UMLS:C0027627 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutive expression of major histocompatibility complex (MHC) class II molecules is normally restricted to professional antigen-presenting cells (APCs) of the immune system, although it also occurs frequently in melanoma. Clinical evidence suggesting that MHC class II expression by melanoma is associated with tumor progression led us to postulate a role for MHC class II-mediated antigen presentation in this disease. First, we investigated whether melanoma cells derived from metastases can process antigen and/or present peptide vi MHC class II molecules to a peptide-specific CD4+ T-cell clone. In all cell lines tested, melanoma cells were able to process antigen and present peptide efficiently to CD4+ T cells, resulting in T-cell proliferation increased 5-26-fold over controls. Next, we found that CD28-mediated costimulation was not required, because blocking with CTLA-4Ig had no effect on the T-cell response to either melanoma or B cells as APCs. In contrast, blocking CD54 (ICAM-1) resulted in a decrease in proliferation in response to peptide presentation by melanoma but not B cells. These data demonstrate that MHC class II molecules on melanoma cells are functional and that antigen-processing pathways are intact. In addition, CD54 seems to play a significant role in peptide presentation by melanoma.
...
PMID:MHC class II-mediated antigen presentation by melanoma cells. 904 57

T-cell hybridomas metastasize widely, and the extent of dissemination correlates with invasiveness in fibroblast cultures. Previously, we provided evidence that both metastasis and in vitro invasion require activation of LFA-1, induced by G-protein-transduced signals triggered by as yet unidentified factors. We show here that LFA-1-mediated adhesion of TAM2D2 T-cell hybridoma cells to ICAM-1 can in fact be induced by direct activation of G-proteins using AIF-4, to the same extent as by using PMA or Mn2+. We assessed effects of protein kinase C (PKC), tyrosine kinase (TK), PI3-kinase (PI3K), and phospholipase C (PLC) inhibitors. Both AIF-4-induced adhesion and invasion were completely blocked by the TK inhibitor genistein and partially blocked by the PI3K inhibitor wortmannin, but not influenced by PKC inhibitor GF109203X. Downregulation of PKC did not affect invasion or adhesion induced by AIF-4 either. In contrast, GF109203X and PKC downregulation blocked PMA-induced adhesion, but genistein and wortmannin had no effect. Invasion and both AIF-4- and PMA-induced adhesion were completely blocked by the PLC inhibitor U73122. Mn(2+)-induced adhesion, which was not or was only partially blocked by the other inhibitors, was delayed by U73122, and spreading of Mn(2+)-treated cells was completely prevented by U73122. However, PLC activity during adhesion was not detected. We conclude that signals required for invasion and G-protein-induced adhesion are similar and are distinct from PKC-induced adhesion, and that in all cases PLC is likely to be activated, but is probably too local and/or transient to be detected.
...
PMID:Activation of G-proteins with AIF-4 induces LFA-1-mediated adhesion of T-cell hybridoma cells to ICAM-1 by signal pathways that differ from phorbol ester- and manganese-induced adhesion. 908 64

IL-10 is a cytokine which shows various effects including inhibition of T-cell proliferation or HLA-dependent antigen presentation. In this study, we analysed the effects of exogenous or autocrine IL-10 on proliferation and expression of immunocritical surface molecules. Fourteen cultures of human melanoma cells were established from primary melanomas, locoregional lymph-node or distant metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10, anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the expression of human leukocyte antigen (HLA) class-I, HLA class-II and intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10 production of melanoma cells was documented by RT-PCR and IL-10 protein was detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab decreased proliferation. IL-10R expression was found in 12 out of 14 (86%) melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL-10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest that IL-10 is an autocrine growth factor with significant impact on immunocritical molecules in melanoma. IL-10 effects have to be considered when planning therapeutic immunointerventions in melanoma patients.
...
PMID:Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. 917 19

Serum 5-S-cysteinyl dopa (5-S-CD), circulating intercellular adhesion molecule-1 (cICAM-1) and soluble interleukin-2 receptor (sIL-2R) have each been reported as useful markers for melanoma progression. To assess the clinical relevance of these three markers, we simultaneously assayed their serum levels in 30 Japanese melanoma patients. Pre-surgical serum levels of 5-S-CD, cICAM-1 and sIL-2R were elevated in six, 13 and five patients respectively. These abnormal values returned to normal after curative surgery in most of the patients, suggesting a direct relationship to the presence of the primary tumour. Pre-surgical values of these three markers, either individually or in combination, did not predict the development of subsequent metastases. The sequential measurements of the three markers in eight patients who had relapse after surgery showed that serum 5-S-CD is the most useful marker for disease progression, although it is dependent on the melanin-producing ability of individual recurrent tumours. sIL-2R seemed to reflect in vivo activation of the host immune system and was a good indicator for predicting occult metastasis in selected cases. Circulating ICAM-1 levels were less relevant to the clinical disease course in our cases, although they tended to increase strikingly after liver metastasis. Our results in this limited number of cases show that the significance of the three markers varied with the individual and suggest that the simultaneous measurement of these markers may facilitate the early detection of metastases and proper therapeutic intervention.
...
PMID:Simultaneous measurement of serum 5-S-cysteinyldopa, circulating intercellular adhesion molecule-1 and soluble interleukin-2 receptor levels in Japanese patients with malignant melanoma. 919 64

Soluble intercellular adhesion molecule-1 (s-ICAM-1) was measured in the sera of 131 patients with primary and 50 patients with recurrent squamous cell cancer of the head and neck (HNSCC). 30 patients with benign ear, nose and throat diseases served as controls. s-ICAM-1 levels in serum are high in patients with HNSCC, particularly in the advanced tumor stages (UICC IV). Highest levels can be measured at the time of tumor recurrence and locoregional lymph node metastases. The sensitivity (95% specificity) of s-ICAM-1 (cutoff-level: 473 ng/ml) is 4% at primary diagnosis and 12% for recurrent disease. A coefficient of correlation for s-ICAM-1 in combination with SCC, carcinoembryonic antigen and CYFRA 21-1 indicates that no correlation can be found of s-ICAM-1 compared with traditional tumor markers. Due to overlapping values in control and patient groups s-ICAM-1 is not suitable for a specific clinical use in HNSCC.
...
PMID:Serum levels of intercellular adhesion molecule-1 in squamous cell carcinoma of the head and neck. 922 6

The cellular adhesion molecules (CAMs) CD44s, CD44v6, CD44v10, ICAM-1 and N-CAM were immunohistologically detected in colorectal cancers using the APAAP method. The expression of CD44s and CD44v6 was associated with the presence of lymph node metastases in the examined tumors. The pattern of ICAM-1 expression was inversely related to that of CD44, i.e. lower numbers of ICAM-1 positive cells were observed in metastasizing tumors. An intense focal staining of N-CAM was observed in the majority of the metastasizing tumors. The expression of CD44v, ICAM-1 or N-CAM on tumor cells did not correlate with the density of the tumor-infiltrating lymphocytes (TIL) within the tumors. The flowcytometric analysis of TIL showed a significant accumulation of CD25+ and HLA-DR+ cells and a reduced number of CD45RA+ cells as compared to autologous peripheral blood lymphocytes (PBL) or intraepithelial lymphocytes of the colon mucosa (IEL). These phenotypic characteristics of TIL did not correlate with the CAMexpression on tumor cells.
...
PMID:Expression of CD44, ICAM-1 and N-CAM in colorectal cancer. Correlation with the tumor stage and the phenotypical characteristics of tumor-infiltrating lymphocytes. 925 53

There have been few reported visual observations of metastatic cancer cell arrest in vivo. To seek evidence that inducible vascular adhesive properties can regulate hepatic metastasis, groups of 9-14 c57bl/6 mice were given 1.5 microg of interleukin-1alpha (IL-1alpha) 4 h before the injection of 3 x 10(5) B16F1 melanoma cells into a mesenteric vein. After 7 days, these mice had an 11-22-fold greater hepatic tumor burden than controls given i.p. saline. In both groups, small metastases were seen in the portal tract region. Twice as many 125I-labeled UdR-labeled B16F1 cells were detected in the livers of IL-1alpha-treated animals 5 min after injection, and 7 times as many were found after 24 h. Intravital videomicroscopy showed marked differences in the arrest pattern of the B16F1 cells between controls and IL-1alpha-treated mice. In controls, arrest occurred at a median distance of 32 microm beyond the sinusoidal inlet, where the median sinusoidal diameter was 16 microm. However, in IL-1alpha-treated mice, arrest occurred in the presinusoidal portal vein branches, which had a median diameter of 34 microm. Maximum observed tumor cell velocities were 2-fold less in the IL-1alpha-treated mice, although there was no significant difference in the flow rate of RBCs. To look for effects on the adhesive properties of the hepatic microvasculature, 5 x 10(4) B16F1 cells were incubated for 15 min on 5-microm sections of liver from control and IL-1alpha-treated mice. Three-fold more cells adhered to sections of liver from IL-1alpha-treated mice. This phenomenon was blocked by GRGDS peptides and by antibodies to E-selectin, ICAM-1, VCAM-1, and the alpha v integrin subunit. We postulate that pretreatment of mice with IL-1alpha alters a number of adhesive interactions between B16F1 cells and the hepatic microvasculature, contributing to the site of arrest and to the subsequent fate of the arrested cells.
...
PMID:Intravital videomicroscopic evidence for regulation of metastasis by the hepatic microvasculature: effects of interleukin-1alpha on metastasis and the location of B16F1 melanoma cell arrest. 930

The expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) seems to have an influence on the metastatic behaviour of tumour cells via immunological mechanisms. Recently, a soluble form of ICAM-1 was identified in physiological fluids. We analysed the serum levels of sICAM-1 in patients with non-small-cell lung cancer (NSCLC) and healthy individuals using a sandwich ELISA technique. Sera from 51 patients with NSCLC were tested for sICAM-1 (46 male, five female; age 38-81 years, median 64 years), 29 of whom presented with localized and 26 with metastatic disease. The control group consisted of 40 healthy individuals (20 smokers, 20 non-smokers). Immunohistochemical analysis of ICAM-1 in tumour cells was performed in 20 cases. Patients with NSCLC had significantly higher serum levels of sICAM-1 compared with healthy non-smokers (P = 0.00001) and smokers (P= 0.0328). Metastatic disease was associated with higher sICAM-1 than localized tumours (P = 0.0013). Only 11 out of 23 patients with localized NSCLC had sICAM-1 levels >300 ng ml(-1), compared with 25 out of 28 patients with metastatic disease. Histological expression of ICAM-1 was positively correlated with serum slCAM-1 (P = 0.0399). No difference was observed between histological tumour types with regard to sICAM-1 or NSCLC expression of ICAM-1. In sequential analysis (13 patients), rising sICAM-1 levels predicted a short-term fatal outcome (P = 0.0054) but, overall, sICAM-1 levels did not correlate with prognosis. In the control group, smokers showed significantly higher levels than non-smokers (P = 0.0016). In contrast to patients with NSCLC, sICAM-1 in the control group was correlated to the leucocyte count (r = 0.580, P = 0.003). In conclusion, serum levels of sICAM-1 seem to be associated with tumour burden and histological expression of ICAM-1 in patients with NSCLC. However, the (patho-) physiological role of ICAM-1 in NSCLC remains to be determined.
...
PMID:Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage. 951 61

The serum levels of intercellular adhesion molecule-1 (sICAM-1) and endothelial leukocyte adhesion molecule-1 (sELAM-1) were determined in 40 patients with colorectal cancer. The sICAM-1 and sELAM-1 levels in the drainage venous blood adjacent to a tumor were significantly correlated with those in the peripheral venous blood in patients without evident hematogenous dissemination of tumor cells. The sICAM-1 levels in peripheral venous blood were significantly higher in patients with hepatic metastases, while the sELAM-1 levels were significantly higher in those with pulmonary metastases. An immunohistochemical study of metastatic sites in the liver revealed that ICAM-1 was expressed in cancer stroma, but not in the cancer cells. In conclusion, the sICAM-1 and sELAM-1 levels in the peripheral venous blood in colorectal cancer patients without any distant metastasis are likely to reflect the topical production of these cell adhesion molecules, and appear to be instructive in predicting hematogenous dissemination in patients with colorectal cancer.
...
PMID:Serum cell adhesion molecules in patients with colorectal cancer. 954 6

T cell-mediated mechanisms are important in the defense against solid organ tumors. Why some tumors are more heavily infiltrated by T cells than others is poorly understood but is likely to depend upon adhesive interactions between circulating lymphocytes and tumor endothelium. In support of this hypothesis, the present study shows that primary human hepatocellular carcinomas (HCC) are more heavily infiltrated with T cells than colorectal hepatic metastases (CHM), and that their tumor vessels express high levels of several adhesion molecules. In HCC, an intense T cell infiltrate is observed within the tumor associated with strong expression of ICAM-1 and vascular adhesion protein-1 (VAP-1) on tumor endothelium. In contrast, fewer T cells infiltrated CHM and these tumors have little ICAM-1 and no detectable VAP-1 or VCAM-1 on tumor endothelium. T cells infiltrating both tumors are LFA-1 and very late Ag (VLA)-4 high. In vitro tissue-binding studies demonstrated that T cells bound readily to tumor endothelium in HCC, and Abs to ICAM-1, VAP-1, and to a lesser extent VCAM-1 could inhibit this binding. VAP-1 supported sialic acid-dependent adhesion under shear stress, suggesting that VAP-1 and ICAM-1 mediate, respectively, tethering and firm adhesion. In contrast, very few T cells bound to tumor vessels in CHM. Thus our data suggest that the VAP-1/VAP-1 receptor and ICAM-1/LFA-1 pathways are important in the recruitment of T cells to HCC. The strong expression of VAP-1 on tumor endothelium distinguishes HCC from CHM and supports our previous hypothesis that VAP-1 is an important hepatic endothelial adhesion molecule.
...
PMID:Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma. 955 6

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>