[1]程勇军,赵晋华.东亚钳蝎氯毒素在胶质瘤靶向显像与治疗中的研究进展[J].国际放射医学核医学杂志,2015,39(1):32-36.[doi:10.3760/cma.j.issn.1673-4114.2015.01.008]
　Cheng Yongjun,Zhao Jinhua.Development of research in targeting image and therapy of gliomas using Buthus martensii Karsch chlorotoxin[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(1):32-36.[doi:10.3760/cma.j.issn.1673-4114.2015.01.008]
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东亚钳蝎氯毒素在胶质瘤靶向显像与治疗中的研究进展(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
39
期数:
2015年第1期
页码:
32-36
栏目:
出版日期:
2015-01-25

文章信息/Info

Title:
Development of research in targeting image and therapy of gliomas using Buthus martensii Karsch chlorotoxin
作者:
程勇军;  赵晋华
上海交通大学附属第一人民医院核医学科, 上海, 200080
Author(s):
Cheng Yongjun;  Zhao Jinhua
Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, China
关键词:
神经胶质瘤; 东亚钳蝎氯毒素; 氯毒素; 靶向显像; 靶向治疗
Keywords:
Glioma; Buthus martensii Karsch chlorotoxin; Chlorotoxin; Targeted imaging; Targeted therapy
DOI:
10.3760/cma.j.issn.1673-4114.2015.01.008
摘要:
神经胶质瘤是颅内最常见的肿瘤,尤其是恶性胶质瘤,具有高复发率和致死率的特点。因其侵袭性生长,目前采取的手术联合放化疗的综合治疗方案疗效欠佳。如何靶向显像和治疗胶质瘤成为研究的重点。近年来,大量研究表明,作为氯毒素的类似物,东亚钳蝎氯毒素能特异性地结合神经胶质瘤细胞表达的氯离子通道和基质金属蛋白酶2,从而抑制胶质瘤细胞的侵润生长和迁移。以东亚钳蝎氯毒素为配体的生物结合物在胶质瘤靶向显像和治疗中的研究越来越多。笔者将全面介绍东亚钳蝎氯毒素的来源、化学结构、作用机制及其在胶质瘤靶向显像与治疗中的应用研究进展,并总结其优势及在未来研究中所面临的挑战。
Abstract:
Gliomas, especially malignant gliomas, are the most common primary brain tumors associated with high recurrence rate and significant mortality. The combination of surgery and radio-chemotherapy is the best treatment for them nowadays. However, due to their biological characteristics of invasive growth, they do not respond well to traditional therapy. How to target the tumor in situ, and inhibit tumor cell proliferation and invasion is the key for study. In recent years, many studies have demonstrated that Buthus martensii Karsch chlorotoxin (BmK CT), an important chlorotoxin-like peptide, specifically inhibited glioma cells growth and metastasis as a blocker of the chloride ion channel and matrix metallopro-teinase-2 (MMP-2). The bioconjugates of BmK CT with other molecules have played an increasing role in targeted imaging and treatment of gliomas. In this review, its source, chemical structure and mechanisms will be provided. Besides, advantages and challenges in the use of BmK CT as a specific agent for imaging and theranostic applications in gliomas will be addressed.

参考文献/References:

[1] Gilbert MR,Dignam JJ,Armstrong TS,et al.A ranaomized trial of bevacizumab for newly diagnosed glioblastoma[J].N Engl J Med,2014,370(8):699-708.
[2] Hervey-Jumper SL,Berger MS.Role of surgical resection in low-and high-grade gliomas[J].Curr Treat Options Neurol,2014,10(4):284-287.
[3] Mukherjee D,Sarmiento JM,Nosova K,et al.Effectiveness of radio-therapy for elderly patients with anaplastic gliomas[J].J Clin Neu-rosci,2014,21(5):773-778.
[4] Cheng YJ,Zhao JH,Qiao WL,et al.Recent advances in diagnosis and treatment of gliomas using chlorotoxin-based bioconjugates[J].Am J Nucl Med Mol Imaging,2014,4(5):385-405.
[5] 戚正武.小分子蛋白酶抑制剂及多肽毒素的研究回顾[J].科学通报,2009,54(18):2734-2745.
[6] DeBin JA,Maggio JE,Strichartz GR.Purification and characteriza-tion of chlorotoxin,a chloride Channel ligand from the venom of the scorpion[J].A m J Physiol,1993,264(2 Pt 1):C361-C369.
[7] Mamelak AN,Jacoby DB.Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601)[J].Expert Opin Drug Deliv,2007,4(2):175-186.
[8] Lyons SA.O’Neal J,Sontheimer H.Chlorotoxin,a scorpion-derived peptide,specifically binds to gliomas and tumors of neuroectoder-mal origin[J].Glia,2002,39(2):162-173.
[9] Qin C,He B,Dai W,et al.The impact of a chlorotoxin-modified li-posome system on receptor MMP-2 and the receptor-associated protein ClC-3[J].Biomaterials,2014,35(22):5908-5920.
[10] Jacoby DB,Dyskin E,Yalcin M,et al.Potent pleiotropic anti-an-giogenic effects of TM601,a synthetic chlorotoxin peptide[J].Anti-cancer Res,2010,30(1):39-46.
[11] Shen S,Mamelak A,Raubitschek A,et al.Dosimetry of phase I/Ⅱ study of intracavitary administered I-131-TM-601 peptide in pa-tients with recurrent high-grade glioma[J/OL].Int J Radiat Oncol Phys,60(1):S259[2014-11-10].http://academic.research.mi-crosoft.com/Publication/30178349/dosimetry-of-phase-i-ii-study-of-intracavitary-administered-i-131tm601-peptide-in-patients-with.
[12] 许均华,吴英亮,罗锋,等.蝎氯毒素结构、功能与应用研究[J].氨基酸和生物资源,2005,27(4):13-16.
[13] Wu JJ,Dai L,Lan ZD,et al.The gene cloning and sequencing of Bm-12,a chlorotoxin-like peptide from the the scorpion Buthus martensii Karsch[J].Toxicon,2000,38(5):661-668.
[14] Fu YJ,Yin LT,Wang W,et al.Synthesis,expression and purifica-tion of a type of chlorotoxin-like peptide from the scorpion,Buthusmartensii Karsch,and its acute toxicity analysis[J].Biotechnol Lett,2005,27(20):1597-1603.
[15] Murnyak B,Csonka T,Klekner A,et al.Occurrence and molecular pathology of low grade gliomas[J].Ideggyogyaszati Szemle,2013,66(9/10):305-311.
[16] Murnyak B,Csonka T,Hegvi K,et al.Occurrence and molecular pathology of high grade gliomas[J].Ideggyogy Sz,2013,66(9-10):312-321.
[17] Quintero-Hernández V,Jimenez-Vargas JM,Gurrola GB,et al.Scorpion venom components that affect ion-channels function[J].Toxicon,2013,76:328-342.
[18] 杨锐,彭方,刘辉,等.东亚钳蝎氯毒素BmKCT的表达和功能鉴定(英文)[J].中国生物化学与分子生物学报,2005,21(1):19-23.
[19] Fu YJ,Yin LT,Liang AH,et al.Therapeutic potential of chlorotox-in-like neurotoxin from the Chinese scorpion for human gliomas[J].Neurosci Lett,2007,412(1):62-67.
[20] Fu YJ,Yin LT,Liang AH.Polyclonal antibody against a recombi-nant chlorotoxin-like peptide from the Chinese scorpion and detection of its putative receptors in human glioma cells[J].Biotechnol Lett,2006,28(18):1439-1443.
[21] Fu YJ,Zheng SH,Huang R,et al.A potential strategy for high-grade gliomas:combination treatment with Lithium chloride and BmK CT[J].Biotechnol Lett,2012,34(1):9-17.
[22] 孙娜,赵晋华,乔文礼,等.BmKCT对胶质瘤细胞侵袭的影响及机制研究[J].上海医学影像,2012,21(4):249-251.
[23] Lippens G,Najib J,Wodak SJ,et al.N M R sequential assignments and solution structure of chlorotoxin,a small scorpion toxin that blocks chloride channels[J].Biochemistry,1995,34(1):13-21.
[24] Fu YJ,An N,Chan KG,et al.A model of BmKCT in inhibiting glioma cell migration via matrix metalloproteinase-2 from experi-mental and molecular dynamics simulation study[J].Biotechnol Lett,2011,33(7):1309-1317.
[25] Wang WX,Ji YH.Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro[J].J Neurooncol,2005,73(1):1-7.
[26] Zhao J,Qiao W,Zhang Y,et al.Preparation and in vitro evaluation of 131 I-BmK CT as a glioma-targeted agent[J].Cancer Biother Ra-diopharm,2010,25(3):353-359.
[27] 乔文礼,赵晋华,邵晓霞,等.131I-BmK CT的制备及其在胶质瘤荷瘤大鼠体内分布与显像研究[J].核技术,2011,34(3):213-216.
[28] Fan SZ,Sun ZB,Jiang DH,et al.BmK CT toxin inhibits glioma proliferation and tumor metastasis[J].Cancer Lett,2010,291(2):158-166.
[29] Zou Q,Hou Y,Shen F,et al.Polarized regulation of glycogen syn-thase kinase-3beta is important for glioma cell invasion[J/OL].PLoS One,2013,8(12):e81814.[2014-11-10].http://www.jour-nals.plos.org/plosone/article?id=10.1371/journal.pone.0081814.
[30] Fu YE,An N,Zheng SH,et al.BmK CT-conjugated fluorescence nanodiamond as potential glioma-targeted imaging and drug[J].Di-am Relat Mater,2012,21:73-76.
[31] Catuogno S,Esposito CL,Quintavalle C,et al.Nucleic acids in hu-man glioma treatment:innovative approaches and recent results[J/OL].J Signal Transduct,2012,2012:735135-735145.[2014-11-10].http://www.hindawi.com/journals/jst/2012/735135/.
[32] Du J,Fu Y,Wang J,et al.Adenovirus-mediated expression of BmK CT suppresses growth and invasion of rat C6 glioma cells[J].Biotechnol Lett,2013,35(6):861-870.
[33] Fu Y,Jiao Y,An N,et al.pEGFP-N1-mediated BmK CT expression suppresses the migration of glioma[J].Cytotechnology,2013,65(4):533-539.

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备注/Memo

备注/Memo:
收稿日期:2014-11-15。
基金项目:国家自然科学基金(81171368,812111366,81301245)
通讯作者:赵晋华,Email:zhaojinhua1963@126.com
更新日期/Last Update: 1900-01-01