RANTES及其受体在胃癌中的表达及其意义探讨

目的:探讨RANTES及其受体(CCR5)在胃癌和转移淋巴结组织中的表达及其与胃癌转移的关系。方法:采用流式细胞仪CCR5/DNA和RANTES/DNA双参数法检测CCR5在胃癌以及RANTES在有癌组织转移的淋巴结中的表达情况。 结果:胃癌组织中CCR5的表达率［（21.53±3.10）%］明显高于癌旁组织［（10.10±1.30）%］（P＜0.05）。有肿瘤转移的淋巴结组织中RANTES的表达［（63.50±5.25）%］明显高于正常淋巴结组织［（44.40±4.76）%］（P＜0.05）。结论:趋化因子RANTES及其受体可能参与了胃癌转移的调控。     

趋化因子受体CCR7及CXCR4在结肠癌组织中的表达及意义

目的:观察趋化因子受体CCR7及CXCR4在结肠癌组织中的表达及与临床病理特征的关系,探讨其评价结肠癌侵袭转移及预后的意义.方法:对110例行结肠癌根治术的结肠癌组织标本采用免疫组织化学方法检测CCR7及CXCR4的表达.结果:CCR7、CXCR4在110例结肠癌组织中阳性表达率分别为59.1%和45.5%,其中淋巴结转移组表达率分别为90.8%、69.2%,无淋巴结转移组表达率分别为13.3%、11.1%,差异有统计学意义(P<0.05).CCR7及CXCR4的表达与结肠癌浸润深度、淋巴结转移、肿瘤分期密切相关(P<0.05),与年龄、性别、肿瘤大小、组织学类型及分化程度无关(P>0.05).CCR7判断结肠癌淋巴结转移的敏感性、特异性、阳性预测值及阴性预测值分别为90.8%、86.7%、90.8%、86.7%;CXCR4判断结肠癌淋巴结转移的敏感性、特异性、阳性预测值及阴性预测值分别为69.2%、88.9%、90.O%、66.7%;联合检测CCR7及CXCR4诊断结肠癌淋巴结转移的准确率为88.1%.结论:趋化因子受体CCR7及CXCR4与结肠癌淋巴结转移密切相关,联合检测CCR7及CXCR4对预测结肠癌淋巴结转移情况、评价预后、判定术后治疗方案具有指导价值.     

趋化因子受体5表达与乳腺癌临床病理特征及预后的相关性研究

目的 探讨趋化因子受体5(CCR5)在乳腺癌病灶和腋窝转移淋巴结中的表达及其与临床病理意义.方法 收集72例乳腺导管浸润癌及其腋窝淋巴结组织,50例乳腺纤维腺瘤组织,40例正常乳腺组织石蜡标本切片.采用免疫组化方法检测CCR5的表达情况;同时检测乳腺癌组织中C-erbB-2,p53,Ki-67,ER,PR的表达情况,并与临床病理资料进行统计学分析.结果 (1)乳腺癌组织中CCR5蛋白表达阳性率达84.72%(61/72),乳腺纤维腺瘤组织中表达阳性率较低(14%,7/50),正常乳腺组织中不表达CCR5;(2)乳腺癌CCR5表达与腋窝淋巴结转移呈正相关(X<'2>=4.982,P=0.026,r=0.305);(3)50例伴腋窝淋巴结转移的患者中,乳腺癌原发灶及转移淋巴结同时表达CCR5阳性者39例,具有较高的同源性;(4)乳腺癌CCR5表达与癌基因C-erbB-2之间呈低度正相关(P<0.05,r=0.291);(5)乳腺癌CCR5表达与患者年龄、绝经与否、肿瘤最大径、肿瘤分期等临床特征无关(均P>0.05);(6)乳腺癌CCR5表达与p53,Ki-67,ER,PR无关表达(均P>0.05).结论 CCR5在乳腺癌的发生、发展及腋窝淋巴结转移方面起一定作用;CCR5可间接作为预测乳腺癌腋窝淋巴结转移及预后判断的指标之一.     

趋化因子受体7蛋白与膀胱尿路上皮癌淋巴结转移的相关性

目的观察趋化因子受体7蛋白(CCR7)在膀胱尿路上皮的表达量,分析CCR7蛋白表达与膀胱尿路上皮癌相关临床参数的相关性。方法对28例膀胱尿路上皮癌患者的标本和5例正常膀胱组织标本,采用免疫组化法检测组织中的CCR7蛋白含量,分析CCR7含量与膀胱尿路上皮癌淋巴结转移发生率、CCR7与肿瘤的分期、分级等临床参数之间的关系。结果膀胱尿路上皮癌组织CCR7阳性率为85.71%,显著高于正常膀胱组织(20.00%);在膀胱尿路上皮癌组织中,淋巴结转移组的CCR7阳性率为90.91%,淋巴结未转移组为41.18%,两组差异有显著性意义(P0.05)。高分期膀胱尿路上皮癌(T3~T4)中CCR7的阳性率也显著高于低分期(T1~T2)(93.75%vs.75.00%),高分级膀胱尿路上皮癌(G3)中的阳性率也显著高于低分级(G1~G2)(93.34%vs.38.46%)。CCR7蛋白表达与肿瘤分期、病理分级以及淋巴结是否转移均有相关性,CCR7蛋白表达是淋巴结转移的独立影响因子(P=0.017,OR=3.152)。结论膀胱尿路上皮癌中CCR7蛋白与淋巴结转移成正相关,是淋巴结转移的独立影响因素。     

SLC及其受体CCR7在胰腺癌中的表达及与淋巴管生成相关性的研究

目的 研究胰腺癌中次级淋巴组织趋化因子(SLC)及其受体CCR7的表达情况,探讨其在胰腺癌淋巴管生成中的作用.方法 采用免疫组织化学和RT-PCR方法检测30例胰腺痛病灶、癌旁组织、正常胰腺和胰周淋巴结中的中SLC、CCR7的表达情况,形态计量学图像分析法测定胰腺癌中微淋巴管密度(MLVD),分析其表达与胰腺癌MLVD间的关系.结果 SLC蛋白在胰腺癌组织、癌旁组织、胰周淋巴结、正常胰腺组织中的阳性率分别为16.7%、43.3%、46.6%和76.7%.CCR7蛋白在上述组织中阳性率分别为76.7%、66.7%、70.0%和30.0%;RT-PeR表明SLC、CCR7 mRNA表达与其蛋白表达强度相同.胰腺癌SLC阳性组与阴性组中MLVD无明显差异(P>0.05),CCR7阳性组中MLVD明显高于阴性组(P=0.004).结论 SLC与胰腺癌的分期及转移无关,CCR7的表达与胰腺癌TNM分期和淋巴结转移密切相关,其高表达对胰腺癌中淋巴管生成及淋巴结转移可能起促进作用.     

乳腺浸润性导管癌腋窝淋巴结转移与趋化因子受体CCR6/CCL20表达的关系

目的 观察CCR6/CCL20在乳腺浸润性导管癌腋窝淋巴结转移中的作用.方法 应用Western blot检测55例乳腺浸润性导管癌患者标本中肿瘤组织、邻近正常组织以及淋巴结转移组织中CCR6/CCL20通路成员的表达情况.结果 乳腺癌组织中CCR6/CCL20表达水平明显增高分别为正常组织的3.6、2.1倍(P＜0.05,P＞0.05);CCR6表达水平与腋窝淋巴结转移相关(P＜0.05).结论 趋化因子受体CCR6/CCL20表达可能在乳腺癌腋窝淋巴结转移过程中起重要作用.     

趋化因子受体CCR7在肝门部胆管癌组织中的表达及其意义

目的：探讨趋化因子受体CCR7在肝门部胆管癌组织中的表达及其与临床病理因素的关系。方法：免疫组织化学染色检测45例肝门部胆管癌手术标本和20例正常胆管组织中CCR7的表达,HE染色检测标本中肿瘤神经浸润情况,与临床病理因素进行相关性分析。结果：CCR7在45例肝门部胆管癌组织阳性表达32例（71.1%）,正常胆管组织中有2例表达弱阳性（10.0%）,二者阳性表达率差异有统计学意义（P〈0.05）。45例肝门部胆管癌组织中38例有神经浸润,其中30例CCR7呈阳性表达。相关分析认为,CCR7表达与淋巴结转移、神经浸润有关（P〈0.05）;与患者的性别、年龄、肿瘤大小和分化程度无关（P〉0.05）。结论：CCR7在肝门部胆管癌组织中高表达,CCR7的表达与肿瘤的淋巴结转移、神经浸润有关。     

趋化因子受体CCR7在胃癌中的表达及其与淋巴结转移的关系

目的探讨趋化因子受体CCR7的表达对预测胃癌淋巴结转移的临床价值。方法对132例行胃癌根治术和30例内镜活检的胃癌组织标本采用免疫组化法检测CCR7的表达。结果CCR7在56.8%的病例中呈阳性表达。CCR7在伴有淋巴结转移病例中的表达显著高于无淋巴结转移者(P<0.001);其与肿瘤大小(P<0.01)、浸润深度(P<0.001)、淋巴管浸润(P<0.001)和TNM分期(P<0.001)相关,并与多层螺旋CT(MSCT)和病理检查判断的淋巴结转移密切相关(P<0.05,P<0.01);但与年龄、性别、肿瘤位置、Lauren分类和血管浸润无关。在回顾性研究中,CCR7表达对胃癌淋巴结转移判断的敏感性、特异性、阳性预测值(PPV)、阴性预测值(NPV)和准确率分别为83.1%、73.8%、78.7%、78.9%和78.8%;在前瞻性研究中,CCR7表达对胃癌淋巴结转移判断的敏感性、特异性、PPV、NPV和准确率分别达85.0%、60.0%、80.9%、66.7%和76.7%。结论CCR7表达与胃癌淋巴结转移密切相关,对内镜活检组织检测CCR7的表达有助于预测胃癌淋巴结转移及决定淋巴结清扫的手术范围。CCR7可能成为胃癌治疗的新靶点。     

死亡相关蛋白激酶在肿瘤组织中的表达及其临床意义

目的 检测死亡相关蛋白激酶(DAPK1)在肿瘤组织中的表达,探讨DAPK1表达与肿瘤患者临床特征间的关系及其意义.方法 通过Western blot法检测DAPK1在人肿瘤组织中的表达,高清晰度彩色图文分析系统(HPIAS)分析各组样本相对吸光度(A)值.结果 DAPK1在部分宫颈上皮内瘤样病变(CIN)和宫颈癌组织中表达,相对A值分别为0.64±0.04和0.36±0.03,两者间差异有统计学意义(P＜0.05);DAPK1在正常宫颈组织均有表达(相对A值为0.89±0.03),且明显高于宫颈CNI和宫颈癌组织,差异有统计学意义(P＜0.05);无淋巴结转移宫颈癌组织DAPK1表达(相对A值为0.39±0.03)明显高于有淋巴结转移组织(0.16±0.04),差异有统计学意义(P＜0.05).而DAPK1的表达与患者年龄、肿瘤大小无明显相关.结论 DAPK1表达降低可能与肿瘤的发生有关;DAPK1基因可能参与宫颈癌的侵袭与转移.     

次级淋巴组织趋化因子及其受体CCR7在肿瘤侵袭和淋巴转移中的研究进展

次级淋巴组织趋化因子（SLC）是近年发现的一种新的趋化因子,高表达于次级淋巴组织,能趋化并活化T淋巴细胞、树突状细胞和自然杀伤细胞等免疫效应细胞,在机体淋巴细胞的迁移归巢、抗肿瘤、抗感染过程中具有重要作用。CCR7是SLC的高亲和力受体,近年来研究发现,CCR7和SLC的表达与肿瘤的淋巴转移密切相关。现综述SLC及其受体CCR7的生物学特性和主要功能,并重点阐述SLC和CCR7在肿瘤侵袭和淋巴转移中的研究现状。     

CCR7在甲状腺乳头状癌组织中的表达及意义

目的：检测趋化因子受体CCR7在甲状腺乳头状癌组织中的表达,探讨CCR7表达与淋巴结转移的关系。方法：采用免疫组织化学法检测30例乳头状癌标本中CCR7的表达。结果：CCR7在30例乳头状癌组织中阳性表达率为56.7%（17/30）,其中淋巴结转移组的阳性表达率为92.3%（12/13）,而无淋巴结转移组的阳性表达率为29.4%（5/17）,差异有统计学意义（P〈0.01）;CCR7的表达与患者性别、年龄及肿瘤大小无关（P〉0.05）。结论：甲状腺乳头状癌组织中CCR7的表达与淋巴结转移关系密切,对甲状腺乳头状癌手术方案的选择及药物靶向治疗具有重要意义。     

The Chemokine Receptors CXCR4 and CCR7 are Associated with Tumor Size and Pathologic Indicators of Tumor Aggressiveness in Papillary Thyroid Carcinoma

Background  Functional chemokine receptors are expressed in many malignant tumors, including papillary thyroid carcinoma (PTC). These receptors promote tumor growth and metastasis in response to endogenous chemokines. The purpose of this study was to examine the expression of two chemokine receptors—CXCR4 and CCR7—in a series of PTCs. We hypothesized that CXCR4 and CCR7 would correlate with indicators of tumor aggressiveness, including tumor size, extrathyroidal extension (ETE), angiolymphatic invasion (ALI), and lymph node metastasis. Methods  CXCR4 and CCR7, as well as their specific chemokine ligands (CXCL12 and CCL21, respectively), were assessed in 88 PTCs from 65 patients using a semiquantitative measure of immunohistochemical (IHC) staining intensity for each molecule. Staining intensity was compared with clinicopathologic features including patient age, gender, tumor size, multifocality, ETE, ALI, and lymph node metastasis. Differences in CXCR4 and CCR7 mRNA levels were sought in a subset of tumors using gene microarrays and quantitative RT-PCR. [Statistics: t test, Mann-Whitney U test; P < .05]. Results  High-intensity IHC staining for CXCR4 was associated with larger tumor size (P = .02), while PTCs exhibiting ETE, ALI, or lymph node metastasis showed higher-intensity IHC staining for CCR7 than those without (P = .01, .03, and .01, respectively). CCR7 mRNA levels were also higher in tumors with ALI (P = .04). Conclusion  Expression of CXCR4 and CCR7 by PTCs is associated with indicators of tumor aggressiveness, including tumor size, ETE, ALI, and lymph node metastasis. Further studies are necessary to define the mechanisms underlying this association and to determine its potential prognostic and therapeutic implications.     

趋化因子受体CCR7表达与胸中段食管癌淋巴结转移及预后的关系

目的 探讨趋化因子受体CCR7表达与胸中段食管鳞癌淋巴结转移及预后的相关性.方法 回顾2003年6月至2005年6月手术治疗184例胸中段食管癌病例临床资料.采用免疫组化进行趋化因子受体CCR7检测,Kaplan-meier法进行生存分析、用Cox回归分析判定独立预后因素.结果 CCR7表达率Ⅱ期和Ⅲ期病例分别为70.3%和85.5%(x2=5.0,P=0.02);T2和T3病例分别为64.9%和80.9%(x2=5.4,P=0.01);有、无淋巴结转移病例分别为86.4%和65.0%(x2=10.8,P=0.00)两组差异均有统计学意义.有、无CCR7表达病例的5年生存率为26.3%和66.0%,差异有统计学意义(x2=23.7,P=0.00);其中T2病例分别为35.1%和70.0%(P=0.01);T3病例分别为22.4%和60.9%(P=0.00);pN0分别为28.8%和66.7%(p=0.00);pN1分别为14.3%和63.6%(P=0.00),两组差异亦均有统计学意义.Cox回归分析结果显示,T分类、N分类和CCR7表达是预后独立的危险因素.结论 食管鳞癌不同的T、N分类中CCR7表达存在差别;CCR7表达者5年生存率降低;肿瘤的T分类、淋巴结转移和CCR7表达是独立的不利预后因素.

Abstract：

Objective To investigate the expression of chemokine receptor CCR7 and its correlation with lymph node metastasis and prognosis in esophageal cancer after esophagectomy. Methods One hundred and eighty-four patients with middle third squamous cell carcinoma of the esophagus were enrolled in this study. All patients underwent operation in Provincial Hospital Affiliated to Shandong University between June, 2003 and June, 2005. The expression of CCR7 was detected by immunohistochemistry. All statistic analyses were performed with SPSS 13.0 statistical software. According to the clinico-patho-logic factors, the difference of CCR7 expression was compared by x2 test. Kaplan-meier method was performed to calculate the survival rate, Cox regression multivariate analysis was performed to determine independent prognostic factors. Results The expression rate of CCR7 in stage Ⅰ , stage Ⅱ and stage Ⅲ patients was 25.0 % , 70.3% and 85.5% , respectively. The difference of CCR7 expression between stage Ⅱ and stageⅢ was statistically significant (x2 =5.0, P =0.02). The CCR7 expression rate in T1, T2 and T3 patients was 33.3% , 64.9% and 80.9% , respectively. The difference of CCR7 expression between T2and T3 was statistically significant (x2 =5.4, P =0.01). The level of expression of CCR7 in patients with lymph node metastasis was significantly higher than those without metastasis (x2 =10.8, P = 0.00). The 5-year survival rate instage Ⅰ , stage Ⅱand stage Ⅲ patients was 100.0% , 38. 3% and 22.4% , respectively. The 5-year survival rate in patients with CCR7 overexpression was significantly lower than those without CCR7 overexpression (x2 = 23.7, P = 0.00). The 5-year survival rate in T2, T3, NO and N1 patients with CCR7 overexpression was significantly lower than those without CCR7 overexpression The result of Cox analysis demonstrated that T , N and CCR7 overexpression were independent prognostic factors. Conclusion CCR7 expression was detected in esophageal squamous cell carcinoma and was found to be significantly associated with T stage,N stage and lymph node metastasis. The patients with CCR7 expression was significantly lower the 5-year survival rate than without CCR7 expression. T stage, lymph node metastasis and CCR7 expression were independent prognostic factors.     

神经生长因子受体p75在膀胱癌组织和缺氧条件下膀胱癌T24细胞株中的表达

目的 探讨神经生长因子受体p75(p75NGFR)在膀胱癌组织中的表达及缺氧条件下在膀胱癌细胞表达的变化.方法 免疫组织化学方法检测107例膀胱癌组织标本(男85例,女22例,平均年龄61岁;T117例、T2 77例、T3～T4 13例;病理分级Ⅰ～Ⅱ级75例、Ⅲ～Ⅳ级32例)和24例转移淋巴结组织标本中p75NGFR的表达,癌旁正常黏膜组织50例为对照.选取膀胱移行细胞癌T24细胞株,免疫组织化学、半定量RT-PCR方法检测常规氧分压和微缺氧条件下 p75NGFR在细胞株中的表达.结果 107例膀胱癌组织标本中p75NGFR阳性表达46例(43.0%),正常对照组标本均为阴性表达.p75NGFR阳性表达率与患者性别、年龄、肿瘤组织学分级和分期无相关性(x2值分别为1.509、3.759、0.011和2.324,P值均0.05).24例转移淋巴结组织标本中p75NGFR阳性表达5例(20.8%),与膀胱癌组织标本阳性率比较差异有统计学意义(r=0.077,P<0.05).微缺氧条件下第3天T24细胞株的p75NGFR mRNA吸光度值为0.52±0.07,正常对照组为0.91±0.01,组间差异有统计学意义(P<0.05).结论 膀胱癌组织中p75NGFR表达与淋巴结转移呈负相关;微缺氧条件下p75NGFR mRNA在膀胱癌细胞株中的表达降低.     

Chemoattraction of T cells expressing CCR5, CXCR3 and CX3CR1 by proximal tubular epithelial cell chemokines.

BACKGROUND: Chemokines produced by resident renal cells promote the infiltration of leukocyte subsets. We have analysed the chemotactic responses of CD3+ peripheral blood lymphocytes (PBLs) to factors secreted by proximal tubular epithelial cells (PTEC), assessing the role of chemokines and chemokine receptors in this process. METHODS: By FACS we analysed expression of the chemokine receptors CCR5, CXCR3, CX3CR1, CCR2, CXCR1 and CXCR2 on both freshly isolated and activated PBLs. Using Boyden chambers we studied the chemotactic activity of supernatant from resting and cytokine-stimulated (TNF-alpha and IFN-gamma) PTEC towards PBLs. Soluble recombinant chemokines and blocking antibodies were used to study the role of individual chemokine receptors. Chemokine secretion by PTEC was analysed by ELISA. RESULTS: Only a small proportion of freshly isolated cells expressed the chemokine receptors and there was low grade chemotaxis of these cells towards cytokine-stimulated PTEC supernatant compared with unstimulated PTEC supernatant. After activation, 84% of PBLs expressed CCR5, 90% expressed CXCR3 and 19% expressed CX3CR1. There remained low expression levels of CXCR1, CXCR2 and CCR2. Activated PBLs showed strong chemotactic responses to supernatant from cytokine-stimulated PTEC compared with unstimulated PTEC (P<0.001). Chemotaxis of these cells was inhibited by blocking CCR5, CXCR3 and CX3CR1 by 69%, 71% and 29% respectively, with complete inhibition following combined blockade. ELISA showed high levels of the chemokine RANTES/CCL5 (for CCR5) and IP-10/CXCL10 (for CXCR3) in cytokine-stimulated PTEC supernatant. CONCLUSIONS: Chemokines produced by cytokine activated PTEC promote the selective recruitment of activated T cells via the receptors, CCR5, CXCR3 and CX3CR1. These receptors may be amenable to therapeutic manipulation in renal inflammation.     

结直肠癌组织中成纤维细胞激活蛋白的表达及临床意义

目的探讨成纤维细胞激活蛋白（FAP）在结直肠癌组织中的表达及其与各病理学指标之间的关系。方法应用免疫组织化学染色法检测55例结直肠癌组织和50例正常结直肠组织中FAP的表达,观察阳性细胞在不同组织中的分布数量,结合肿瘤分期、有无淋巴结转移及不同浸润深度等病理学指标,评价FAP表达与结直肠癌病理特征的相关性。结果正常结直肠组织中几乎无FAP表达,少数癌细胞有微弱表达。FAP阳性细胞主要为结直肠癌间质组织中的肿瘤相关成纤维细胞（CAFs）。TNMⅢ～Ⅳ期标本中FAP阳性细胞为（40．1±15．9）个,多于Ⅰ-Ⅱ期的（18．3±7．7）个（P〈0.01）;且阳性细胞数量与分期程度相关（r=0．544,P〈0．01）。淋巴结转移组中阳性细胞为（44．4±13．3）个,多于无淋巴结转移的（18．5±8．1）个（P〈0．01）;且阳性细胞数量与有无淋巴结转移相关（r=0．793,P〈0．01）。不同浸润深度T2、T1和T4组标本中FAP阳性细胞数分别为（25．2±8．9）、（32．4±19．3）和（29．2±16．5）个（P〉0．05）;阳性细胞数量与浸润深度无关（r=0．003,P〉0．05）。结论FAP在正常结直肠组织中无表达．而主要表达于结直肠癌组织中的CAFs中。FAP阳性细胞与结直肠癌的TNM分期及淋巴结转移相关。     

Lymphogenous and hematogenous metastasis of thymic epithelial tumors

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.