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采用抗人组织因子单克隆抗体的原位脑胶质瘤异种移植模型的分子成像。

Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model.

机构信息

Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-0811, Japan.

出版信息

Sci Rep. 2017 Sep 26;7(1):12341. doi: 10.1038/s41598-017-12563-5.

Abstract

Nuclear medicine examinations for imaging gliomas have been introduced into clinical practice to evaluate the grade of malignancy and determine sampling locations for biopsies. However, these modalities have some limitations. Tissue factor (TF) is overexpressed in various types of cancers, including gliomas. We thus generated an anti-human TF monoclonal antibody (mAb) clone 1849. In the present study, immunohistochemistry performed on glioma specimens using anti-TF 1849 mAb showed that TF expression in gliomas increased in proportion to the grade of malignancy based on the World Health Organization (WHO) classification, and TF was remarkably expressed in necrosis and pseudopalisading cells, the histopathological hallmarks of glioblastoma multiforme (GBM). Furthermore, in both fluorescence and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging studies, anti-TF 1849 IgG efficiently accumulated in TF-overexpressing intracranial tumours in mice. Although further investigation is required for a future clinical use of immuno-SPECT with In-labelled anti-TF 1849 IgG, the immuno-SPECT may represent a unique imaging modality that can visualize the biological characteristics of gliomas differently from those obtained using the existing imaging modalities and may be useful to evaluate the grade of malignancy and determine sampling locations for biopsies in patients with glioma, particularly GBM.

摘要

核医学检查已被引入临床实践,用于评估脑胶质瘤的恶性程度,并确定活检的采样位置。然而,这些方法存在一些局限性。组织因子(TF)在各种类型的癌症中过度表达,包括脑胶质瘤。因此,我们产生了一种抗人 TF 单克隆抗体(mAb)克隆 1849。在本研究中,使用抗 TF 1849 mAb 对脑胶质瘤标本进行免疫组织化学染色显示,TF 的表达随着世界卫生组织(WHO)分级的恶性程度而增加,并且在多形性胶质母细胞瘤(GBM)的坏死和假栅状细胞中表达明显。此外,在荧光和单光子发射计算机断层扫描/计算机断层扫描(SPECT/CT)成像研究中,抗 TF 1849 IgG 能够有效地在 TF 过表达的颅内肿瘤中积累。尽管未来使用 In 标记的抗 TF 1849 IgG 进行免疫 SPECT 还需要进一步研究,但免疫 SPECT 可能代表一种独特的成像方式,可以不同于现有成像方式来可视化脑胶质瘤的生物学特征,并且可能有助于评估脑胶质瘤患者的恶性程度,并确定活检的采样位置,特别是 GBM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4584/5615035/b0690e5cb85c/41598_2017_12563_Fig1_HTML.jpg

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