title: Bortezomib-induced peripheral neurotoxicity in human multiple myeloma-bearing mice.
abstract: The proteasome inhibitor bortezomib is an antineoplastic drug mainly used for the treatment of multiple myeloma (MM). Despite its effectiveness, bortezomib clinical use is often limited by the onset of peripheral neuropathy (BiPN). To better understand the mechanisms of BiPN several rat and mice models have been proposed, but no studies in MM-bearing animals allowing to test the antitumor activity of the selected schedules and the role of MM by itself in peripheral nervous system damage have been reported to date. Here, we carried out a study using immunodeficient C.B-17/Prkdcscid (SCID) mice injected with RPMI8266 human MM cells and treated with bortezomib 1 mg/kg once a week for five weeks. Animals were assessed with neurophysiological, behavioral and pathological methods and tumor volume measurement was performed along the study. At the end of the study BiPN was evident in bortezomib-treated animals, and this neurotoxic effect was evident using a schedule able to effectively prevent tumor growth. However, neurophysiological and pathological evidence of MM induced peripheral nervous system damage was also reported. This model based on MM-bearing animals is more reliable in the reproduction of the clinical setting and it is, therefore, more suitable than the previously reported models of BiPN to study its pathogenesis. Moreover, it represents an optimal model to test the efficacy of neuroprotective agents and at the same time their non-interference with bortezomib antineoplastic activity.
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: C
authors: C
authors: Meregalli
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: V A
authors: VA
authors: Carozzi
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: B
authors: B
authors: Sala
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: A
authors: A
authors: Chiorazzi
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: A
authors: A
authors: Canta
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: N
authors: N
authors: Oggioni
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: V
authors: V
authors: Rodriguez-Menendez
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: E
authors: E
authors: Ballarini
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: C
authors: C
authors: Ceresa
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: G
authors: G
authors: Nicolini
authors: Veterinary Pathology Labs, ISTOVET, Monza, Italy.
authors: L
authors: L
authors: Crippa
authors: Department of Clinical and Molecular Sciences-Histology, Marche Polytechnic University, Ancona, Italy.
authors: M
authors: M
authors: Orciani
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: G
authors: G
authors: Cavaletti
authors: Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan Bicocca, Monza (MB), Italy.
authors: P
authors: P
authors: Marmiroli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001897:Boronic Acids / Q000009:adverse effects*; D000069286:Bortezomib; D004195:Disease Models, Animal; D006801:Humans; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D011719:Pyrazines / Q000009:adverse effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib