Mitoxantrone, Etoposide, and Cytarabine With or Without Valspodar in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome: A Phase III Trial (E2995)

Greenberg, Peter L.; Lee, Sandra J.; Advani, Ranjana H.; Tallman, Martin S.; Šikić, Branimir I.; Letendre, Louis; Dugan, Kathleen; Lum, Bert L.; Chin, David L.; Dewald, Gordon W.; Paietta, Elisabeth; Bennett, John M.; Rowe, Jacob M.

doi:10.1200/jco.2004.07.048

Cited by 213 publications

(135 citation statements)

References 45 publications

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“…23) A third generation of inhibitors, including PSC833 and MS-209, are now being developed. 19) Therefore, combination therapy with TP-110 and an ABCB1 inhibitor might produce beneficial effects in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Increased ABCB1 Expression in TP-110-Resistant RPMI-8226 Cells

Iijima

Momose

Ikeda

2010

Bioscience, Biotechnology, and Biochemistry

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, a novel proteasome inhibitor, has been found to possess potent growth inhibition in human multiple myeloma cells. To enhance its therapeutic effects, we established TP-110-resistant RPMI-8226 (RPMI-8226/ TP-110) cells and elucidated their resistance mechanisms. The IC 50 value for TP-110 cytotoxicity in the RPMI-8226/TP-110 cells was about 10-fold higher than that of the parental sensitive cells. The RPMI-8226/TP-110 cells exhibited distinct drug resistance to other proteasome inhibitors. Furthermore, they showed high cross-resistance to the cytotoxic effects of doxorubicin, etoposide, taxol, and vincristine. P-glycoprotein (MDR1), encoded by ABCB1, was elevated in the RPMI-8226/TP-110 cells, and the MDR1 inhibitor verapamil overcame their resistance to TP-110. The results of DNA microarray and RT-PCR suggested that the expression of ABCB1 is significantly elevated in RPMI-8226/TP-110 cells. This indicates that resistance in RPMI-8226/TP-110 cells is involved in the expression of P-glycoprotein, a drug-efflux pump.

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Section: Discussionmentioning

confidence: 99%

“…Verapamil, cyclosporin A and tamoxifen are first-generation MDR inhibitors, 18) and the next generation of inhibitors and antibodies for MDR are now being studied. 19) These inhibitors or antibodies might significantly contribute to overcoming anticancer drug resistance.…”

mentioning

confidence: 99%

Increased ABCB1 Expression in TP-110-Resistant RPMI-8226 Cells

Iijima

Momose

Ikeda

2010

Bioscience, Biotechnology, and Biochemistry

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“…94 To improve treatment efficacy, combination of MDR1 inhibitors with specific drugs have been tested, showing notably encouraging results in term of overall survival in patients with AML. 22,95–97 Most of these studies used first or second generation inhibitors. The use of much more specific third or upcoming fourth generation inhibitors could allow to improve these results and decrease toxicities associated with combination treatments.…”

Section: Introductionmentioning

confidence: 99%

MDR1 in immunity: friend or foe?

et al. 2018

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MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. This review provides an overview of what is known on MDR1 expression in immune cells in human, and its implications in different pathologies and their treatment options.

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“…There are 49 human genes in the ATP-binding cassette (ABC) transporter superfamily encoding transmembrane proteins, which mediate drug efflux via ATP-dependent pumps (17)(18)(19)(20)(21). Among the ABC transporters, expression of multidrug resistance protein 1 (MDR1 or P-glycoprotein) and breast cancer resistance protein 1 (BCRP1) have been associated with chemotherapy resistance in AML in some studies (22)(23)(24)(25)(26)(27)(28) although not in all (29)(30)(31)(32). One possible reason for the conflicting prognostic relevance suggested for ABC transporter expression in AML is the variety of methods used to assess that expression in previous studies (33).…”

Section: Introductionmentioning

confidence: 99%