细胞间粘附分子—1在膀胱移行细胞癌中的表达及意义

目的:探讨细胞间粘附分子-1(ICAM-1)在膀胱移行细胞癌中的表达及意义.方法:应用免疫组织化学方法对59例膀胱移行细胞癌中细胞间粘附分子-1的表达进行研究.结果:59例膀胱移行细胞癌中25例呈阳性表达,而正常膀胱粘膜未见表达,ICAM-1阳性表达的组织中常伴有大量淋巴细胞浸润.ICAM-1在膀胱移行细胞癌中的阳性表达率为42.37%,其阳性率在肿瘤病理分级、临床分期等方面差异有显著性(P<0.01).结论:ICAM-1在膀胱肿瘤中的表达与机体抗肿瘤免疫有关,同时可作为判断肿瘤恶性程度的指标.     

P16基因在肾癌中的表达及其与生物学行为的关系

目的 :研究P16基因在肾细胞癌中的表达及其与肾细胞癌生物学行为之间的关系。方法 :采用免疫组织化学方法检测肾细胞癌中P16基因表达情况。结果 :在肾细胞癌中 ,P16基因阳性表达率为 5 2 .9% ,在G1、G2 、G3 中 ,阳性表达率分别为 6 6 .7%、71.4 %和 37.0 % (P <0 .0 5 ) ,在透明细胞癌和颗粒细胞癌中 ,阳性表达率分别为 6 9.7%和 2 2 .2 % (P <0 .0 5 )。在阳性表达组和阴性表达组中 ,患者生存率差异有显著性意义。结论 :基因的表达与肾细胞癌的发生发展密切相关 ,是肿瘤恶性程度和预后的一个参考指标     

肾癌p53蛋白表达及其点突变相关研究

目的探讨肾细胞癌发病机制中致癌基因突变规律。方法以ｐ５３蛋白表达及其点突变率为实验观测指标,对以往１１６例各类肾肿瘤以免疫组化ＡＢＣ法检测病理切片的ｐ５３表达。并以ＰＣＲＳＳＣＰ观测５９外显子点突变,并以１２例非瘤新鲜肾组织作对照。结果三类恶性肾细胞癌的ｐ５３阳性表达率介于４２％～５４％之间,且随癌细胞恶性度增加及分期增加而升高,而良性瘤及正常肾组织为阴性。点突变率介于２５％～７１％之间,与恶性度及分期相关。第９外显子点突变率明显高于其它区域,良性瘤及正常肾无点突变。结论肾癌发病机制与ｐ５３基因突变密切相关。ｐ５３蛋白阳性表达与其点突变相辅并存,协同一致,二者阳性率与生存期及预后密切相关     

膀胱癌多向耐药基因P－GP_（170）表达的研究

应用ＭＤＲ（Ａｂ－１）和Ｃ２１９单克隆抗体，免疫组化法对４２例膀胱癌ＭＤＲ１和ＭＤＲ３基因编码的Ｐ－ＧＰ１７０的表达进行了研究。结果发现，３０例膀胱初发瘤Ｐ－ＧＰ１７０的阳性表达率为７０％（２１／３０），其中８例（２７％）为强阳性染色，１２例（４３％）为阳性或部分阳性染色。１２例化疗后复发的肿瘤切片，Ｐ－ＧＰ１７０的阳性表达率为８３．３％，２４例Ｇ（１～２）肿瘤Ｐ－ＧＰ１７０阳性表达率为７９％（１９／２４）。而１８例Ｇ３肿瘤Ｐ－ＧＰ１７０的阳性表达率仅占４４％（８／１８）。４２例膀胱肿瘤总的Ｐ－ＧＰ１７０阳性表达率为７３．８％（３１／４２）。实验结果提示，Ｐ－ＧＰ１７０的表达水平与肿瘤的恶性度或病理组织学分级不相关。复发性肿瘤Ｐ－ＧＰ１７０的表达率高于初发肿瘤，可能是腔内灌注化疗失败的重要因素。     

肾肿瘤和良性肾病组织βhCGmRNA表达的研究

目的：探讨βhCGmRNA在肾细胞癌（RCC）和良性肾脏疾病组织中的表达情况。方法：采用RT-PCR并结合限制性内切酶法检测44例RCC和24例良性肾脏疾病组织βhCG基因及其亚型的表达。结果：RCC的βhCGmRNA阳性表达率为52%，晚期和低分化RCC的阳性表达率较高，但无统计学意义。良性肾脏疾病组织的βhCGmRNA阳性表达率为54%，包括3例多囊肾（3/6），7例肾萎缩（7/13），2例嗜酸性细胞瘤，1例肾盂肾炎，β7基因是RCC和良性肾脏疾病组织中最常见的βhCGmRNA亚型。结论：βhCG基因可能在恶性肾肿瘤和良性肾脏疾病中发挥作用，其病理生理和临床意义值得进一步研究。     

Fas配体基因在肾细胞癌中的表达及其意义

目的 探讨Ｆａｓ配体（ｒａｓ ｌｉｇａｎｄ,ＦａｓＬ）基因在肾细胞癌中的表达及临床临床。方法 应用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）及免疫组织技术化学分别检测ＦａｓＬ ｍＲＮＡ及蛋白在５１例肾细胞癌中的表达。结果 ５１例肿瘤 ３２例ＦａｓＬ基因阳性表达。其中１、２、３级肿瘤中ＦａｓＬ的阳性表达率分别为２５．０％、６３．６％、８８．２％,１、２、３、４期肿瘤肿瘤中Ｆａｓｌ的阳性表达率分别为３１．６     

膀胱癌多向耐药基因P—GP170表达的研究

应用ＭＤＲ（Ａｂ－１）和Ｃ２１９单克隆抗体，免疫组化法对４２例膀胱癌ＭＤＲ１和ＭＤＲ３基因编码的Ｐ－ＧＰ１７０的表达进行了研究，结果发现，３０例膀胱初发瘤Ｐ－ＧＰ１７０的阳性表达率为７０％（２１／３０），其中８例（２７％）为强性染色，１２例（４３％）为阳性或部分阳性染色。１２例化疗后复发的肿瘤切片，Ｐ－ＧＰ１７０的阳性表达率为８３．３％，２４例Ｇ１～２肿瘤Ｐ－ＧＰ１７０阳性表达率为７９％（１９／２     

膀胱移行细胞癌中P16及Rb基因表达的关系

应用免疫组织化学方法对５９例膀胱移行细胞癌中Ｐ１６及Ｒｂ基因的表达进行研究。结果显示：５９例中Ｐ１６及Ｒｂ基因阳性表达率分别为４７４６％、７１１９％，其中１１例肿瘤组织（１８６４％）Ｐ１６及Ｒｂ基因均阳性表达，未发现同一肿瘤组织中同时存在Ｐ１６及Ｒｂ基因的表达缺失。Ｐ１６及Ｒｂ基因在膀胱移行细胞癌中的阳性表达率在肿瘤病理分级及临床分期的差异中均有显著性（Ｐ＜００５）。结果提示：Ｐ１６及Ｒｂ基因的异常表达在膀胱肿瘤的发生、发展过程中起重要作用，膀胱肿瘤中Ｐ１６及Ｒｂ基因同时表达缺失是少见现象     

Fhit基因和Survivin基因在膀胱移行细胞癌中的表达和意义

目的探讨Fhit基因和Survivin基因在膀胱移行细胞癌（TCC）中的表达和意义。方法用免疫组织化学sP法检测49例膀胱TCC组织和10例正常膀胱组织中Fhit蛋白和Survivin蛋白的表达。结果10例正常膀胱组织中Fhit蛋白表达均为阳性，Survivin蛋白表达均为阴性；Fhit蛋白在膀胱TCC中阳性表达率为46．9％（23／49），随恶性程度和临床分期增高而阳性表达减少，差异有统计学意义（P〈0．05）；Survivin蛋白在膀胱TCC中阳性表达率为57．1％（28／49），随恶性程度和临床分期增高而阳性表达增高，差异有统计学意义（P〈0．05）；膀胱TCC中Fhit蛋白和Survivin蛋白表达呈负相关（P〈0．05）。结论Fhit基因和Survivin基因可能是膀胱TCC发生的晚期分子事件，Fhit蛋白和Survivin蛋白异常表达可作为膀胱TCC的肿瘤标志物。Fhit蛋白可能通过肿瘤凋亡抑制途径发挥作用。     

ICAM-1、VEGF与MVD在胆囊癌及癌前病变中检测的意义

细胞粘附分子-1（ICAM-1）是细胞表面粘附分子，属免疫球蛋白超家属．主要参与细胞间的连接。研究表明越是恶性程度高＼侵袭能力越强的恶性肿瘤．则越表现出ICAM-1的过度表达。血管内皮生长因子（VEGF）则通过多种机制诱导宿主新生血管形成，促进肿瘤生长，ICAM-1、VEGF和血管生成这三者相互作用．对肿瘤的发生发展、肿瘤的转移和病人的预后发挥重要作用。但ICAM-1，VEGF和血管生成在胆囊病变中的关系和意义如何，至今为止仍报道不多。现有不少证据表明，肿瘤生长与转移依赖于新的血管生成。近年报道乳腺、前列腺和膀胱等实体肿瘤，其血管生成与肿瘤的转移和预后呈正相关。本文试图探讨ICAM-1、VEGF和血管生成鞋胆囊病变中的表达及其意义。     

肾细胞癌及尿路移行细胞癌组织中黑色素瘤抗原基因mRNA的表达

目的　评价肿瘤特异性黑色素瘤抗原 (MAGE) 1、 3基因作为肾细胞癌及尿路移行细胞癌组织中的免疫学检测和免疫治疗、基因治疗分子标志物的可行性。　方法　肾细胞癌组织标本 18例 ,尿路移行细胞癌组织标本 2 6例 ,相应的癌旁组织 10例 ,采用RT PCR方法对MAGE 1、MAGE 3基因进行测定。　结果　 18例肾癌组织中MAGE 1mRNA阳性表达 10例 (5 6 % ) ,MAGE 3mRNA阳性表达11例 (6 1% ) ,MAGE 1及MAGE 3同时表达 8例 (44 % ) ;2 6例尿路移行细胞癌组织中MAGE 1mRNA阳性表达 16例 (6 2 % ) ,MAGE 3mRNA阳性表达 15例 (5 8% ) ,MAGE 1及MAGE 3同时表达 12例 (46 % )。癌旁组织 10例均不表达MAGE 1及MAGE 3。　结论　MAGE 1、MAGE 3基因有可能作为肾癌及尿路移行细胞癌组织免疫学检测的分子标志物 ,并且具有作为免疫治疗、基因治疗特异性靶位的潜在价值。     

SSX2基因mRNA在泌尿系统肿瘤组织中的表达

目的探讨肿瘤特异性SSX2基因mRNA在肾细胞癌及尿路移行细胞癌组织中的表达.方法采用逆转录聚合酶链反应方法,检测26例肾细胞癌患者、27例尿路移行细胞癌患者的癌组织,及15例患者相应的癌旁组织中SSX2基因mRNA的表达.结果 26例肾癌患者癌组织中,18例(69%)SSX2 基因mRNA表达阳性;27例尿路移行细胞癌组织中,22例(81%)SSX2 基因mRNA表达阳性.癌旁组织均不表达.在肿瘤不同分期之间及不同分级之间SSX2 基因mRNA的表达差异均无统计学意义(P均＞0.05).结论 SSX2基因mRNA在肾癌及尿路移行细胞癌组织中高表达.     

Cells isolated from the human cortical interstitium resemble myofibroblasts and bind neutrophils in an ICAM-1--dependent manner.

Progressive renal disease is frequently accompanied by renal interstitial inflammation and fibrosis in which the activity of resident fibroblasts may be of central importance. Because there are relatively few fibroblasts in the normal cortical interstitium and there is no specific marker to permit their identification, these cells have proved difficult to characterize in vitro. In this study, these cells were isolated and established in culture, using CD90 as a positive selection marker. Antibodies to CD90 bound to tubular epithelial cells and fibroblasts, but not to glomerular cells in kidney sections. In culture, only fibroblasts were CD90-positive. These normal renal cortical fibroblasts (RCF) were alpha-smooth muscle actin- and vimentin-positive, but desmin-, cytokeratin-, and factor VIII-negative, identifying them as myofibroblasts. They expressed platelet-derived growth factor alpha and beta receptors; CD44; and alpha 2, beta 1, and beta 3 integrin chains: this combination of markers was also characteristic of fibroblasts in sections of normal cortex. These cells were positive for ICAM-1 but negative for VCAM-1. Similarly, proliferating or growth-arrested renal cortical fibroblasts (RCF) in culture expressed ICAM-1 but not VCAM-1. The expression of VCAM-1 was detected, however, and that of ICAM-1 was increased on fibroblasts associated with inflammatory infiltrates in sections from fibrotic kidneys, and ICAM-1 and VCAM-1 were up-regulated on RCF in culture after incubation with increasing doses of interleukin-1 beta or tumor necrosis factor alpha (maximum between 24 and 48 h). These adhesion molecules were functional, and neutrophils adhered to resting and cytokine-activated RCF. Binding was maximal between 24 and 48 h after cytokine treatment and was inhibited by anti-CD18 antibodies. ICAM-1 is the principal adhesion molecule controlling inflammatory cell infiltration of the interstitium. The study presented here suggests that cortical fibroblasts may be central to the control of this infiltration.     

Circulating adhesion molecules during kidney allograft reperfusion

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR). Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion. Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection. The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.     

int-2 and c-erbB-2 gene amplification in urological cancers]

We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract, 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%) of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle invasion and the remaining was G1, pTa tumor with subsequent recurrence of multiple tumors. The other 2 cases (6.3%) with invasive transitional cell carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross rearrangement of EGFR gene was detected in transitional cell carcinoma. On the other hand, renal cell carcinomas and prostatic carcinomas had neither amplification nor gross rearrangement of these 3 genes. These results suggest that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have a specific role in carcinogenesis and in progression of transitional cell carcinoma through their gene amplifications.     

VCAM-1, ICAM-1, and E-selectin in IgA nephropathy and Schönlein-Henoch syndrome: differences between tissue expression and serum concentration

The tissue expressions of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin-1) were investigated in biopsy specimens from 28 patients with different stages of IgA nephropathy (IgAN) and 20 patients with acute renal failure (ARF) or chronic renal diseases (amyloidosis, Alport's glomerulopathy) by immunohistochemistry. The results were compared with the serum levels of the three adhesion molecules. VCAM-1 expression was significantly increased on parietal/tubular epithelial cells in IgAN and ARF. Significantly elevated circulating VCAM-1 levels were measured in IgAN and amyloidosis, but did not correlate with renal function (creatinine clearance). Significantly increased glomerular endothelial/epithelial ICAM-1 expression was found in IgAN and ARF. Intense mesangial ICAM-1 expression was found in mild stages of IgAN and in Sch?nlein-Henoch syndrome. Circulating ICAM-1 was not significantly elevated in IgAN and different renal diseases. VCAM-1 and ICAM-1 expressions of interstitial infiltrating cells were significantly higher in severe than in mild IgAN and associated with an increased infiltration of inflammatory leukocytes. Patients with IgAN and different renal diseases had decreased mesangial and almost absent interstitial E-selectin expression as compared with controls. The circulating E-selectin levels were significantly elevated in ARF. In conclusion, the tissue expression of adhesion molecules in IgAN reflects a continuous inflammatory renal activity. However, only increased circulating VCAM-1 serum levels correlated significantly with the histological state of renal inflammation and could be used as a disease marker.     

Inflammation and endothelial activation are linked to renal function in long-term kidney transplantation

The aim of this study was to investigate the relationships between inflammation and adhesion molecules in long-term kidney transplantation. We measured serum concentrations of tumor necrosis factor-alpha (TNFalpha) and intercellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) in 35 renal transplant recipients (mean age of transplantation 5 +/- 3 years) and in 35 chronic renal insufficiency (CRI) patients; twenty-six healthy subjects were enrolled as controls. Transplanted showed higher values than controls of TNFalpha (P < 0.0001), ICAM-1 (P < 0.0001), and VCAM-1 (P < 0.0001). CRI group as well exhibited higher concentrations than controls of TNFalpha (P < 0.0001), ICAM-1 (P < 0.0001), and VCAM-1 (P < 0.0001). Transplanted and CRI patients had similar blood pressure and renal function levels, and TNFalpha, ICAM-1, and VCAM-1 were not significantly different in the two groups. In transplanted group ICAM-1, VCAM-1, and TNFalpha correlated negatively and independently with glomerular filtration rate (GFR) -P < 0.00001 for all. TNFalpha as well correlated with ICAM-1 and VCAM-1 (P < 0.001, respectively). In CRI group, TNFalpha correlated with serum creatinine, ICAM-1, and VCAM-1 (P = 0.01 for all). In conclusion, in long-term renal transplantation, the level of kidney function and both inflammation and endothelial activation are closely related. In fact, the multiple regression analysis demonstrated that the level of kidney insufficiency and the levels of the studied molecules were independently associated.     

Circulating adhesion molecules during kidney allograft reperfusion

Adhesion molecule expression is an important event during early transplant failure. The aim of the present study was to examine the release of adhesion molecules during the first minutes of kidney allograft reperfusion in relation to delayed graft function and acute graft rejection. We enrolled 49 renal transplant recipients, including 13 cases of delayed graft function (DGF) and 11 cases of acute graft rejection (AR).Plasma concentrations of E-selectin, VCAM-1 and ICAM-1 after 3 min of reperfusion were significantly higher than in the iliac vein before reperfusion. There was no statistically significant difference between patients with and without DGF as regards E-selectin, VCAM-1 and ICAM-1 concentrations in the iliac vein before and in the renal vein after 3 min of reperfusion.Concentrations of adhesion molecules in the iliac vein before reperfusion and in the renal vein after 3 min of reperfusion did not differ significantly between patients with and without AR except for ICAM-1 iliac vein concentration which was significantly increased in AR patients. Plasma levels of E-selectin, ICAM-1 and VCAM-1 were increased after kidney allograft reperfusion. Moreover, elevated serum levels of ICAM-1 before transplantation correlated with subsequent acute kidney allograft rejection.The results suggest that elevated ICAM-1 levels may be implicated in acute graft rejection.