Masao Sasai1, Hiroyuki Nakamura2, Nagako Sougawa3, Yoshinori Sakurai4, Minoru Suzuki4, Chun Man Lee5. 1. Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan. 2. Department of Electronic Chemistry, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan. 3. Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 4. Particle Radiation Oncology Research Center Laboratory, Research Reactor Institute, Kyoto University, Osaka, Japan. 5. 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.
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. MATERIALS AND 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. CONCLUSION: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM. Copyright
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. MATERIALS AND 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. CONCLUSION: Modifying BSH with HA is a promising strategy for enhancing the efficacy of BNCT for therapy of MPM. Copyright