Synergistic Leukemia Eradication by Combined Treatment with Retinoic Acid and HIF Inhibition by EZN-2208 (PEG-SN38) in Preclinical Models of PML-RARα and PLZF-RARα–Driven Leukemia
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چکیده
منابع مشابه
Inhibition of Promyelocytic Leukemia (PML)/Retinoic Acid
The fusion protein promyelocytic leukemia (PML)/retinoic acid receptor (RAR)a is tightly linked to the pathogenesis of acute promyelocytic leukemia (APL); hence, it represents a tumor-associated, transformationrelated molecule. In this study, three anti-PML adamantyl-conjugated peptide nucleic acid (PNA) oligomers previously described as in vitro inhibitors of PML/RARa translation were combined...
متن کاملTargeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides
In acute promyelocytic leukemia (APL), hematopoietic differentiation is blocked and immature blasts accumulate in the bone marrow and blood. APL is associated with chromosomal aberrations, including t(15;17) and t(11;17). For these two translocations, the retinoic acid receptor alpha (RARα) is fused to the promyelocytic leukemia (PML) gene or the promyelocytic zinc finger (PLZF) gene, respectiv...
متن کاملComparative Analysis of Genes Regulated by PML/RARα and PLZF/RARα in Response to Retinoic Acid Using Oligonucleotide Arrays
Acute promyelocytic leukemia (APL) is associated with chromosomal translocations involving RAR and its fusion partners including PML and PLZF. Using oligonucleotide arrays, we examined changes in global gene expression mediated by the ectopic expression of either PML/RAR (retinoid-sensitive) or PLZF/RAR (retinoid-resistant) in U937 cells. Of over 5000 genes analyzed, 16 genes were commonly upre...
متن کاملTumor regression and curability of preclinical neuroblastoma models by PEGylated SN38 (EZN-2208), a novel topoisomerase I inhibitor.
PURPOSE Treatment of neuroblastoma is successful in less than half of patients with high-risk disease. The antitumor activity of a water soluble pegylated SN38 drug conjugate, EZN-2208, was compared with CPT-11 (a prodrug for SN38) in preclinical models of human neuroblastoma. EXPERIMENTAL DESIGN The in vitro cytotoxicity of EZN-2208 was tested by counting trypan blue dye- and Annexin V-posit...
متن کاملEZN-2208 (PEG-SN38) Overcomes ABCG2-Mediated Topotecan Resistance in BRCA1-Deficient Mouse Mammary Tumors
BRCA1 dysfunction in hereditary breast cancer causes defective homology-directed DNA repair and sensitivity towards DNA damaging agents like the clinically used topoisomerase I inhibitors topotecan and irinotecan. Using our conditional K14cre;Brca1(F/F);p53(F/F) mouse model, we showed previously that BRCA1;p53-deficient mammary tumors initially respond to topotecan, but frequently acquire resis...
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ژورنال
عنوان ژورنال: Clinical Cancer Research
سال: 2015
ISSN: 1078-0432,1557-3265
DOI: 10.1158/1078-0432.ccr-14-3022