口腔鳞癌中单核细胞趋化蛋白-1在巨噬细胞浸润、聚集中的意义

目的:探讨口腔鳞癌中单核细胞趋化蛋白-1(monocyte chemoattractant protein-1 MCP-1)表达与肿瘤中浸润巨噬细胞的关系.方法:应用免疫组化方法检测口腔鳞癌中MCP-1的表达和巨噬细胞的浸润,光镜进行高倍视野下巨噬细胞记数和MCP-1表达的分级.结果:在口腔鳞癌中MCP-1的表达与肿瘤分化有关,并与肿瘤内浸润的巨噬细胞有关(P＜0.05).结论:巨噬细胞可能受MCP-1趋化作用的影响,参与肿瘤的生长和转移.     

单核细胞趋化蛋白-1及其受体与肿瘤侵袭转移的研究进展

趋化因子已被证实是肿瘤微环境中的核心调节因子,可募集多种免疫细胞至肿瘤微环境.趋化因子通过在多种类型癌细胞增殖、迁移、侵袭和血管生成中的作用而促进恶性肿瘤的进展.单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1/CCL2)是 CC 类趋化因子家族成员之一.CCL2可...     

单核细胞趋化蛋白在肾盂尿路上皮癌中的表达及临床意义

目的　探讨肾盂尿路上皮癌组织单核细胞趋化蛋白（ＭＣＰ-１）及其基因表达情况,以及它们与临床病理特征的相关性。方法　收集２００７年１月至２００８年１月肾盂尿路上皮癌患者２０例,男性１２例,女性８例,分别取其血液、癌及癌旁组织标本。同期选取３０例非肿瘤患者,男性１８例,女性１２例,取血液标本。ＥＬＩＳＡ方法测定血浆ＭＣＰ-１含量,免疫组化法检测组织ＭＣＰ-１的表达。实时荧光定量ＰＣＲ检测ＭＣＰ-１ＲＮＡ水平。结果　肾盂尿路上皮癌患者血浆ＭＣＰ-１浓度为（１７３.４±８２.１）ｐｇ／ｍｌ,高于非肿瘤患者的（９１.８±３４.６）ｐｇ／ｍｌ（Ｐ＜０.０５）;高级别肾盂尿路上皮癌患者血浆ＭＣＰ-１浓度为（２５４.１±１２５.８）ｐｇ／ｍｌ,高于低级别的（１５１.３±７９.５）ｐｇ／ｍｌ。肾盂尿路上皮癌组织中ＭＣＰ-１阳性表达率为９０.０％（１８／２０）,癌旁组织为６５.０％（１３／２０）,两组差异有统计学意义（Ｐ＜０.０１）;高级别肾盂尿路上皮癌组织ＭＣＰ-１阳性表达率为１００.０％（４／４）,高于低级别者的8７.５％（１４／１６）。肾盂尿路上皮癌组织ＭＣＰ-１总ＲＮＡ和ｍＲＮＡ水平均高于其相应的癌旁组织（Ｐ＜０.０５）。结论　肾盂尿路上皮癌组织较其癌旁组织的ＭＣＰ-１基因表达上调,提示ＭＣＰ-１可能在肾盂尿路上皮癌的发生及转移中发挥一定的作用。     

单核细胞趋化蛋白及MCP-1基因在肾细胞癌组织中的表达及临床意义

目的：探讨肾细胞癌（RCC）组织及癌旁组织中单核细胞趋化蛋白（MCP-1）基因的表达与肾细胞癌发病机制的相关性。方法：RCC患者30例,男20例,女10例,分别取血液和肾癌组织标本。对照组30例为非肿瘤患者,男20例,女10例,取血液标本,ELISA方法测定血浆中MCP-1定量。癌旁组织标本为对照组,免疫组化方法检测MCP-1表达情况。实时RT—PCR定量检测MCP-1表达。分析RCC临床特点与MCP-1表达的关系。结果：肾癌组患者血浆中MCP-1（203．5±155．8）pg／ml较非肿瘤组（92．1±35．2）pg／ml高（P〈0．05）。免疫组化显示肾癌组织中MCP-1表达阳性率为73．3％（22／30）,癌旁组织中的表达阳性率为40．0％（12／30）,肾癌组织中MCP-1表达阳性率明显高于癌旁,差异有统计学意义（P〈0．01）。同时发现肾癌组织中MCP-1的阳性强度（＋＋）-（＋＋＋）也明显高于癌旁组织（＋）。肾癌组织MCP-1总RNA和mRNA水平与癌旁组织比较差异有统计学意义（P〈0．05）。结论：MCP-1基因表达上调可能在肾细胞癌的发生及转移中发挥重要作用。     

单核细胞趋化蛋白及MCP-1基因在肾细胞癌组织中的表达及临床意义

目的:探讨肾细胞癌(RCC)组织及癌旁组织中单核细胞趋化蛋白 (MCP-1)基因的表达与肾细胞癌发病机制的相关性.方法:RCC患者30例,男20例,女10例,分别取血液和肾癌组织标本.对照组30例为非肿瘤患者,男20例,女10例,取血液标本,ELISA方法测定血浆中MCP-1定量.癌旁组织标本为对照组,免疫组化方法检测MCP-1表达情况.实时RT-PCR定量检测MCP-1表达.分析RCC临床特点与MCP-1表达的关系.结果:肾癌组患者血浆中MCP-1(203.5±155.8)pg/ml较非肿瘤组(92.1±35.2)pg/ml高(P＜0.05).免疫组化显示肾癌组织中MCP-1表达阳性率为73.3%(22/30),癌旁组织中的表达阳性率为40.0%(12/30),肾癌组织中MCP-1表达阳性率明显高于癌旁,差异有统计学意义(P＜0.01).同时发现肾癌组织中MCP-1的阳性强度(++)-(+++)也明显高于癌旁组织(+).肾癌组织MCP-1总RNA和mRNA水平与癌旁组织比较差异有统计学意义(P＜0.05).结论:MCP-1基因表达上调可能在肾细胞癌的发生及转移中发挥重要作用.     

血小板反应蛋白-1的表达与骨肉瘤新生血管生成的研究

目的：检测血小板反应蛋白-1（thrombospodin-1,TSP-1）在骨肉瘤中的表达,探讨其与骨肉瘤组织血管生成、侵袭性的关系。方法：收集2003年1月-2007年2月手术切除的54例骨肉瘤标本,应用免疫组化法,检测骨肉瘤组织中TSP-1的表达,CD34单克隆抗体标记血管内皮细胞计数骨肉瘤微血管密度（mi—eI＇ovesse]density,MVD）。结果：骨肉瘤TSP-1的表达程度与MVD呈负相关,TSP-1高表达组的MVD明显低于TSP-1低表达组;骨肉瘤TSP-1表达与骨肉瘤临床病理因素无相关性,但与肺转移显著负相关。结论：TSP-1在骨肉瘤发生发展中起重要作用,并影响血管形成及肿瘤侵袭性,有望成为治疗骨肉瘤的新靶点。     

血小板反应蛋白-1的表达与骨肉瘤新生血管生成的研究

目的:检测血小板反应蛋白-1(thrombospodin-1,TSP-1)在骨肉瘤中的表达,探讨其与骨肉瘤组织血管生成、侵袭性的关系.方法:收集2003年1月-2007年2月手术切除的54例骨肉瘤标本,应用免疫组化法,检测骨肉瘤组织中TSP-1的表达,CD34单克隆抗体标记血管内皮细胞计数骨肉瘤微血管密度(microvessel density,MVD ).结果: 骨肉瘤TSP-1的表达程度与MVD呈负相关,TSP-1高表达组的MVD明显低于TSP-1低表达组;骨肉瘤TSP-1表达与骨肉瘤临床病理因素无相关性,但与肺转移显著负相关.结论:TSP-1在骨肉瘤发生发展中起重要作用,并影响血管形成及肿瘤侵袭性,有望成为治疗骨肉瘤的新靶点.     

胃癌组织中ＭＣＰ-１、ＭＭＰ-９的表达与间质中ＴＡＭｓ浸润的关系

目的　检测胃癌组织中单核细胞趋化蛋白-１（ＭＣＰ-１）和基质金属蛋白酶-９（ＭＭＰ-９）的表达,分析它们与肿瘤相关巨噬细胞（ＴＡＭｓ）浸润的关系及对胃癌生物学行为的影响。方法　采用免疫组化ＳＰ法检测５０例胃癌组织中ＭＣＰ-１、ＭＭＰ-９的表达及ＴＡＭｓ计数,以２０例胃炎作对照组。结果　（１）ＭＣＰ-１在胃癌组织中的阳性率为（５３.２７±３０.９８）％,高于对照组的（１６.２１±７.６４）％,两者差异有统计学意义（Ｐ＜０.０１）;ＭＣＰ-１与胃癌的淋巴结转移有关（Ｐ＜０.０５）,与分化及分型均无关。（２）胃癌中ＭＭＰ-９表达的阳性率为（３７.６４±２４.８８）％,高于对照组的（１６.９６±１２.８８）％,两者差异有统计学意义（Ｐ＜０.０５）;ＭＭＰ-９与胃癌的分化、分型和转移均相关（Ｐ＜０.０５）。（３）ＴＡＭｓ在胃癌组织中的计数为１６.９４±５.９８,高于对照组的６.７２±３.４１,两者差异有统计学意义（Ｐ＜０.０１）;在胃癌组织中ＴＡＭｓ计数与胃癌的组织学分型及分化无关（Ｐ＞０.０５）,但有淋巴结转移组的ＴＡＭｓ计数明显高于无淋巴结转移组（Ｐ＜０.０５）。结论　ＭＣＰ-１与ＴＡＭｓ之间可能具有协同作用,共同促进肿瘤的生长和转移;ＴＡＭｓ有可能通过上调肿瘤细胞ＭＭＰ-９表达,促进肿瘤的侵袭和转移。     

骨肉瘤中Rb、p16、CDK4、cyclinD1蛋白的表达及其意义

目的 探讨骨肉瘤中Ｒｂ、ｐ１６、ＣＤＫ４、ｃｙｃｌｉｎＤ１的蛋白表达、相互关系及其意义。方法 应用免疫组化方法对４０例骨肉瘤组织中Ｒｂ、ｐ１６、ＣＤＫ、ｃｙｃｌｉｎＤ１的蛋白表达状况进行检测。结果 ４０例骨肉瘤Ｒｂ、ｐ１６蛋白表达缺失分别为７２．５％（２９／４０和）２２．５％（９／４０）;１１例ｐＲｂ阳性的骨肉瘤中的８例ｐ１６阴性,２９例ｐＲｂ阴性的骨肉瘤中２８例ｐ１６阳性;５２．５％（２１／４０     

p27KIP1和CyclinE在骨肉瘤中表达的意义

目的：研究p27^KIP1和CyclinE蛋白在骨肉瘤中的表达，探讨其在骨肉瘤发生、发展中的可能作用。方法：应用免疫组化S－P方法检测28例骨肉瘤石蜡标本中p27^KIP1和CyclinE蛋白的表达情况。结果：p27^KIP1蛋白在28例骨肉瘤中表达阳性率为42．9％，在对照组20例骨软骨瘤中为75．0％，骨肉瘤与骨软骨瘤相比有显著差异（P＜0．05）。CyclinE蛋白在28例骨肉瘤中表达阳性率为67．9％，在20例骨软骨瘤中为10．0％，骨肉瘤与骨软骨瘤相比有显著差异（P＜0．01）。p27^KIP1蛋白在骨肉瘤中的表达阴性率为57．1％，与CyclinE蛋白在骨肉瘤中表达阴性率67．9％相比二者差异不显著（P＞0．05）。结论：p27^KIP1在骨肉瘤中表达降低，CyclinE在骨肉瘤中高表达，二者与骨肉瘤发生机制有关，且具有相关性。     

Glut-1蛋白在结直肠癌组织中的表达及其临床意义

目的探讨葡萄糖转运蛋白1(Glut-1蛋白)在人结直肠癌组织表达情况及其临床意义。方法应用免疫组化方法检测60例结直肠癌及26例正常肠组织标本中Glut-1蛋白表达水平。结果在正常肠组织中未见Glut-1蛋白的表达,结直肠癌组织中Glut-1蛋白表达率为80.0%。Glut-1蛋白的表达量与结直肠癌分化程度有关(P<0.01)。结论结直肠癌组织中Glut-1蛋白表达水平异常增高在结直肠癌发生、发展中起重要作用,与结直肠癌预后不良有关。     

Monocyte Chemoattractant Protein-1 Modulates Invasion and Apoptosis of PC-3M Prostate Cancer Cells Via Regulating Expression of VEGF,MMP9 and Caspase-3

Prostate cancer is a form of malignancy that is most likely to develop in older males, but because of thepropensity to metastasize to parts of the body, particularly the bones, can have a deleterious impact on qualityof life. Recently monocyte chemoattractant protein-1 (MCP-1) has been shown to play important role in prostatecancer progression and metastasi. In this study we aimed to investigate the mechanisms underlying its functionalroles. In vitro transwell invasion assays with PC-3M prostate cancer cells demonstrated MCP-1 promotion ofinvasion, while annexin V-FITC and TUNEL confirmed inhibition of apoptosis. Treatment MCP-1 further ledto significant upregulation of VEGF and MMP-9 and downregulation of Caspase-3 at both mRNA and proteinlevels compared with untreated control (P<0.05), while siRNA mediated knockdown reversed these changes.Taken together, our results indicate important roles of MCP-1 in prostate cancer progression and metastasisand our finding of regulation of VEGF, MMP-9 and Caspase-3 expression open up new possibilities for targetedtherapy.     

CCL2 (Monocyte Chemoattractant Protein-1) in cancer bone metastases

The paradigm of cancer development and metastasis is a comprehensive, complex series of events that ultimately reflects a coordinated interaction between the tumor cell and the microenvironment within which the tumor cell resides. Despite the realization that this relationship has changed the current paradigm of cancer research, the struggle continues to more completely understand the pathogenesis of the disease and the ability to appropriately identify and design novel targets for therapy. A particular area of research that has added a significant understanding to cancer metastasis is the role of chemokines and chemokine receptors. Here we review the current concepts of CCL2 (monoctye chemoattractant protein 1) and its role in tumor metastasis with particular interest to its role in the development of bone metastases.     

Enforced effect of tk-MCP-1 fusion gene in ovarian cancer

ABSTRACT: OBJECTIVE: The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo. METHODS: A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot were performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were comparable to those of SKOV3 expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene. RESULTS: The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes. CONCLUSION: These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.     

Knockdown of VEGF receptor-1 (VEGFR-1) impairs macrophage infiltration, angiogenesis and growth of clear cell renal cell carcinoma (CRCC)

Angiogenesis is essential for tumor growth and metastasis. VEGF has been shown to be a central player in this process. The biological activity of VEGF is mainly mediated by two tyrosine kinase receptors, VEGFR-1 and VEGFR-2. While increasing evidence suggests that VEGF/VEGFR-1 signaling is crucial for tumor angiogenesis, its molecular mechanism is not well understood. Here we show that VEGFR-1 knockdown dramatically inhibits tumor growth. This inhibition is associated with significant decrease of tumor VEGF levels and tumor angiogenesis as well as an increased tumor necrosis. Moreover, we demonstrate that VEGF in CRCC tumors is mainly produced by tumor stromal cells instead of the tumor cells themselves. It has been shown that macrophages constitute a significant part of tumor stromal cells and produce a large amount of VEGF. We therefore examined the macrophage infiltration in the xenograft tumors. Remarkably, VEGFR-1 knockdown attenuates the tumor macrophages infiltration. To understand the mechanism, we investigated the impact of VEGFR-1 knockdown on the expression of monocyte chemoattractant protein-1 (MCP-1), one of the main chemoattractants for macrophages. Significantly, VEGFR-1 knockdown inhibits MCP-1 expression of CRCC cells. Taken together, these data indicate that VEGF/VEGFR-1 signaling plays an essential role in initiating tumor angiogenesis by regulating MCP-1 expression, which in turn, attracts macrophages infiltration and VEGF production. Thus, these studies suggest that blockade of VEGFR-1 function may provide a tumor-specific, VEGF-based therapeutic strategy for treatment of CRCC.     

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients.

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study comprises 86 patients with ovarian cancer, 48 with primary ovarian cancer and 38 with recurrent ovarian cancer, 67 patients with benign ovarian cysts and 42 healthy women. Median serum levels in patients with primary ovarian cancer, recurrent ovarian cancer, benign ovarian cysts and in healthy women were 535.6 (range 129.6-1200) pg ml(-1), 427.3 (range 193.4-1101) pg ml(-1), 371.2 (range 222-986.8) pg ml(-1) and 318.7 (range 241.3-681.4) pg ml(-1) respectively (Mann-Whitney U-test, P < 0.001). Univariate logistic regression models revealed a significant influence of MCP-1 serum levels on the odds of presenting with primary ovarian cancer versus benign cysts and versus healthy women respectively (univariate logistic regression, P < 0.001 and P < 0.001 respectively). In a multivariate logistic regression model considering MCP-1 and CA 125 serum levels simultaneously, both MCP-1 and CA 125 revealed statistical significance on the odds of presenting with primary ovarian cancer versus benign cysts (multivariate logistic regression, P = 0.05 and P < 0.001 respectively). In ovarian cancer patients, MCP-1 serum levels showed a statistically significant correlation with histological grade (Mann-Whitney U-test, P = 0.02) and age at the time of diagnosis (Mann-Whitney U-test, P = 0.03). Elevated MCP-1 serum levels prior to therapy were not associated with disease-free and overall survival (log-rank test, P = 0.2 and P = 0.7 respectively). In summary these data indicate that MCP-1 might play a functional role in the natural history of ovarian cancer and might serve as differentiation marker between benign ovarian cysts and ovarian cancer, providing additional information to the established tumour marker CA 125.     

粘合连接相关蛋白1在脑胶质瘤中的研究现状及进展

粘合连接相关蛋白1（adherens junction associated protein-1,AJAP1）,也称为SHREW1,最初发现是在上皮细胞粘合连接有关的一种新奇的跨膜蛋白,位于染色体1p36.32区域。大量的人类癌症病例研究证明,1p36是一个突变热点,在肿瘤发生过程中,肿瘤抑制功能的丧失与1p36区域有关。脑胶质瘤是中枢神经系统最常见的原发性肿瘤,研究显示AJAP1缺失与脑胶质瘤进展有重要关系。在胶质瘤中,AJAP1能够与β-连环蛋白（β-catenin）结合,易位至细胞核内,调节基因转录,影响细胞周期、凋亡及改变细胞骨架结构和细胞极性,抑制细胞的运动及迁移。AJAP1可能是胶质瘤重要的抑制相关靶点,与胶质瘤的发生发展、增殖、凋亡、侵袭及迁移及预后密切相关,但其机制尚未明确。本文就胶质瘤中AJAP1的研究现状及进展进行综述。     

非小细胞肺癌组织中MRP1和LRPmRNA的表达及其临床意义

目的探讨多药耐药相关蛋白1(MRP1)和肺耐药蛋白(LRP)基因在非小细胞肺癌(NSCLC)中的表达及其临床意义。方法应用RT-PCR半定量法检测60例NSCLC患者癌组织及癌旁组织中MRP1和LRPmRNA的表达。结果NSCLC患者的癌组织中MRP1、LRPmRNA表达量显著高于癌旁组织(P≤0.02),且两者在癌组织中的表达呈正相关;MRP1mRNA在肿瘤直径>3cm组表达量明显高于肿瘤直径≤3cm组(P=0.013);LRPmRNA表达量NSCLC腺癌组高于鳞癌组(P=0.02),中高分化组高于低分化组(P=0.033)。结论MRP1、LRP在NSCLC的多药耐药(MDR)中可能起重要作用,且在形成MDR的过程有某种程度的关联,联合检测MRP1、LRPmRNA对于预测NSCLC患者化疗效果、协助临床选择化疗方案可能具有一定的意义。