Kamida Akitoshi, Obayashi Shigeki, Kato Itsuro, Ono Koji, Suzuki Minoru, Nagata Kenji, Sakurai Yoshinori, Yura Yoshiaki
Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Osaka, Japan.
Int J Radiat Biol. 2006 Jan;82(1):21-9. doi: 10.1080/09553000600570453.
The effect of boronophenylalanine (BPA)-mediated boron neutron capture therapy (BNCT) on human oral squamous cell carcinoma (SCC) xenografts in nude mice was examined.
Tumor-bearing mice were given BPA at a dose of 250 mg/kg body weight. The tumor (10)B concentration 2 h after an injection of BPA was higher than those 1 or 3 h after the injection. Neutron irradiation was performed beginning 1, 2 or 3 h after an injection of BPA and the effects on body weight of the animals, tumor growth, survival of tumor-bearing animals, and histology of tumor and normal tissue were examined. Fragmented nuclear DNA, 5-bromo-2'-deoxyuridine (BrdU), and von Willebrand Factor (vWF) were detected by immunohistochemical staining.
Tumor volumes of untreated control animals increased continuously, whereas those of BNCT-treated animals were markedly decreased. Animals given neutron irradiation 2 h after the injection of BPA survived for a longer period as compared with those given neutron irradiation 1 or 3 h after the injection. BNCT reduced the incorporation of BrdU into tumor cells, and induced the enlargement and vacuolation of tumor cells. Disintegration of blood vessels and dense inflammatory cell infiltration were also observed in the stroma of the tumor, but not surrounding normal tissues.
These results indicate that BPA-mediated BNCT can exert a curative effect on human oral SCC xenografts in nude mice, if an optimal 10B concentration in tumors is achieved and that the disintegration of blood vessels in tumor stroma may contribute to tumor remission by BNCT.
研究硼苯丙氨酸(BPA)介导的硼中子俘获疗法(BNCT)对裸鼠人口腔鳞状细胞癌(SCC)异种移植瘤的影响。
给荷瘤小鼠注射剂量为250mg/kg体重的BPA。注射BPA后2小时肿瘤的(10)B浓度高于注射后1小时或3小时。在注射BPA后1、2或3小时开始进行中子照射,并检测其对动物体重、肿瘤生长、荷瘤动物存活情况以及肿瘤和正常组织组织学的影响。通过免疫组织化学染色检测断裂的核DNA、5-溴-2'-脱氧尿苷(BrdU)和血管性血友病因子(vWF)。
未治疗的对照动物肿瘤体积持续增大,而接受BNCT治疗的动物肿瘤体积明显减小。与注射BPA后1小时或3小时接受中子照射的动物相比,注射BPA后2小时接受中子照射的动物存活时间更长。BNCT减少了BrdU掺入肿瘤细胞,并诱导肿瘤细胞肿大和空泡化。在肿瘤间质中也观察到血管解体和密集的炎性细胞浸润,但周围正常组织未出现。
这些结果表明,如果肿瘤中达到最佳的10B浓度,BPA介导的BNCT可对裸鼠人口腔SCC异种移植瘤发挥治疗作用,并且肿瘤间质中的血管解体可能有助于BNCT导致肿瘤缓解。