Early effects of boron neutron capture therapy on rat glioma models

Early effects of boron neutron capture therapy (BNCT) on malignant glioma are characterized by reduction of the enhancement area and regression of the peritumoral edema radiologically. The aim of this study was to investigate the early histological changes of tumors and inflammatory cells after BNCT in the rat brain. Rats were treated with BNCT using boronophenylalanine (BPA) 7 days after implantation of C6 glioma cells. The tumors were assessed with magnetic resonance imaging and histopathological examination at 4 days after BNCT. The mean tumor volumes were 39 ± 2 mm³ in the BNCT group and 134 ± 18 mm³ in the control group. In the BNCT group, tumor cells showed a less pleomorphic appearance with atypical nuclei and mitotic figures. The Ki-67 labeling index was 6.5% ± 4.7% in the BNCT and 35% ± 3.8% in the control group. The reactions of the inflammatory cells were examined with ED-1 as macrophage marker and OX42 as microglia marker. ED-1- and OX-42-positive cells were reduced both in the core and the marginal area of the tumor in the BNCT group. It is suggested that BNCT reduced tumor progression by suppression of proliferation. Inhibition of the activated macrophages may relate to reduced peritumoral edema in the early phase.     

Boron neutron capture therapy in the treatment of locally recurred head and neck cancer

PURPOSE: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. METHODS AND MATERIALS: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. RESULTS: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). CONCLUSIONS: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.     

A novel concept of treatment of diffuse or multiple pleural tumors by boron neutron capture therapy (BNCT)

Two patients, one with malignant pleural mesothelioma and one with a malignant short spindle cell tumor, received boron neutron capture therapy (BNCT). In each case, the tumors regressed or remained stable in size for 3-6 months following BNCT. No acute or late adverse events higher than grade 2 were observed.     

硼氯溶液无菌检查方法的建立

目的：建立硼氯溶液的无菌检查方法。方法采用薄膜过滤法进行无菌检查法验证。通过预实验,确定阳性对照菌和比较不同量的冲洗液对检查结果的影响。结果用薄膜过滤法,以金黄色葡萄球菌为阳性对照菌,冲洗总量500mL,检验结果符合规定。结论该法准确可靠,适用于硼氯溶液的无菌检查。     

Long-term stability of dental adhesive incorporated by boron nitride nanotubes

Objective

The aim of this study was to evaluate physicochemical properties, long-term microtensile bond strength and cytotoxicity of methacrylate-based adhesive containing boron nitride nanotubes (BNNTs) as fillers.

硼氯溶液质量标准的改进

目的:改进并建立硼氯溶液的质量控制标准。方法:参照《中国药典》2010年版相关鉴别方法,在原质量标准只有硼酸鉴别项目的基础上,增加了硼氯溶液中盐酸萘甲唑啉和氯霉素的鉴别方法,并改进了硼酸的含量测定中滴定反应的介质(由甘露醇改为中性甘油)及确定了取样量为5 ml。结果:硼氯溶液中的主要成分硼酸、盐酸萘甲唑啉及氯霉素鉴别反应均呈阳性。硼酸检测质量浓度线性范围为10³2 mg/ml(r=0.999 5,n=7),平均加样回收率为101.0%,RSD=1.10%(n=3)。与原标准方法比较,改进后方法终点明确,误差减小。结论:建立的质量控制方法简单、灵敏、准确度高,可提高硼氯溶液的质量标准。     

硼中子俘获治疗头颈部肿瘤临床试验进展

硼中子俘获治疗（boron neutron capture therapy,BNCT）是结合靶向治疗和重离子治疗的先进二元放疗技术。其原理是利用含有¹⁰B同位素的硼药在肿瘤细胞中靶向聚集,随后中子束流外部照射肿瘤部位,发生¹⁰B（n,α）⁷Li核反应,释放出杀伤范围为一个细胞大小（5~9 μm）的高传能线密度α粒子和⁷Li粒子杀死肿瘤细胞。BNCT具有精准的肿瘤靶向性,对正常组织损伤小,分割次数（1~3次）少于传统放疗（30次）等优点。BNCT使用的中子由反应堆或加速器产生,临床使用的硼药包括BPA和BSH两种。本文介绍国内外开展的头颈部肿瘤BNCT临床试验及取得的重要进展。BNCT对于头颈部肿瘤治疗具有良好疗效。随着加速器中子源的推广应用和新型硼药的研发,BNCT将会在临床放射治疗领域发挥更大的作用。     

Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter

Boron neutron capture therapy (BNCT) is a radiotherapy utilizing the neutron capture and nuclear fission reaction of ¹⁰B taken up into tumor cells. The most commonly used boron agent in BNCT, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumor cells. Here, by using dipeptides of BPA and tyrosine (BPA-Tyr and Tyr-BPA), we propose a novel strategy of selective boron delivery into tumor cells via oligopeptide transporter PEPT1 upregulated in various cancers. Kinetic analyses indicated that BPA-Tyr and Tyr-BPA are transported by oligopeptide transporters, PEPT1 and PEPT2. The intrinsic oligopeptide transport activity in tumor cells clearly correlated with PEPT1 protein expression level but not with PEPT2, suggesting that PEPT1 is the predominant oligopeptide transporter at least in tumor cell lines. Furthermore, using BPA-Tyr and Tyr-BPA, boron was successfully delivered into PEPT1-expressing pancreatic cancer AsPC-1 cells via a PEPT1-mediated mechanism. Intravenous administration of BPA-Tyr into the mice bearing AsPC-1 xenograft tumors resulted in significant boron accumulation in the tumors. It is proposed that the oligopeptide transporters, especially PEPT1, are promising candidates for molecular targets of boron delivery in BNCT. The BPA-containing dipeptides would have a potential for the development of novel boron carriers targeting PEPT1.     

岛礁反渗透海水淡化水的水质检测及卫生学探讨

目的:分析岛礁反渗透海水淡化水的水质,从卫生学探讨长期饮用岛礁反渗透淡化水对人们健康的可能影响。方法:按照GB/T5750-2006《生活饮用水标准检验方法》进行水质分析,比较岛礁反渗透海水淡化水质与GB5749-2006《生活饮用水卫生标准》、GJB1335-92《低矿化度饮用水矿化卫生标准》的差异。结果:岛礁反渗透海水淡化水中硼0.68 mg/L,是GB5749-2006限值的1.38倍,其它水质指标符合GB5749-2006;镁6.30 mg/L、钙5.65 mg/L、硫酸盐5.52 mg/L、重碳酸盐4.0 mg/L,低于GJB1335-92的适宜浓度范围,属于典型的软水。结论:长期饮用岛礁反渗透海水淡化水对人们健康可能有影响,建议对岛礁反渗透海水淡化水进行调质处理,使其符合GB5749-2006、GJB1335-92,更好地保护人们的身心健康。     

Recent developments with boron as a platform for novel drug design

ABSTRACT

Introduction: After decades of development, the medicinal chemistry of compounds that contain a single boron atom has matured to the present status of having equal rights with other branches of drug discovery, although it remains a relative newcomer. In contrast, the medicinal chemistry of boron clusters is less advanced, but it is expanding and may soon become a productive area of drug discovery.

Areas covered: The author reviews the current developments of medicinal chemistry of boron and its applications in drug design. First generation boron drugs that bear a single boron atom and second generation boron drugs that utilize boron clusters as pharmacophores or modulators of bioactive molecules are discussed. The advantages and gaps in our current understanding of boron medicinal chemistry, with a special focus on boron clusters, are highlighted.

Expert opinion: Boron is not a panacea for every drug discovery problem, but there is a good chance that it will become a useful addition to the medicinal chemistry tool box. The present status of boron resembles the medicinal chemistry status of fluorine three decades ago; indeed, currently, approximately 20% of pharmaceuticals on the market contain fluorine. The fact that novel boron compounds, especially those based on abiotic polyhedral boron hydrides, are currently unfamiliar could be advantageous because organisms may be less prone to developing resistance against boron cluster-based drugs.