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用于准确评估脑肿瘤进展的远红荧光小鼠胶质瘤模型

Far-Red Fluorescent Murine Glioma Model for Accurate Assessment of Brain Tumor Progression.

作者信息

Mishchenko Tatiana A, Balalaeva Irina V, Klimenko Maria O, Brilkina Anna A, Peskova Nina N, Guryev Evgenii L, Krysko Dmitri V, Vedunova Maria V

机构信息

Department of Neurotechnology, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.

Department of Basic and Medical Genetics, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia.

出版信息

Cancers (Basel). 2022 Aug 6;14(15):3822. doi: 10.3390/cancers14153822.

Abstract

Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy.

摘要

神经胶质瘤是最常见的脑肿瘤,目前其预期寿命和生活质量尚无显著改善。创建稳定的荧光神经胶质瘤细胞系是深入研究神经胶质瘤起始和发病机制的分子机制以及开发新的抗癌策略的一种有前景的工具。在此,我们生成并表征了一种稳定表达远红光荧光蛋白(TurboFP635;Katushka)的新型荧光神经胶质瘤GL261-kat细胞系,然后在小鼠原位神经胶质瘤模型中进行了验证。通过落射荧光成像,我们在接种神经胶质瘤细胞后第14天开始在小鼠体内检测到荧光神经胶质瘤GL261-kat细胞,并且随着神经胶质瘤的进展荧光信号强度增加。通过磁共振成像和组织学证实了肿瘤生长。在神经胶质瘤进展过程中观察到小鼠神经功能缺损和行为改变逐渐发展。总之,我们的结果证明了使用新型神经胶质瘤GL261-kat细胞系作为神经胶质瘤生物学模型的意义和可行性,该模型可用于研究神经胶质瘤的起始,并通过对神经胶质瘤细胞进行终身非侵入性追踪来监测其生长,有望监测对抗癌治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c509/9367351/080b7d1f72ed/cancers-14-03822-g001.jpg

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