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本文引用的文献

1
Tumour treating fields therapy for glioblastoma: current advances and future directions.肿瘤电场治疗胶质母细胞瘤:当前进展和未来方向。
Br J Cancer. 2021 Feb;124(4):697-709. doi: 10.1038/s41416-020-01136-5. Epub 2020 Nov 4.
2
Quantitation of the ROS production in plasma and radiation treatments of biotargets.定量检测生物靶区的血浆和辐射处理中的 ROS 产生。
Sci Rep. 2019 Dec 27;9(1):19837. doi: 10.1038/s41598-019-56160-0.
3
Cyclin D-CDK4 relieves cooperative repression of proliferation and cell cycle gene expression by DREAM and RB.周期蛋白 D-CDK4 通过 DREAM 和 RB 缓解增殖和细胞周期基因表达的协同抑制作用。
Oncogene. 2019 Jun;38(25):4962-4976. doi: 10.1038/s41388-019-0767-9. Epub 2019 Mar 4.
4
Treatment of Glioblastoma (GBM) with the Addition of Tumor-Treating Fields (TTF): A Review.添加肿瘤治疗电场(TTF)治疗胶质母细胞瘤(GBM):综述
Cancers (Basel). 2019 Feb 2;11(2):174. doi: 10.3390/cancers11020174.
5
Functional Biological Activity of Sorafenib as a Tumor-Treating Field Sensitizer for Glioblastoma Therapy.索拉非尼作为一种肿瘤治疗电场增敏剂的功能生物学活性用于治疗脑胶质瘤。
Int J Mol Sci. 2018 Nov 21;19(11):3684. doi: 10.3390/ijms19113684.
6
Selective toxicity of tumor treating fields to melanoma: an in vitro and in vivo study.肿瘤治疗电场对黑色素瘤的选择性毒性:一项体外和体内研究。
Cell Death Discov. 2018 Oct 3;4:46. doi: 10.1038/s41420-018-0106-x. eCollection 2018.
7
A Review on Tumor-Treating Fields (TTFields): Clinical Implications Inferred From Computational Modeling.肿瘤治疗电场(TTFields)综述:基于计算模型推断的临床意义。
IEEE Rev Biomed Eng. 2018;11:195-207. doi: 10.1109/RBME.2017.2765282. Epub 2018 Feb 13.
8
Retrospective study of nivolumab for patients with recurrent high grade gliomas.尼伏鲁单抗治疗复发性高级别胶质瘤患者的回顾性研究。
J Neurooncol. 2018 Sep;139(3):625-631. doi: 10.1007/s11060-018-2907-4. Epub 2018 May 19.
9
Tumor-Treating Fields: Answering the Concern About Quality of Life.肿瘤治疗电场:回应关于生活质量的关切
JAMA Oncol. 2018 Apr 1;4(4):504-505. doi: 10.1001/jamaoncol.2017.5062.
10
Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells.肿瘤治疗电场(TTFields)会延迟胶质细胞瘤细胞放射治疗后 DNA 损伤的修复。
Radiat Oncol. 2017 Dec 29;12(1):206. doi: 10.1186/s13014-017-0941-6.

肿瘤治疗电场作为胶质母细胞瘤治疗的质子束增敏剂。

Tumor-treating fields as a proton beam-sensitizer for glioblastoma therapy.

作者信息

Lee Won Seok, Seo Seung-Jun, Chung Hye Kyung, Park Jang Woo, Kim Jong-Ki, Kim Eun Ho

机构信息

Department of Biochemistry, School of Medicine, Daegu Catholic University 33 17-gil, Duryugongwon-ro, Nam-gu, Daegu, Republic of Korea.

Department of Biomedical Engineering and School of Medicine, Daegu Catholic University Nam-gu, Daegu 42472, Republic of Korea.

出版信息

Am J Cancer Res. 2021 Sep 15;11(9):4582-4594. eCollection 2021.

PMID:34659907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8493382/
Abstract

Few advances in GBM treatment have been made since the initiation of the Stupp trials in 2005. Experimental studies on immunotherapy drugs, molecular inhibitors, radiation dosage escalation and vascular growth factor blockers have all failed to provide satisfactory outcomes. TTFields therapy, on the other hand, have emerged as a viable substitute to therapies like radiation in GBM patients having a highly immunosuppressive tumor microenvironment. To enhance the biofunctional impacts, we explored the combination events with TTFields and proton treatment in this study. We conducted a cell viability test, a cell death detection evaluation, a ROS analysis, a three-dimensional (3D) culture system, and a migration assay. The combination of proton radiation and TTFields therapy laid a substantial anticancer impact on the F98 and U373 as compared to the consequences of either of these therapies used separately. The combination proton beam therapy used by TTFields was very successful in curbing GBM from migrating. GBM cell metastasis is restricted by TTFields combined proton by downregulating the MAPK, NF-κB, and PI3K/AKT indicating pathways, caused by reduced EMT marker expression. These findings furnish biological proof for the molecular grounds of TTFields in combination with proton used for GBM therapy.

摘要

自2005年开展Stupp试验以来,胶质母细胞瘤(GBM)治疗方面几乎没有取得进展。对免疫治疗药物、分子抑制剂、放射剂量递增和血管生长因子阻滞剂的实验研究均未能取得令人满意的结果。另一方面,肿瘤治疗电场(TTFields)疗法已成为在具有高度免疫抑制肿瘤微环境的GBM患者中替代放疗等疗法的可行选择。为了增强生物功能影响,我们在本研究中探索了TTFields与质子治疗的联合应用。我们进行了细胞活力测试、细胞死亡检测评估、活性氧(ROS)分析、三维(3D)培养系统和迁移试验。与单独使用这两种疗法的结果相比,质子放疗与TTFields疗法的联合对F98和U373细胞产生了显著的抗癌作用。TTFields联合使用的质子束疗法在抑制GBM迁移方面非常成功。TTFields联合质子可通过下调MAPK、NF-κB和PI3K/AKT信号通路,减少上皮-间质转化(EMT)标志物表达,从而限制GBM细胞转移。这些发现为TTFields联合质子用于GBM治疗的分子机制提供了生物学证据。