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硼中子俘获疗法(BNCT)的远隔效应:结肠癌实验模型中的原理验证

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

作者信息

Trivillin Verónica A, Pozzi Emiliano C C, Colombo Lucas L, Thorp Silvia I, Garabalino Marcela A, Monti Hughes Andrea, González Sara J, Farías Rubén O, Curotto Paula, Santa Cruz Gustavo A, Carando Daniel G, Schwint Amanda E

机构信息

Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA San Martin, Provincia Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.

出版信息

Radiat Environ Biophys. 2017 Nov;56(4):365-375. doi: 10.1007/s00411-017-0704-7. Epub 2017 Aug 8.

DOI:10.1007/s00411-017-0704-7
PMID:28791476
Abstract

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

摘要

本研究的目的是首次评估硼中子俘获疗法(BNCT)的远隔效应。将26只BDIX大鼠的右后腹侧皮下接种1×10个DHD/K12/TRb同基因结肠癌细胞。接种后三周,对12只带有肿瘤结节的大鼠的右腿在位于阿根廷布宜诺斯艾利斯的RA - 3核反应堆中进行BPA - BNCT(硼苯丙氨酸 - 硼)治疗,作为剂量限制组织的皮肤吸收剂量为7.5 Gy。其余14只荷瘤大鼠不进行治疗,用作对照。BNCT治疗后两周,在26只BDIX大鼠的每只大鼠的对侧左后腹侧皮下注射1×10个DHD/K12/TRb细胞。每周测量双腿的肿瘤体积,持续7周,以确定右腿对BNCT的反应,并评估右腿的BNCT对左腿肿瘤发展的潜在影响。在BNCT组中,与未产生反应的动物(治疗后/治疗前肿瘤体积≥1)相比,右腿肿瘤对BNCT产生反应的动物(治疗后/治疗前肿瘤体积<1)的对侧左肿瘤体积出现了统计学上的显著减小,即13±15 vs 271±128 mm³。此外,与未治疗的动物相比,对BNCT有反应的动物(治疗后/治疗前<1)的对侧左腿肿瘤体积出现了统计学上的显著减小,即13±15 vs 254±251 mm³。在一个简单动物模型中进行的本研究提供了原理证明,即肿瘤对BNCT的阳性反应能够诱导远隔效应。

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本文引用的文献

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Anticancer Drugs. 2016 Apr;27(4):269-77. doi: 10.1097/CAD.0000000000000337.
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Abscopal Effects: Case Report and Emerging Opportunities.远隔效应:病例报告及新出现的机遇
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From the laboratory to the clinic: How translational studies in animals have lead to clinical advances in boron neutron capture therapy.从实验室到临床:动物实验研究如何推动硼中子俘获治疗的临床进展。
在大鼠异位结肠癌模型中,以低聚岩藻糖胶和谷氨酰胺作为佐剂,在RA-3核反应堆进行硼中子俘获疗法(BNCT)的治疗效果、放射毒性及远隔效应
Life (Basel). 2023 Jul 11;13(7):1538. doi: 10.3390/life13071538.
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Next-Generation Boron Drugs and Rational Translational Studies Driving the Revival of BNCT.下一代硼药物和合理的转化研究推动 BNCT 的复兴。
Cells. 2023 May 16;12(10):1398. doi: 10.3390/cells12101398.
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Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy.局部核反应打破了装载免疫佐剂的硼药物胶囊,用于癌症免疫治疗。
Nat Commun. 2023 Apr 5;14(1):1884. doi: 10.1038/s41467-023-37253-x.
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Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer.探索硼中子俘获疗法(BNCT)作为乳腺癌一种有前景的治疗前沿的生物学和物理基础。
Cancers (Basel). 2022 Jun 18;14(12):3009. doi: 10.3390/cancers14123009.
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