title: The preclinical activity of lenalidomide in indolent urothelial carcinoma.
abstract: BACKGROUND
  Lenalidomide is an IMiD® immunomodulatory drug, which may warrant evaluation in urothelial carcinoma (UC).
  
  
  METHODS
  The in vitro and in vivo activity of lenalidomide was evaluated in human and murine UC cell lines. Tumors were evaluated by immunohistochemistry for (CD31), cleaved caspase-3 (CC3) and CD3+/CD20+ lymphocyte infiltration. Cereblon, a molecular target of lenalidomide was analyzed by immunohistochemistry.
  
  
  RESULTS
  Significant pro-apoptotic activity, and reduction of cell viability was seen at low micromolar concentrations of lenalidomide against indolent human RT4 UC cells in vitro. Cereblon expression was quantitatively lower in sensitive RT4 cells compared to resistant 5637 cells. In RT4 xenografts, lenalidomide significantly reduced tumor size and CD31 expression, and increased expression of CC3 (p<0.05). Cereblon expression increased in lenalidomide-treated RT4 xenografts (p<0.05).
  
  
  CONCLUSIONS
  Lenalidomide demonstrated preclinical activity against superficially-invasive low-grade UC cells attributable to direct tumor cell apoptosis and anti-angiogenic activity. Clinical trials are warranted in patients with indolent UC.
authors: Department of Urology, Baylor College of Medicine, Houston, TX, U.S.A.
authors: Weiguo
authors: W
authors: Jian
authors: Department of Immunology, Baylor College of Medicine, Houston, TX, U.S.A.
authors: Jonathan M
authors: JM
authors: Levitt
authors: Department of Urology, Baylor College of Medicine, Houston, TX, U.S.A.
authors: Seth P
authors: SP
authors: Lerner
authors: Department of Medicine, Division of Hematology-Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, U.S.A. gsonpavde@uabmc.edu.
authors: Guru
authors: G
authors: Sonpavde
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002554:Cerebrosides / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077269:Lenalidomide; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D002554:Cerebrosides; D013792:Thalidomide; D000077269:Lenalidomide; C014753:phrenosin
keywords: Urothelial carcinoma; angiogenesis; apoptosis; cereblon; lenalidomide