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RCAS-tva诱导的血小板衍生生长因子B驱动的实验性胶质瘤的多参数纵向分析

Multiparametric Longitudinal Profiling of RCAS-tva-Induced PDGFB-Driven Experimental Glioma.

作者信息

Becker Hannes, Castaneda-Vega Salvador, Patzwaldt Kristin, Przystal Justyna M, Walter Bianca, Michelotti Filippo C, Canjuga Denis, Tatagiba Marcos, Pichler Bernd, Beck Susanne C, Holland Eric C, la Fougère Christian, Tabatabai Ghazaleh

机构信息

Department of Neurology & Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, Center for Neuro-Oncology, Comprehensive Cancer Center, University Hospital Tübingen, Eberhard Karls University Tubingen, 72072 Tubingen, Germany.

Department of Neurosurgery, University Hospital Tubingen, Eberhard Karls University Tubingen, 72072 Tubingen, Germany.

出版信息

Brain Sci. 2022 Oct 24;12(11):1426. doi: 10.3390/brainsci12111426.

Abstract

Glioblastomas are incurable primary brain tumors harboring a heterogeneous landscape of genetic and metabolic alterations. Longitudinal imaging by MRI and [F]FET-PET measurements enable us to visualize the features of evolving tumors in a dynamic manner. Yet, close-meshed longitudinal imaging time points for characterizing temporal and spatial metabolic alterations during tumor evolution in patients is not feasible because patients usually present with already established tumors. The replication-competent avian sarcoma-leukosis virus (RCAS)/tumor virus receptor-A (tva) system is a powerful preclinical glioma model offering a high grade of spatial and temporal control of somatic gene delivery in vivo. Consequently, here, we aimed at using MRI and [F]FET-PET to identify typical neuroimaging characteristics of the platelet-derived growth factor B (PDGFB)-driven glioma model using the RCAS-tva system. Our study showed that this preclinical glioma model displays MRI and [F]FET-PET features that highly resemble the corresponding established human disease, emphasizing the high translational relevance of this experimental model. Furthermore, our investigations unravel exponential growth dynamics and a model-specific tumor microenvironment, as assessed by histology and immunochemistry. Taken together, our study provides further insights into this preclinical model and advocates for the imaging-stratified design of preclinical therapeutic interventions.

摘要

胶质母细胞瘤是无法治愈的原发性脑肿瘤,具有遗传和代谢改变的异质性格局。通过MRI和[F]FET-PET测量进行的纵向成像使我们能够动态地可视化不断演变的肿瘤的特征。然而,由于患者通常已患有已形成的肿瘤,因此在患者肿瘤演变过程中用于表征时间和空间代谢改变的密集纵向成像时间点是不可行的。具有复制能力的禽肉瘤-白血病病毒(RCAS)/肿瘤病毒受体-A(tva)系统是一种强大的临床前胶质瘤模型,可在体内对体细胞基因传递进行高度的时空控制。因此,在这里,我们旨在使用MRI和[F]FET-PET来识别使用RCAS-tva系统的血小板衍生生长因子B(PDGFB)驱动的胶质瘤模型的典型神经影像学特征。我们的研究表明,这种临床前胶质瘤模型显示出与相应的已确诊人类疾病高度相似的MRI和[F]FET-PET特征,强调了该实验模型的高度转化相关性。此外,我们的研究揭示了指数生长动力学和特定模型的肿瘤微环境,这是通过组织学和免疫化学评估的。综上所述,我们的研究为该临床前模型提供了进一步的见解,并倡导临床前治疗干预的成像分层设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/9688186/4ee34367adc8/brainsci-12-01426-g001.jpg

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