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建立中华树鼩()基底细胞癌动物模型。

Establishment of basal cell carcinoma animal model in Chinese tree shrew ().

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming Yunnan 650204, China.

出版信息

Zool Res. 2017 Jul 18;38(4):180-190. doi: 10.24272/j.issn.2095-8137.2017.045.

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog (Hh) signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews () are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened (Smo) used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lentiviral SmoA1 and shRNA targeting Chinese tree shrew . This work provides a useful animal model for further BCC studies and future drug discoveries.

摘要

基底细胞癌(BCC)是全球最常见的皮肤癌,其发病率持续上升。紫外线辐射是主要的环境风险因素,大多数 BCC 中 Hedgehog(Hh)信号通路失调。局部晚期和转移性 BBC 的治疗仍然是一个挑战,需要一种比广泛使用的啮齿动物更好的动物模型,用于药物开发和测试。中国树鼩()与灵长类动物密切相关,在表征人类疾病方面具有许多优于啮齿动物的生理和生化优势。在这里,我们通过感染尾巴皮肤的慢病毒 SmoA1 成功建立了中国树鼩 BCC 模型,SmoA1 是 Smoothened(Smo)的一种活性形式,用于组成性激活 Hh 信号通路。通过免疫组织化学分析验证了病理特征。有趣的是,慢病毒 SmoA1 和针对中国树鼩的 shRNA 的联合使用大大增强了 BCC 的进展。这项工作为进一步的 BCC 研究和未来的药物发现提供了一个有用的动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9f/5571474/a11465707ad0/ZoolRes-38-4-180-g1.jpg

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