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1.
Oncol Rep ; 42(5): 2057-2064, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545443

RESUMO

The interaction between tumor necrosis factor receptor superfamily, member 4 (OX40) on T cells and the OX40 ligand (OX40L) on antigen­presenting cells (APCs) is a pivotal step for T­cell activation and the promotion of antitumor immunity. However, it is hypothesized that soluble OX40 (sOX40) in blood suppresses T­cell activation by blocking the OX40/OX40L interaction. In the present study, the association between blood sOX40 levels and the clinical characteristics of advanced colorectal cancer (CRC) patients was investigated. Blood was collected from 22 patients with advanced CRC. Blood sOX40 levels were determined by enzyme­linked immunosorbent assay (ELISA). Messenger RNA (mRNA) expression encoding OX40 or cytokines was analyzed by quantitative RT­PCR. Blood sOX40 levels were positively correlated with the blood levels of carbohydrate antigen (CA) 19­9, carcinoembryonic antigen (CEA), C­reactive protein (CRP) and soluble programmed cell death ligand­1 (PD­L1) in patients but negatively correlated with the blood levels of albumin. Blood sOX40 levels were not correlated with the mRNA expression of interferon (IFN)­gamma, interleukin (IL)­6, IL­10 and IL­4 in the peripheral blood mononuclear cells (PBMCs) of the patients and were not correlated with the frequency of programmed cell death­1 (PD­1) expressing CD4+, CD8+ and CD56+ cells. Notably, according to both univariate and multivariate analyses, high blood sOX40 levels were significantly correlated with a reduced survival time in patients. Although activated Jurkat cells (a human T cell line) exhibited an upregulation of sOX40 production and OX40 mRNA expression, the OX40 mRNA expression of the PBMCs of patients was not correlated with blood sOX40 levels. High blood levels of sOX40 were correlated with a reduced survival time in patients with advanced CRC, possibly associated with the suppression of antitumor immunity by sOX40.


Assuntos
Neoplasias Colorretais/mortalidade , Receptores OX40/sangue , Receptores OX40/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Proteína C-Reativa/metabolismo , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células Jurkat , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organotiofosforados/sangue , Albumina Sérica Humana/metabolismo , Análise de Sobrevida
2.
J Immunol Res ; 2019: 1780567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467932

RESUMO

This study analyzed the expression of membrane OX40 and OX40L (mOX40 and mOX40L) and levels of soluble OX40 and OX40L (sOX40 and sOX40L) in T1D patients to determine their clinical significance. Peripheral blood (PB) was collected from patients with T1D and healthy control participants. Expression of mOX40 and mOX40L on immune cells was detected by flow cytometry. Levels of sOX40 and sOX40L in sera were measured by ELISA. We demonstrated for the first time enhanced sOX40 and sOX40L expression and reduced mOX40 and mOX40L levels in T1D patients which correlated with the clinical characteristics and inflammatory factors. These results suggest that OX40/OX40L signal may be promising biomarkers and associated with the pathogenesis of T1D.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Ligante OX40/metabolismo , Receptores OX40/metabolismo , Adolescente , Adulto , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Ligante OX40/sangue , Receptores OX40/sangue , Adulto Jovem
3.
Biomol Concepts ; 10(1): 62-67, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30995203

RESUMO

Neuromyelitis optica (NMO), also known as Devic's disease, is an autoimmune disorder of the central nervous system (CNS) in which immune system cells and antibodies primarily attack the optic nerves and the spinal cord. OX40 (CD134) is a tumor necrosis factor (TNF)-receptor family member expressed primarily on activated CD4+ and CD8+ T-cells. In an autoimmune disease, OX40 is typically up-regulated at sites of inflammation, and increases in the number of peripheral CD4+ T-cells expressing OX40. OX40 and its ligand OX40L are key TNF members that augment T-cell expansion, cytokine production, and promote T-cell survival. The aim of this study was to evaluate and compare of OX40 gene expression and its serum levels in patients with NMO and healthy controls. Twenty sex-/age-matched healthy controls (HC) (median age = 32 years, 15 females/5 males) were engaged for the present study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays, respectively. The results indicated OX40 expression in patients was significantly lower than in healthy controls (p = 0.001). However, the serum level of OX40 was not significantly different between groups (p = 0.37). In addition, the results indicated that CD134 expression was not age-related (p = 0.041). Overall, this study suggests to us that OX40 levels are not a suitable marker for diagnosis or treatment of NMO.


Assuntos
Neuromielite Óptica/sangue , Receptores OX40/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores OX40/genética , Receptores OX40/metabolismo
4.
Immunol Invest ; 48(5): 480-489, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30794011

RESUMO

This study determined the roles of OX40 and OX40L in women with recurrent spontaneous abortion (RSA). We compared the expression of OX40 and OX40L genes in peripheral blood mRNA levels and serum levels of OX40L in women with a history of RSA to the control group. In this case-control study, 40 women with a history of RSA (case group), and 40 others with no history of abortion (control group) were investigated. The expressions of OX40 mRNA and OX40L mRNA were determined in the two groups using the quantitative polymerase chain reaction. Also, the enzyme-linked immunosorbent assay was used to determine the levels of serum OX40L in the two groups. There were no significant differences in the maternal age of women in the two groups (30.1 ± 4.28 years in the case vs. 30.03 ± 4.23 years in the control group). There was no difference in terms of the levels of OX40 and OX40L mRNA between the groups (p = 0.08 and p = 0.56, respectively). In addition, there was no significant correlation between the expression of OX40 and OX40L mRNA levels with age or the number of abortions. The correlation between OX40 and OX40L mRNA levels was not significant. RSA history group turned to show a higher level of serum OX40L than the control group (p = 0.03). In conclusion, our findings demonstrated that the expression of OX40 mRNA and OX40L mRNA was similar between women with a history of RSA and the control group. The elevation of serum OX40L level may be considered as a risk factor for RSA.


Assuntos
Aborto Habitual/imunologia , Ligante OX40/genética , RNA Mensageiro/genética , Receptores OX40/genética , Aborto Habitual/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Ligante OX40/sangue , Gravidez , Receptores OX40/sangue , Fatores de Risco , Regulação para Cima
5.
Arthritis Rheumatol ; 71(6): 972-982, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30624031

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc-associated ILD. METHODS: Serum samples from a combined cohort of SSc patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme-linked immunosorbent assay for concentrations of lung epithelial-derived surfactant protein D (SP-D), Krebs von den Lungen 6 glycoprotein (KL-6), CCL18, and OX40 ligand (OX40L). Lung fibrosis was measured by high-resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean ± SD follow-up 3.2 ± 4.4 years) were investigated. RESULTS: In SSc patients at baseline, serum levels of KL-6 correlated with the forced vital capacity (FVC) (r = -0.317, P < 0.001), diffusing capacity for carbon monoxide (r = -0.335, P < 0.001), and extent of lung fibrosis (r = 0.551, P < 0.001). In multivariate analyses, serum levels of KL-6 and SP-D, but not CCL18 and OX40L, were associated with lung fibrosis (odds ratio [OR] 2.41, 95% confidence interval [95% CI] 1.43-4.07 [P = 0.001] and OR 3.15, 95% CI 1.81-5.48 [P < 0.001], respectively). In SSc patients with ILD at baseline, longitudinal, multivariate analyses showed that CCL18 serum levels were an independent predictor of a >10% decrease in the FVC (hazard ratio [HR] 2.90, 95% CI 1.25-6.73; P = 0.014) and de novo development of extensive disease (HR 3.71, 95% CI 1.02-13.52; P = 0.048). Matrix-based logistic regression models for the diagnosis and prognosis of SSc-associated ILD were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of SP-D (for diagnosis) and serum levels of CCL18 (for progression of disease). CONCLUSION: These results show that SP-D is a relevant diagnostic biomarker for SSc-associated ILD, whereas KL-6 could be used to assess the severity of lung fibrosis. CCL18 appears to be a potential predictive marker for progression of ILD in SSc.


Assuntos
Quimiocinas CC/sangue , Doenças Pulmonares Intersticiais/sangue , Mucina-1/sangue , Proteína D Associada a Surfactante Pulmonar/sangue , Receptores OX40/sangue , Escleroderma Sistêmico/sangue , Idoso , Biomarcadores/sangue , Feminino , França , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Noruega , Prognóstico , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Testes de Função Respiratória , Escleroderma Sistêmico/complicações , Tomografia Computadorizada por Raios X , Capacidade Vital
6.
Int J Hematol ; 109(3): 319-327, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30652238

RESUMO

OX40, a member of the tumor necrosis factor receptor (TNFR) superfamily, co-stimulates activated T cells following interaction with its own ligand OX40L. Human T-cell leukemia virus type-1 (HTLV-1) is an etiological agent of adult T-cell leukemia (ATL). ATL cells are known to express cell surface OX40; however, the level of soluble OX40 (sOX40) in blood samples from ATL patients is unknown. Quantitative enzyme-linked immune-sorbent assay (ELISA) showed that sOX40 levels were significantly higher in plasma from acute ATL patients than those from asymptomatic HTLV-1 carriers and healthy donors, and correlated with sCD25 levels and HTLV-1 proviral loads in peripheral blood mononuclear cells (PBMCs). Fresh PBMCs from acute ATL patients showed a higher percentage of OX40-positive cells compared with those from carriers, and shed sOX40 into culture supernatants. Shedding of sOX40 was partially inhibited by a matrix metalloproteinase (MMP) inhibitor, GM6001. A fraction of sOX40 was capable of binding to OX40L. These results suggest that high levels of sOX40 are shed into blood from a large number of ATL cells in acute ATL patients. Thus, abnormally elevated plasma sOX40 levels may be useful as an additional diagnostic marker of acute ATL.


Assuntos
Biomarcadores Tumorais/sangue , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto/sangue , Proteínas de Neoplasias/sangue , Receptores OX40/sangue , Animais , Linhagem Celular Tumoral , Dipeptídeos/farmacologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Camundongos , Camundongos SCID
7.
Cell Rep ; 25(13): 3786-3799.e4, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590049

RESUMO

Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show that compared with WT mice, OX40-/- mice exhibit decreased liver fat accumulation, lobular inflammation, and focal necrosis after feeding with diets that induce NASH. Mechanistically, OX40 deficiency suppresses Th1 and Th17 differentiation, and OX40 deficiency in T cells inhibits monocyte migration, antigen presentation, and M1 polarization. Soluble OX40 stimulation alone upregulates antigen presentation, chemokine receptor expression, and proinflammatory cytokine secretion by liver monocytes. Furthermore, plasma soluble OX40 levels are positively associated with NASH in humans, suggesting clinical relevance of the findings. In conclusion, we show a mechanism for T cell regulation of innate immune cells. OX40 is a key regulator of both intrahepatic innate and adaptive immunity, generates two-way signals, and promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores OX40/metabolismo , Animais , Apresentação do Antígeno , Diferenciação Celular , Sobrevivência Celular , Citocinas/metabolismo , Regulação para Baixo , Humanos , Mediadores da Inflamação/metabolismo , Fígado/imunologia , Fígado/patologia , Ativação Linfocitária/imunologia , Camundongos Endogâmicos C57BL , Monócitos/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Receptores OX40/sangue , Receptores OX40/deficiência , Solubilidade , Linfócitos T/imunologia
8.
Arthritis Res Ther ; 16(5): 474, 2014 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-25359291

RESUMO

INTRODUCTION: OX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA). METHODS: Soluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37). Adalimumab was discontinued after the first year, and patients were followed for additional 12 months. For comparison, sOX40 and sOX40L were measured in patients with chronic RA (cRA, n = 15) and healthy volunteers (HV, n = 34). Membrane-bound OX40 and OX40L expression on T cells, B cells and monocytes were quantified. RESULTS: Soluble OX40 plasma levels of eRA patients were not different at the time of treatment initiation, but were significantly higher after 12 months of treatment, compared with HV or cRA patients. Soluble OX40L was significantly elevated throughout the first 12 months of treatment compared with HVs and patients with cRA. Adalimumab treatment did not influence sOX40 or sOX40L plasma levels. At baseline, sOX40L levels were strongly associated with the presence of anti-citrullinated protein antibodies (ACPA) (P <0.001) and IgM-RF (P <0.0001). The sOX40/sOX40L ratio was decreased in eRA, and a low ratio at the time of adalimumab discontinuation was associated with increased DAS28CRP and risk of flare the following year. T cells in the synovial fluid had the highest expression of OX40, while monocytes and B cells were the main expressers of OX40L in the joint. CONCLUSIONS: Plasma levels of sOX40 and sOX40L were increased in eRA and sOX40L was correlated with ACPA and IgM-RF. Further, expression of membrane-bound OX40 and OX40L was increased in eRA and cRA. Combined, these findings could reflect that increased activity in the OX40 systems facilitate to drive disease activity and autoantibody production in RA. TRIAL REGISTRATION: Clincaltrials.gov NCT00660647, 10 April 2008.


Assuntos
Artrite Reumatoide/sangue , Autoanticorpos/sangue , Ligante OX40/sangue , Líquido Sinovial/metabolismo , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Linfócitos B/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Monócitos/metabolismo , Ligante OX40/metabolismo , Peptídeos Cíclicos/imunologia , Receptores OX40/sangue , Receptores OX40/metabolismo , Solubilidade , Linfócitos T/metabolismo , Fatores de Tempo , Resultado do Tratamento
9.
J Immunol Methods ; 396(1-2): 74-86, 2013 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-23954271

RESUMO

Microsphere immunoassays (MIAs) allow rapid and accurate evaluation of multiple analytes simultaneously within a biological sample. Here we describe the development and validation of domestic cat-specific MIAs for a) the quantification of total IgG and IgA levels in plasma, and b) the detection of IgG and IgA antibodies to feline immunodeficiency virus (FIV) capsid (CA) and surface (SU) proteins, and feline CD134 in plasma. These assays were used to examine the temporal antibody response of domestic cats infected with apathogenic and pathogenic FIVs, and domestic cats infected with parental and chimeric FIVs of varying pathogenicity. The results from these studies demonstrated that a) total IgG antibodies increase over time after infection; b) α-CA and α-SU IgG antibodies are detectable between 9 and 28 days post-infection and increase over time, and these antibodies combined represent a fraction (1.8 to 21.8%) of the total IgG increase due to infection; c) measurable α-CD134 IgG antibody levels vary among individuals and over time, and are not strongly correlated with viral load; d) circulating IgA antibodies, in general, do not increase during the early stage of infection; and e) total IgG, and α-CA and α-SU IgG antibody kinetics and levels vary with FIV viral strain/pathogenicity. The MIAs described here could be used to screen domestic cats for FIV infection, and to evaluate the FIV-specific or total antibody response elicited by various FIV strains/other diseases.


Assuntos
Anticorpos Antivirais/sangue , Síndrome de Imunodeficiência Adquirida Felina/diagnóstico , Síndrome de Imunodeficiência Adquirida Felina/imunologia , Vírus da Imunodeficiência Felina/imunologia , Animais , Anticorpos Antivirais/imunologia , Antígenos de Superfície/imunologia , Proteínas do Capsídeo/imunologia , Gatos , Síndrome de Imunodeficiência Adquirida Felina/sangue , Imunoensaio/métodos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Microesferas , Receptores OX40/sangue , Receptores OX40/imunologia , Carga Viral
10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 29(8): 862-5, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23948416

RESUMO

OBJECTIVE: To investigate the expressions of costimulatory molecules OX40 and OX40L on peripheral blood mononuclear cells (PBMC) and their relationship with clinical characteristics of patients with primary Sjogren's syndrome (pSS). METHODS: Peripheral blood samples were collected from 51 pSS patients and 36 healthy subjects (HC). The expressions of OX40 and OX40L on PBMC were detected by immunofluorescence and flow cytometry. In addition, we observed the changes in the levels of OX40 and OX40L after treatment in 11 patients with primary pSS and searched for the relationship between their expression levels and patients' clinical manifestations. RESULTS: The expression of OX40 on CD4(+);T cells in pSS patients was significantly higher than that in the HC group (8.65%±3.51% vs 5.68%±1.68%, P<0.01). However, there was no significant difference in OX40 expression on CD8(+);T cells between patient group and HC group. In comparison with HC group, the expression of OX40L on CD14(+); monocytes (6.76%±3.60% vs 3.15%±1.89%, P<0.01) and CD19(+);B cells (4.69%±2.40% vs 2.76%±1.33%, P<0.01) significantly increased in pSS patients. Moreover, OX40 expression on CD4(+);T cells and OX40L expression on monocytes and B cells rose significantly in active pSS patients compared with those in inactive patients. The expression levels of OX40 and OX40L were higher in pSS patients with multiple system damage than in patients with simple exocrine gland injury. In addition, immunosuppressive therapy significantly reduced the expressions of OX40 and OX40L. CONCLUSION: The expressions of OX40 and OX40L on peripheral lymphocytes was upregulated in pSS patients. The high levels of OX40 and OX40L expression were significantly correlated with clinical outcome and therapeutic response, suggesting that OX40/OX40L pathway may play a critical role in pSS pathogenesis.


Assuntos
Leucócitos Mononucleares/metabolismo , Ligante OX40/sangue , Receptores OX40/sangue , Síndrome de Sjogren/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligante OX40/genética , Receptores OX40/genética , Síndrome de Sjogren/genética
11.
Acta Clin Croat ; 51(1): 3-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22919996

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Data from the literature show that systemic immune activation plays a role in ALS. OX40 (CD134) is member of the tumor necrosis factor receptor family and is expressed selectively on activated T lymphocytes. The aim of the study was to measure serum soluble OX40 (sOX40) levels in patients with ALS. The study included 25 ALS patients and 15 control subjects. Serum sOX40 levels were determined by the enzyme-linked immunosorbent method. Study showed that sOX40 levels were significantly decreased in serum of ALS patients compared with controls (P=0.05). There was no significant correlation between serum sOX40 levels and clinical parameters ofALS such as severity of the ALS patient clinical state and duration of the disease (P>0.05). In conclusion, decrease in serum sOX40 levels in patients with ALS suggests that this cytokine may be implicated in the pathomechanisms of this disease.


Assuntos
Esclerose Amiotrófica Lateral/sangue , Receptores OX40/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Pol Przegl Chir ; 83(8): 424-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22166715

RESUMO

UNLABELLED: Colorectal carcinoma (CRC) is one of the most common reasons of mortality in patients diagnosed with neoplasms. In nearly 20% of patients with colorectal carcinoma metastatic lesions are diagnosed. In general, survival of patients with metastatic lesions to the liver and other organs is poor. Conventional therapy of colorectal carcinoma is based on the surgical excision of the tumor, chemotherapy, and radiotherapy. THE AIM OF THE STUDY: was to determine the expression of CD134 and CD137 molecules inside the tumor, at the border of the tumor, in the healthy tissue, and peripheral blood, considering patients with colorectal carcinoma metastases to the liver. MATERIAL AND METHODS: The study group comprised 39 patients subject to surgical treatment at the Department of General and Gastroenterological Surgery, due to colorectal carcinoma with liver metastases. CD134 and CD137 adhesive molecule levels were determined inside the tumor, at the border of the tumor, and in the healthy margins of the surgical incision. Additionally, the authors evaluated the peripheral blood level of the above-mentioned molecules on the day of the surgical procedure, and 10 days, thereafter. RESULTS: The mean CD134 levels were the highest inside the tumor, significantly decreasing towards the direction of healthy tissues. The average peripheral blood molecule levels were four-fold higher on the day of the surgical procedure, as compared to values obtained on the tenth postoperative day. This dependency also concerned the remaining statistical measures.The mean CD137 levels showed no significant difference, regardless their location. The authors observed significant, peripheral blood, CD137 level differences, considering the day of the surgical procedure and tenth postoperative period. The mean CD137 peripheral blood level was several times higher on the day of the surgical procedure, as compared to the postoperative period. CONCLUSIONS: The determination of the activity of CD134 and CD137 molecules might create opportunities to plan treatment and predict prognosis in case of colorectal carcinoma. Proper immuno-therapeutic management which is based on the expression of the above-mentioned molecules might help determine the risk of metastases, preventing from their development. In advanced cases treatment of liver metastases might be possible.


Assuntos
Ligante 4-1BB/análise , Biomarcadores Tumorais/análise , Neoplasias Colorretais/química , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/secundário , Receptores OX40/análise , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Ligante 4-1BB/sangue , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Feminino , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Receptores OX40/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue
13.
Hypertens Res ; 34(9): 999-1003, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21654753

RESUMO

The aim of this study was to explore the role of circulating endothelial progenitor cells (EPCs) and endothelial apoptotic microparticles in hypertensive patients with and without electrocardiographic left ventricular hypertrophy (LVH). Flow cytometry was used to assess endothelial cell apoptosis and circulating EPC level by quantification of circulating EPC markers (defined as CD34(+)CD133(+), CD34(+)KDR(+)) and endothelial apoptotic microparticles (defined as CD31(+)/annexin V(+)) in peripheral blood samples. The LVH was defined by ECG with the Cornell voltage criteria. In total, 128 hypertensive patients (83 men and 45 women, aged 59±14 years) were enrolled in this study, in which 107 patients (84%) showed no electrocardiographic evidence of LVH, and 21 patients (16%) fulfilled the LVH criteria by ECG. There were no significant differences in basic characteristics between the two groups, but hypertensive patients with LVH had a higher urine albumin excretion rate than those without LVH (P=0.027). Furthermore, hypertensive patients with LVH were shown to have decreased circulating EPC numbers (all P<0.05) and adhesive function compared with those without LVH (LVH vs. no LVH: 14±6 vs. 30±6 cells per high-power field, P<0.001). Increased numbers of endothelial apoptotic microparticles were noted in hypertensive patients with LVH (4.2±4.9 vs. 2.4±3.4%, P=0.115), although the difference was not significant. This study showed that essential hypertensive patients with electrocardiographic LVH evidence have decreased circulating EPC numbers and adhesive function compared with those without LVH. These findings may explain the pathogenetic processes that link hypertensive LVH and endothelial injury in cardiovascular disease.


Assuntos
Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Células-Tronco/fisiologia , Idoso , Albuminúria/fisiopatologia , Antígenos CD/sangue , Antígenos CD34/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Apoptose , Biomarcadores/sangue , Micropartículas Derivadas de Células , Eletrocardiografia , Células Endoteliais/fisiologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino , Pessoa de Meia-Idade , Receptores OX40/sangue , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico
14.
Ann Saudi Med ; 31(1): 29-34, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21245596

RESUMO

BACKGROUND AND OBJECTIVES: OX40-OX40L interaction is implicated in the pathogenesis of systemic lupus erythematosus (SLE). We evaluated the role of OX40/OX40L as markers of disease activity and nephritis in SLE patients. DESIGN AND SETTING: Case-control study conducted in 2009 on SLE patients attending the outpatient clinics of Ain Shams University Hospital, Egypt. PATIENTS AND METHODS: We assessed the percentage of CD4+ T-lymphocytes expressing OX40 by flowcytometry, and serum OX40 ligand (OX40L) levels in 40 patients with SLE (20 with lupus nephritis and 20 without) and in 20 healthy controls. Disease activity was assessed by the University of Toronto SLE disease activity index (SLEDAI). RESULTS: The percentage of CD4+ T-lymphocytes expressing OX40 was significantly higher in SLE patients than in controls, and in patients with lupus nephritis than in those without. OX40 expression correlated positively with both serum creatinine levels and SLEDAI. OX40 expression was the highest in patients with class V lupus nephritis and lowest in class II. Serum OX40L levels were significantly higher in SLE patients than in controls, and in patients with nephritis than in those without. Serum OX40L levels correlated with serum creatinine levels but not with SLEDAI. OX40 expression on CD4+ T-cells had a higher sensitivity and specificity in diagnosing lupus nephritis than both OX40L and anti-double-stranded DNA levels. CONCLUSION: OX40-OX40L interaction plays a role in the pathogenesis of SLE. The expression of OX40 on CD4+ T-lymphocytes and the serum level of OX40L may act as markers of lupus nephritis. Measurements of percentages of CD4+ T-lymphocytes expressing OX40 may serve as an indicator of disease activity in SLE.


Assuntos
Anticorpos Antinucleares/sangue , Linfócitos T CD4-Positivos/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Nefrite/sangue , Ligante OX40/sangue , Receptores OX40/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite/diagnóstico , Curva ROC , Índice de Gravidade de Doença , Adulto Jovem
15.
Pol Przegl Chir ; 83(12): 641-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22343199

RESUMO

UNLABELLED: Epidemiological studies prove that incidence of colorectal cancer is increasing. The first line therapy of colorectal cancer is surgical resection of the primary tumor and elimination of regional and remote metastases. THE AIM OF THE STUDY was to determine expression of adhesion molecules CD134 and CD137 in the peripheral blood in colorectal cancer patients, depending on clinical cancer stage, size and invasion of the tumor. MATERIAL AND METHODS: The study enrolled 72 patients with primary colorectal adenocarcinoma. An average patient age was 64.55 years. Clinical tumor stage was assessed using two scales: Dukes: A and Astler-Coller scale. Expression of adhesion molecules was determined in the peripheral blood collected on the day of the procedure and 10 days after the procedure. RESULTS: An average activity of CD134 molecules (12.66%) was significantly higher than that of CD137 (6.26%) (p<0.001). Clinical tumor stage was assessed on Dukes scale and was unrelated to CD134 activity, while activity of CD137 was related to clinical cancer stage. CONCLUSIONS: CD137 activity is directly proportional to colorectal cancer stage. Surgical resection of the tumor results in increased CD134 and CD137 expression. Long term studies, enrolling larger groups of patients, including their subdivision to colon and rectal cancer, are required to utilize CD134 and CD137 in immune therapy of colorectal cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Receptores OX40/sangue , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Idoso , Neoplasias Colorretais/sangue , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
16.
J Int Med Res ; 37(3): 601-10, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19589242

RESUMO

This study investigated the effect of simvastatin on the expression of OX40 and OX40 ligand (OX40L) in vitro and in vivo. OX40 and OX40L mRNA and protein levels were measured in human peripheral blood mononuclear cells, using reverse transcription-polymerase chain reaction and Western blot, respectively, in response to simvastatin alone or given in combination with interferon-gamma, mevalonate or GW9662, a peroxisome proliferators-activated receptor-gamma (PPAR-gamma) antagonist. Simvastatin induced down-regulation of OX40 and OX40L mRNA and protein in a concentration-dependent manner, and antagonized the interferon-gamma-induced increase in OX40 and OX40L mRNA and protein levels. Mevalonate, but not GW9662, reversed the simvastatin-induced down-regulation of OX40 and OX40L expression, indicating that these effects were mediated through the mevalonate pathway. Serum levels of soluble OX40L and matrix metalloproteinase 9 levels were significantly reduced in patients with atherosclerotic cerebral infarction who were treated for 6 months with routine therapy plus simvastatin (n = 46) compared with patients receiving routine therapy alone (n = 30). These findings improve our understanding of the anti-inflammatory and immunomodulatory properties of simvastatin treatment for atherosclerotic disorders.


Assuntos
Aterosclerose/complicações , Infarto Cerebral/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Leucócitos Mononucleares/metabolismo , Ligante OX40/genética , Receptores OX40/genética , Sinvastatina/farmacologia , Aterosclerose/sangue , Aterosclerose/enzimologia , Infarto Cerebral/sangue , Infarto Cerebral/enzimologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Ligante OX40/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores OX40/sangue
17.
J Immunol ; 183(4): 2827-36, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19635903

RESUMO

Ag-specific human CD4(+) memory T lymphocytes have mostly been studied using assays of proliferation in vitro. Intracellular cytokine and ELISPOT assays quantify effector cell populations but barely detect responses to certain recall Ags that elicit strong proliferative responses, e.g., tetanus toxoid, that comprise non-Th1 CD4(+) cells. We have found that culturing whole blood with Ag for 40-48 h induces specific CD4(+) T cells to simultaneously express CD25 and CD134. This new technique readily detects responses to well-described CD4(+) T cell recall Ags, including preparations of mycobacteria, CMV, HSV-1, influenza, tetanus toxoid, Candida albicans, and streptokinase, as well as HIV-1 peptides, with high specificity. The assay detects much higher levels of Ag-specific cells than intracellular cytokine assays, plus the cells retain viability and can be sorted for in vitro expansion. Furthermore, current in vitro assays for human CD4(+) memory T lymphocytes are too labor-intensive and difficult to standardize for routine diagnostic laboratories, whereas the whole-blood CD25(+)CD134(+) assay combines simplicity of setup with a straightforward cell surface flow cytometry readout. In addition to revealing the true extent of Ag-specific human CD4(+) memory T lymphocytes, its greatest use will be as a simple in vitro monitor of CD4(+) T cell responses to Ags such as tuberculosis infection or vaccines.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Subunidade alfa de Receptor de Interleucina-2/sangue , Ativação Linfocitária/imunologia , Receptores OX40/sangue , Adulto , Sequência de Aminoácidos , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Células Cultivadas , Doença Crônica , Epitopos de Linfócito T/sangue , Fluoresceínas , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Estudos Longitudinais , Macaca nemestrina , Dados de Sequência Molecular , Receptores OX40/biossíntese , Succinimidas , Timidina , Trítio
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