CXCR4在膀胱癌转移淋巴结中的表达及意义

通过免疫组化方法检测24例膀胱癌转移的淋巴结、黏膜内癌组织中CXCR4的表达。结果显示,与黏膜内癌组织相比,CXCR4在癌转移淋巴结中有较高水平表达,CXCR4的高表达与膀胱癌患者的年龄、性别、膀胱癌组织类型和分化程度无关。提示CXCR4在转移灶中有较高表达,可能是高转移性膀胱癌的一个指标。     

CXCR4在食管鳞癌组织中的表达及临床意义

目的探讨趋化因子受体CXCR4在食管鳞癌组织中的表达及其与食管鳞癌发生、发展的关系。方法采用RT-PCR及Western blot法检测35例食管鳞癌及其癌旁对照组织中CXCR4的表达水平。结果CXCR4 mR-NA及蛋白在食管鳞癌组织中的表达水平显著高于癌旁对照组（P〈0．05）,癌组织中淋巴结转移组的CXCR4 mR-NA及蛋白表达显著高于无淋巴结转移组（P〈0．05）;癌组织中CXCR4蛋白在侵及外膜组高于未侵及外膜组（P〈0．05）,在Ⅲ期的表达高于Ⅱ期（P〈0．05）。结论趋化因子受体CXCR4与食管鳞癌的发生、侵袭和转移密切相关,可能成为抑制食管鳞癌侵袭转移的新靶点。     

CXCR4在皮肤基底细胞癌中的表达及意义

目的研究CXCR4在皮肤基底细胞癌中的表达及其在皮肤基底细胞癌发生、发展中的作用。方法收集168例皮肤基底细胞癌组织、癌旁组织及癌旁正常组织标本,应用组织/细胞RNA快速提取试剂盒和RIPA裂解液分别提取组织RNA,制备组织蛋白。采用RT-PCR和Western印迹方法检测CXCR4 mRNA和蛋白的表达。结果与癌旁正常组织对比,基底细胞癌和癌旁组织CXCR4 mRNA表达均显著增加(P=0.003,0.027),基底细胞癌组织CXCR4 mRNA的表达高于癌旁组织(P=0.037);基底细胞癌和癌旁组织CXCR4蛋白的表达均显著增加(P=0.005,0.025),基底细胞癌组织CXCR4蛋白的表达高于癌旁组织(P=0.039)。结论 CXCR4在皮肤基底细胞癌组织中高表达,参与基底细胞癌的增殖、存活。     

胃癌组织中CXCL12、CXCR4的表达及意义

目的 探讨胃癌组织中趋化因子CXCL12及其受体CXCR4蛋白表达与肿瘤浸润、转移的关系.方法 选择胃癌患者50例,取其癌组织和癌旁正常组织标本,应用免疫组化SP方法,检测CXCL12及CXCR4在胃癌组织、正常黏膜及转移淋巴结中的表达情况.结果 与正常黏膜相比,CXCL12和CXCR4在胃癌组织中的表达升高(P＜0.01),胃癌有淋巴结转移者较无淋巴结转移者表达升高(P＜0.01).结论 胃癌组织中CXCL12与CXCR4的高表达与胃癌的浸润及淋巴结转移有关;CXCL12和CXCR4检测可作为判断胃癌预后的一项指标.     

不同分化程度膀胱癌细胞中CXCR4的表达变化及意义

目的观察趋化因子受体CXCR4在分化程度不同的膀胱癌（BBC）细胞中的表达情况。方法分别用细胞涂片免疫组化法、RT-PCR和免疫荧光标记流式细胞术检测CXCR4在BBC细胞系SCaBER、T24和5637中的表达情况。结果CXCR4在三个细胞系胞质内均有表达,以SCaBER表达最明显,124表达最弱,5637细胞表达居中,SCaBER细胞中CXCR4表达阳性者占6.44%±0.42%,T24占1.50%±0.17%,5637占2.13%±0.11%,三者相比,P均〈0.05。SCaBER、T24、5637中CXCR4 mRNA的光密度值分别为1.64±0.22、0.46±0.11、0.99±0.35,三者相比,P均〈0.05。结论CXCR4在不同分化程度的BBC细胞中均有表达,分化程度低者表达更强。     

CXCR4与MMP-2在人直肠癌组织中的表达及临床意义

目的探讨人直肠癌中CXCR4和MMP-2蛋白的表达及意义。方法采用免疫组织化学方法检测50例人直肠正常黏膜组织、癌组织和相关淋巴结中CXCR4和MMP-2的蛋白表达,并分析其与直肠癌临床病理特征的关系。结果 CXCR4和MMP-2在直肠癌组织中阳性率均明显高于正常黏膜组织;CXCR4和MMP-2的表达强度与肿瘤分期、分化程度和淋巴结转移有关,且两者存在正相关性。结论 CXCR4和MMP-2在直肠癌的表达呈正相关,并与直肠癌肿瘤的侵润、转移有关。     

Ezrin蛋白在膀胱癌中的表达及意义

用EnVision免疫组织化学方法检测Ezrin蛋白在膀胱癌中的表达。结果膀胱癌组织Ezrin蛋白阳性表达率高于癌旁组织,癌旁组织高于正常膀胱组织（P均〈0．05）;Ezrin蛋白的表达与组织学分级和病理学分期无相关性（P〉0．05）。提示Ezrin蛋白可能参与膀胱癌的发生,但其表达水平与肿瘤恶性程度无关。     

SDF-1／CXCR4在老年卵巢癌组织中的表达及意义

目的探讨趋化因子SDF-1及其受体CXCR4在老年人上皮性卵巢癌组织中的表达及意义。方法应用westernblotting方法定量检测43例老年患者上皮性卵巢癌组织中SDF-1和CXCR4的蛋白表达情况。结果老年人上皮性卵巢癌组织中SDF-1／CXCR4蛋白表达较卵巢良性肿瘤对照组明显增加,其相对表达量分别为（2．38±0．20）和（3．32±0．26）,差异具有统计学意义（P〈0．05）。结论SDF-1／CXCR4生物学轴可能在老年人卵巢癌的发生与转移过程中起着重要作用。     

膀胱癌组织中趋化因子受体CXCR7的表达变化及意义

目的观察膀胱癌组织中趋化因子受体CXCR7的表达变化及意义。方法收集37例膀胱癌患者的癌组织（观察组）和29例癌旁正常组织（对照组）,采用逆转录聚合酶链反应法（RT—PCR）和免疫组化法分别检测其中的CXCR7 mRNA和蛋白。结果观察组CXCR7 mRNA相对表达量为0．692±0．071,明显高于对照组的0．432±0．148,P〈0．05。观察组中浅表性膀胱癌CXCR7 mRNA相对表达量为0．676±0．065,明显低于浸润性膀胱癌组织中的0．731±0．074,但二者均高于对照组,P均〈0．05。观察组11例CXCR7蛋白低表达、26例高表达,对照组分别为23、6例,两组CXCR7蛋白表达情况相比P〈0．05。观察组26例浅表性膀胱癌中15例CXCR7高表达,11例浸润性膀胱癌CXCR7均为高表达。CXCR7表达情况与膀胱癌临床分期有关（P〈0．05）。CXCR7表达情况与膀胱癌患者年龄、性别无关（P均〉0．05）。结论膀胱癌组织中CXCR7 mRNA和蛋白表达升高。检测膀胱癌组织中的CXCR7 mRNA或蛋白可能有助于判断膀胱癌的临床分期。     

MRP1/CD9在膀胱癌组织中的表达及意义

目的 探讨MRP1／CD9在膀胱癌组织的表达及其临床意义。方法 用免疫组化SP法检测MRP1／CD9在膀胱癌组织和正常膀胱黏膜组织中的表达。结果 正常膀胱组织中MRP1／CD9均为阳性。膀胱癌组织中MRP1／CD9表达降低，且与病理分期呈负相关，与临床分期无相关性。结论 在膀胱癌组织中MRP1／CD9表达降低，可能与膀胱癌的发展有关。其降低程度可以作为评估膀胱癌恶性程度的一个重要指标。     

趋化因子受体CXCR4在胃肠道肿瘤组织及细胞系中的异常表达

目的:检测CXCR4在胃肠道肿瘤中的表达状态,探讨CXCR4在胃肠道肿瘤发病中的作用.方法:采用即时定量PCR(Real-time PCR)检测胃肠道肿瘤标本中CXCR4的表达.采用逆转录PCR(RT-PCR)和Western blot检测CXCR4在胃肠道肿瘤细胞系中的表达.结果:CXCR4 mRNA在24例结直肠癌组织标本的表达水平显著高于其配对的癌旁正常组织( P<0.001).CXCR4 mRNA在30例胃癌组织标本中的表达水平亦显著高于其配对的癌旁正常组织( P<0.001).CXCR4 mRNA和蛋白质在结肠癌细胞系HT-29和SW-480及胃癌细胞系SGC-7901和AGS中均存在明显表达.CXCR4表达与胃癌患者分期及淋巴结转移状态具有相关性( P = 0.01,0.02).结论:CXCR4在胃肠道肿瘤中存在过度表达,其参与了胃肠道肿瘤的发病过程.     

Surface Expression of Neutrophil CXCR4 is Down-Modulated by Bacterial Endotoxin

The chemokine receptor CXCR4 and its unique ligand, stromal-derived factor 1 (SDF-1), play critical roles in the retention of hematopoietic cells within bone marrow and in their mobilization into the circulation. Surface CXCR4 down-regulation in hematopoietic cells is associated with a loss of retention of the cells in bone marrow. Lipopolysaccharide (LPS), commonly referred to as endotoxin, induces neutrophilia in vivo, but the mechanism of mobilization related to neutrophilia has not been fully clarified. We show that LPS reduces CXCR4 surface expression in a dose- and time-dependent manner in neutrophils and monocytes, but not in lymphocytes. Polymyxin B neutralization of LPS in culture supernatants still induced this down-modulation, and LPS-stimulated neutrophils released interferon gamma and interleukin 1beta. These results provide evidence that CXCR4 down-regulation can be attributed to soluble factors released by neutrophils upon LPS treatment. Moreover, LPS treatment increased CXCR4 messenger RNA in neutrophils, suggesting that the down-regulation of surface CXCR4 is caused by a posttranslational mechanism, and the chemotactic migration of neutrophils in response to SDF-1 was reduced by LPS pretreatment. Thus, the present study has shown that by down-regulating neutrophil CXCR4 expression and attenuating neutrophil responsiveness to SDF-1, LPS can mobilize neutrophils from bone marrow to the peripheral blood through reducing neutrophil retention in bone marrow.     

CXCR7在胶质瘤中的表达及其与预后的相关性

目的探讨CXCR7在胶质瘤中的表达及其与预后的相关性。方法收集89例不同病理级别胶质瘤,应用免疫组化方法检测CXCR7在胶质瘤中的表达。结果 23例患者的CXCR7呈强阳性染色(),24例呈中度阳性染色(),17例呈弱阳性染色(+),25例呈阴性染色(-),且CXCR7在胶质瘤组织中的表达与胶质瘤的病理级别呈正相关。较强的CXCR7染色患者的存活时间较短。结论 CXCR7可以做为胶质瘤病理级别分类及预后判断的生物学标记物。     

CXCR4/CXCL12与胃癌生物学行为

胃癌是一种常见恶性肿瘤,总体疗效欠佳,尤其发生腹膜转移者,预后较差.近年来,CXCR4及CXCL12在肿瘤研究中已逐渐成为热点;在胃癌研究中已逐渐见相关报道,如在胃癌生长、迁徙、转移和肿瘤新生血管形成等诸方面均起着重要作用.CXCR4受体拮抗剂在胃癌动物模型中的治疗效果也显示了其应用前景.此文综述了CXCR4/CXCL12在胃癌中作用机制,对CXCR4/CXCL12的深入研究将有望使其成为胃癌靶向治疗的特异靶点.     

Plasma malondialdehyde levels and CXCR4 expression in peripheral blood cells of breast cancer patients

Introduction  Breast cancer is one of the most common neoplasms in women and is a leading cause of cancer related deaths worldwide. Chemokines and their receptors are involved in the control of lymphocyte traffic, a critical component of systemic immunity. CXCR4 mRNA could be involved in the development of variety of diseases. Lipid peroxidation, the result of nonenzymatic autooxidation of polyunsaturated fatty acids, presents numerous harmful effects on biological systems and has been implicated in diseases like cancer. This study examined CXCR4 mRNA expression in peripheral blood cells and malondialdehyde (MDA) in plasma from blood donors and breast cancer patients. Materials and methods  CXCR4 expression in peripheral blood cells from 59 breast cancer patients and 76 healthy blood donors was analyzed by real-time PCR. Plasma MDA was analyzed using high-performance liquid chromatography (HPLC). Conclusion  In all stages, MDA levels in total breast cancer patients (1.41 ± 0.11) were significantly higher (P < 0.01) than those in healthy subjects (0.34 ± 0.03). No statistically significant difference occurred between CXCR4 expression in peripheral blood cells from breast cancer patients (1.69 ± 1.05) and the normal healthy control group (1.8 ± 0.65). However, stage II samples differed statistically (4.3 ± 1.72) from control, total cancer patients and stages I, III and IV samples.     

人CXCR4基因启动子萤光素酶报告载体的构建及鉴定

目的构建并鉴定人CXCR4基因启动子萤光素酶报告载体,为AIDS的靶向基因治疗奠定基础。方法利用PCR技术扩增人CXCR4基因启动子的核心片段,克隆至含新霉素抗性的萤光素酶表达载体pGL3-neo,构建含CXCR4启动子的萤光素酶表达载体pGL3-neo-CXCR4,重组子经双酶切、PCR及测序鉴定。再将构建的载体用脂质体转染体外培养的Jurkat细胞株,检测萤光素酶的表达活性。结果扩增得到CXCR4基因启动子序列,克隆入pGL3-neo-CXCR4的CXCR4基因启动子序列与GenBank报道的一致,实验组（pGL3-neo-CXCR4组）萤光素酶的表达活性为869159．0±62618．8,与空白组（未转染组）的464．2±44．0和对照组（pGL3-neo组）的39088．4±3867．9相比,差异有统计学意义（F=1415．124,P均〈0．05）。结论成功构建了含人CXCR4基因启动子的萤光素酶报告基因表达载体pGL3-neo-CXCR4。     

Characterization of the CXCR4 signaling in pancreatic cancer cells

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.