Abstract
YM155, a novel small-molecule that down-regulates survivin, exhibits broad, potent antitumor activity against a range of human tumors. We evaluated the activity of YM155 in aggressive non-Hodgkin lymphoma. In a number of diffuse large B-cell lymphoma lines, YM155 exhibited 50% growth inhibition with values between 0.23 and 3.9 nM. Within in vivo xenograft models, continuous infusion of YM155 eradicated large, established subcutaneous WSU-DLCL-2 and Ramos tumors, with sustained efficacy observed through 4 cycles of YM155 therapy. YM155 increased survival significantly versus rituximab in disseminated Ramos models. This study suggests that YM155 may represent an effective treatment for aggressive lymphomas.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Humans
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Imidazoles / pharmacology*
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Immunohistochemistry
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Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / metabolism
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Lymphoma, Non-Hodgkin / drug therapy*
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Lymphoma, Non-Hodgkin / metabolism
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Lymphoma, Non-Hodgkin / pathology
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Mice, SCID
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Naphthoquinones / pharmacology*
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Repressor Proteins / antagonists & inhibitors*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Analysis
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Survivin
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Treatment Outcome
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Xenograft Model Antitumor Assays / methods*
Substances
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Antineoplastic Agents
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Birc5 protein, mouse
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Imidazoles
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Inhibitor of Apoptosis Proteins
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Naphthoquinones
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Repressor Proteins
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Survivin
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sepantronium