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您的检索式：作者名="Robert W.Robey"
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| 1 | ATP-binding cassette transporters at the zebrafish blood-brain barrier and the potential utility of the zebrafish as an in vivo model显示文摘The brain is protected from toxins by a tightly regulated network of specialized cells,including endothelial cells,pericytes,astrocyes,and neurons,known collectively as the blood-brain barrier(BBB).This selectively permeable barrier permits only the most crucial molecules essential for brain function to enter and employs a number of different mechanisms to prevent the entry of potentially harmful toxins and pathogens.In addition to a physical barrier comprised of endothelial cells that form tight junctions to restrict paracellular transport,there is an active protective mechanism made up of energy-dependent transporters that efflux compounds back into the bloodstream.Two of these ATP-binding cassette(ABC)transporters are highly expressed at the BBB:P-glycoprotein(P-gp,encoded by the ABCB1 gene)and ABCG2(encoded by the ABCG2 gene).Although a number of in vitro and in vivo systems have been developed to examine the role that ABC transporters play in keeping compounds out of the brain,all have inherent advantages and disadvantages.Zebrafish(Danio rerio)have become a model of interest for studies of the BBB due to the similarities between the zebrafish and mammalian BBB systems.In this review,we discuss what is known about ABC transporters in zebrafish and what information is still needed before the zebrafish can be recommended as a model to elucidate the role of ABC transporters at the BBB. | Jordan M.Hotz Joanna R.Thomas Emily N.Katz Robert W.Robey Sachi Horibata Michael M.Gottesman | 2021 | Cancer Drug Resistance2021，4，3： | 0 |
| 2 | The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers显示文摘Aim:Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid peroxidation.Several small molecule ferroptosis inducers(FINs)have been reported,yet little information is available regarding their interaction with the ATP-binding cassette(ABC)transporters P-glycoprotein(P-gp,ABCB1)and ABCG2.We thus sought to characterize the interactions of FINs with P-gp and ABCG2,which may provide information regarding oral bioavailability and brain penetration and predict drug-drug interactions.Methods:Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs;confirmatory studies were performed in OVCAR8 and NCI/ADR-RES cells.The ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18,respectively.Results:P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin.P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of ABCB1.The FINs ML-162,GPX inhibitor 26a,and PACMA31 at 10µM were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing MDR-19 cells.GPX inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 cells.Conclusion:Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the brain.The ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions. | William J.E.Frye Lyn M.Huff JoséM.González Dalmasy Paula Salazar Rachel M.Carter Ryan T.Gensler Dominic Esposito Robert W.Robey Suresh V.Ambudkar Michael M.Gottesman | 2023 | Cancer Drug Resistance2023，6，3： | 0 |
| 3 | New mechanisms of multidrug resistance: an introduction to the Cancer Drug Resistance special collection显示文摘Cancer Drug Resistance publishes contributions to understanding the biology and consequences of mechanisms that interfere with successful treatment of cancer. Since virtually all patients who die of metastatic cancer have multidrug-resistant tumors, improved treatment will require an understanding of the mechanisms of resistance to design therapies that circumvent these mechanisms, exploit these mechanisms, or inactivate these multidrug resistance mechanisms. One example of a resistance mechanism is the expression of ATP-binding cassette efflux pumps, but unfortunately, inhibition of these transporters has not proved to be the solution to overcome multidrug resistance in cancer. Other mechanisms that confer multidrug resistance, and the confluence of multiple different mechanisms (multifactorial multidrug resistance) have been identified, and it is the goal of this Special Collection to expand this catalog of potential multidrug resistance mechanisms, to explore novel ways to overcome resistance, and to present thoughtful reviews on the problem of multidrug resistance in cancer. | Michael M.Gottesman Robert W.Robey Suresh V.Ambudkar | 2023 | Cancer Drug Resistance2023，6，3： | 0 |
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