Levels of circulating intercellular adhesion molecule-1 in patients with Behçet's disease

The purpose of this study was to investigate the possible relationship between circulating intercellular adhesion molecule-1 (cICAM-1) plasma levels and Beh?et's disease. Plasma levels of cICAM-1 were measured in 44 patients with Beh?et's disease and in 30 healthy controls. cICAM-1 levels were higher in patients with Beh?et's disease than in the controls (P=0.001). The difference was more marked between patients with active Beh?et's disease and controls (P < 0.001). cICAM-1 levels were also higher in patients with active Beh?et's disease than in those with inactive disease (P<0.001). cICAM-1 seems to be related to disease activity in Beh?et's disease. It may be useful in assessing disease activity in Beh?et's disease, as well as in monitoring response to treatment.     

Clinical significance of serum vascular cell adhesion molecule-1 levels in patients with hepatocellular carcinoma

AIM:To evaluate the correlation between serum vascularcellular adhesion molecule-1 (VCAM-1) levels andclinicopathological features in patients with hepatocellularcarcinoma (HCC).METHODS:Ninety-six patients who underwent HCCresection were recruited in the study.Preoperative serumlevels of soluble VCAM-1 were measured by enzyme-linkedimmunosorbent assay.RESULTS:Serum VCAM-1 level in HCC patients wasinversely correlated with platelet count (r=-0.431,P<0.001)and serum albumin level (r=-0.279,P<0.001),and positivelycorrelated with serum bilirubin level (r=0.379,P<0.001).Serum VCAM-1 level was not associated with tumorcharacteristics such as tumor size,venous invasion,presence of microsatellite nodules,tumor grade and tumorstage.Serum VCAM-1 level was significantly higher in HCCpatients with cirrhosis compared with those without cirrhosis(median 704 vs 546 ng/mL,P<0.001).Furthermore,asignificantly better disease-free survival was observed inHCC patients with low VCAM-1 level (P=0.019).CONCLUSION:Serum VCAM-1 level appears to reflectthe severity of underlying chronic liver disease rather thanthe tumor status in HCC patients,and low preoperativeserum VCAM-1 level is predictive of better disease-freesurvival after surgery.     

Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet's disease

The objective of this study was to measure soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Behçet's disease (BD) and to analyse the relationship of sICAM-1 levels with clinical and some laboratory measures of disease activity. Forty patients with BD fulfilling the International Study Group Criteria for the diagnosis of BD and 20 healthy controls were studied. Twenty patients had active, and 20 patients had inactive disease. Serum sICAM-1 was determined by a sandwich ELISA. The mean (±SD) sICAM-1 level was significantly higher in the whole BD group (297.3±86.6 ng/ml) than in the healthy controls (213±83.5 ng/ml; P< 0.05). The mean sICAM-1 levels in active and inactive BD patients were 315.7±76.3 ng/ml and 258.3±73.3 ng/ml, respectively. The mean sICAM-1 level in active patients was significantly higher than in inactive patients and healthy controls (P< 0.02 and P< 0.001, respectively). No statistically significant difference in mean sICAM-1 levels was found between inactive BD patients and healthy controls (P>0.05). There was no statistically significant difference between the mean sICAM-1 levels of active patients with (351.3±77.2 ng/ml) or without vascular lesions (292±68.8; P>0.05). In spite of a positive correlation between disease activity and both erythrocyte sedimentation rate and C-reactive protein (CRP; P< 0.01), we found no correlation between sICAM-1 and either of them (P>0.05). The elevated levels of sICAM-1 may be due to endothelial cell activation and/or damage or may be the result of inflammation. In either case it did not seem to be superior to more conventional measures of disease activity.     

Intercellular adhesion molecule-1 polymorphisms in patients with Behçet disease: A meta-analysis

Abstract

Objectives. To examine the association between the Intercellular adhesion molecule-1 (ICAM1) Polymorphisms and Behçet's disease.

Methods. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials for original studies up to July 31, 2012 were searched for relevant studies. All pooled odds ratios (ORs) were derived from either fixed or random-effects model with its 95% confidence intervals (CI).

Results. Five studies met the inclusion criteria. Overall, ICAM1 E469 (OR = 1.45, 95% CI = 1.06–1.97), genotype ICAM1 469 E/E (OR = 1.45, 95% CI = 1.09–1.94), ICAM1 241 G/R (OR = 3.65, 95% CI = 1.69–7.89), had significant associations with Behçet's disease. A significant association was found between the presence of skin lesions and genotype ICAM1 469 E/E (OR = 3.52, 95% CI = 1.62–7.66).

Conclusions. Behçet's disease was associated with the ICAM1 E469, genotype ICAM1 469 E/E, ICAM1 241 G/R polymorphisms in different ethnic groups. Among patients, genotype ICAM1 469 E/E had a significant association with skin lesion.     

Expression of intercellular adhesive molecule-1 in liver cancer tissues and liver cancer metastasis

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High sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic syndrome and insulin resistance (CURES-105)

Aim

The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR).

Methodology

From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5.

Results

Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR.

Conclusion

In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.     

Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

AIM:To explore the cooperative effects of antisenseoligonucleotide (ASON) of cell adhesion molecules andcimetidine on the expression of E-selectin and ICAM-1 inendothelial cells and their adhesion to tumor cells.METHODS:After treatment of endothelial cells with ASONand/or cimetidine and induction with TNF-α,the proteinand mRNA changes of E-selectin and ICAM-1 in endothelialcells were examined by flow cytometry and RT-PCR,respectively.The adhesion rates of endothelial cells to tumorcells were measured by cell adhesion experiment.RESULTS:In comparison with TNF-α inducing group,lipo-ASON and lipo-ASON/cimetidine could significantly decreasethe protein and mRNA levels of E-selectin and ICAM-1 inendothelial cells,and lipo-ASON/cimetidine had mostsignificant inhibitory effect on E-selectin expression (from36.37±1.56% to 14.23±1.07%, P<0.001).Meanwhile,cimetidine alone could inhibit the expression of E-selectin(36.37±1.56% vs 27.2±1.31%,P<0.001),but not ICAM-1(69.34±2.50% vs 68.07±2.10%,P<0.05)and the two kinds ofmRNA,either.Compared with TNF-α inducing group,the rateof adhesion was markedly decreased in lipo-E-selectin ASONand lipo-E-selectin ASON/cimetidine treated groups(P<0.05),and lipo-E-selectin ASON/cimetidine worked better thanlipo-E-selectin ASON alone except for HepG2/ECV304 group(P<0.05).However,the decrease of adhesion was notsignificant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidinetreated groups except for HepG2/ECV304 group (P>0.05).CONCLUSION:These data demonstrate that ASON incombination with cimetidine in vitro can significantly reducethe adhesion between endothelial cells and hepatic orcolorectal cancer cells,which is stronger than ASON orcimetidine alone.This study provides some useful proofsfor gene therapy of antiadhesion.     

Integrin β7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion

Integrin-β7 (ITGB7) mRNA is detected in multiple myeloma (MM) cells and its presence is correlated with MAF gene activation. Although the involvement of several integrin family members in MM-stoma cell interaction is well documented, the specific biologic functions regulated by integrin-β7 in MM are largely unknown. Clinically, we have correlated integrin-β7 expression in MM with poor survival outcomes post autologous stem cell transplantation and postsalvage therapy with bortezomib. Functionally, we have found that shRNA-mediated silencing of ITGB7 reduces MM-cell adhesion to extra-cellular matrix elements (fibronectin, E-cadherin) and reverses cell-adhesion-mediated drug resistance (CAM-DR) sensitizing them to bortezomib and melphalan. In addition, ITGB7 silencing abrogated MM-cell transwell migration in response to SDF1α gradients, reduced vessel density in xenografted tumors, and altered MM cells in vivo homing into the BM. Mechanistically, ITGB7 knockdown inhibited focal adhesion kinase (FAK) and Src phosphorylation, Rac1 activation, and SUMOylation, reduced VEGF production in MM-BM stem cell cocultures and attenuated p65-NF-κB activity. Our findings support a role for integrin-β7 in MM-cell adhesion, migration, and BM homing, and pave the way for a novel therapeutic approach targeting this molecule.     

Expression of focal adhesion kinase and α5andβ1integrins in carcinonas and its clinical significance

AIM：To detect the expression pattern of FAK(focal adhesion kinase)and integrinα5andβ1 subunits in different kinds of cancerous tissues and to study their correlation with clinicopathological data including tumor type,grade and lymph node status.METHODS:Using an immunohistochemical technique,we examined the expression of FAK and integrin and subunits in cancerous and noncancerous tissues obtained from75patients with gastric carcinomas,21colorectal carcinomas,16 hepatocellular carcinomas,20uterocervical carcinomas,and20breast carcinomas.RESULTS:The staining of FAK was stronger in cancerous than in noncancerous areas,Enhanced expression of FAKwas detected in poor-differentiated carcinoma of the stomach and colorectum.Tumors with lymph node metastases had more FAKprotein than those without metastases.In addition.the deeper the extent of tumor infiltration,the higher the FAKexpression.The expression of integrinα5andβ1subunits was lower in cancerous areas than in noncancerous areas,but it was higher in well-differentiated cancerous tissues than in poor differentiated tissues.The relationship between the expression of integrinα5andβ1subunits and infiltration or metastasis was not significant.Cancerous tissues with stronger FAK expression(++or+++)also had a higher expression of integrinα5andβ1subunits in the tumor and its unaffected margins.CONCLUSION:FAKis a better marker for carcinogenesis and the progression of cancer than integrinα5orβ1subunit,and it may be not only a transformation-linked enzyme but also a progression-linked enzyme.     

Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schönlein purpura

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a small sized vasculitis affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have recently been implicated in the susceptibility to some vasculitides. To further investigate the clinical implication of ICAM-1 polymorphisms in HSP, we examined their potential association and influence in the development of severe complications in an unselected series of patients with HSP. METHODS: Fifty-two patients, of which 41 were children, were diagnosed with HSP using classification criteria of Michel, et al at the Hospital Xeral-Calde (Lugo, Spain); 129 ethnically matched controls were included. Patients had at least one year of followup. Patients and controls were genotyped by allelic oligonucleotide techniques for ICAM-I polymorphism at codon 241 and 469. RESULTS: The frequency distribution of the alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between HSP patients and controls. Also, no differences between patients with or without renal manifestations were found. However, the frequency of the codon 469 K/E genotype was significantly decreased in patients without severe gastrointestinal manifestations compared to those with them (22.29 vs 65%, OR 0.1, p = 0.02, after correction for age, sex, and disease duration). None of the 11 adults exhibited the R/G genotype at codon 241 compared with 7 of 41 children (OR 0.0, 95% CI 0.0-2.9, p = 0.14). Patients with the R/G genotype were associated with low incidence of renal manifestations and none developed permanent renal involvement (renal sequelae); however, this finding did not achieve statistical significance. CONCLUSION: ICAM-1 polymorphisms alone are not associated with development of HSP, but patients not carrying the codon 469 K/E genotype are at decreased risk of developing severe gastrointestinal complications. The R/G polymorphism at codon 241 may reduce the risk of renal sequelae in the development of HSP in adulthood.     

Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells

Purpose

Associated with many molecules, metastasis includes cell adhesion to extracellular matrix, migration towards specific direction and invasion into local vessel of distant organs. The purpose of the present study was to evaluate the role of ecto-5′-nucleotidase (eN, ecto-5-NT, CD73) generated extracellular adenosine in biologically malignant behaviors of human breast cancer cell lines.

Materials and methods

Two human breast cancer cell lines, T-47D with lower expression of CD73 and MB-MDA-231 with higher expression of CD73, were used to investigate the functions of CD73. The effects of CD73 over-expression on invasion, migration and adhesion were observed in T-47D transfected with pcDNA-NT5E plasmid. The effects of specific CD73 inhibitor, α, ß-methylene ADP (APCP), were observed in MB-MDA-231 cells.

Results

The results showed CD-73 overexpression increased invasion, migration and adhesion to ECM of the pcDNA-NT5E transfected T-47D cells compared to the saline and mock vector controls. The increased cell mobility of CD-73-overexpressed T-47D cells was blocked by APCP. Adenosine increased the mobility of wild type T-47D cells. APCP inhibited the mobility of the MB-MDA-231 cells.

Conclusion

Taken together, our results indicated that CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine. This study provided a possibly molecular mechanism of metastasis of breast carcinoma.     

Circulating intercellular adhesion molecule 1 predicts non-specific elevation of α1-fetoprotein

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R=–0.397,P<0.001), aspartate aminotransferase (R=0.421,P<0.001), bilirubin (R=0.231,P<0.05) and cICAM-1 (R=0.430,P<0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.Abbreviations AFP 1-fetoprotein - cICAM-1 circulating intercellular adhesion molecule 1     

High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-ϰB-dependent

Aims/hypothesis. Infiltration of mononuclear cells and glomerular enlargement accompanied by glomerular cell proliferation are very early characteristics of the pathophysiology of diabetes. To clarify the mechanism of early diabetic nephropathy, we measured [³H]-thymidine incorporation and cell numbers to show the influence of a high ambient glucose concentration and the osmotic effect on rat mesangial cell proliferation. We also measured the effect of high glucose on the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 by flow cytometry and semiquantitative RT-PCR in mesangial cells and the adhesion of leukocytes to mesangial cells. Methods/results. Cells exposed to high d-glucose (30 mmol/l) caused an increase in [³H]-thymidine incorporation and cell numbers at 24 and 48 h and normalized at 72 h (p < 0.05), whereas these changes were not found in high mannitol (30 mmol/l), IL-1β, or TNFα-stimulated mesangial cells. Cells exposed to high-glucose (15, 30, or 60 mmol/l) or osmotic agents (l-glucose, raffinose and mannitol) showed that intercellular adhesion molecule-1 expression began to increase after 24 h, reached its maximum at 24 and 48 h and gradually decreased afterwards. The stimulatory effects of high glucose and high mannitol on mRNA expression were observed as early as 6 h and reached its maximum at 12 h. Up-regulation of ICAM-1 protein and mRNA was also found in IL-1-β and TNF-α-stimulated mesangial cells. Neither vascular adhesion molecule-1 protein nor mRNA expression was, however, affected by high glucose and high mannitol. Notably, the protein kinase C inhibitors calphostin C and staurosporine reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation. Furthermore, the NF-ϰB inhibitor N-tosyl-l-phenylalanine chloromethyl ketone reduced high glucose- or high mannitol-induced intercellular adhesion molecule-1 mRNA expression and high glucose-induced proliferation. Results showed that high glucose (15, 30 mmol/l) or high concentrations of osmotic agents remarkably increased the number of adherent leukocytes to mesangial cells (p < 0.01) compared with control cells (5 mmol/l d-glucose). Functional blocking of intercellular adhesion molecule-1 on mesangial cells with rat intercellular adhesion molecule-1 monoclonal antibody, calphostin C, staurosporine, or N-tosyl-l-phenylalanine chloromethyl ketone significantly inhibited high glucose- or high mannitol-induced increase in leukocyte adhesion (p < < 0.05). Conclusion/interpretation. These results suggest that high glucose can upregulate intercellular adhesion molecule-1 protein and mRNA expression but not vascular adhesion molecule-1 expression in mesangial cells and promote leukocyte adhesion through up-regulation of intercellular adhesion molecule-1 through osmotic effect, possibly depending on the protein kinase C nuclear factor-kappa B (PKC-NF-ϰB) pathway. High glucose itself can also promote mesangial cell proliferation through the PKC-NF-ϰB pathways. We conclude that hyperglycaemia in itself seems to be an important factor in the development of early diabetic nephropathy. [Diabetologia (2000) 43: 1544–1553] Received: 21 June 2000 and in revised form: 10 August 2000     

Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin β1 signaling in human hepatocellular carcinoma

Angiopoietin-like protein 4 (ANGPTL4) plays complex and often contradictory roles in vascular biology and tumor metastasis, but little is known about its function in hepatocellular carcinoma (HCC) metastasis. In the present study, we showed that hypoxia-inducible factor 1α (HIF-1α) directly up-regulates ANGPTL4, and its stableness positively correlates with ANGPTL4 expression in HCC tissue. Overexpression of ANGPTL4 significantly increased HCC cell transendothelial migration in vitro and intrahepatic and distal pulmonary metastasis in vivo, whereas silencing ANGPTL4 expression or treatment with a neutralizing antibody specific for ANGPTL4 protein resulted in a reduced transendothelial migration. We also found that serum ANGPTL4 is higher in HCC patients, compared to healthy control, and correlates with intrahepatic metastasis and histological grade. Further, secreted ANGPTL4 promotes transendothelial migration and metastasis of HCC cells in vitro and in vivo through the up-regulation of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells and the activation of the VCAM-1/integrin β1 axis. Conclusion: ANGPTL4 is a target gene of HIF-1α and acts as an important regulator in the metastasis of HCC. Serum ANGPTL4 correlates with tumor progression and metastasis and might be used to indicate prognosis in HCC patients.     

Two α-dicarbonyls downregulate migration,invasion, and adhesion of liver cancer cells in a p53-dependent manner

Background

Hepatocellular carcinoma accounts for more than 600,000 deaths per year due to it being a highly invasive tumor. The α-dicarbonyl, methylglyoxal demonstrates efficacy at reducing tumor burden, however the anti-cancerous activities of 3-deoxyglucosone, have never been studied.

Aims

To determine the anti-cancerous potential of methylglyoxal and 3-deoxyglucosone on liver tumor cells.

Methods

The in vitro effects of methylglyoxal and 3-deoxyglucosone were studied by investigating migration, invasion, and adhesion of Huh-7, HepG2, and Hep3B cells.

Results

3-Deoxyglucosone inhibited migration of Huh-7 and HepG2 cells. Methylglyoxal decreased migration of HepG2 cells. Additionally, 3-deoxyglucosone and methylglyoxal impaired invasion, and adhesion of Huh-7 and HepG2 cells. In Hep3B cells, a p53 null cell line, 3-deoxyglucosone and methylglyoxal had no effect on migration, invasion, or adhesion. However, both compounds inhibited invasion of wild-type p53 transfected Hep3B cells. Silencing of p53 in Huh-7 and HepG2 cells abrogated the effects of the α-dicarbonyls on cell invasion. 3DG and MG did not alter p53 total protein but promoted nuclear translocation of p53.

Conclusions

These studies suggest that 3-deoxyglucosone and methylglyoxal impair invasion, migration, and adhesion of hepatocellular carcinoma. The effects of both compounds on cell invasion are dependent on p53 and imply that α-dicarbonyls could be efficacious in the treatment of p53-expressing invasive liver tumors.     

αB-crystallin/HspB5 regulates endothelial–leukocyte interactions by enhancing NF-κB-induced up-regulation of adhesion molecules ICAM-1, VCAM-1 and E-selectin

αB-crystallin is a small heat shock protein, which has pro-angiogenic properties by increasing survival of endothelial cells and secretion of vascular endothelial growth factor A. Here we demonstrate an additional role of αB-crystallin in regulating vascular function, through enhancing tumor necrosis factor α (TNF-α) induced expression of endothelial adhesion molecules involved in leukocyte recruitment. Ectopic expression of αB-crystallin in endothelial cells increases the level of E-selectin expression in response to TNF-α, and enhances leukocyte–endothelial interaction in vitro. Conversely, TNF-α-induced expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin is markedly inhibited in endothelial cells isolated from αB-crystallin-deficient mice. This is associated with elevated levels of IκB in αB-crystallin deficient cells and incomplete degradation upon TNF-α stimulation. Consistent with this, endothelial adhesion molecule expression is reduced in inflamed vessels of αB-crystallin deficient mice, and leukocyte rolling velocity is increased. Our data identify αB-crystallin as a new regulator of leukocyte recruitment, by enhancing pro-inflammatory nuclear factor κ B-signaling and endothelial adhesion molecule expression during endothelial activation.