title: Increased in vivo efficacy of lenalidomide and thalidomide by addition of ethacrynic acid.
abstract: BACKGROUND
  It was recently confirmed that ethacrynic acid (EA) inhibits Wnt/beta catenin signalling in myeloma.
  
  
  METHODS
  This study investigated the antitumor effect of EA in vitro and in vivo in a murine myeloma model.
  
  
  RESULTS
  EA demonstrated major apoptotic activity in different human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In addition β-catenin expression was down-regulated when EA was added to lymphoma cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with EA as compared to untreated mice. Interestingly, in vitro, a significant additive effect was seen with the combination of lenalidomide plus EA as compared to single applications.
  
  
  CONCLUSIONS
  These results reveal a significant selective induction of apoptosis by EA and suggest a significant in vivo effect against myeloma.
authors.affiliation: Center for Integrated Oncoogy (CIO), Department of Internal Medicine III, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.forename: Sanna-Marie
authors.initials: SM
authors.lastname: Gast
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; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology; D000069283:Rituximab; D015398:Signal Transduction / Q000187:drug effects; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D011719:Pyrazines; D051153:Wnt Proteins; D051176:beta Catenin; D000069283:Rituximab; D013792:Thalidomide; D000069286:Bortezomib; D004317:Doxorubicin; D000077269:Lenalidomide; D004976:Ethacrynic Acid; D004121:Dimethyl Sulfoxide