Abstract
Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro, showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone. We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20 (rituximab, RIT) or anti-CD52 (campath, CAM) monoclonal antibodies on B-CLL cells. Both BOR+RIT and BOR+CAM combinations exerted additive cytotoxicity, triggering caspase-dependent apoptosis. The treatment significantly modified expression of several apoptosis-regulating proteins, including upregulation of Bax or downregulation of Bcl-2 and Mcl-1 by BOR+RIT, as well as downregulation of Bcl-2 and XIAP by BOR+CAM. These data suggest the feasibility of concomitant use of those agents for the treatment of B-CLL patients.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Alemtuzumab
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal, Humanized
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Antibodies, Monoclonal, Murine-Derived
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Antibodies, Neoplasm / pharmacology*
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Apoptosis Regulatory Proteins / drug effects
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Apoptosis Regulatory Proteins / metabolism
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Boronic Acids / pharmacology*
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Bortezomib
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Caspase 3 / drug effects
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Caspase 3 / metabolism
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Cell Death / drug effects
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Female
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
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Leukemia, Lymphocytic, Chronic, B-Cell / immunology
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
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Leukocytes, Mononuclear / drug effects
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Male
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Middle Aged
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Pyrazines / pharmacology*
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Rituximab
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Monoclonal, Murine-Derived
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Antibodies, Neoplasm
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Apoptosis Regulatory Proteins
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Boronic Acids
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Pyrazines
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Alemtuzumab
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Rituximab
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Bortezomib
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Caspase 3