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1复方苦参注射液对胃癌SGC-7901细胞VEGF、CXCR4表达的影响显示文摘目的:探讨复方苦参注射液(matrine injection,MI)对人胃癌SGC-7901细胞血管内皮生长因子(vascular endothelial growth factor,VEGF)、趋化因子受体(CXC chemokine receptor 4,CXCR4)mRNA及蛋白表达水平的影响。方法:采用四甲基偶氮唑蓝(MTT)法观察不同浓度复方苦参注射液对人胃癌SGC-7901细胞增殖的影响;采用逆转录聚合酶链反应法(RT-PCR)、免疫荧光法、酶联免疫吸附法(ELISA)分别检测不同浓度复方苦参注射液对人胃癌SGC-7901细胞中VEGF、CXCR4mRNA及蛋白表达水平的影响。结果:复方苦参注射液可以抑制SGC-7901细胞增殖,并呈剂量和时间依赖性;不同浓度复方苦参注射液作用于SGC-7901细胞24h后,随着药物浓度的增高,细胞中VEGF、CXCR4在mRNA及蛋白表达水平逐渐降低,与对照组相比有统计学差异(P<0.05)。结论:复方苦参注射液具有抑制相关肿瘤血管生成因子的作用,这可能是复方苦参注射液抗肿瘤血管生成的机制之一。杨勤 张亚声 2010现代肿瘤医学2010,18,8:38
2趋化因子SDF-1与受体CXCR4的研究进展显示文摘趋化因子SDF-1(stromal cell-derived factor-1)与其受体CXCR4(CXC chemokine receptor4)分别属于CXC类趋化因子和CXCR类G蛋白偶联受体超家族。功能研究表明,SDF-1/CXCR4轴在机体的免疫、炎症、胚胎发育、器官发生、肿瘤、HIV病、WHIM综合征等多种生物学过程中发挥着重要的作用,已成为当今生物学研究的热点之一。本文对SDF-1及CXCR4的结构、信号转导、生物学意义就当前研究的进展情况进行了综述。G蛋白依赖的信号转导通路和非G蛋白依赖的信号转导通路两个方面(见图1)。1.2非G蛋白依赖的信号转导通路SDF-1与CXCR4结合后可以通过其自身构象的改变激活非受体酪氨酸激酶JAK2、JAK3,从而活化JAK-STAT信号通路。JAK-STAT信号通路的活化与细胞的免疫反应及细胞的发育和肿瘤的发生密切相关。此外,活化后的CXCR4羧基末端可被G蛋白调节激酶(GRK)磷酸化,这一结果促进了其与β-arrestins结合。CXCR4-β-arrestin复合物具有多种生物学功能:诱导CXCR4的内化;抑制G蛋白依赖的信号转导通路的活化;与GTPaseRaf结合激活p42/44MAPK信号通路;激活ASK1而活化p38MAPK信号通路。其中两条MAPKs信号通路的活化与SDF-1诱导细胞的趋化、迁徙密切相关[5]。2SDF-1/CXCR4生物学意义2.1SDF-1/CXCR4与胚胎发育、器官发生SDF-1或CXCR4基因敲除的小鼠会出现心脏室间隔缺损、小脑发育异常、造血细胞生成的减少、肠道血管发育的异常以及造成小鼠胚胎期死亡或出生后生存期缩短的现象。现在已证实在胚胎细胞、造血干细胞及神经细胞等早期细胞表面已有CXCR4表达,这可能与上面这些现象的出现有关。最近也证实了SDF-1/CXCR4在促进损伤组织修复中的作用,这也从另一个侧面证明了SDF-1/CXCR4与早期细胞的分化及生长的关系。Takahashi综述了SDF-1/CXCR4在心肌梗塞病理生理过程中的作用[6]。以上这些都说明了SDF-1/CXCR4在胚胎发育、器官发生及修复中发挥着重要的作用。2.2SDF-1/CXCR4与造血、免疫SDF-1或CXCR4基因敲除的小鼠骨髓内造血细胞生成减少,后来Lataillade等通过体外实验也证明SDF-1可以诱导CD34+造血干/祖细胞的增殖,并与SCF和IL-3具有协调作用。SDF-1/CXCR4还可以介导造血干/祖细胞的动员与归巢[7]。骨髓中的造血干/祖细胞的动员到外周血就必须摆脱骨髓基质的束缚以及穿越骨髓内皮细胞的隔膜,脱离骨髓基质的束缚过程就包括去除SDF-1与CXCR4结合后所产生黏附及趋化作用。当然在这一过程中蛋白水解酶和基质金属蛋白酶也起着重要的作用。来源于骨髓、脐血、动员的CD34+造血干/祖细胞的表面均表达CXCR4,而骨髓基质细胞和内皮细胞均能表达对CXCR4产生特异性趋化作用的SDF-1。因此,1.1G蛋白依赖的信号转导通路SDF-1与CXCR4结合后可促使其胞内域偶联的异源三聚体G蛋白α亚基的GDP转变成GTP,进而引起构象的改变从而使其激活。激活后Gα亚基从异源三聚体中分离下来。其中主要的是Gαi亚基,激活的Gαi亚基可以抑制腺苷酸环化酶(AC)的活性,降低胞内cAMP水平,从而抑制cAMP-PKA信号通路;Gαi亚基还可以通过激活非受体酪氨酸激酶Src而活化Ras-Raf-Mek-MAPKp42/44信号转导通路[3]。从激活后的异源三聚体G蛋白分离出来的Gβγ亚基在SDF-1诱导的信号通路中具有重要的作用。活化的Gβγ亚基可以激活磷脂酰肌醇-3激酶(PI3K),激活后的PI3K可以活化多种信号分子,其中最重要的是能够激活PI3K-AKT信号通路。AKT激活后又可以作用于多种底物蛋白,如I-κB激酶、ASK1、BAD、CREB、P21、Procaspase9、AR等底物。PI3K-AKT信号通路总的效应是抗凋亡和促进细胞的生长与增殖。激活后的PI3K也可以促进Ras-Raf-Mek-MAPKp42/44信号通路的激活,还可以通过活化PAK、Cdc42、PYK2、FAK、Crk、P130cas、Paxillin等下游信号分子而介导细胞的运动、趋化、黏附等生物学行为[4]。活化后的Gβγ亚基还可以通过PLCβ而激活PLC-IP3-Ca2+信号通路及PLC-DAG-PKC信号途径。杨志峰 杨清玲 陈昌杰 2011分子诊断与治疗杂志2011,3,1:35
3胃癌中SDF-1、CXCR4、MMP-2和MMP-9的表达及意义显示文摘目的研究趋化因子SDF-1及其受体CXCR4以及MMP-2和MMP-9在胃癌中的表达,探讨SDF-1对MMP-2和MMP-9表达的影响。方法应用免疫组化EnVision两步法检测109例胃癌组织中SDF-1、CXCR4、MMP-2和MMP-9的表达。结果 (1)SDF-1、CXCR4、MMP-2、MMP-9在胃癌组的表达阳性率分别为88.1%、56.9%、80.7%和83.4%,高于切缘对照组的47.8%、30.4%、43.4%和47.8%,差异有显著性(P<0.05);(2)SDF-1和CXCR4的表达在淋巴结转移组高于无转移组(P<0.05),SDF-1、MMP-9表达程度与淋巴结转移、组织学分级、浆膜侵犯、临床分期指标呈正相关(P<0.05);MMP-2、CXCR4表达程度与淋巴结转移、浆膜侵犯、临床分期呈正相关(P<0.05);(3)SDF-1与其受体CXCR4的表达及与MMP-2、MMP-9均呈正相关(P<0.05)。结论 (1)SDF-1、CXCR4、MMP-2和MMP-9的表达水平与胃癌的发生、侵袭及淋巴结转移密切相关,可作为预测胃癌淋巴结转移及预后的指标;(2)SDF-1/CXCR4轴可通过加强肿瘤细胞MMP-2和MMP-9分泌的途径促进肿瘤的浸润和转移,提示SDF-1可能是药物靶向治疗的重要靶点。陈友权 于燕妮 2012临床与实验病理学杂志2012,28,2:40
4SDF-1及其受体CXCR4在急性白血病与淋巴瘤表达的初步研究显示文摘为了探讨血液肿瘤患者外周血基质细胞源因子-1(SDF-1)及其骨髓细胞表面特异性受体CXCR4的表达 及其临床意义,对28例血液肿瘤患者及12例正常人的骨髓及外周血指标进行了检测,采取流式细胞术检测骨髓 细胞表面CXCR4的表达,用ELISA法检测血清中的SDF-1表达。结果显示:28例血液肿瘤患者外周血SDF-1和 骨髓细胞表面CXCR4的表达均高于正常对照组(P<0.01),且SDF-1和CXCR4两因子之间的表达有相关性(r= 0.831,P<0.01)。部分存在明显的髓外转移和多个淋巴结浸润的血液肿瘤患者CXCR4的表达较高。不同类型 的血液肿瘤之间CXCR4的表达可能存在差异(P<0.01)。结论:骨髓细胞与外周血清CXCR4和SDF-1的高表达 可能作为一种特异性的血液肿瘤标志,CXCR4的高表达可能与血液肿瘤的浸润程度相关。曾东风 孔佩艳 陈幸华 彭贤贵 魏立 常诚 刘林 刘红 王庆余 2005中国实验血液学杂志2005,13,2:29
5Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells显示文摘Chemokines are involved in human hepatocellular carcinoma (HCC) carcinogenesis. However, the exact mechanism of chemokines in HCC carcinogenesis remains unknown. Here we investigated the roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in the metastasis of HCC. We found that the expression levels of CXCR4 mRNA in HCC tissues, MHCC97 cells, and HUVEC cells were 2.52 ± 1.13, 2.34 ± 1.16 and 1.63 ± 1.26, respectively and that the CXCR4 protein levels were 1.38 ± 0.13, 1.96 ± 0.32 and 1.86 ± 0.21, respectively. In contrast, CXCR4 was not detected in normal hepatic tissues. In 78 HCC patients, we also found that the concentration of CXCL12 in cancerous ascitic fluid was 783-8,364 pg/ml and that CXCL12 mRNA level in HCC metastasis portal lymph nodes was 1.21 ± 0.87 but undetectable in normal hepatic tissues. Finally we discovered that recombinant human CXCL12 could induce MHCC97 cells and HUVEC cells to migrate with chemotactic indexes (CI) of 3.9 ± 1.1 and 4.1 ± 1.6, respectively. Cancerous ascitic fluid could also induce the migration of MHCC97 cells with a CI of 1.9 ± 0.8. Thus, our data suggest that CXCR4 and CXCL12 may play an important role in the metastasis of HCC by promoting the migration of tumor cells.Hui Liu Zeya Pan Aijun Li Siyuan Fu Yin Lei Hangyong Sun Mengchao Wu Weiping Zhou 2008Cellular & Molecular Immunology2008,5,5:30
6CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma显示文摘AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.Bao-Cheng Zhao Zhen-Jun Wang Wei-Zheng Mao Hua-Chong Ma Jia-Gang Han Bo Zhao Hui-Min Xu 2011World Journal of Gastroenterology2011,17,19:30
7Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-KB pathway显示文摘Zong-chao LIU Zhen-long WANG Chen-yi HUANG Zhi-jiang FU Yong LIU Zhang-chao WEI Shi-gui LIU Chuan MA Jie-liang SHEN Dayue Darrel DUAN 2018Acta Pharmacologica Sinica2018,39,6:29
8Roles of the MEK1/2 and AKT pathways in CXCL12/CXCR4 induced cholangiocarcinoma cell invasion显示文摘AIM:To evaluate the expression of C-X-C motif chemokine receptor 4(CXCR4)and its signaling cascades,which were previously identified as a key factor for cancer cell progression and metastasis,in cholangiocarcinoma cell lines.METHODS:The expression of CXCR4 and its signaling cascades were determined in the cholangiocarcinoma cell lines(RMCCA1 and KKU100)by Western blotting.The invasion assays and the detection of actin polymerization were tested in these cholangiocarcinoma cells treated with CXC chemokine ligand-12(CXCL12).RESULTS:Expression of CXCR4 was detected in both cholangiocarcinoma cell lines and activation of CXCR4 with CXCL12 triggered the signaling via the extracellular signal-regulated kinase-1/2(ERK1/2)and phosphoinositide 3-kinase(PI3K)and induction of cholangiocarcinoma cell invasion,and displayed high levels of actin polymerization.Addition of CXCR4 inhibitor(AMD3100)abrogated CXCL12-induced phosphorylation of MEK1/2 and Akt in these cells.Moreover,treatment with MEK1/2 inhibitor(U0126)or PI3K inhibitor(LY294 002)also attenuated the effect of CXCL12-induced cholangiocarcinoma cell invasion.CONCLUSION:These results indicated that the activation of CXCR4 and its signaling pathways(MEK1/2 and Akt)are essential for CXCL12-induced cholangiocarcinoma cell invasion.This rises Implications on a potential role for the inhibition of CXCR4 or its signal cascades in the treatment of cholangiocarcinoma.Kawin Leelawat Surang Leelawat Siriluck Narong Suradej Hongeng 2007World Journal of Gastroenterology2007,13,10:27
9穿山龙总皂苷对痛风性关节炎大鼠关节炎滑膜IL-1β及其信号转导通路的影响显示文摘目的:考察穿山龙总皂苷(total saponins from rhizoma Dioscoreae nipponicae,RDN)对痛风性关节炎大鼠关节炎滑膜IL-1β及其介导的信号转导通路的影响。方法:40只雄性Wistar大鼠随机分为四组,分别为正常组、模型组、穿山龙总皂苷低(40mg/kg)、高剂量组(160mg/kg),连续灌胃穿山龙总皂苷5天。第3d灌胃穿山龙总皂苷1h后,膝关节上方髌上韧带进针,注射0.2ml浓度为25mg/ml的微晶尿酸钠结晶混悬液到关节腔,造成实验性痛风性关节炎模型。采用HE和伊红染色观察关节滑膜组织病理学变化,免疫组化法检测穿山龙总皂苷对大鼠膝关节滑膜组织中IL-1β、SDF-1、CXCR4、PI3K、PKC和NF-κB表达的影响。结果:与正常组比较,模型组大鼠膝关节滑膜组织中IL-1β、SDF-1、CXCR4、PI3K、PKC和NF-κB表达水平显著升高(0.087±0.021,0.064±0.017,0.146±0.042,0.139±0.057,0.088±0.021,0.079±0.018),穿山龙总皂苷低剂量组能显著降低CXCR4表达水平(0.081±0.006)。穿山龙总皂苷高剂量组能显著降低IL-1β、CXCR4、PI3K、PKC和NF-κB表达水平(0.035±0.007,0.104±0.011,0.077±0.017,0.039±0.011,0.030±0.009)。结论:穿山龙总皂苷可抑制IL-1β及其介导的信号转导通路;穿山龙总皂苷具有治疗痛风性关节炎(Gouty Arthritis,GA)的潜在价值。周琦 张宁 卢芳 刘树民 2013中药药理与临床2013,29,6:28
10The unique structural and functional features of CXCL12显示文摘The CXC chemokine CXCL12 is an important factor in physiological and pathological processes, includingembryogenesis, hematopoiesis, angiogenesis and inflammation, because it activates and/or induces migration ofhematopoietic progenitor and stem cells, endothelial cells and most leukocytes. Therefore, CXCL12 activity istightly regulated at multiple levels. CXCL12 has the unique property of existing in six splice variants in humans,each having a specific tissue distribution and in vivo activity. Controlled splice variant transcription and mRNAstability determine the CXCL12 expression profile. CXCL12 fulfills its functions in homeostatic and pathologicalconditions by interacting with its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3(ACKR3) and by binding to glycosaminoglycans (GAGs) in tissues and on the endothelium to allow a properpresentation to passing leukocytes. Homodimerizaton and heterodimerization of CXCL12 and its receptors can altertheir signaling activity, as exemplified by the synergy between CXCL12 and other chemokines in leukocyte migrationassays. Receptor binding may also initiate CXCL12 internalization and its subsequent removal from theenvironment. Furthermore, CXCL12 activity is regulated by posttranslational modifications. Proteolytic removal ofNH2- or COOH-terminal amino acids, citrullination of arginine residues by peptidyl arginine deiminases or nitrationof tyrosine residues reduce CXCL12 activity. This review summarizes the interactions of CXCL12 with the cellularenvironment and discusses the different levels of CXCL12 activity regulation.Rik Janssens Sofie Struyf Paul Proost 2018Cellular & Molecular Immunology2018,15,4:28
11我国HIV-1主要流行株外膜蛋白(env)基因V3~V4区变异及其与生物学特性的关系显示文摘目的 研究我国HIV 1主要流行毒株亚型的envV3~V4区变异与生物学特性的关系。方法 应用nested PCR对 1 57份获自我国 1 2个省份的HIV 1毒株env区序列进行扩增 ,并使用ABI 377型测序仪测序 ,然后应用BLAST、GCG和MEGA等生物学软件或程序对env基因V3~V4区序列进行分析。结果 B′亚型毒株V3顶端四肽存在着 4种类型 :GPGR ( 54% )、GPGQ ( 2 8% )、GPGK( 1 6 % )和GPGA( 2 % ) ,B′/C重组毒株全部为GPGQ( 1 0 0 % ) ,CRF0 1 AE重组毒株呈现GPGQ( 95% )和GPGR( 5% )两种类型 ;B′/C和CRF0 1 AE重组毒株V3~V4区及其临近区域N 糖基化位点比B′亚型毒株N 糖基化位点保守。而B′亚型毒株V3环的净电荷分别显著高于B′/C和CRF0 1 AE毒株 (P <0 .0 1 ) ;根据V3环关键氨基酸推测辅助受体使用情况的结果显示 :B′亚型毒株有 9.2 6 %可能使用CCR5,7.4 1 %可能使用CXCR4 ,其余 83.33%不能对辅助受体的使用作出预测。所有B′/C重组毒株被预测可能使用CCR5。CRF0 1 AE重组毒株有 90 .4 8%被预测可能使用CCR5,没有被预测为使用CXCR4的序列 ,9.52 %不能作出预测。结论 B′亚型毒株大部分可能为NSI型 ,少部分可能为SI型 ,而B′/C和CRF0 1 AE重组毒株绝大部分为NSI型。我国主要流行株的V3~V4区尤其是V3环的氨基酸?邢辉 梁浩 洪坤学 魏民 赵全壁 冯毅 陈建平 全宇 滕涛 邵一鸣 2005中华微生物学和免疫学杂志2005,25,3:25
12CXCR4在肺癌组织中的表达及临床意义显示文摘目的:探讨CXCR4在肺癌组织中的表达及其临床意义。方法:分别通过定量RTPCR和免疫组织化学方法检测36例肺癌、10例癌旁正常肺组织中CXCR4的表达。结果:与癌旁正常肺组织相比,36例中34例肺癌组织表达较高水平的CXCR4。CXCR4的高表达与肺癌患者的年龄、性别、肺癌组织类型和分化程度无关,而与临床转移(淋巴结转移和局部浸润)有关。结论:CXCR4的上调表达见于肺癌的发生早期,其高水平与肺癌转移有关。苏丽萍 张进平 陈晋 王缨 熊思东 2005中国癌症杂志2005,15,2:23
13CXCR4和CXCR7在肿瘤中的研究进展显示文摘以往的研究认为趋化因子受体4(chemokine receptor 4,CXCR4)是趋化因子CXCL12的唯一受体,CXCL12/CXCR4生物轴在肿瘤发展过程中起重要作用,然而最近研究发现CXCL12尚存在CXCR7这一新的受体,并且CXCL12/CXCR7生物轴同样对肿瘤的发生发展起重要作用。本文就有关趋化因子受体CXCR4和CXCR7在肿瘤中的表达、促进肿瘤增殖和转移、促进血管新生以及肿瘤治疗等方面的研究作一综述。邱明远(综述) 李健文 郑民华(审校) 2010中国癌症杂志2010,20,3:23
14趋化因子CXCL12及其受体与肿瘤转移的关系显示文摘趋化因子CXCL12(C-X-C chemokine ligand 12)及其受体CXCR4(c-x-c chemokine receptor4)在胚胎发育、干细胞的迁移和各种免疫反应中发挥重要作用,是许多生理和病理过程中指导细胞运动的中心因素。最近发现肿瘤细胞的转移机制和白细胞的迁移相类似,趋化因子CXCL12及其受体与肿瘤的生长、侵袭、转移和分泌密切相关,动物实验表明CXCR4可能成为抑制肿瘤生长、转移的重要靶目标。本文将对趋化因子CXCL12及其受体CXCR4在肿瘤转移、进展中的作用以及与此相关的信号转导、调节因子进行综述。蒋玉萍 吴小华 2007癌症2007,26,2:21
15CXCL12和CXCR4在食管鳞癌组织中的表达及其与预后的关系显示文摘背景与目的:新近研究显示CXCL12/CXCR4在多种肿瘤组织中有表达,并与肿瘤细胞的增殖、侵袭特性相关;本研究旨在检测CXCL12及其受体CXCR4在食管鳞癌中的表达,研究两者对食管癌预后的影响及其与临床及病理因素之间的关系。方法:收集食管癌术后标本186例及正常食管上皮组织20例(对照组),应用免疫组化法检测食管癌组织中CXCR4与CXCL12的表达。结果:186例食管癌组织中CXCR4的表达率为67.2%,CXCL12的表达率为63.4%,20例正常食管上皮组织中无CXCR4及CXCl12蛋白表达。多因素分析:PTNM分期及CXCR4的表达是影响食管癌根治术后患者预后的独立因素(P<0.05);CXCL12阳性组与阴性组5年生存率分别为18.8%和21.0%,差异无统计学意义(P>0.05),CXCR4阳性组与阴性组5年生存率分别为2.2%和28.5%,差异有统计学意义(P<0.05);有淋巴结转移组及病理分期T3期组CXCR4表达率较无淋巴结转移组及病理分期T1-2组高(P<0.05),食管癌组织中CXCR4的表达与CXCL12的表达之间无相关性。结论:CXCL12和CXCR4在食管癌组织中均有较高的表达,CXCR4的表达水平与食管肿瘤的发展及预后有一定的关系。汪道峰 娄宁 曾灿光 张旭 陈福进 2009癌症2009,28,2:20
16CXCR4在肺癌转移中的作用及其机制研究显示文摘目的探讨CXCR4在肺癌转移中的作用及其机制。方法将CXCR4不同表达水平的肺癌细胞(95C、95C pC、95C X4、95D、95D pC、95D ASX4)接种于裸鼠皮下并分析其转移能力。分别通过趋化侵袭实验、明胶酶谱法、黏附实验、RT PCR法检测CXCR4/SDF1对肺癌细胞迁移、基质金属蛋白酶(MMP2)活性、黏附能力、生长相关癌基因α(GROα)表达的调控;通过流式细胞术和共聚焦显微镜观察肺癌细胞内纤维肌动蛋白的合成和聚合情况;Western印迹分析CXCR4/SDF1对ERK1/2磷酸化的影响。结果CXCR4不同表达水平的肺癌细胞在裸鼠体内具有不同的转移能力,95D ASX4组有2/5的小鼠发生了转移,其肺转移结节的数目明显少于95D、95D pC组(P=0.044)。CXCR4特异配体SDF1α可以诱导肺癌细胞的迁移和细胞骨架蛋白纤维肌动蛋白的合成和聚合;SDF1α促进肺癌细胞MMP2活性、黏附能力和GROα表达的增加;CXCR4中和抗体可以在一定程度上抑制这些作用。SDF1α可以诱导ERK1/2的磷酸化。结论肺癌转移在一定程度上依赖于CXCR4/SDF1的相互作用,他们通过调控肺癌细胞的运动性、MMP活性、黏附能力及GROα的表达参与肺癌的转移。苏丽萍 张进平 徐焕宾 陈晋 王缨 储以微 熊思东 2005中华医学杂志2005,85,17:19
17基质细胞衍生因子SDF及其受体CXCR4在造血干/祖细胞动员及归巢过程中的作用显示文摘基质细胞衍生因子 (SDF)属CXC型趋化因子 ,主要在骨髓基质细胞和骨髓内皮等细胞表达 ,特异性地引起表达CXCR4的造血干细胞的趋化反应 ,因此在造血干细胞的迁移和归巢中起着重要作用。本文对SDF及其受体CXCR4在造血干细胞动员以及归巢过程中的机理进行简要综述。王承艳 苗振川 丰美福 2004中国实验血液学杂志2004,12,1:19
18CXCR4及其配体SDF-1在宫颈癌转移中的作用及其机制研究显示文摘背景与目的:趋化因子CXCR4[chemokine(C-X-C)receptor 4]受体及其配体基质细胞衍生因子1(stromal cell derived factor-1,SDF-1)可能与某些恶性肿瘤的迁移、侵袭和转移有关。本研究拟探讨CXCR4受体及其配体SDF-1(CXCR4/SDF-1轴)通过激活丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路在宫颈癌转移中的作用及其机制。方法:采用激光共聚焦显微镜检测宫颈癌HeLa细胞内钙离子波动,Western blot法分析CXCR4/SDF-1对宫颈癌HeLa细胞中细胞外调节信号激酶(extracellular signal-regulated kinase,ERK)(包括ERK1和ERK2)磷酸化的影响;分别通过粘附实验、明胶酶谱法检测CXCR4/SDF-1对宫颈癌细胞粘附能力、基质金属蛋白酶(matrix metalloproteinase,MMP)分泌的影响。结果:SDF-1α与CXCR4相互结合后诱导了HeLa细胞胞内钙的迅速动员,其荧光强度(fluorescent intensity,FI)平均基础值与峰值差异有统计学意义(P<0.01);诱导了HeLa细胞ERK1/2快速磷酸化,作用后30min时磷酸化程度最强;增加了HeLa细胞粘附能力,不同浓度的SDF-1α与CXCR4结合后不同程度地增加了HeLa细胞粘附于纤维连接蛋白(fibronectin,FN)、层粘连蛋白(laminin,LN)的粘附细胞数,与对照组比较其差异均有统计学意义(P<0.05);加入ERK1/2信号通路抑制剂PD98059后,粘附于FN和LN的细胞数下降,与对照组相比差异有统计学意义(P<0.05);促进宫颈癌HeLa细胞分泌活性的MMP-2,这一作用随SDF-1α浓度升高而增强,SDF-1α在800ng/mL浓度处分泌达高峰,以后开始下降。结论:CXCR4/SDF-1通过激活MAPK通路调控宫颈癌细胞的粘附能力,促进活性MMP-2分泌,进而参与宫颈癌侵袭和转移。沈晓燕 王绍海 梁铭霖 汪宏波 肖兰 王泽华 2008癌症2008,27,10:18
19Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes incervical in traepithelial neoplasia and cervical cancer显示文摘The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.Yu Huang Jia Zhang Zhu-Mei Cui Jing Zhao Ye Zheng 2013Chinese Journal of Cancer2013,32,5:18
20SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用显示文摘背景:骨性关节炎的发病机制错综复杂,其预防与治疗是当今医学界的难题之一,与其相关的信号通路的研究已成为国内外研究的热点,其靶向治疗有望成为攻克骨性关节炎的关键。目的:总结SDF-1/CXCR4信号通路在诸多疾病尤其是在骨性关节炎发病中的作用,为骨性关节炎的靶向治疗提供科学依据。方法:应用计算机检索PubMed和CBM数据库中2008-09/2010-07发表的相关文献。以主题检索为主要检索方法,结合限定检索等方法,以'SDF-1/CXCR4信号通路、骨性关节炎'和'SDF-1/CXC4 signaling pathway,osteoarthritis'为中英文检索词,选择与骨性关节炎SDF-1/CXCR4信号通路有关的文献,排除内容陈旧、重复的文章。结果与结论:共检索到2147篇文章,按纳入和排除标准对文献进行筛选,保留32篇文章进行综述。目前,SDF-1/CXCR4信号通路在诸多疾病的发生发展过程中具有重要作用,已成为目前世界医学的研究热点之一。有研究表明,SDF-1/CXCR4信号通路可能在骨性关节炎的发病中具有重要作用,而对该信号通路的干预可能成为预防与治疗骨性关节炎的靶点,有望成为今后骨性关节炎防治方面研究的热点。李晓林 李彦林 马珂 曹斌 王国梁 杨光 许鹏 2011中国组织工程研究与临床康复2011,15,15:16
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