Measurement of serum circulating intercellular adhesion molecule-1 and its clinical significance in hepatocellular carcinoma: preliminary report

Serum circulating intercellular adhesion molecule-1 (cICAM-1) was measured in 50 patients with hepatocellular carcinoma (HCC). The mean cICAM-1 level in the 50 patients was 2220 ng/ml and 43 patients (86%) had a high level of cICAM-1 — more than 1000 ng/ml. Comparative analysis of cICAM-1 and alpha-fetoprotein (AFP) levels in the HCC patients showed that serum AFP level was negative (<20 ng/ml) in five patients or "questionable positive" (20–90 ng/ml) in ten patients, while the levels of cICAM-1 in these patients were 1810 and 1710 ng/ml, respectively. Seven patients who underwent hepatectomy had tumor recurrences during a follow-up period of 6–18 months. Their serum AFP levels were lower than 200 ng/ml (mean value, 27 ng/ml), but their mean cICAM-1 level was 1956 ng/ml at the time tumor recurrence was diagnosed. We suggest that the measurement of serum cICAM-1 is not only useful for prediction of the progression and prognosis of HCC, but that it may also be an important marker for the early diagnosis of the disease, and for monitoring postoperative recurrence, particularly in patients with low levels of serum AFP. Received for publication on Aug. 24, 1998; accepted on Jan. 4, 1999     

p38 MAPK在LPS诱导内皮细胞表达ICAM-1中的作用

目的 研究p38丝裂原激活蛋白激酶(MAPK)信号转导通路在脂多糖(LPS)诱导人脐静脉内皮细胞(HUVEC)表达细胞间粘附分子-1(ICAM—1)中的作用。方法 脐静脉内皮细胞培养后分为两组：(1)刺激组,设不同时相点分别用LPS刺激内皮细胞;(2)预处理组,在LPS刺激前2h,用SB203580预处理内皮细胞。观察ICAM—1蛋白和mRNA表达的变化,检测内皮细胞p38MAPK活性变化。结果 LPS刺激后,内皮细胞表面ICAM—1分子在8～36h显增加,胞浆中mRNA在2h即有显增加;LPS刺激HUVEC后15min,p38MAPK活性即有升高,30～60min达高峰。p38抑制剂SB203580可显抑制LPS的诱导作用。结论 LPS可能通过激活p38MAPK信号转导通路,调节HUVEC的ICAM—1基因和蛋白表达。     

Endothelial cell activation in men with erectile dysfunction without cardiovascular risk factors and overt vascular damage

PURPOSE: Endothelial cell activation (ECA) is an initiating event in atherosclerosis. Biochemical measures of ECA were evaluated in patients with erectile dysfunction (ED) associated or not associated with cardiovascular risk factors (VRFs) to assess whether ED is a sentinel of atherosclerosis. MATERIALS AND METHODS: Circulating soluble P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and endothelin-1 concentrations were assessed in 45 men with ED but no VRFs, 45 men with ED associated with VRFs and 25 healthy men. Ultrasound intima-media thickness of carotid arteries and pharmacologically stimulated peak systolic velocity of cavernous arteries were used to assess vascular damage. RESULTS: Measures of ECA were higher in men with ED but no VRFs than in controls (p <0.01) and all were comparable among groups of men with ED. Levels of endothelin-1 in men with ED and no VRFs versus healthy men of the same age resulted in the best independent predictor for ED after adjusting for the confounding effect of increased body mass index and smoking (OR 5.37, 95% CI 2.12 to 19.70). Intima-media thickness of carotid arteries was comparable in controls and in men with ED but no VRFs, and ruled out the bias of overt damage of large arteries in the latter. Peak systolic velocity of cavernous arteries excluded vasculogenic ED in the majority of patients with no VRFs. CONCLUSIONS: Increased biochemical measures of ECA were associated with ED independent of coexisting VRFs and overt vascular damage, suggesting that ED is a sentinel of early atherosclerosis.     

Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome

Plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay in four groups of children. Group 1 consisted of 20 patients with acute diarrhoea-associated haemolytic uraemic syndrome (D+HUS), the aetiology of HUS being verocytotoxin-producingEscherichia coli infection in each case. Controls consisted of 11 patients who had previously had D+HUS (group 2), 12 with chronic renal failure (group 3) and 8 healthy controls (group 4). When compared with healthy controls, the acute D+HUS group had higher sVCAM-1 (median 1,875 ng/ml, range 1,200–6,450 ng/ml vs. 1,200 ng/ml, range 975–2,125 ng/ml), von Willebrand factor antigen, (1.9 U/ml, range 0.85–5.1 U/ml vs. 0.55 U/ml, range 0.3–1.57 U/ml), white cell count (WBC, 14.5×10⁹/l, range 7.8–43.1 10⁹/l vs. 8.9 10⁹/l, range 5.7–10.8 10⁹/l) and neutrophil count (PMN, 10.1×10⁹/l, range 4.3–26.5 10⁹/l vs. 4.3 10⁹/l, range 3.7–6.6 10⁹/l), allP<0.005, and sICAM-1 was reduced (230 ng/ml, range 130–340 ng/ml vs. 400 ng/ml, range 260–690 ng/ml),P<0.05. Within the acute D+HUS group there was a significant correlation between sICAM-1 and PMN (r=0.56,P<0.01). There was no correlation between any adhesion molecule and plasma creatinine or von Willebrand factor. Comparing the acute HUS group with children with chronic renal failure, WBC (P<0.001), PMN (P<0.01) and sVCAM-1 (P<0.01) were significantly elevated, but there was no difference between the von Willebrand factor (P=0.08) or the sICAM-1 (P>0.1). sVCAM-1 is elevated and sICAM-1 decreased in acute D+HUS. This pattern of altered adhesion molecule concentration is unlike that in adults with vasculitis and suggests that different endothelial regulatory factors are at play.     

Adhesion molecules in patients after lung transplantation

Leukocyte adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and its ligands, are involved in inflammatory processes of the lung. For ICAM-1, differential expression during different kinds of complications after transplantation has been proposed. We analyzed the role of ICAM-1, CD18, CD11a, CD11b, and CD11c during episodes of rejection or infection in patients after lung transplantation and compared the results to episodes without apparent complication. A total of 98 bronchoalveolar lavage (BAL) samples and 90 serum samples were analyzed. ICAM-1, CD18, CD11a, CD11b, and CD11c expressions were detected immunocytochemically on alveolar macrophages. Soluble ICAM-1 was quantified in serum and BAL. In the control group, 49.8 +/- 18% of macrophages stained positive for CD11b. During rejection, the mean of cells showing CD11b on the surface was significantly higher (64.6 +/-11.4%) with no difference compared to episodes of infection (59.7 +/-22.7). All other epitopes were not expressed differently with regard to a normal clinical course or episodes of infection and rejections. In summary, assessment of ICAM-1 and corresponding ligands did not allow for a reliable discrimination between episodes of rejection or infection in lung transplantation.     

抗黏附药物对结肠癌术后肝转移的干预作用

目的 观察抗黏附药物丹参、蛇毒对结肠癌术后肝转移的影响。方法 选用24只Balbc/c裸鼠,用保脾法建立人结肠癌裸鼠肝转移模型,随机分为4组,分别自腹腔注射生理盐水1.4ml(对照组)、丹参0.7 ml(丹参组)、蛇毒(3.125×10~(-2))U(蛇毒组)、丹参0.7 ml加蛇毒(3.125×10~(-2))U(丹参加蛇毒组);比较各组原位移植瘤生长及肝转移发生情况,肝表面转移癌结节数与结节细胞表面细胞间黏附分子-1(ICAM-1)表达的关系。结果 实验各组均有脾内原位移植瘤生长,24只裸鼠均存活。对照组和丹参加蛇毒组各有5只裸鼠发生肝转移,丹参组和蛇毒组各有4只裸鼠发生肝转移。各组间肝转移结节数相比差异有显著性意义(P=0.007);对照组高于丹参组(P=0.018)和蛇毒组(P=0.018)及丹参加蛇毒组(P=0.008)。平均肝转移癌结节数与癌细胞表面ICAM=1的表达呈直线正相关(r=0.657,P<0.05)。结论 抗黏附药物可减少肝转移结节数目,有效干预实验性结肠癌的转移,其机制可能与降低癌细胞表面ICAM-1的表达有关。     

心脏跳动中二尖瓣置换术心肌组织黏附分子的变化

目的观察心脏跳动中二尖瓣置换术围术期心肌细胞间黏附分子-1（ICAM-1）和血管细胞间黏附分子-1（VCAM-1）的表达。方法30例风湿性二尖瓣病变病人分为两组，试验组（浅低温下阻断主动脉）16例与对照组（中度低温阻断主动脉）14例。分别于CPB前、CPB后30min留取右心房标本，采用免疫组织化学技术检测心肌细胞上ICAM-1和VCAM-1的表达。结果与CPB前比较较，两组CPB后心肌细胞上ICAM-1和VCAM．1的表达明显升高（P〈0．01）。与对照组相比，试验组CPB后ICAM-1和VCAM-1的表达明显降低（P〈0．01）。结论心脏跳动中二尖瓣置换术对心肌细胞上黏附分子的影响较停跳手术少，减轻了术后的炎症反应。     

不同手术方式对门静脉高压症患者血浆中ICAM-1水平影响的临床研究

目的研究不同手术方式对门静脉高压症患者手术后血浆中细胞粘附因子-1(ICAM-1以下同)水平的动态变化规律及其意义。方法采用随机、双盲法收集外伤性脾破裂和门静脉高压症患者手术前和手术后3、7、14天、6月血浆标本,采用双抗体夹心酶联免疫吸附法(EL ISA)测定血浆中ICAM-1及检测同期肝功能。结果所有患者手术后血浆中ICAM-1水平升高,至术后14天达到高峰,门静脉高压症组手术后,早期增高更明显(P<0.05);14天后下降,与同时期肝功能变化呈正相关;6月后联合手术组患者血浆中ICAM-1明显低于其它手术组。结论门静脉高压症患者手术后早期血浆中ICAM-1水平升高,是门静脉血栓形成的高峰时间。     

细胞间黏附分子-1在自发性高血压大鼠肾损害作用的研究

目的：研究细胞间黏附分子-1（ICAM-1）在自发性高血压大鼠（SHR）肾组织的表达及其与肾损害的关系。方法：以同龄雄性正常血压大鼠（WKY）和SHR为研究对象,分别于10周龄和28周龄检测两种大鼠尾动脉压、24h尿蛋白定量、肾功能等;留取肾组织行HE染色、免疫组织化学及RT-PCR法检测ICAM-1蛋白及mRNA表达情况,并作分析。结果：与同龄WKY大鼠比较,SHR尾动脉压和24h尿蛋白定量明显增高（P〈0.05和P〈0.05）;与12周龄SHR比较,28周龄SHR尾动脉压和24h尿蛋白定量明显增加（P〈0.05和P〈0.05）。SHR组肾组织ICAM-1蛋白及mRNA表达较同龄WKY增强（P〈0.05）,28周龄SHR较10周龄SHR表达增强（P〈0.05）,ICAM-1表达与24h尿蛋白定量呈正相关（P〈0.05）。结论：SHR出现蛋白尿时,肾组织ICAM-1表达增强,炎症参与了高血压肾损害的发生。     

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目的 研究胃癌瘤体中血管细胞粘附分子（VCAM－1）对胃癌的血管生成、生长、转移的影响。方法 对30例胃癌、8例胃溃疡,10例正常人标本进行了免疫组化染色、图像分析,分析瘤体VCAM－1的表达与胃癌病理参数的关系。结果 VCAM－1不仅表现在胃癌血管内皮细胞上高表达,在胃癌细胞膜上也有表达,而且VCAM－1的表达强度表达率与胃癌的血管的生成和转移有关。结论 VCAM－1在胃癌的血管生成、瘤细胞转移中可能起到重要作用,其促进了胃癌肿瘤血管的形成。     

细胞间粘附分子-1在胃癌组织中的表达及临床意义

目的:探讨细胞间粘附分子-1(ICAM-1)在胃癌中的表达及其临床意义。方法:采用免疫组织化学法检测胃癌组织中ICAM-1的表达情况,并与临床病理参数作相关分析。结果:58例胃癌组织中,ICAM-1的阳性表达率为34.5%,其表达率与肿瘤浸润深度、肝转移及血管侵犯无明显相关(P＞0.05);ICAM-1表达阳性率在肠型胃癌显著高于弥漫型胃癌(P＜0.01),淋巴结转移者显著低于无淋巴结转移者(P＜0.01);随肿瘤TNM分期的增高,ICAM-1的阳性表达率也逐渐下降(P＜0.05)。结论:胃癌组织中ICAM-1表达与淋巴结转移和肿瘤分期密切相关。     

体外循环炎症反应中粘附分子变化及干预性治疗的研究

目的探讨体外循环(CPB)围术期中药川芎嗪干预性治疗的作用机制及临床意义.方法选取诊断明确的先天性心脏病病人32例,随机分成川芎嗪组20例,对照组12例.前者在体外循环预充液中加入盐酸川芎嗪5 mg/kg,后者不用.分别于麻醉诱导后,转机15 min,停机2、6、12、24 h共6个时点,抽取动脉血,采用双抗体夹心法酶联免疫吸附试验测定血浆中可溶性细胞间粘附分子(sICAM-1)、可溶性P-选择素(sP-Selectin)的表达值.结果麻醉诱导后(基值)川芎嗪组和对照组sICAM-1、sP-Selectin无明显差异(P＞0.05);转机后15 min、停机2、6、12 h两组的sICAM-1、sP-Selectin表达值均明显升高,其中停机6、12 h最为明显,与基值比较 ,差异有显著性(P＜0.05);但川芎嗪组较对照组为低(P＜0.05).结论川芎嗪能减弱CPB致炎症反应中sICAM-1、sP-Selectin表达,减轻CPB所致炎症反应,从而减少CPB下心脏直视手术并发症的发生.     

氯沙坦对尿酸性肾病大鼠肾组织MCP-1和ICAM-1mRNA表达的影响

目的 探讨氯沙坦对尿酸性肾病大鼠血清尿酸、尿素氮、肌酐、尿蛋白以及单核细胞趋化蛋白-1（MCP-1）和细胞间黏附分子-1（ICAM-1）在肾脏中表达的影响.方法 分别给予右侧肾脏切除术后大鼠氧嗪酸钾或者联合别嘌呤醇或者联合氯沙坦灌胃8周,监测上述指标变化情况,并采用实时荧光定量PCR测定各组大鼠肾脏MCP-1和ICAM-1mRNA表达的情况.结果 别嘌呤醇和氯沙坦均有效降低血清尿酸水平（P〈0.01）,改善肾功能（P〈0.05）.肾切除联合氧嗪酸钾灌胃组大鼠肾脏组织MCP-1和ICAM-1明显高于单纯肾切除组（P〈0.01）,别嘌呤醇和氯沙坦均能减少氧嗪酸钾所致的上述基因表达的增加（P〈0.01）.结论 MCP-1和ICAM-1介导的炎症反应可能参与高尿酸血症加速肾脏病进展过程,氯沙坦可能通过抑制尿酸所致的炎症反应而延缓肾脏病的进展.     

Effects of laparoscopy-assisted radical gastrectomy on the expression of intercellular adhesion molecule β1 and integrin 1 in peritoneal mesothelial cells and its significance

Objective To investigate the changes of the expression of intercellular adhesion molecule-1 (ICAM-1) and integrin β1 in peritoneal mesothelial cells during laparoscopy-assisted radical gastrectomy (LARG) and to explore the possible effects of LARG on the peritoneal metastasis. Methods From April to August 2008, LARG was performed for 26 patients with gastric cancer (laparoscopy group), while 20 cases underwent open radical gastrectomy (open group). Peritoneum of right upper belly was collected at 3 operation time points (the beginning, 2 hours, 4 hours). The expressions of ICAM-1 and integrin β1 in peritoneal mesothelial cells at 3 time points were detected by immunohistochemistry. Results With the operation prolonging, the expression of ICAM-1 and integrin β1 was increased gradually in both LARG and open groups. The expression of integrin β1 in two groups was obviously increased at 4-hour time point as compared to the beginning (P<0.05). Besides, there were no significant differences of these two adhesion molecules among the three operation time points between two groups (P>0.05). Conclusions Compared with open surgery, LARG is not associated with a greater effect on the expression of ICAM-1 and integrin β1 in peritoneal mesothelial cells, and may not promote peritoneal metastasis of gastric cancer through increasing the expression of adhesion molecule in peritoneal mesothelial cells.     

Effects of laparoscopy-assisted radical gastrectomy on the expression of intercellular adhesion molecule β1 and integrin 1 in peritoneal mesothelial cells and its significance

Objective To investigate the changes of the expression of intercellular adhesion molecule-1 (ICAM-1) and integrin β1 in peritoneal mesothelial cells during laparoscopy-assisted radical gastrectomy (LARG) and to explore the possible effects of LARG on the peritoneal metastasis. Methods From April to August 2008, LARG was performed for 26 patients with gastric cancer (laparoscopy group), while 20 cases underwent open radical gastrectomy (open group). Peritoneum of right upper belly was collected at 3 operation time points (the beginning, 2 hours, 4 hours). The expressions of ICAM-1 and integrin β1 in peritoneal mesothelial cells at 3 time points were detected by immunohistochemistry. Results With the operation prolonging, the expression of ICAM-1 and integrin β1 was increased gradually in both LARG and open groups. The expression of integrin β1 in two groups was obviously increased at 4-hour time point as compared to the beginning (P<0.05). Besides, there were no significant differences of these two adhesion molecules among the three operation time points between two groups (P>0.05). Conclusions Compared with open surgery, LARG is not associated with a greater effect on the expression of ICAM-1 and integrin β1 in peritoneal mesothelial cells, and may not promote peritoneal metastasis of gastric cancer through increasing the expression of adhesion molecule in peritoneal mesothelial cells.     

缺血再灌注对大鼠肺细胞间粘附分子-1表达的影响

目的 观察缺血再灌注（Ｉ／Ｒ）对肺组织细胞间粘附分子－１（ＩＣＡＭ－１）表达的影响，分析ＩＣＡＭ－１表达与肺内中性粒细胞浸润的关系。方法 Ｗｉｓｔａｒ大鼠单肺原位热缺血再灌注损伤模型分７组，左肺缺血９０ｍｉｎ，再灌注时间分别为０、１、２、４、８、１６、２４ｈ。逆转录－聚合酶链式反应（ＲＴ－ＰＣＲ）法及Ｗｅｓｔｅｒｎ ｂｌｏｔ法检测肺组织ＩＣＡＭ－１ｍＲＮＡ及蛋白表达，测定各组肺组织髓过氧化物酶活性     

n-3多不饱和脂肪酸预防同种异体移植血管硬化的作用

目的研究n-3多不饱和脂肪酸预防同种异体移植血管硬化的作用。方法SD和Wistar大鼠各240只,随机配对成240对建立颈总动脉同种异体移植血管模型,并随机平均分成4组,每组60对。对照组:术前、术后未喂食n-3多不饱和脂肪酸;A组:术前2周始喂食n-3多不饱和脂肪酸600mg/kg(以EPA含量计,下同),直至摘取标本;B组:喂食300mg/kg;C组:喂食150mg/kg。分别于术后1、7、14、21和28d摘取受者移植血管,观察移植血管在活体的搏动情况,HE染色光学显微镜下观察移植血管的组织学病理改变,电子显微镜观察移植血管的超微结构变化,免疫组织化学染色检测细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)和细胞核因子κB(NF-κB)在移植血管的表达。结果对照组术后7d移植血管开始有病理改变,28d时最为明显,管腔已基本堵塞;A组、B组、C组移植血管的病理改变均较对照组迟缓,管腔通畅率优于对照组。对照组ICAM-1,VCAM-1,NF-κB的表达较A组、B组和C组明显增强(P<0.05)。移植术后1d、7dICAM-1、VCAM-1、NF-κB的表达A组、B组、C组间比较差异无统计学意义(P>0.05),移植术后14、21和28d的表达C组较A组、B组明显增强(P<0.05),而A组与B组比较差异无统计学意义(P>0.05)。结论n-3多不饱和脂肪酸能够预防同种异体移植血管硬化,表现为移植血管病理改变发生迟缓,管腔通畅率高,ICAM-1,VCAM-1和NF-κB的表达减弱,n-3多不饱和脂肪酸以300mg/kg用量达到的效果最佳。