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Toll样受体在多发性骨髓瘤中的作用及最新进展

Role of toll-like receptors in multiple myeloma and recent advances.

作者信息

Thakur Krishan K, Bolshette Nityanand B, Trandafir Cristiana, Jamdade Vinayak S, Istrate Alexandru, Gogoi Ranadeep, Cucuianu Andrei

机构信息

Laboratory of Biotechnology, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Gauhati Medical College, Assam, India.

Laboratory of Biotechnology, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Gauhati Medical College, Assam, India.

出版信息

Exp Hematol. 2015 Mar;43(3):158-67. doi: 10.1016/j.exphem.2014.11.003. Epub 2014 Nov 15.

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When TLRs bind to their ligands, they trigger two major signaling pathways such that both share overlapping downstream signals: one is a myeloid differentiation primary response 88 (MyD88)-dependent production and activation of nuclear factor-κB, whereas the other is a MyD88-independent production of type-I interferon. Whereas the MyD88 pathway results in proinflammatory cytokine production, the other pathway stimulates cell proliferation. Dysregulations of these pathways may eventually lead to abnormal cell proliferation and MM. Despite recent biomedical advances, MM continues to be an incurable disease. There are an increasing number of TLR-based therapeutic approaches currently being tested in a number of preclinical and clinical studies. We here attempt to outline in detail the currently available information on TLRs in various types of cancer.

摘要

多发性骨髓瘤(MM)是一种血液系统恶性肿瘤,其特征为浆细胞异常增殖并侵入骨髓。Toll样受体(TLRs)连接先天性和适应性免疫反应,是炎症与癌症之间重要且可能的联系要素。当TLRs与其配体结合时,会触发两条主要信号通路,二者共享重叠的下游信号:一条是髓样分化初级反应88(MyD88)依赖的核因子κB的产生和激活,另一条是MyD88非依赖的I型干扰素的产生。MyD88通路导致促炎细胞因子的产生,而另一条通路则刺激细胞增殖。这些信号通路的失调最终可能导致细胞异常增殖和MM。尽管近期生物医学取得了进展,但MM仍然是一种无法治愈的疾病。目前,越来越多基于TLR的治疗方法正在多项临床前和临床研究中进行测试。我们在此试图详细概述目前关于各类癌症中TLRs的可用信息。

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