title: Enhanced efficacy of CKD-516 in combination with doxorubicin: pre-clinical evaluation using a hepatocellular carcinoma xenograft model.
abstract: OBJECTIVE
  To evaluate the anticancer efficacy of CKD-516, a novel vascular-disrupting agent, alone and in combination with doxorubicin in the treatment of hepatocellular carcinoma (HCC).
  
  
  METHODS
  In mice bearing luciferized HCC cells, therapeutic efficacy was assessed for seven days after single administration of CKD-516, doxorubicin, or combination of CKD-516 and doxorubicin.
  
  
  RESULTS
  Bioluminescence-imaging (BLI) signals in the CKD-516 group abruptly decreased initially, but recovered at seven days after treatment. BLI signals in the doxorubicin group gradually decreased over the 7-day period. In the combination group, BLI signals were abruptly reduced and remained suppressed for the 7-day period. On histopathological examination, CKD-516-treated tumors showed extensive central necrosis, whereas the peripheral layers remained viable. Doxorubicin-treated tumors showed mild and scattered necrosis. Tumors from the combination group showed more extensive central and peripheral necrosis, with smaller viable peripheral layers than the CKD-516 group.
  
  
  CONCLUSIONS
  Combination therapy can have additive effects for treatment of HCC compared with CKD-516 or doxorubicin monotherapy.
authors.affiliation: Research Institute and Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. medimash@gmail.com; kyungwon_kim@amc.seoul.kr.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Han Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Jisuk
authors.initials: J
authors.lastname: Park
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Hyewon
authors.initials: H
authors.lastname: Youn
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Dal-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Tseng
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000008:administration & dosage / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047368:Tumor Burden / Q000187:drug effects; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D001577:Benzophenones; C552333:N-(4-(3-(1H-1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl)thiazol-2-yl)-2-amino-3-methylbutanamide; D004317:Doxorubicin; D014633:Valine
keywords: CKD-516; doxorubicin; hepatocellular carcinoma; tubulin-binding agents; vascular-disrupting agent