sepantronium and Lymphoma--Non-Hodgkin

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.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Imidazoles; Immunohistochemistry; Inhibitor of Apoptosis Proteins; Lymphoma, Non-Hodgkin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Naphthoquinones; Repressor Proteins; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Survivin; Treatment Outcome; Xenograft Model Antitumor Assays