"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in t..."Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.展开更多
合欢皮作为常用中药,临床常用于治疗失眠、焦虑、肿瘤等。现代药理中针对合欢皮总皂苷(TSAJ)抗肿瘤活性多有报道,但由于单体成分分离困难,药理机制难以开展。该研究采用MTT法和Hoechst 33258染色法,确认了TSAJ对肝癌细胞的生长抑制作用...合欢皮作为常用中药,临床常用于治疗失眠、焦虑、肿瘤等。现代药理中针对合欢皮总皂苷(TSAJ)抗肿瘤活性多有报道,但由于单体成分分离困难,药理机制难以开展。该研究采用MTT法和Hoechst 33258染色法,确认了TSAJ对肝癌细胞的生长抑制作用,构建了表面修饰有TSAJ的固相亲合微球,利用该固相微球特异性地从人肝癌细胞裂解液中富集靶点蛋白,再利用高分辨质谱对富集到的靶点蛋白进行鉴定。采用Matabo Analyst 3.0处理数据,筛选并确定了Exportin-2,Beta-actin-like protein 2,Myosin-9,Protein transport protein Sec61 subunit beta,Cytochrome c oxidase copper chaperone等5个靶点蛋白。这些蛋白分别具有调控细胞凋亡及细胞生长、分化、运动等功能,提示TSAJ的抗肿瘤机制可能与诱导细胞凋亡及抑制肿瘤血管生成有关。综上所述,该研究利用TSAJ修饰的固相亲和微球,特异性富集并鉴定了TSAJ的靶点蛋白,从靶点源头上解释了TSAJ抗肿瘤作用机制,同时也为中药复杂体系的分子药理机制研究提供了一种全新的思路。展开更多
Integrin is a large family of cell adhesion molecules(CAMs) which involves in the interaction of cells/cells and cells/extracellular matrix(ECM) to mediate cell proliferation, differentiation, adhesion, migration, etc...Integrin is a large family of cell adhesion molecules(CAMs) which involves in the interaction of cells/cells and cells/extracellular matrix(ECM) to mediate cell proliferation, differentiation, adhesion, migration, etc. In recent years, aberrant expression of integrin has been clearly found in many tumor studies, indicating that integrin is closely related to tumor formation and development. Meanwhile, it has effects on tumor cell differentiation, cell migration, proliferation and tumor neovascularization. The study of drugs targeting integrins is of great significance for the clinical treatment of tumors. Because of its important role in tumorigenesis and development, integrin has become a promising target for the treatment of cancer. This review summarizes the role of integrin in tumor development and the current state of integrin inhibitors to provide a valuable reference for subsequent research.展开更多
目的综述高渗透长滞留效应(enhanced permeability and retention effect,简称EPR效应)的发现历史、影响因素及其在大分子药物肿瘤传递中的广泛应用。方法查阅近年来国内外相关文献50篇,对其进行归纳、总结和分析。结果大分子理化性质...目的综述高渗透长滞留效应(enhanced permeability and retention effect,简称EPR效应)的发现历史、影响因素及其在大分子药物肿瘤传递中的广泛应用。方法查阅近年来国内外相关文献50篇,对其进行归纳、总结和分析。结果大分子理化性质、肿瘤血管结构及血管调节因子对EPR效应有重要影响,临床上使用硝酸甘油、血管紧张肽转化酶抑制剂等外源性物质来提升EPR效应,以加强微粒给药系统的肿瘤靶向效果。结论 EPR效应作为大分子抗癌药物设计的"金标准",为肿瘤靶向药物传递系统设计的研究与开发提供了重要参考。展开更多
基金Supported by A grant from the National Nature Science Foundation of China,No. 30672073
文摘"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.
文摘合欢皮作为常用中药,临床常用于治疗失眠、焦虑、肿瘤等。现代药理中针对合欢皮总皂苷(TSAJ)抗肿瘤活性多有报道,但由于单体成分分离困难,药理机制难以开展。该研究采用MTT法和Hoechst 33258染色法,确认了TSAJ对肝癌细胞的生长抑制作用,构建了表面修饰有TSAJ的固相亲合微球,利用该固相微球特异性地从人肝癌细胞裂解液中富集靶点蛋白,再利用高分辨质谱对富集到的靶点蛋白进行鉴定。采用Matabo Analyst 3.0处理数据,筛选并确定了Exportin-2,Beta-actin-like protein 2,Myosin-9,Protein transport protein Sec61 subunit beta,Cytochrome c oxidase copper chaperone等5个靶点蛋白。这些蛋白分别具有调控细胞凋亡及细胞生长、分化、运动等功能,提示TSAJ的抗肿瘤机制可能与诱导细胞凋亡及抑制肿瘤血管生成有关。综上所述,该研究利用TSAJ修饰的固相亲和微球,特异性富集并鉴定了TSAJ的靶点蛋白,从靶点源头上解释了TSAJ抗肿瘤作用机制,同时也为中药复杂体系的分子药理机制研究提供了一种全新的思路。
基金supported by the National Natural Science Foundation of China(Nos.81773774,81473231,81830105)Science Foundation for Distinguished Young Scholars of Jiangsu Provience(BK20150028)
文摘Integrin is a large family of cell adhesion molecules(CAMs) which involves in the interaction of cells/cells and cells/extracellular matrix(ECM) to mediate cell proliferation, differentiation, adhesion, migration, etc. In recent years, aberrant expression of integrin has been clearly found in many tumor studies, indicating that integrin is closely related to tumor formation and development. Meanwhile, it has effects on tumor cell differentiation, cell migration, proliferation and tumor neovascularization. The study of drugs targeting integrins is of great significance for the clinical treatment of tumors. Because of its important role in tumorigenesis and development, integrin has become a promising target for the treatment of cancer. This review summarizes the role of integrin in tumor development and the current state of integrin inhibitors to provide a valuable reference for subsequent research.
文摘目的:运用网络药理学方法分析康艾注射液抗肿瘤的作用机制。方法:利用中药系统药理学技术平台(TCMSP)筛选康艾注射液的组成中药的有效成分及对应靶蛋白。利用Cytoscape 3.6.1构建康艾注射液有效化合物-靶蛋白网络并进行网络拓扑学分析。借助STRING在线数据库进行蛋白互作(PPI)网络构建并进行分析。通过生物学信息注释数据库(DAVID)对靶点进行生物过程(Gene Ontology Biological Process,GO-BP)富集分析及基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。结果:共获得83个候选化合物,包含了黄酮类、人参皂苷、苦参碱等有效组分;240个靶点,关键靶点是COX1、COX2、HSP90、TP53、AKT1、JUN等;生物过程条目共250条,涉及转录翻译、细胞信号转导、细胞增殖与凋亡过程、免疫反应、血管生成等生物过程;KEGG信号通路共127条,其中癌症通路、PI3K-Akt信号通路、淋巴瘤病毒感染、癌症中的蛋白聚糖、MAPK信号通路、TNF信号通路、前列腺癌、钙离子信号通路、癌症的mRNA等通路与肿瘤密切相关。结论:作用于COX1、COX2、HSP90、TP53、AKT1、JUN等靶点,康艾注射液中的黄酮类、人参皂苷、苦参碱等有效组分通过抑制肿瘤细胞增殖、促进其凋亡,调节肿瘤血管生成和免疫反应等生物过程,影响肿瘤微环境,从而发挥抗肿瘤作用,体现了多成分、多靶点、多通路的特点。
