新型透明质酸制剂增强硼中子俘获疗法对小鼠间皮瘤的疗效。
Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.
作者信息
Sasai Masao, Nakamura Hiroyuki, Sougawa Nagako, Sakurai Yoshinori, Suzuki Minoru, Lee Chun Man
机构信息
Medical Center for Translational Research, Osaka University Hospital, Osaka, Japan.
Department of Electronic Chemistry, Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan.
出版信息
Anticancer Res. 2016 Mar;36(3):907-11.
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.
背景
恶性胸膜间皮瘤（MPM）是一种因接触石棉而引发的难治性胸膜癌。MPM难以治疗，因为它容易扩散。硼中子俘获疗法（BNCT）是一种放射疗法，其中选择性摄取含硼（10）化合物的癌细胞被破坏，而正常细胞不受损伤。透明质酸（HA）是分化簇44（CD44）的配体，在MPM细胞上表达。
材料与方法
为了增强BNCT对MPM肿瘤的治疗效果，我们开发了一种新型的含HA的硼（10）（硼卡钠：BSH）制剂（HA-BND-S）。我们使用MPM细胞和小鼠MPM模型研究了HA-BND-S的疗效。
结果
HA-BND-S优先以剂量依赖的方式结合MPM细胞，并且在体外与BSH相比增加了BNCT的细胞毒性。在BNCT中相同的硼（10）剂量下，与BSH相比，给予HA-BND-S显著提高了荷MPM肿瘤小鼠的存活率。
结论
用HA修饰BSH是增强BNCT治疗MPM疗效的一种有前景的策略。
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