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Wang Y, Yuan H, Zhao M, Fang L. Identification of signature of gene expression in biliary atresia using weighted gene co-expression network analysis. Medicine (Baltimore) 2022; 101:e30232. [PMID: 36123893 PMCID: PMC9478247 DOI: 10.1097/md.0000000000030232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Biliary atresia (BA) is the most common cause of obstructive jaundice during the neonatal period. This study aimed to identify gene expression signature in BA. The datasets were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis identified a critical module associated with BA, whereas Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed the functions of the essential modules. The high-connectivity genes in the most relevant module constructed protein-protein interaction networks via the string website and Cytoscape software. Hub genes screened by lasso regression consisted of a disease classification model using the randomforest method. Receiver operating characteristic curves were used to assess models' sensitivity and specificity and the model was verified using the internal and external validation sets. Ten gene modules were constructed by WGCNA, of which the brown module had a strong positive correlation with BA, comprising 443 genes. Functional enrichment analysis revealed that module genes were mainly involved in biological processes, such as extracellular matrix organization, cell adhesion, inflammatory response, and the Notch pathway (P < .001), whereas these genes were involved in the metabolic pathways and cell adhesion molecules (P < .001). Thirty-nine high-connectivity genes in the brown module constructed protein-protein interaction networks. keratin 7 (KRT7) and C-X-C motif chemokine ligand 8 (CXCL8) were used to construct a diagnostic model that had an accuracy of 93.6% and the area under the receiver operating curves for the model was 0.93. The study provided insight into the signature of gene expression and possible pathogenesis of BA; furthermore, it identified that the combination of KRT7 and CXCL8 could be a potential diagnostic model for BA.
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Affiliation(s)
- Yongliang Wang
- Hepatological Surgery Department, The First People’s Hospital of Guiyang City, Guizhou Province, China
| | - Hongtao Yuan
- Hepatological Surgery Department, The First People’s Hospital of Guiyang City, Guizhou Province, China
- *Correspondence: Hongtao Yuan, Hepatological Surgery Department, The NO.1 People’s Hospital of Guiyang City, Guizhou Province, China (e-mail:
| | - Maojun Zhao
- Emergency Department, The First People’s Hospital of Guiyang City, Guizhou Province, China
| | - Li Fang
- Department of Critical Care Medicine, The First People’s Hospital of Guiyang City, Guizhou Province, China
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The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis. Cells 2019; 8:cells8121503. [PMID: 31771248 PMCID: PMC6952767 DOI: 10.3390/cells8121503] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 11/17/2019] [Accepted: 11/18/2019] [Indexed: 01/09/2023] Open
Abstract
Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.
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Shaker OG, Ay El-Deen MA, Abd El-Rahim MT, Talaat RM. Gene Expression of E-Selectin in Tissue and its Protein Level in Serum of Breast Cancer Patients. TUMORI JOURNAL 2019; 92:524-30. [PMID: 17260494 DOI: 10.1177/030089160609200610] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Aims and background This study aims to detect the expression of E-selectin in tissue and the serum level of its soluble form in patients with primary breast cancer and benign breast tumors and to correlate the results with the clinicopathological data of the subjects. Methods Fifty participants were included in the study and stratified into 3 subgroups. Group A comprised 30 patients with primary breast cancer, group B 9 patients with benign breast tumors, and group C 11 healthy control women undergoing reduction mammoplasty. E-selectin gene expression was investigated in breast tissues by PCR techniques and soluble E-selectin was measured in sera by ELISA. Results The E-selectin gene was expressed in 73.3% of group A, 44.4% of group B and 9.1% of group C. It was expressed in 61.5% of patients with grade 2 breast cancer and in 82.4% of patients with grade 3 breast cancer. E-selectin gene expression was detected in 60%, 73.3% and 100% of patients with stage II, III and IV tumors, respectively. It was detected in 81.8% of patients with node-positive primary breast cancer and in 50% of patients with node-negative cancer. PCR in situ hybridization was done to locate the site of E-selectin expression. E-selectin was found on the membranes of peritumoral endothelial cells while it was not found on breast epithelial cells. Serum levels of soluble E-selectin were significantly elevated in group A compared to groups B and C ( P <0.001). They increased significantly with increasing breast cancer stage ( P <0.001) and were significantly higher in patients with lymph node involvement than in patients without node involvement ( P <0.001). Conclusions The studied marker showed associations with established prognostic parameters such as lymph node involvement and histological tumor grade. Further studies are needed to evaluate E-selectin as a possible target for antimetastat-ic therapy through modulation of the expression of the cell adhesion molecule. E-selectin can be regarded as a promising strategy in improving tumor therapy.
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Affiliation(s)
- Olfat G Shaker
- Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.
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Lo Iacono O, Rincón D, Hernando A, Ripoll C, Catalina MV, Salcedo M, Clemente G, Gomez J, Nuñez O, Matilla A, Bañares R. Serum levels of soluble vascular cell adhesion molecule are related to hyperdynamic circulation in patients with liver cirrhosis. Liver Int 2008; 28:1129-35. [PMID: 18482273 DOI: 10.1111/j.1478-3231.2008.01763.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND In patients with liver cirrhosis, serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) have been associated with increasing fibrosis and are related to angiogenesis. AIM To assess the possible correlation between sVCAM-1 and splanchnic and systemic haemodynamic and clinical staging of cirrhotic patients. METHODS We assessed, using immunoassays, the serum levels of sVCAM-1, in the peripheral and hepatic vein, in all consecutive patients with liver cirrhosis, who underwent a haemodynamic study as part of its routine clinical work-up. RESULTS We studied 86 patients [61 M/25 F; age 51.1 (8.3) years] with alcoholic (31) or viral (HBV:6, HCV:49) cirrhosis, 10 of them with hepatocellular carcinoma (Milan criteria). The mean follow-up was 391(187) days; 29 patients died or underwent transplantion during follow-up. A strong correlation in serum levels of sVCAM-1 was observed between the peripheral and the hepatic vein (r=0.8; P=0.0001). There was no correlation between levels of sVCAM-1 and hepatic venous pressure gradient. At univariate analysis, sVCAM-1 was inversely related with mean arterial pressure (r=-0.292; P=0.007), systemic vascular resistance (SVR) (r=-0.37; P=0.005) and serum sodium levels (r=-0.326; P=0.002). In multivariate linear regression only SVR remained as an independent variable associated to sVCAM-1. A correlation of sVCAM-1 with Child-Pugh scores, model for end-stage liver disease (MELD) and the clinical stage proposed in the Baveno IV consensus conference was also observed. Finally, patients who died or underwent transplantion during follow-up had significantly greater values of sVCAM-1 at baseline than those who did not [3505(1329) vs. 2488(1208) P=0.001]. CONCLUSION This study supports a potential role of sVCAM-1 as a marker of hyperdynamic circulation, closely related to the different stage of liver cirrhosis.
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Affiliation(s)
- Oreste Lo Iacono
- CIBEREHD and Servicio de Aparato Digestivo, Sección de Hepatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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5
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Gion M, Fabricio AS. Editor's Comments. Int J Biol Markers 2008. [DOI: 10.1177/172460080802300201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Qi K, Qiu H, Sun D, Minuk GY, Lizardo M, Rutherford J, Orr FW. Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice. Hepatology 2004; 40:1144-50. [PMID: 15382152 DOI: 10.1002/hep.20421] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Metastases rarely occur in human livers with cirrhosis in clinical studies. We postulated that this phenomenon would also occur in experimental cirrhosis. Cirrhosis was established in C57BL/6 mice by carbon tetrachloride (CCl(4)) gastrogavage. B16F1 melanoma cells were injected into the mesenteric vein to induce hepatic metastases. Contrary to our postulate, there was greater than 4-fold increase in metastasis in animals with cirrhosis compared to controls. Intravital videomicroscopy showed that the hepatic sinusoids were narrower and more tumor cells were retained in the terminal portal vein (TPV) in cirrhotic livers. Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis. Using confocal microscopy and the fluorescent nitric oxide (NO) probe 4,5-diaminofluorescein diacetate, a significantly lower level of NO release was detected in livers with cirrhosis both in basal conditions and after tumor cell arrest. Eight hours after mesenteric vein tumor cell injection, the percentage of apoptotic tumor cells in the sinusoids was 17% +/- 2% in livers with cirrhosis and 30% +/- 5% in normal livers. More mitotic and Ki-67 labeled tumor cells were seen in livers with cirrhosis. In conclusion, the changes in architecture and adhesion molecule expression in livers with cirrhosis may cause more tumor cells to arrest in the TPV. Lower levels of NO production may reduce apoptosis of B16F1 cells in livers with cirrhosis. As a result, these changes may promote the growth of metastasis in this cirrhotic model.
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MESH Headings
- Animals
- Apoptosis
- Cell Division
- Cell Line, Tumor
- Female
- Fluorescein
- Immunohistochemistry
- Indicators and Reagents
- Liver/pathology
- Liver Cirrhosis, Experimental/complications
- Liver Cirrhosis, Experimental/metabolism
- Liver Cirrhosis, Experimental/pathology
- Liver Neoplasms/complications
- Liver Neoplasms/pathology
- Liver Neoplasms/physiopathology
- Liver Neoplasms/secondary
- Melanoma, Experimental/complications
- Melanoma, Experimental/pathology
- Melanoma, Experimental/physiopathology
- Melanoma, Experimental/secondary
- Mice
- Mice, Inbred C57BL
- Microscopy, Confocal
- Microscopy, Video
- Nitric Oxide/metabolism
- Vascular Cell Adhesion Molecule-1/metabolism
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Affiliation(s)
- Ke Qi
- Department of Pathology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada R3E 0W3
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Ho JW, Poon RT, Tong CS, Fan ST. Clinical significance of serum vascular cell adhesion molecule-1 levels in patients with hepatocellular carcinoma. World J Gastroenterol 2004; 10:2014-8. [PMID: 15237425 PMCID: PMC4572324 DOI: 10.3748/wjg.v10.i14.2014] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To evaluate the correlation between serum vascular cellular adhesion molecule-1 (VCAM-1) levels and clinicopathological features in patients with hepatocellular carcinoma (HCC).
METHODS: Ninety-six patients who underwent HCC resection were recruited in the study. Preoperative serum levels of soluble VCAM-1 were measured by enzyme-linked immunosorbent assay.
RESULTS: Serum VCAM-1 level in HCC patients was inversely correlated with platelet count (r = -0.431, P < 0.001) and serum albumin level (r = -0.279, P < 0.001), and positively correlated with serum bilirubin level (r = 0.379, P < 0.001). Serum VCAM-1 level was not associated with tumor characteristics such as tumor size, venous invasion, presence of microsatellite nodules, tumor grade and tumor stage. Serum VCAM-1 level was significantly higher in HCC patients with cirrhosis compared with those without cirrhosis (median 704 vs 546 ng/mL, P < 0.001). Furthermore, a significantly better disease-free survival was observed in HCC patients with low VCAM-1 level (P = 0.019).
CONCLUSION: Serum VCAM-1 level appears to reflect the severity of underlying chronic liver disease rather than the tumor status in HCC patients, and low preoperative serum VCAM-1 level is predictive of better disease-free survival after surgery.
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Affiliation(s)
- Joanna-W Ho
- Centre for the Study of Liver Disease, Department of Surgery, University of Hong Kong, Hong Kong, China
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Takegoshi K, Tohyama T, Okada E. A case of advanced primary biliary cirrhosis treated with granulocyte and monocyte apheresis. Ther Apher Dial 2003; 7:468-72. [PMID: 12887733 DOI: 10.1046/j.1526-0968.2003.00085.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Generally, the most effective treatment for advanced primary biliary cirrhosis (PBC) is liver transplantation, but adjunct therapies are needed. We report here a first case of advanced PBC treated with a new immunotherapy, granulocyte and monocyte apheresis (GCAP). A column (Adacolumn, Japan Immunoresearch Laboratory Takasaki, Japan) was filled with cellulose acetate beads to selectively adsorb granulocytes and monocytes/macrophages. A 49-year-old woman was diagnosed with PBC in 1987. In June 2001, steroid pulse therapy and adjuvant fresh frozen plasma was given for moderate jaundice but without success. In July, as total bilirubin rapidly increased, treatment with GCAP was started and succeeded in suppressing the rapid deterioration of total bilirubin (value changes after each of four applications: 15.4-->14.0, 27.2-->25.1, 25.8-->24.0, 25.7-->23.7 mg/dL) and improving prothrombin time (16.4-->14.5 s). Although GCAP therapy did not prevent a fatal outcome, it suppressed rapid deterioration of jaundice and increased quality of life for a month.
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Kobayashi H, Horikoshi K, Long L, Yamataka A, Lane GJ, Miyano T. Serum concentration of adhesion molecules in postoperative biliary atresia patients: relationship to disease activity and cirrhosis. J Pediatr Surg 2001; 36:1297-301. [PMID: 11479880 DOI: 10.1053/jpsu.2001.25798] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND/PURPOSE Biliary atresia (BA) is associated with progressive liver fibrosis, which may be mediated by immunologic abnormalities involving adhesion molecules. This study investigates the relationship between serum intercellular adhesion molecule-1 (sICAM-1), serum vascular cell adhesion molecule-1 (sVCAM-1), and the clinical and histologic severity of BA. METHODS Serum ICAM-1 and VCAM-1 levels were measured by enzyme-linked immunosorbent assay in 35 patients with BA and 20 healthy controls. Standard liver function tests (LFTs), and frozen section liver biopsy specimens were used to determine liver status. On the basis of LFT results, the BA patients were classified into group I (n = 10; normal LFTs), group II (n = 15; elevated LFTs, anicteric), and group III (n = 10; elevated LFTs, icteric). Eight subjects in group II, and all subjects in group III had portal hypertension (PH). RESULTS sICAM-1 levels were significantly elevated in group III (1760.0 +/- 717.5 ng/mL) compared with group II (555.1 +/- 199.4 ng/mL), group I (272.1 +/- 59.9 ng/mL) and controls (256.3 +/- 71.6 ng/mL). Although sVCAM-1 levels were significantly elevated in group III (1932.9 +/- 282.6 ng/mL) compared with group II (1054.3 +/- 297.0 ng/mL), group I (605.4 +/- 112.4 ng/mL), and controls (616.0 +/- 112.0 ng/mL; P <.001), there was no statistically significant difference between groups I, II, or controls. sVCAM-1 levels were elevated significantly in BA subjects in group II with PH (1253.0 +/- 245.1 ng/mL) compared with those who did not have PH (827.3 +/- 151.7 ng/mL; P <.01). PH did not affect sICAM-1 levels. There was strong expression of ICAM-1 and VCAM-1 in proliferating bile ductules, endothelial cells, and liver cells in group III compared with group II and controls. CONCLUSIONS In BA, sICAM-1 and sVCAM-1 levels could be useful as markers of end-stage liver disease, with sVCAM-1 being more specific for PH. Induction of ICAM-1 and VCAM-1 may be an important factor in the development of cirrhosis.
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Affiliation(s)
- H Kobayashi
- Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan
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10
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Montalto G, Giannitrapani L, Soresi M, Virruso L, Martino DD, Gambino R, Carroccio A, Cervello M. Circulating E-selectin levels in chronic hepatitis C patients with normal or elevated transaminase before and after alpha-interferon treatment. Inflammation 2001; 25:101-108. [PMID: 11321356 DOI: 10.1023/a:1007118605861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte adhesion to the endothelium and in the cellular immunological reactions. Expression of this molecule, in fact, is physiologically absent, but it becomes evident on sinusoidal lining cells during inflammatory liver disease. The aim of this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH-C) patients with persistently normal transaminase in comparison to patients with CH-C and elevated transaminase, and its changes during alpha-interferon therapy. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of both groups. Fifty-eight subjects were divided into 3 groups: group A included 18 patients with CH-C and persistently normal transaminase; group B 20 patients with CH-C and persistently elevated transaminase levels and group C included 20 healthy subjects, representing the control group. The first two groups were treated with r-IFN alpha at a dose of 6 MU 3 times a week for 3 months and followed-up with 3 MU 3 times a week for another 3 months. Serum baseline values of E-selectin in groups A and B were significantly higher than those in group C (P < 0.04), but there was no difference between groups A and B. Furthermore, there was a trend toward higher E-selectin values as histological severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values showed a moderate decrease in both groups, but only among responder patients; while E-selectin levels were unchanged in non responders. Immunohistochemical localization showed no staining for E-selectin in normal liver specimens, while there was a quite similar staining for E-selectin in the two groups of patients. In conclusion, this study shows that serum E-selectin levels in patients with CH-C and persistently normal transaminase are higher than in controls and they are associated with severity of liver disease. Liver of these patients express E-selectin molecules, suggesting an activation of the immune system almost identical to that of patients with CH-C and elevated transaminase. In both groups only responder patients showed a moderate decrease below baseline serum values.
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Affiliation(s)
- G Montalto
- Istituto di Medicina Interna e Geriatria, Cattedra di Medicina Interna, Universitá di Palermo, Italy
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Battista S, Bar F, Mengozzi G, Pollet C, Torchio M, Cavalli G, Rosina F, David E, Cutrin JC, Cavalieri B, Poli G, Molino G. Evidence of an increased nitric oxide production in primary biliary cirrhosis. Am J Gastroenterol 2001; 96:869-75. [PMID: 11280567 DOI: 10.1111/j.1572-0241.2001.03470.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.
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Affiliation(s)
- S Battista
- Department of Pathology, San Giovanni Battista Hospital of Turin, Italy
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12
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Martinez-Mier G, Toledo-Pereyra LH, Ward PA. Adhesion molecules in liver ischemia and reperfusion. J Surg Res 2000; 94:185-94. [PMID: 11104660 DOI: 10.1006/jsre.2000.6006] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- G Martinez-Mier
- Surgery Research Sciences and Molecular Biology, Borgess Research Institute, Kalamazoo, Michigan 49001, USA
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13
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Kurkijärvi R, Yegutkin GG, Gunson BK, Jalkanen S, Salmi M, Adams DH. Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease. Gastroenterology 2000; 119:1096-103. [PMID: 11040196 DOI: 10.1053/gast.2000.18163] [Citation(s) in RCA: 87] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS Vascular adhesion protein 1 (VAP-1) is an endothelial glycoprotein that supports adhesion of lymphocytes to hepatic endothelium and has sequence homology with semicarbazide-sensitive amine oxidases (SSAOs). We investigated whether soluble VAP-1 (sVAP-1) displays SSAO activity and thereby accounts for increased monoamine oxidase activity in the serum of patients with liver diseases. METHODS sVAP-1 concentration and SSAO activity were measured in peripheral, hepatic, and portal blood and in bile from patients with liver disease and in peripheral blood of control subjects, using enzyme-linked immunosorbent assay and enzymatic assays. RESULTS sVAP-1 concentration (mean [+/-SE], 143. 67 [34.97-92.67] ng/mL) and SSAO activity (18.8 [12.0-24.6] nmol. mL(-1). h(-1)) were significantly increased in chronic liver diseases compared with healthy controls (87.1 [53.5-127] ng/mL [P<0.001] and 10.7 [6.5-12.7] nmol. mL(-1) x h(-1) [P<0.05]) but not in massive necrosis caused by paracetamol poisoning (109 [80.3-140] ng/mL and 8.9 [5.7-12.3] nmol. mL(-1) x h(-1)). sVAP-1 correlated with serum transaminase and bilirubin but not with creatinine. In 5 paired samples, sVAP-1 concentration was higher in hepatic (median, 113 [range, 53-122]) than in portal vein (102 [42-109]; 2P<0.05), and was not detected in bile. There was a highly significant correlation between serum sVAP-1 and SSAO activity in normal subjects, patients with acute liver failure, and those with chronic liver disease (r = 0.895; P<0.001). When serum was depleted of sVAP-1 by immunoaffinity chromatography, SSAO activity was eliminated. CONCLUSIONS sVAP-1 levels are increased in chronic liver disease, and sVAP-1 is likely derived from the liver. Serum sVAP-1 displays SSAO activity and accounts for most of the monoamine oxidase activity in human serum.
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Affiliation(s)
- R Kurkijärvi
- MediCity Research Laboratories, University of Turku and National Public Health Institute Department in Turku, Turku, Finland
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Fukuda Y, Nakano I, Katano Y, Marui A, Hayakawa T. Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in asymptomatic carriers of hepatitis C virus. J Int Med Res 1998; 26:313-8. [PMID: 10399113 DOI: 10.1177/030006059802600605] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
High levels of serum-soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have been noted in patients with chronic hepatitis C. This study aimed to measure serum levels of sICAM-1 and sVCAM-1 in asymptomatic hepatitis C virus carriers and clarify the clinical significance of measuring soluble forms. Serum levels of sICAM-1 were significantly higher than in healthy controls but serum sVCAM-1 levels did not differ statistically from those in healthy controls. Liver biopsy obtained from 12 asymptomatic hepatitis C virus carriers showed evidence of hepatitis. Estimating sICAM-1 and sVCAM-1 in asymptomatic carriers may be helpful, especially in cases in which liver biopsy is not possible.
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Affiliation(s)
- Y Fukuda
- Second Department of Internal Medicine, Nagoya University School of Medicine, Japan
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Velikova G, Banks RE, Gearing A, Hemingway I, Forbes MA, Preston SR, Jones M, Wyatt J, Miller K, Ward U, Al-Maskatti J, Singh SM, Ambrose NS, Primrose JN, Selby PJ. Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer. Br J Cancer 1997; 76:1398-404. [PMID: 9400933 PMCID: PMC2228185 DOI: 10.1038/bjc.1997.569] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).
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Affiliation(s)
- G Velikova
- ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds, UK
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Marui A, Fukuda Y, Koyama Y, Nakano I, Urano F, Yamada M, Hayakawa T. Serum levels of soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in liver disease, and their changes by treatment with interferon. J Int Med Res 1996; 24:258-65. [PMID: 8725986 DOI: 10.1177/030006059602400304] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured by an enzyme-linked immunosorbent assay in patients with chronic hepatitis (n = 57), liver cirrhosis (n = 19) and hepatocellular carcinoma (n = 33). Serum levels of sICAM-1 and sVCAM-1 were significantly higher in liver disease than those in controls (P < 0.0001 and P < 0.0005, respectively). A total of 22 patients with chronic hepatitis C were treated with interferon. Pretreatment levels of sICAM-1 and sVCAM-1 were not significantly different between complete responders and non-responders. In complete responders, serum sICAM-1 and sVCAM-1 levels 1 year after interferon treatment significantly decreased compared to the pretreatment levels (P < 0.005 and P < 0.05, respectively). Post-treatment levels of sICAM-1 and sVCAM-1 in complete responders were also significantly lower than those in non-responders (P < 0.005 and P < 0.05, respectively). This suggests that monitoring soluble adhesion molecules might be useful in the follow-up of patients with liver disease.
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Affiliation(s)
- A Marui
- Second Department of Internal Medicine, Nagoya University School of Medicine, Japan
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Affiliation(s)
- A G Lim
- Division of Biochemical Medicine, St George's Hospital Medical School, London
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