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(1) Background: Metastasis is a complex process in which the primary cancer cells spread to a distant organ or organs, creating a secondary tumor location, which in many patients leads to treatment failure and death. The aim of the present study was to assess the association of endothelial markers (i.e., sP-selectin, sE-selectin and von Willebrand factor) with the leptin-to-adiponectin ratio (LAR) and to perform an analysis of the predictive value on the survival of patients with luminal A and B invasive breast cancer (IBrC). (2) Methods: The trial included 70 treatment-naïve early-stage IBrC patients with a median age of 54.5 years and a median tumor diameter of 1.5 cm. The median duration of follow-up was 5.7 years, with a relapse rate of 15.71%. Specific immunoenzymatic kits were used to determine pre- and post-treatment concentrations of analyzed factors. (3) Results: Regardless of the treatment pattern, endothelial marker concentrations and the LAR increased after adjuvant treatment. The follow-up showed a significantly higher relapse rate in patients with IBrC who had higher pre-treatment sP-selectin and post-treatment LAR levels. According to receiver operating characteristic (ROC) analysis, a post-treatment LAR with a sensitivity of 88.9% and specificity of 57.9% discriminating cases with or without disease relapse. Additionally, a higher risk of breast cancer relapse was associated with a lower post-treatment sP-selectin concentration. (4) Conclusions: Our results showed mainly that pre-treatment sP-selectin levels and post-treatment LAR may have value as prognostic indicators and may contribute to predicting the future outcomes in patients with early-stage IBrC.
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High-density lipoproteins (HDL) play an important role in the prevention of atherosclerosis. The aim of the study was to assess the relationship between serum HDL-C concentration and proinflammatory/prothrombic activation in coronary artery disease (CAD) patients. The study group included 27 acute myocardial infarction (AMI) patients and 30 stable angina pectoris (SA) patients. The control group consisted of 23 people without cardiac symptoms. In the AMI and SA groups, a lower HDL-C and a higher LDL-C/HDL-C index were observed. The SA patients had lower total cholesterol, LDL-C, sE-selectin ligand, as well as higher triglycerides and CD40 concentration in comparison with both the control and AMI groups. A higher von Willebrand Factor and intercellular adhesion molecule-1 were found in both study groups. Low HDL-C concentration in the CAD patients may intensify pro-inflammatory endothelial activation and prothrombotic processes. A low concentration of HDL-C and a high value of the LDL-C/HDL-C index seem to be better indices of atherogenic processes than the LDL-C concentration alone.
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Aterosclerose , Doença da Artéria Coronariana , Infarto do Miocárdio , HDL-Colesterol , LDL-Colesterol , Humanos , Lipoproteínas HDL , Projetos PilotoRESUMO
Mesothelioma, a malignant neoplasm of mesothelial cells, has overall poor prognosis. Cell adhesion molecules (CAMs) are proteins that contribute to the immune response. In this study the clinical utility and prognostic significance of serum and pleural fluid soluble CAM (sCAM) levels were assessed in patients with mesothelioma. Mesothelioma patients were retrospectively recruited (2016-2020). Clinical characteristics, serum and pleural sCAM levels (sE-cadherin, sE-selectin, intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1)) and histopathological characteristics were gathered. A total of 51 healthy controls were also recruited for a secondary cross-sectional analysis. 92 mesothelioma patients were analyzed (mean age 64.5 years, 87% males, performance status 0-2). Patients with increased pleural sE-cadherin had higher risk for disease progression (adjusted HR 1.11 (1.02, 1.20), p = 0.013). Serum and pleural sE-selectin were decreased in patients with high-grade mesothelioma. Patients with increased serum or pleural sE-selectin levels had lower risk for death (adjusted HR 0.88 (0.81, 0.96), p = 0.003; 0.90 (0.82, 0.99), p = 0.039, respectively). Serum sE-cadherin, sE-selectin and sICAM-1 levels were significantly increased in mesothelioma patients compared to healthy controls. Further studies are needed to indicate the clinical utility of serum and pleural sCAMs in mesothelioma patients.
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OBJECTIVES: This study aims to determine serum levels of human Krüppel-like factors (KLFs), sP-selectin and sE-selectin and establish correlations between them in patients with gestational diabetes mellitus (GDM). METHODS: Twenty-six GDM patients aged between 22 and 35 years and 25 healthy pregnant women aged between 23 and 34 years were recruited. Maternal serum levels of KLF2, KLF4, and their target proteins sP-selectin, sE-selectin were measured using enzyme-linked immunosorbent assays at 24-28 weeks of gestation. RESULTS: Women with GDM had significantly lower serum KLF2 than controls. However, the differences in levels of serum KLF4 between the control and GDM groups were not significant. Additionally, elevated serum sP-selectin and sE-selectin were found in the GDM group and not in the healthy group. Importantly, we also found that serum KLF2 levels were negatively correlated with indicators of glucose metabolism, including insulin, fasting blood glucose, 1-h oral glucose tolerance test, and glycated hemoglobin. CONCLUSION: We conclude that (i) serum KLF2 might be indicative of GDM risk, and (ii) sP-selectin and sE-selectin were increased in GDM patients.
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Diabetes Gestacional , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem , Glicemia/metabolismo , Teste de Tolerância a Glucose , Insulina , Fatores de Transcrição Kruppel-Like , Selectinas , Selectina-PRESUMO
Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.3243A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). To identify robust circulating markers of m.3243A>G disease, we first performed discovery proteomics, targeted metabolomics, and untargeted metabolomics on plasma from a deeply phenotyped cohort (102 patients, 32 controls). In a validation phase, we measured concentrations of prioritized metabolites in an independent cohort using distinct methods. We validated 20 analytes (1 protein, 19 metabolites) that distinguish patients with MELAS from controls. The collection includes classic (lactate, alanine) and more recently identified (GDF-15, α-hydroxybutyrate) mitochondrial markers. By mining untargeted mass-spectra we uncovered 3 less well-studied metabolite families: N-lactoyl-amino acids, ß-hydroxy acylcarnitines, and ß-hydroxy fatty acids. Many of these 20 analytes correlate strongly with established measures of severity, including Karnofsky status, and mechanistically, nearly all markers are attributable to an elevated NADH/NAD+ ratio, or NADH-reductive stress. Our work defines a panel of organelle function tests related to NADH-reductive stress that should enable classification and monitoring of mitochondrial disease.
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Síndrome MELAS/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Hidroxibutiratos/sangue , Ácido Láctico/sangue , Síndrome MELAS/genética , Masculino , Pessoa de Meia-Idade , Mutação , Índice de Gravidade de DoençaRESUMO
Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan-Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan-Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.
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COVID-19/complicações , COVID-19/mortalidade , Endotélio Vascular/patologia , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , Estudos de Coortes , Estado Terminal , Endotélio Vascular/virologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
OBJECTIVE: To determine the serum concentration of soluble E-selectin (sE-selectin) in HIV associated preeclampsia. STUDY DESIGN: The study population (n = 72) consisted of normotensive pregnant (n = 36) and preeclamptic (n = 36) women stratified by HIV status (negative vs. positive). Serum concentrations of sE-selectin were quantified using the MilliPlex multiplex immunoassay method. Statistical analyses were conducted using GraphPad Prism software. RESULTS: When stratified by pregnancy type and HIV status, serum sE-selectin levels were elevated in the preeclamptic HIV-negative group compared to the normotensive HIV-negative group (p = 0.0070**). Gestational age, systolic blood pressure, diastolic blood pressure and baby weight were statistically different across the study groups (p < 0.0001). CONCLUSION: This study demonstrates an elevation of sE-selectin in preeclamptic HIV-negative compared to the normotensive HIV-negative group. However, when stratified by HIV status, there was no significant difference observed in preeclamptic HIV-positive and normotensive HIV-positive groups. The findings of this small-scale study suggest that sE-selectin may be used as a biomarker or an early identifier of preeclampsia. Studies with large numbers should be considered to confirm our findings.
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Infecções por HIV , Pré-Eclâmpsia , Biomarcadores , Estudos de Casos e Controles , Selectina E , Feminino , Idade Gestacional , Infecções por HIV/complicações , Humanos , GravidezRESUMO
AIM: The present study aimed mainly to demonstrate the effect of the antihistamine azelastine (AZ) and Angiotensin receptor blocker ( ARB), represented by losartan (LOS) either alone or in combined form on certain metabolic aspects, endothelial dysfunction and platelets activation markers in diabetic hyperlipidemic rat model. METHODS: Rats were randomly classified to five groups: One group fed normal chow diet (NC). Four groups received alloxan and CCT-diet. One group received no treatment (DHC while the other three groups received AZ, LOS and their combination form, respectively for 8 weeks. Serum and tissue samples were collected for biochemical and histological evaluations. RESULTS: DHC rats demonstrated significant hyperglycaemia, dyslipidemia, disturbances in endothelial and platelet activation markers. AZ or LOS administration demonstrated hypoglycaemic and hypolipidemic effects. VCAM-1 and sE-selectin (Endothelial function markers) along with CD63 (Platelet activation marker) showed significant decrease as compared to control group. AZ administration exerted little prominent effects than that of LOS, while their combination demonstrated remarkable changes compared to monotherapy. Histopathological findings were in agreement to certain extent with the biomarkers results. CONCLUSIONS: Both drug categories may be expressed as suitable therapeutic tools for atherosclerotic complications either alone or along with other hypolipidemic drugs.
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Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Antagonistas não Sedativos dos Receptores H1 da Histamina/farmacologia , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Losartan/farmacologia , Ftalazinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Aloxano , Animais , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Plaquetas/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Quimioterapia Combinada , Células Endoteliais/metabolismo , Hiperlipidemias/sangue , Hiperlipidemias/induzido quimicamente , Masculino , RatosRESUMO
A laboratory study of the cytokine profile and the content of the intercellular adhesion molecules was performed in 38 patients with initial signs of aortic hemilunus calcification. It has been determined that the content of IL-6 and IL-8 had significantly higher values compared with the control group, which indicates the direct role of nonspecific chronic inflammation in the development of calcifying aortic valve damage. A significantly lower content of sE-selectin was also identified, which may indicate the absence of activation of adhesion molecules at the initial stage of aortic valve calcification. Further study of the dynamics of sE- and sP-selectins content in the process of development of acceleration of blood flow in the aortic valve and the formation of stenosis is needed.
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Estenose da Valva Aórtica/sangue , Calcinose/sangue , Moléculas de Adesão Celular/sangue , Citocinas/sangue , Selectinas/sangue , Idoso , Valva Aórtica , HumanosRESUMO
Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium. Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups. Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.
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OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a main risk factor for development of cardiovascular diseases (CVDs) and endothelial dysfunction. This study aimed to investigate serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), and endothelium selectin (sE-selectin) in T2DM patients with macrovascular complications. METHODS: A cross-sectional study of 21 controls, 30 T2DM patients without CVDs, and 30 T2DM patients with CVDs was conducted. Serum levels of soluble adhesion molecules including sVCAM-1, sICAM-1, and sE-selectin were determined using ELISA. RESULTS: Serum levels of sVCAM-1, sICAM-1, and sE-selectin were higher in T2DM patients than in controls. Levels of serum sVCAM-1 were higher in T2DM patients with CVDs compared with T2DM patients without CVDs. In T2DM patients with CVDs, significant positive associations were observed between sVCAM-1, sICAM-1, and sE-selectin levels (r = 0.575, p = 0.001 and r = 0.378, p = 0.040). CONCLUSIONS: Circulating levels of soluble adhesion molecules were elevated in T2DM patients, regardless of whether the patients had cardiovascular complications. Only sVCAM-1 was considered a useful marker for the prediction of CVDs in T2DM patients.
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Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2 , Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Moléculas de Adesão Celular , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , HumanosRESUMO
Endothelium plays a key role in maintaining vascular homeostasis by secreting active factors involved in many biological processes such as hemostasis, angiogenesis, and inflammation. Hyperglycemia in diabetic patients causes dysfunction of endothelial cells. Soluble fractions of adhesion molecules like sE-selectin and vascular cell adhesion molecule (sVCAM) are considered as markers of endothelial damage. The low-level laser therapy (LLLT) effectively supports the conventional treatment of vascular complications in diabetes, for example hard-to-heal wounds in patients with diabetic foot syndrome. The aim of our study was to evaluate the effect of low-energy laser at the wavelength of 635 nm (visible light) and 830 nm (infrared) on the concentration of adhesion molecules: sE-selectin and sVCAM in the supernatant of endothelial cell culture of HUVEC line. Cells were cultured under high-glucose conditions of 30 mM/L. We have found an increase in sE-selectin and sVCAM levels in the supernatant of cells cultured under hyperglycemic conditions. This fact confirms detrimental influence of hyperglycemia on vascular endothelial cell cultures. LLLT can modulate the inflammation process. It leads to a decrease in sE-selectin and sVCAM concentration in the supernatant and an increase in the number of endothelial cells cultured under hyperglycemic conditions. The influence of LLLT is greater at the wavelength of 830 nm.
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Moléculas de Adesão Celular/metabolismo , Hiperglicemia/metabolismo , Hiperglicemia/radioterapia , Terapia com Luz de Baixa Intensidade , Contagem de Células , Selectina E/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Humanos , Hiperglicemia/patologia , Solubilidade , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND/OBJECTIVE: This study was performed to compare soluble levels of adhesion molecules between diabetic patients and controls and to assess their possible association with long-term complications of type 1 diabetes (T1D). METHODS: Forty-eight patients with T1D and 39 healthy controls were enrolled in this study. The plasma level of adhesion molecules was measured by sandwich enzyme-linked immunosorbent assay technique. RESULTS: Higher sVCAM 1 (soluble vascular cell adhesion molecule 1) levels correlated with older age of onset of T1D. The plasma level of sICAM 1 (soluble intercellular adhesion molecule 1) was significantly increased, while sE selectin was significantly decreased in patients with T1D, compared to controls. There was no significant relationship between these plasma-level variations and the long-term complications of T1D. CONCLUSION: Although plasma levels of cell adhesion molecules are different in T1D patients and healthy controls, they might not be good candidate markers for prognosis of disease.
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Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Complicações do Diabetes/sangue , Feminino , Humanos , Masculino , Adulto JovemRESUMO
AIMS/HYPOTHESIS: Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes. METHODS: We investigated, in an inception cohort of 277 individuals with type 1 diabetes, the course, tracking and temporal inter-relationships of BP, specifically pulse pressure (a marker of arterial stiffening) and hypertension, and the following biomarkers of systemic and vascular inflammation/endothelial dysfunction: C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin). These biomarkers and other risk factors were measured at baseline and repeatedly up to 20 years after the onset of type 1 diabetes. Data were analysed with generalised estimating equations including adjustments for age, sex, smoking status, BMI, HbA1c, serum creatinine, total cholesterol, urinary AER, insulin treatment dose and mean arterial pressure. RESULTS: Increases were noted in all biomarkers except sE-selectin, which decreased over time. Levels differed from baseline at 2-4 years and preceded the increase in pulse pressure, which occurred at 8-10 years after the onset of type 1 diabetes. Higher levels of sICAM-1 and sVCAM-1, but not CRP or sE-selectin, at baseline and throughout the 20 year follow-up, were significantly associated with higher (changes in) pulse pressure at subsequent time points. Higher levels of sVCAM-1 at baseline and during follow-up were also significantly associated with the prevalence (OR 3.60 [95% CI 1.36, 9.53] and OR 2.28 [1.03, 5.25], respectively) and incidence (OR 2.89 [1.08, 7.75] and OR 3.06 [1.01, 9.26], respectively) of hypertension. We also investigated the longitudinal associations between BP or hypertension as determinants of subsequent (changes in) levels of CRP, sICAM-1, sVCAM-1 and sE-selectin, but did not find evidence to support a reverse causality hypothesis. CONCLUSIONS/INTERPRETATION: These findings support the involvement of vascular endothelial dysfunction and inflammation in the development of premature arterial stiffening and hypertension in type 1 diabetes.
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Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Inflamação/sangue , Pressão Sanguínea/fisiologia , Proteína C-Reativa/metabolismo , Selectina E/sangue , Humanos , Hipertensão/sangue , Hipertensão/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Rigidez Vascular/efeitos dos fármacosRESUMO
BACKGROUND: Typical features of Sjögren's syndrome (SS) are severe xerostomia and xerophthalmia which are basic diagnostic criteria. OBJECTIVES: The aim of this study was to compare the serum levels of soluble (s) intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sE-selectin between primary (pSS), secondary (sSS) and healthy subjects (HS). We correlated these results with selected clinical parameters of disease activity and parameters of the severity of xerostomia and xerophthalmia. MATERIAL AND METHODS: The serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by enzyme-linked immunosorbent assay (ELISA) in 16 patients with pSS, 18 with sSS and 15 HS. Eye dryness and xerostomia were assessed by the Schirmer's test, the Fox test and the visual analogue scale (VAS). RESULTS: The levels of sICAM-1 in pSS and sVCAM-1 in sSS patients were significantly higher when compared to HS (p = 0.02 and p = 0.048, respectively). There were no differences between pSS and sSS. In pSS, sVCAM-1 correlated positively with VAS (rS = 0.52, p = 0.04) and the Fox test (rS = 0.66, p=0.01). In sSS, sE-selectin correlated positively with sICAM-1 (rS = 0.54, p = 0.01), the duration of the disease (rS = 0.51, p = 0.03) and negatively with the Schirmer's test (rS = 0.59, p = 0.04). sICAM-1 correlated positively with the erythrocyte sedimentation rate (ESR) value (rS = 0.59, p = 0.01). CONCLUSIONS: sVCAM-1 reflects xerostomia in pSS. sICAM-1 and sE-selectin may be additional parameters of sSS activity.
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Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Síndrome de Sjogren/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Xeroftalmia/etiologia , Xerostomia/etiologia , Adulto JovemRESUMO
CONTEXT: Selectins probably participate in the interactions between platelets and other inflammatory cells in cancer invasion and metastasis formation. We assessed a potential relationship of P-, L- and E-selectin in colorectal cancer (CRC) patients in relation to tumour advancement according to TNM classification, and tumour location. MATERIALS AND METHODS: The study group was composed of 53 CRC patients and 25 healthy subjects. Plasma levels of soluble P-, L- and E-selectins were measured using the immunoenzymatic method with Quantikine kits (R&D Systems, Minneapolis, MN). RESULTS: The mean levels of all selectins were significantly higher in CRC patients compared to healthy controls. The highest level of sP-selectin was observed in patients with metastases to the liver (stage IV), and was significantly higher than in patients without metastases (stage I/II) and with lymph node metastases (stage III), p = .02. The highest levels of sL- and sE-selectin were observed in patients with lymph node metastasis. We also found sP-selectin to be the best predictor of CRC. CONCLUSION: Our finding show possible involvement of tested selectins in CRC advancement and forming metastasis. Among sL- and E- selectins, P-selectin plays an important role in the progression of CRC and could be an attractive biomarker with clinical significance.
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Biomarcadores Tumorais/sangue , Moléculas de Adesão Celular/sangue , Neoplasias Colorretais/patologia , Selectina-P/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Selectina E , Feminino , Humanos , Selectina L , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnósticoRESUMO
CXCL4 is an antiangiogenic and immunomodulatory chemokine. We aimed to investigate serum levels of CXCL4 in primary Sjögren's syndrome (pSS), looking for associations with disease features. Thirty-nine consecutive pSS patients underwent clinical-serological assessment and nailfold videocapillaroscopy (NVC). Thirty-six patients and 30 controls affected by osteoarthritis were also investigated for serum levels of CXCL4 and soluble E-selectin (sE-selectin). CXCL4 was higher in pSS patients than in controls (1.79 [0.2-11.18] vs 1.023 ng/ml [0.02-14.45], p < 0.05), particularly in those without anti-La/SSB antibodies (2.89 [1.01-11.18] vs 1.69 ng/ml [0.2-2.72], p < 0.05), while it was lower in pSS patients with a focus score ≥1 at lip biopsy (1.44 [0.86-2.1] vs 2.24 ng/ml [1.64-3.25], p < 0.05) and clinically evident lymphadenopathy (1.53 [0.38-1.7] vs 2.08 ng/ml [1.45-3.03], p < 0.05). CXCL4 correlated with disease duration (r = 0.35, p < 0.05) and sE-selectin (r = 0.45, p < 0.01). Patients with Raynaud's phenomenon (RP) had more frequently abnormal CXCL4 levels than patients without RP (11/15 vs 3/21, p < 0.001), enlarged capillaries (14/16 vs 7/23, p < 0.001) and capillary loss at NVC (14/16 vs 6/23, p < 0.001). The hitherto unknown association of increased serum CXCL4 with features of microvascular impairment in pSS, along with the negative association with features of lymphocytic response (i.e., the absence of subset disease-specific autoantibodies, a low focus score, and the absence of lymphadenopathy) suggest clarifying the possible implication of this chemokine in pSS pathogenesis in larger studies.
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Capilares/patologia , Linfonodos/patologia , Fator Plaquetário 4/sangue , Doença de Raynaud/sangue , Glândulas Salivares/patologia , Síndrome de Sjogren/sangue , Adulto , Idoso , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/etiologia , Doença de Raynaud/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/patologiaRESUMO
Hydroxychloroquine (HCQ) has been demonstrated to reduce the risk to develop diabetes mellitus (DM). However no previous experimental study had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in insulin resistance (IR). In addition, the mechanism by which HCQ can prevent DM is not well understood. In this study, we hypothesized that the possible favorable outcome of HCQ may be partly achieved by its molecular effect on the endothelial stress markers as well as on the imparied balance of the adipokines that usually accompanies IR. A total of 54 rats were divided equally into; control, high fat diet (HFD) and HFD+HCQ groups (received standard chow, HFD and HFD+HCQ respectively). After 12 weeks, samples from pancreas as well as visceral adipose tissue (VAT) were histologically studied for the consequent changes. In the HFD group, there were mild degenerative changes and expansion of the IOL accompanied with a significantly increased (p<0.05) ß-cell area%, mass, proliferation and neogenesis as well as a significantly decreased (p<0.05) α-cell area% compared with the other groups. On combining HCQ with HFD, reversal of these changes along with correction of the impaired adipokines levels (leptin, adiponectin, resistin, visfatin and lipocalin-2) and significant decrease (p<0.05) of the vascular endothelial stress markers (sE-selectin, sICAM and sVICAM) were manifested compared with the HFD group. Therefore, HCQ favorable effects in IR may be attributed to relieving of the endothelial stress as well as normalization of the skewed balance of adipokines.
Assuntos
Adipocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Hidroxicloroquina/farmacologia , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Células Endoteliais/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Leptina/metabolismo , Masculino , Nicotinamida Fosforribosiltransferase/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ratos Sprague-DawleyRESUMO
BACKGROUND: Distant metastasis resulting from vascular dissemination of cancer cells is the primary cause of mortality from breast cancer. We have previously reported that E-selectin expression on the endothelial cell surface mediates shear-resistant adhesion and migration of circulating cancer cells via interaction with CD44. As a result of shedding, soluble E-selectin (sE-selectin) from the activated endothelium is present in the serum. In this study, we aimed to understand the role of sE-selectin in tumor progression and metastasis. METHODS: We investigated the effect of sE-selectin on shear-resistant adhesion and migration of metastatic breast cancer cells and leukocytes in vitro and in vivo. RESULTS: We found that sE-selectin promoted migration and shear-resistant adhesion of CD44(+) (/high) breast cancer cell lines (MDA-MB-231 and MDA-MB-468) to non-activated human microvessel endothelial cells (ES-HMVECs), but not of CD44(-/low) breast cancer cell lines (MCF-7 and T-47D). This endothelial E-selectin independent, sE-selectin-mediated shear-resistant adhesion was also observed in a leukocyte cell line (HL-60) as well as human peripheral blood mononuclear cells (PBMCs). Additionally, the incubation of MDA-MB-231 cells with sE-selectin triggered FAK phosphorylation and shear-resistant adhesion of sE-selectin-treated cells resulted in increased endothelial permeabilization. However, CD44 knockdown in MDA-MB-231 and HL-60 cells resulted in a significant reduction of sE-selectin-mediated shear-resistant adhesion to non-activated HMVECs, suggesting the involvement of CD44/FAK. Moreover, functional blockade of ICAM-1 in non-activated HMVECs resulted in a marked reduction of sE-selectin-mediated shear-resistant adhesion. Finally, the pre-incubation of CD44(+) 4 T1 murine breast cancer cells with sE-selectin augmented infiltration into the lung in E-selectin K/O mice and infusion of human PBMCs pre-incubated with sE-selectin stimulated MDA-MB-231 xenografted breast tumor growth in NSG mice. CONCLUSIONS: Our data suggest that circulating sE-selectin stimulates a broad range of circulating cells via CD44 and mediates pleiotropic effects that promote migration and shear-resistant adhesion in an endothelial E-selectin independent fashion, in turn accelerating tissue infiltration of leukocytes and cancer cells.
Assuntos
Neoplasias da Mama/secundário , Selectina E/fisiologia , Endotélio Vascular/patologia , Leucócitos Mononucleares/patologia , Células Neoplásicas Circulantes/patologia , Animais , Apoptose , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Adesão Celular , Movimento Celular , Proliferação de Células , Progressão da Doença , Endotélio Vascular/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Células Neoplásicas Circulantes/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
UNLABELLED: The study aimed to evaluate the value of soluble endothelial selectin (sE-selectin) plasma level measurement in predicting acute lung injury (ALI) outcome in children. METHODS: The study was a prospective, controlled study that involved 50 children with ALI and 50 healthy children as a control. Soluble endothelial selectin and C-reactive protein plasma levels were measured at days 1 and 7 of development of ALI for the patient group and done only once for the control group. RESULTS: Plasma sE-selectin was significantly higher in the patients than the control group (P = .001). Mortality reached 32% of children with ALI. The deceased subgroup had significantly higher plasma sE-selectin levels both at days 1 and 7 than the survived (P = .02 and P < .001 respectively). There was positive correlation between plasma sE-selectin at day 7 with durations of both pediatric intensive care unit and mechanical ventilation. Levels of sE-selectin at days 1 and 7 had significant positive correlation with C-reactive protein level and ALI severity. Soluble endothelial selectin plasma levels of 302 ng/mL at day 7 were the best cutoff value to predict ALI-related deaths. CONCLUSION: Plasma sE-selectin level served as a good predictor biomarker for both mechanical ventilation duration and the mortality risk in children with ALI.