Monti Hughes A, Pozzi Ecc, Thorp S I, Curotto P, Medina V A, Martinel Lamas D J, Rivera E S, Garabalino M A, Farías R O, Gonzalez S J, Heber E M, Itoiz M E, Aromando R F, Nigg D W, Trivillin V A, Schwint A E
Department of Radiobiology, National Atomic Energy Commission, San Martin, Province Buenos Aires, Argentina.
Department of Research and Production Reactors, National Atomic Energy Commission, Ezeiza, Province Buenos Aires, Argentina.
Oral Dis. 2015 Sep;21(6):770-7. doi: 10.1111/odi.12346. Epub 2015 Jun 8.
Searching for more effective and selective therapies for head and neck cancer, we demonstrated the therapeutic effect of boron neutron capture therapy (BNCT) to treat oral cancer and inhibit long-term tumor development from field-cancerized tissue in the hamster cheek pouch model. However, BNCT-induced mucositis in field-cancerized tissue was dose limiting. In a clinical scenario, oral mucositis affects patients' treatment and quality of life. Our aim was to evaluate different radioprotectors, seeking to reduce the incidence of BNCT-induced severe mucositis in field-cancerized tissue.
Cancerized pouches treated with BNCT mediated by boronophenylalanine at 5 Gy were treated as follows: control: saline solution; Hishigh : histamine 5 mg kg(-1) ; Hislow : histamine 1 mg kg(-1) ; and JNJ7777120: 10 mg kg(-1).
Hislow reduced the incidence of severe mucositis in field-cancerized tissue to 17% vs
55%; Hishigh : 67%; JNJ7777120: 57%. Hislow was non-toxic and did not compromise the long-term therapeutic effect of BNCT or alter gross boron concentration.
Histamine reduces BNCT-induced mucositis in experimental oral precancer without jeopardizing therapeutic efficacy. The fact that both histamine and boronophenylalanine are approved for use in humans bridges the gap between experimental work and potential clinical application to reduce BNCT-induced radiotoxicity in patients with head and neck cancer.
为寻找更有效、更具选择性的头颈癌治疗方法，我们在仓鼠颊囊模型中证明了硼中子俘获疗法（BNCT）治疗口腔癌并抑制癌前病变组织长期肿瘤发展的疗效。然而，BNCT诱发的癌前病变组织黏膜炎具有剂量限制性。在临床情况下，口腔黏膜炎会影响患者的治疗和生活质量。我们的目的是评估不同的辐射防护剂，以降低BNCT诱发的癌前病变组织严重黏膜炎的发生率。
用硼苯丙氨酸介导的BNCT以5 Gy治疗癌前病变颊囊，治疗方式如下：对照组：生理盐水；高组胺组：组胺5 mg kg⁻¹；低组胺组：组胺1 mg kg⁻¹；JNJ7777120组：10 mg kg⁻¹。
低组胺组将癌前病变组织中严重黏膜炎的发生率降至17%，而对照组为55%；高组胺组为67%；JNJ7777120组为57%。低组胺组无毒，且不影响BNCT的长期治疗效果，也不改变总硼浓度。
组胺可减轻实验性口腔癌前病变中BNCT诱发的黏膜炎，且不影响治疗效果。组胺和硼苯丙氨酸均已获批用于人体这一事实，填补了实验工作与潜在临床应用之间的差距，以降低头颈癌患者BNCT诱发的放射毒性。
