title: Effects of peritumoral nanoconjugated cisplatin on laryngeal cancer stem cells.
abstract: To evaluate the efficacy of peritumoral hyaluronic acid (HA)-cisplatin therapy in a murine model of laryngeal squamous cell carcinoma and to evaluate its effect on cancer stem cells (CSCs).
  
  
  
  An orthotopic murine study utilizing University of Michigan squamous cell carcinoma-12 (UMSCC-12) laryngeal cancer cells was conducted in randomized controlled fashion with three treatment arms: saline, systemic cisplatin, and peritumoral HA-cisplatin.
  
  
  
  UMSCC-12 laryngeal cancer cells were inoculated into the buccal mucosa of athymic nude mice followed by weekly treatment with saline, systemic cisplatin, or peritumoral HA-cisplatin for 3 weeks. Tumor response and animal weight was monitored and change in CD44 proportion was analyzed ex vivo.
  
  
  
  HA-cisplatin demonstrated superior antitumor efficacy and greater reduction in CD44 positivity on ex vivo analysis.
  
  
  
  Peritumoral nanoconjugated HA-cisplatin provides superior antitumor efficacy compared to standard cisplatin therapy in an in vivo laryngeal cancer model. There was also selective targeting of CD44+ cancer cells with HA-cisplatin. This therapeutic strategy could represent the first selective laryngeal CSC-targeted therapy. Further preclinical investigation is warranted to evaluate its role for locally advanced head and neck cancer treatment.
  
  
  
  NA Laryngoscope, 126:E184-E190, 2016.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sim
authors.affiliation: University of Kansas School of Medicine, Kansas City, Kansas.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Grogan
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Chitra
authors.initials: C
authors.lastname: Subramanian
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
authors.affiliation: University of Kansas School of Pharmacy, Kansas City, Kansas, U.S.A.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cohen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects; D006820:Hyaluronic Acid / Q000494:pharmacology; D007822:Laryngeal Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D058726:Nanoconjugates / Q000008:administration & dosage; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D058726:Nanoconjugates; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: CD44; Larynx cancer; cancer stem cells; hyaluronan nanoconjugate; targeted therapy