title: Increased in vivo efficacy of lenalidomide by addition of piroctone olamine.
abstract: BACKGROUND
  It was recently confirmed that the antifungal agent ciclopirox olamine inhibits Wnt/beta catenin signaling in myeloma. Piroctone olamine (PO) has very similar chemical features to ciclopirox olamine.
  
  
  METHODS
  This study investigated the antitumor effect of PO in vitro and in vivo in a murine myeloma model.
  
  
  RESULTS
  PO demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with PO as compared to untreated mice. Interestingly, concerning tumor growth and survival of the animals, a significant additive effect was seen by the combination of lenalidomide plus PO as compared to single application.
  
  
  CONCLUSIONS
  These results reveal a significant selective induction of apoptosis by PO and suggest a significant in vivo effect against myeloma.
authors.affiliation: Center for Integrated Oncology (CIO), Department of Internal Medicine III, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.forename: Petra
authors.initials: P
authors.lastname: Alpmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Blaum-Feder
authors.forename: Simon
authors.initials: S
authors.lastname: Krämer
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Endo
authors.forename: Desheng
authors.initials: D
authors.lastname: Lu
authors.forename: Dennis
authors.initials: D
authors.lastname: Carson
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D006801:Humans; D000077269:Lenalidomide; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000188:drug therapy*; D011728:Pyridones / Q000627:therapeutic use*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D004983:Ethanolamines; D011728:Pyridones; D013792:Thalidomide; C052599:piroctone olamine; D000077269:Lenalidomide