肝癌微环境中巨噬细胞的表达及意义及其靶向治疗研究进展
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摘要
肝癌肿瘤微环境中巨噬细胞(TAMs)能减弱机体对肿瘤的免疫反应,促进恶性肿瘤的组织重建、血管生成。在动物实验中,特定类型巨噬细胞能促使肿瘤转移,而相关临床研究发现,TAMs和肿瘤的不良预后密切相关。TAMs具有多种表型状态,主要来源于血液循环中的单核细胞,肿瘤微环境影响巨噬细胞后,使其处于非正常激活状态,即M2型TAMs,其特点是可塑性高、分化不完全。基于巨噬细胞的促肿瘤作用,目前针对巨噬细胞的募集、活化、促血管生成活性、基质重塑、存活等方面制定的靶向药物治疗进入了临床试验。
Macrophages in liver tumor microenvironment(TAMs) can weaken the body's immune response to tumor, promote the malignant tumor tissue reconstruction, and angiogenesis. In animal experiments, specific type macrophages can cause tumor metastasis, and the related clinical studies found that TAMs and closely related to the poor prognosis of the tumor. TAMs had many phenotypic state, mainly comes from the circulation of the blood mononuclear cells,tumor microenvironment influence after the macrophages, make its tracker is activated, the M2 TAMs, characterized by high plasticity, incomplete differentiation. Based on the effect on promoting tumor macrophages, at present, in view of the macrophages collect, activation, promote angiogenesis activity, matrix remodeling and survival of targeted drug therapy had entered clinical trials.
Macrophages in liver tumor microenvironment(TAMs) can weaken the body's immune response to tumor, promote the malignant tumor tissue reconstruction, and angiogenesis. In animal experiments, specific type macrophages can cause tumor metastasis, and the related clinical studies found that TAMs and closely related to the poor prognosis of the tumor. TAMs had many phenotypic state, mainly comes from the circulation of the blood mononuclear cells,tumor microenvironment influence after the macrophages, make its tracker is activated, the M2 TAMs, characterized by high plasticity, incomplete differentiation. Based on the effect on promoting tumor macrophages, at present, in view of the macrophages collect, activation, promote angiogenesis activity, matrix remodeling and survival of targeted drug therapy had entered clinical trials.
引文
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[19]Wang J.L.,Tang G.P.,Shen J,et al.A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of hepatocellular carcinoma[J].Biomaterials,2012,33(18):4597-4607.
[2]束平,秦净,秦新裕,等.巨噬细胞分泌的可溶性因子诱导Hep G2细胞发生上皮间质化[J].中华肝胆外科杂志,2013,19(5):378-381.
[3]徐建,王艳红,沈沪佳,等.大鼠肝癌组织中巨噬细胞与细胞毒性T细胞关系[J].中华实验外科杂志,2011,28(11):1877-1880.
[4]王甲南,向邦德,刘星,等.瘤内注射MIP-3α对小鼠肝癌生长抑制作用的研究[J].中国免疫学杂志,2012,28(5):407-411.
[5]缪俊俊(综述),李国利,贾筱琴(审校),等.肿瘤相关巨噬细胞在肝癌中的研究进展[J].肿瘤预防与治疗,2014,21(4):204-208.
[6]葛勇胜,许戈良,刘维峰,等.肿瘤相关巨噬细胞与肝癌的研究进展[J].国际外科学杂志,2012,39(4):260-263.
[7]刘金颖,宫金伶,樊晓晖,等.NDV7793体外激活的小鼠单核巨噬细胞(MΦ)对小鼠肝癌细胞的杀伤作用及其机制[J].肿瘤防治研究,2012,39(5):502-505.
[8]陈芳艳,郝运伟,林巍然,等.急性肝损伤过程中肝内不同来源巨噬细胞的作用研究[J].军事医学,2014,12(3):181-188.
[9]祝甜甜,段菊,张刘强,等.巨噬细胞极化在动脉粥样硬化中的作用和药物靶标[J].中国药理学通报,2014,20(6):748-751.
[10]耿华,袁小林.巨噬细胞的研究进展[J].国际免疫学杂志,2013,36(6):450-454.
[11]柯君.巨噬细胞在肿瘤发展中的作用研究进展[J].安徽农业科学,2012,40(24):12110-12112.
[12]范鸣,滕云飞,虞丽平,等.新型肝癌标志CA125及其靶向毒素在肝癌生物治疗中的作用研究[J].中国免疫学杂志,2014,30(3):342-346.
[13]鲍冬梅,马艳,金小宝,等.多肽在肝癌靶向治疗中的应用进展[J].广东医学,2014,15(7):1115-1117.
[14]孙力超,赵璇,遇珑,等.抗肝癌干细胞功能性单克隆抗体的研制[J].中国肿瘤生物治疗杂志,2010,17(2):121-127.
[15]李先亮,陈大志.硬化型肝癌靶向治疗的目标与应用进展[J].中华肝胆外科杂志,2011,17(12):963-968.
[16]Pingsheng F,Tengyue Z,Qiang H,et al.Basic and Clinical Research on the Therapeutic Effect of Intervention in Primary Liver Cancer by Targeted Intra-Arterial Verapamil Infusion[J].Cell biochemistry and biophysics,2012,62(1):59-67.
[17]Ji Z.,Lin G.,Lu Q,et al.Targeted therapy of SMMC-7721 liver cancer in vitro and in vivo with carbon nanotubes based drug delivery system[J].Journal of Colloid and Interface Science,2012,365(1):143-149.
[18]Liu M.,Li Z.H,Xu F.J,et al.An oligopeptide ligand-mediated therapeutic gene nanocomplex for liver cancer-targeted therapy[J].Biomaterials,2012,33(7):2240-2250.
[19]Wang J.L.,Tang G.P.,Shen J,et al.A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of hepatocellular carcinoma[J].Biomaterials,2012,33(18):4597-4607.