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淋巴结转移研究中的临床前模型。

Preclinical models in the study of lymph node metastasis.

作者信息

Wei Liya, Li Zizhan, Zhong Niannian, Cao Leiming, Wang Guangrui, Xiao Yao, Cai Bo, Liu Bing, Bu Linlin

机构信息

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.

School of Environment and Health, Jianghan University, Wuhan 430056, China.

出版信息

J Zhejiang Univ Sci B. 2025 Jun 24;26(8):740-762. doi: 10.1631/jzus.B2400052.

Abstract

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.

摘要

淋巴结转移(LNM)是影响特定癌症预后不良的关键危险因素。基础研究有助于我们理解肿瘤行为并确定有价值的治疗靶点。然而,基础理论的探索和临床治疗的验证依赖于临床前实验。在此背景下,临床前模型充当了连接基础理论与临床结果的桥梁。在动物体内建立的模型为全面观察肿瘤细胞与生物体之间的相互作用提供了宝贵的平台。利用包括小鼠在内的各种实验动物,通过致癌物诱导肿瘤发生、肿瘤细胞系或人肿瘤移植、基因工程和人源化等多种方法,已有效地构建了众多用于肿瘤LNM的模型。致癌物诱导的模型模拟肿瘤发生和转移的全过程。移植模型使用人肿瘤细胞系或患者来源的肿瘤,提供了一个紧密反映人类肿瘤组织学和临床行为的研究平台。基因工程模型已被用于深入研究完整微环境中原发性肿瘤发生的机制。人源化模型用于克服人类和小鼠免疫系统之间的障碍。除了小鼠模型,各种其他动物模型都有独特的优势和局限性,所有这些都有助于探索LNM。本综述总结了现有的体外和动物临床前模型,确定了临床前研究当前的瓶颈,并对即将出现的临床前模型进行了展望。

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