title: Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma.
abstract: OBJECTIVE
  To investigate whether the combination of the imidazoquinoline immune response modifier, imiquimod, and the multitargeted tyrosine-kinase inhibitor, sorafenib, inhibits the growth of renal cell carcinoma in mice.
  
  
  METHODS
  Female BALB/c mice were implanted subcutaneously with 2 × 10(5) RENCA mouse kidney cancer cells, and were treated with transcutaneously applied cream containing imiquimod and oral administrations of sorafenib beginning 5 days after implantation of the cells. Tumor incidence and burden were determined at 28 days after initiation of therapy. T cell infiltration in the tumor was determined by immunofluorescence staining with anti-CD3-ε and CD8-α antibodies.
  
  
  RESULTS
  Therapy with imiquimod, sorafenib or their combination was well tolerated. Combination therapy with imiquimod and sorafenib significantly inhibited tumor growth when compared with administration of control vehicle, imiquimod or sorafenib alone (P < 0.05). The CD3- and CD8-positive T cells infiltrated into tumors to a greater degree in response to the combination therapy when compared with tumors treated with control vehicle or sorafenib alone.
  
  
  CONCLUSIONS
  Combination therapy with a tyrosine-kinase inhibitor and an imidazoquinoline could be a promising therapeutic strategy for patients with renal cell carcinoma.
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Nankoku, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Karashima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Komatsu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Niimura
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kamada
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Keiko
authors.initials: K
authors.lastname: Udaka
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D000077271:Imiquimod; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077157:Sorafenib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009536:Niacinamide; D000077157:Sorafenib; D000077271:Imiquimod
keywords: imiquimod; renal cell carcinoma; sorafenib