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硼中子俘获治疗延迟转移性脊柱肿瘤小鼠模型中神经功能下降。

Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors.

机构信息

Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka, Japan.

Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Osaka, Japan.

出版信息

Cancer Sci. 2024 Aug;115(8):2774-2785. doi: 10.1111/cas.16245. Epub 2024 Jun 11.

Abstract

Metastatic spinal tumors are increasingly prevalent due to advancements in cancer treatment, leading to prolonged survival rates. This rising prevalence highlights the need for developing more effective therapeutic approaches to address this malignancy. Boron neutron capture therapy (BNCT) offers a promising solution by delivering targeted doses to tumors while minimizing damage to normal tissue. In this study, we evaluated the efficacy and safety of BNCT as a potential therapeutic option for spine metastases in mouse models induced by A549 human lung adenocarcinoma cells. The animal models were randomly allocated into three groups: untreated (n = 10), neutron irradiation only (n = 9), and BNCT (n = 10). Each mouse was administered 4-borono-L-phenylalanine (250 mg/kg) intravenously, followed by measurement of boron concentrations 2.5 h later. Overall survival, neurological function of the hindlimb, and any adverse events were assessed post irradiation. The tumor-to-normal spinal cord and blood boron concentration ratios were 3.6 and 2.9, respectively, with no significant difference observed between the normal and compressed spinal cord tissues. The BNCT group exhibited significantly prolonged survival rates compared with the other groups (vs. untreated, p = 0.0015; vs. neutron-only, p = 0.0104, log-rank test). Furthermore, the BNCT group demonstrated preserved neurological function relative to the other groups (vs. untreated, p = 0.0004; vs. neutron-only, p = 0.0051, multivariate analysis of variance). No adverse events were observed post irradiation. These findings indicate that BNCT holds promise as a novel treatment modality for metastatic spinal tumors.

摘要

转移性脊柱肿瘤由于癌症治疗的进步而日益普遍,导致生存率延长。这种患病率的上升突出表明需要开发更有效的治疗方法来解决这种恶性肿瘤。硼中子俘获治疗(BNCT)通过向肿瘤提供靶向剂量,同时最大限度地减少对正常组织的损伤,提供了一种有前途的解决方案。在这项研究中,我们评估了 BNCT 作为 A549 人肺腺癌细胞诱导的小鼠模型中脊柱转移的潜在治疗选择的疗效和安全性。动物模型随机分为三组:未治疗组(n=10)、仅中子照射组(n=9)和 BNCT 组(n=10)。每只小鼠静脉注射 4-硼代-L-苯丙氨酸(250mg/kg),2.5 小时后测量硼浓度。照射后评估总生存率、后肢的神经功能和任何不良事件。肿瘤与正常脊柱脊髓的硼浓度比为 3.6,与正常和受压脊柱脊髓组织之间无显著差异。与其他组相比,BNCT 组的生存率显著延长(与未治疗组相比,p=0.0015;与仅中子照射组相比,p=0.0104,对数秩检验)。此外,与其他组相比,BNCT 组的神经功能保持较好(与未治疗组相比,p=0.0004;与仅中子照射组相比,p=0.0051,多变量方差分析)。照射后未观察到不良事件。这些发现表明 BNCT 作为转移性脊柱肿瘤的一种新的治疗方法具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbdb/11309935/2a0f6fe80c4c/CAS-115-2774-g002.jpg

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