintaining hNSPCs in an undifferentiated state. Those data are corroborated by a recent review from Mizutani et al. (108) who reported that high expression of P-gp prevents stem-cell differentiation, leading to the proliferation and ampliﬁcation of this cell repertoire. Links between ABCB1 expression and the differentiation stage were also investigated in neoplastic cells treated with all-trans retinoic acid (ATRA), which is used against certain forms of leukemia.
Data appeared controversial, as reported by Stromskaya et al. (109). The authors showed that increasing differentiation of leukemic cells (induced by RARα overexpression) induced an increase in ABCB1 gene expression in cells from solid tumors. Nevertheless, it did not result in elevation of constitutive P-gp functional activity, but it could participate in the control of P-gp induction. Sulová et al. (110) recently reported that combined treatment of P-gp positive cells with verapamil and ATRA induced a depression of P-gp expression and/or transport function whereas ATRA alone did not.
On the other hand, Bennis et al. (129) observed a preferential accumulation of doxorubicin in subcellular components distinct from nuclei in doxorubicinresistant K562 cells. 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.
ABC Transporters and Multidrug Resistance by Ahcène Boumendjel, Jean Boutonnat, Jacques Robert