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[白细胞介素-11在骨肉瘤中的作用]

[The role of interleukin-11 in osteosarcoma].

作者信息

Lokau Juliane, Schoeder Victor, Garbers Christoph

机构信息

Institut für Pathologie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, 39120, Magdeburg, Deutschland.

出版信息

Pathologe. 2020 Mar;41(2):163-167. doi: 10.1007/s00292-020-00756-1.

Abstract

Osteosarcoma is an often highly malignant mesenchymal tumor. By definition, osteosarcoma cells are able to form osteoid, which can mature into tumor bone. Osteosarcoma metastasizes preferentially to the lung. In Europe, the incidence is between 2 and 5 new diagnoses per 1,000,000 people per year. The underlying mechanisms for osteosarcoma formation are not well understood. However, previous radiotherapy or exposition to nuclear radiation increase the risk of osteosarcoma. Patients are usually treated with a neoadjuvant chemotherapy, followed by complete surgical resection of the tumor and post-surgical chemotherapy, which leads to a five-year survival rate of approximately 70% for all stages. Scientific publications in recent years have shown that expression of the cell surface protein interleukin-11 receptor (IL-11R) correlates with a worse prognosis for patients. The IL-11R is activated by its ligand, the cytokine IL-11. IL-11 activates several intracellular signaling cascades within its target cells and is known to be an important regulator of bone homeostasis. Patients with dysfunctional IL-11 signaling display different forms of craniosynostosis. IL-11 induces proliferation of osteosarcoma cell lines in vitro, and the IL-11 signaling cascade was further used to reduce tumor growth and lung metastasis in preclinical mouse models of primary intratibial osteosarcoma. This article gives a comprehensive overview of the frequency, classification, and etiology of osteosarcoma and describes the basic biology of the cytokine IL-11. Furthermore, it summarizes current knowledge about the functional role of IL-11 in osteosarcoma and lists possible therapeutic opportunities.

摘要

骨肉瘤是一种通常具有高度恶性的间充质肿瘤。根据定义,骨肉瘤细胞能够形成类骨质,后者可成熟为肿瘤骨。骨肉瘤优先转移至肺部。在欧洲,每年每100万人中有2至5例新诊断病例。骨肉瘤形成的潜在机制尚不完全清楚。然而,既往接受过放疗或接触过核辐射会增加患骨肉瘤的风险。患者通常接受新辅助化疗,随后对肿瘤进行完整的手术切除及术后化疗,这使得所有分期患者的五年生存率约为70%。近年来的科学出版物表明,细胞表面蛋白白细胞介素-11受体(IL-11R)的表达与患者较差的预后相关。IL-11R被其配体细胞因子IL-11激活。IL-11在其靶细胞内激活多个细胞内信号级联反应,并且已知是骨稳态的重要调节因子。IL-11信号功能失调的患者表现出不同形式的颅缝早闭。IL-11在体外可诱导骨肉瘤细胞系增殖,并且在原发性胫骨骨肉瘤的临床前小鼠模型中,IL-11信号级联反应进一步被用于减少肿瘤生长和肺转移。本文全面概述了骨肉瘤的发病率、分类和病因,并描述了细胞因子IL-11的基本生物学特性。此外,总结了目前关于IL-11在骨肉瘤中功能作用的知识,并列出了可能的治疗机会。

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