title: Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured. Hyaluronan (HA) is a ligand of cluster of differentiation 44 (CD44), that is expressed on MPM cells.
  
  
  METHODS
  In order to enhance BNCT for MPM tumors, we developed a novel HA-containing (10)B (sodium borocaptate: BSH) formulation (HA-BND-S). We examined the efficacy of HA-BND-S using MPM cells and a mouse MPM model.
  
  
  RESULTS
  HA-BND-S preferentially bound MPM cells dose-dependently, and increased the cytotoxicity of BNCT compared to BSH in vitro. HA-BND-S administration significantly increased the survival of MPM tumor-bearing mice compared to BSH at the same (10)B dosage in BNCT.
  
  
  CONCLUSIONS
  Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM.
authors.affiliation: Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Sasai
authors.affiliation: Department of Electronic Chemistry, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Nagako
authors.initials: N
authors.lastname: Sougawa
authors.affiliation: Particle Radiation Oncology Research Center Laboratory, Research Reactor Institute, Kyoto University, Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Particle Radiation Oncology Research Center Laboratory, Research Reactor Institute, Kyoto University, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan tg4c_1211@hp-mctr.med.osaka-u.ac.jp.
authors.forename: Chun Man
authors.initials: CM
authors.lastname: Lee
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D008654:Mesothelioma / Q000401:mortality / Q000628:therapy*; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016019:Survival Analysis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D011838:Radiation-Sensitizing Agents; D006820:Hyaluronic Acid
keywords: BNCT; BSH; CD44; HA; MPM; hyaluronan formulation