A novel retinoic/butyric hyaluronan ester for the treatment of acute promyelocytic leukemia: preliminary preclinical results
| Autor: | Gianni Sava, Sonia Zorzet, C. Pellizzaro, Gabriella Abolafio, Silvia Cantoni, Danila Coradini, C. Garrovo, Alberto Perbellini, Maria Grazia Daidone, Ignazio Scarlata, Maya Fedeli, Annalisa Speranza |
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| Přispěvatelé: | Coradini, D., Pellizzaro, C., Scarlata, I., Zorzet, Sonia, Garrovo, C., Abolafio, G., Speranza, A., Fedeli, M., Cantoni, S., Sava, Gianni, Daidone, M. G., Perbellini, A. |
| Rok vydání: | 2006 |
| Předmět: |
Acute promyelocytic leukemia
Cancer Research Myeloid Oncogene Proteins Fusion medicine.drug_class Retinoic acid Apoptosis Tretinoin Caspase 3 In Vitro Techniques Biology Histones chemistry.chemical_compound Leukemia Promyelocytic Acute In vivo Histone deacetylase inhibitors Cell Line Tumor Ha-But CCAAT-Enhancer-Binding Protein-alpha Tumor Cells Cultured medicine Humans Hyaluronic Acid Cell Proliferation Histone deacetylase inhibitor CCAAT-Enhancer-Binding Protein-beta Promyelocytic leukemia Preclinical Cell Differentiation Esters Hematology medicine.disease Neoplasm Proteins medicine.anatomical_structure Oncology chemistry Cell culture Immunology Cancer research Butyric Acid Drug Screening Assays Antitumor Protein Binding |
| Zdroj: | Leukemia. 20:785-792 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2404179 |
| Popis: | All-trans retinoic acid (ATRA) represents the therapy of choice for patients with acute promyelocytic leukemia (APL). However, patients often relapse due to ATRA-resistance. The molecular basis of APL alterations indicates that addition of a histone deacetylase inhibitor to ATRA may restore the sensitivity to retinoids. We explored the in vitro and in vivo effects of a novel retinoic/butyric hyaluronan ester (HBR) on a retinoic acid (RA)-sensitive human myeloid cell line, NB4, and on its RA-resistant subclone, NB4.007/6. In vitro, HBR induced growth arrest and terminal differentiation in RA-sensitive NB4 cells (as confirmed by an increased expression of CD11 family members and nitroblue tetrazolium assay), whereas it inhibited the growth of RA-resistant cells by apoptosis, paralleled by an increase in the levels of caspase 3 and 7. In vivo, HBR treatment of NB4-inoculated severe combined immunodeficient mice resulted in a statistically significant increase in survival time (P |
| Databáze: | OpenAIRE |
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