Abstract
Cytarabine combined with an anthracycline or an anthracenedione represents the usual intensive induction therapy for the treatment of AML. However, this protocol induces severe side effects and treatment-related mortality due to the lack of selectivity of these cytotoxic agents. In this paper, we present the study of the first galactosidase-responsive molecular "Trojan Horse" programmed for the delivery of doxorubicin exclusively inside AML blasts over-expressing the folate receptor (FR). This targeting system allows the selective killing of AML blasts without affecting normal endothelial, cardiac or hematologic cells from healthy donors suggesting that FDC could reduce adverse events usually recorded with anthracyclines.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Adult
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Aged
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Aged, 80 and over
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Antibiotics, Antineoplastic / administration & dosage
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / pharmacology
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Blast Crisis / drug therapy
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Blast Crisis / metabolism
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Blast Crisis / pathology
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cells, Cultured
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Dose-Response Relationship, Drug
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Doxorubicin / administration & dosage
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Doxorubicin / chemistry
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Doxorubicin / pharmacology*
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Drug Delivery Systems / methods
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Female
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Folate Receptor 1 / genetics
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Folate Receptor 1 / metabolism
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Folate Receptor 2 / genetics
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Folate Receptor 2 / metabolism
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Folic Acid / chemistry
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HEK293 Cells
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HL-60 Cells
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Humans
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Leukemia, Myeloid / drug therapy
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Leukemia, Myeloid / genetics
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Leukemia, Myeloid / pathology
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Male
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Middle Aged
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Neoplastic Stem Cells / drug effects*
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Young Adult
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beta-Galactosidase / metabolism*
Substances
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Antibiotics, Antineoplastic
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Folate Receptor 1
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Folate Receptor 2
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Doxorubicin
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Folic Acid
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beta-Galactosidase