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通过高亲和力重组抗体鉴定胶质母细胞瘤相关的腱生蛋白-C异构体

Identification of a glioblastoma-associated tenascin-C isoform by a high affinity recombinant antibody.

作者信息

Carnemolla B, Castellani P, Ponassi M, Borsi L, Urbini S, Nicolo G, Dorcaratto A, Viale G, Winter G, Neri D, Zardi L

机构信息

Laboratory of Cell Biology and Laboratory of Anatomic Pathology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.

出版信息

Am J Pathol. 1999 May;154(5):1345-52. doi: 10.1016/S0002-9440(10)65388-6.

Abstract

Tenascin-C exists in several polymorphic isoforms due to alternative splicing of nine fibronectin-like type III repeats. Large Tenascin-C isoforms are present in almost all normal adult tissues but are upregulated in fetal, regenerating, and neoplastic tissues. Here, we report a human antibody fragment, TN11, derived from a phage library with high affinity for the spliced repeat C and demonstrate that this repeat is undetectable in normal adult tissues, barely detectable or undetectable in breast, lung and gastric carcinomas, meningioma, and low grade astrocytoma, but extremely abundant in high grade astrocytoma (grade III and glioblastoma), especially around vascular structures and proliferating cells. The antibody appears to have potential for development of a therapeutic agent for patients with high grade astrocytoma.

摘要

由于九个纤连蛋白样III型重复序列的可变剪接,腱生蛋白-C以几种多态性异构体形式存在。大的腱生蛋白-C异构体几乎存在于所有正常成人组织中,但在胎儿、再生和肿瘤组织中上调。在此,我们报道了一种源自噬菌体文库的人抗体片段TN11,它对剪接重复序列C具有高亲和力,并证明该重复序列在正常成人组织中无法检测到,在乳腺癌、肺癌和胃癌、脑膜瘤及低级别星形细胞瘤中几乎检测不到或无法检测到,但在高级别星形细胞瘤(III级和胶质母细胞瘤)中极其丰富,尤其是在血管结构和增殖细胞周围。该抗体似乎有开发用于高级别星形细胞瘤患者治疗药物的潜力。

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Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas: a six-year clinical experience.
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Human tenascin-C: identification of a novel type III repeat in oral cancer and of novel splice variants in normal, malignant and reactive oral mucosae.
Int J Cancer. 1997 Jul 17;72(2):236-40. doi: 10.1002/(sici)1097-0215(19970717)72:2<236::aid-ijc6>3.0.co;2-s.
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Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.
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