title: Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.
abstract: Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies, such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side-effect profile. In this study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo We successfully demonstrated decreased cellular proliferation, invasion and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should be further investigated as a developing therapeutic in these rare and difficult-to-treat pediatric solid organ tumors. Mol Cancer Ther; 15(5); 911-21. ©2016 AACR.
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Waters
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Stewart
authors.affiliation: Department of Chemistry, University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Venkatram R
authors.initials: VR
authors.lastname: Atigadda
authors.affiliation: Department of Pathology University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mroczek-Musulman
authors.affiliation: Department of Chemistry, University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Muccio
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, Birmingham, Alabama.
authors.forename: Clinton J
authors.initials: CJ
authors.lastname: Grubbs
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, Birmingham, Alabama. elizabeth.beierle@childrensal.org.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Beierle
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms; D008113:Liver Neoplasms; D051379:Mice; D008819:Mice, Nude; D009281:Naphthalenes / Q000494:pharmacology*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; D047488:Retinoid X Receptors; C112106:UAB 30