| Multidrug transporter proteins and cellular factors involved in free and mAb linked calicheamicin-gamma1 (gentuzumab ozogamicin, GO) resistance and in the selection of GO resistant variants of the HL60 AML cell line. | |
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MedLine Citation:
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PMID: 20428776 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study we elucidated the role of ATP-binding cassette (ABC) multi-drug transporter proteins and cellular factors such as Bcl-2 expression and CD33 down-modulation contributing to free and hP67.6 mAb linked calicheamicin-gamma1 (CalC-gamma1) resistance. We analyzed in a well designed HL60 cell system the relationship between the expression of ABC proteins, Bcl-2 and CD33 modulation with the activity of free and mAb-linked CalC-gamma1. The results herein reported and discussed, strongly suggest that both MDR1-Pgp and MRP1 efflux systems are engaged by CalC-gamma1, but only MDR1-Pgp over-expression efficiently abrogates drug cytotoxicity in MDR cells. Paradoxically, Bcl-2 expression, as observed for other anticancer compounds belonging to the enediyne family of drugs, confers CalC-gamma1 susceptibility rather than resistance in HL60 cells. Further, the isolation of a resistant HL60 subline (HL60AL) that was developed by exposing the parental sensitive cells to sub-effective doses of gemtuzumab ozogamicin (GO) over an extended period of time shows a reduced level of CD33 expression that represents an important escape mechanism of HL60 MDR cells to the cytotoxic effect of GO. |
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Authors:
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Maurizio Cianfriglia; Alessandra Mallano; Alessandro Ascione; Maria Luisa Dupuis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 36 ISSN: 1791-2423 ISO Abbreviation: Int. J. Oncol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-29 Completed Date: 2010-08-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 1513-20 Citation Subset: IM |
Affiliation:
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Section of Pharmacogenetics, Drug Resistance and Experimental Therapeutics, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. maurizio.cianfriglia@iss.it |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminoglycosides
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pharmacology* Antibiotics, Antineoplastic / pharmacology* Antibodies, Monoclonal / pharmacology* Antigens, CD / genetics, metabolism Antigens, Differentiation, Myelomonocytic / genetics, metabolism Apoptosis / drug effects Blotting, Western Cell Line, Tumor Cell Proliferation / drug effects Drug Resistance, Neoplasm / genetics* Enediynes / pharmacology* Humans Multidrug Resistance-Associated Proteins / biosynthesis, genetics* P-Glycoprotein / biosynthesis, genetics* Phenotype Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Aminoglycosides; 0/Antibiotics, Antineoplastic; 0/Antibodies, Monoclonal; 0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD33 antigen; 0/Enediynes; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; 0/gemtuzumab; 0/multidrug resistance-associated protein 1; 108212-75-5/calicheamicin gamma(1)I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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