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Fibrosarcomas are soft tissue mesenchymal tumors originating from transformed fibroblasts. Fibroblast growth factor-2 (FGF2) and its tyrosine-kinase receptors (FGFRs) play pivotal roles in fibrosarcoma onset and progression, FGF2 being actively produced by fibroblasts in all stages along their malignant transformation to the fibrosarcoma stage. The soluble pattern recognition receptor long pentraxin-3 (PTX3) is an extrinsic oncosuppressor whose expression is reduced in different tumor types, including soft tissue sarcomas, via hypermethylation of its gene promoter. PTX3 interacts with FGF2 and other FGF family members, thus acting as a multi-FGF antagonist able to inhibit FGF-dependent neovascularization and tumor growth. Here, PTX3 overexpression significantly reduced the proliferative and tumorigenic potential of fibrosarcoma cells in vitro and in vivo. In addition, systemic delivery of human PTX3 driven by the Tie2 promoter inhibited the growth of fibrosarcoma grafts in transgenic mice. In a translational perspective, the PTX3-derived small molecule FGF trap NSC12 prevented activation of the FGF/FGFR system in fibrosarcoma cells and reduced their tumorigenic activity in vivo. In conclusion, impairment of the FGF/FGFR system by FGF trap molecules may represent a novel therapeutic approach for the treatment of fibrosarcoma.
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BACKGROUND: Mannose binding lectin (MBL) is a protein of the complement system and pentraxin-3 (PTX3) is an acute phase protein both with an important role in inflammatory diseases, such as diabetic retinopathy (DR). AIM OF THE STUDY: To evaluate whether plasma MBL and PTX3 levels are associated with the development of DR and if patients with and without DR can be distinguished. METHODS: The patients were divided into three groups: diabetic without DR; with mild/moderate DR, and with severe/proliferative DR. PTX3 and MBL levels were measured with enzyme-linked immunosorbent assay kits. RESULTS: A total of 74 patients were included. A significant association was observed between high levels of MBL and severe DR; 47% of patients with severe/proliferative DR had high levels of MBL, whereas 12% of the patients with diabetes but no DR had high levels of MBL (p = 0.008; odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.4-25.0). High levels of MBL were more frequent in patients with severe/proliferative disease (47%) when compared to those with mild/moderate DR (20%), p = 0.04 (OR: 3.46; 95% CI: 1.0-11.8). PTX3 levels were similar among the groups and were not related to the development or severity of DR. CONCLUSION: We found a significant association between high plasma MBL levels and DR development as well as with severe/proliferative DR. We observed no relationship between plasma PTX3 levels and the development or severity of DR.
Assuntos
Biomarcadores/sangue , Proteína C-Reativa/análise , Retinopatia Diabética/sangue , Lectina de Ligação a Manose/sangue , Componente Amiloide P Sérico/análise , Brasil , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de ChancesRESUMO
CONTEXT: Determining the disease's inflammatory activity in spondyloarthritis (SpA) is difficult although very important as it is this that drives treatment. OBJECTIVE: To investigate if plasma pentraxin-3 (PTX3) could act as an inflammatory marker in SpA. METHODS: Eighty one SpA patients (11 with psoriatic arthritis (PsoA) and 70 with ankylosing spondylitis (AS)) and 90 gender and age paired controls were studied for plasma PTX3 levels by ELISA. Patients had determinations of disease activity through C reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Epidemiological, clinical and treatment data were collected through chart review. RESULTS: SpA patients had lower concentrations of plasma PTX3 than controls (median of 0.95 ng/mL vs 1.64 ng/mL; p < 0.0001). Correlation of PTX3 levels and BASDAI, ASDAS-CPR, CRP levels and ESR could not be found. No differences in PTX3 levels were detected between PSoA and AS patients (p = 0.42). Uveitis, presence of HLA B27, tobacco exposure, age and disease duration did not influence PTX3 levels. CONCLUSIONS: PTX3 plasma levels do not reflect disease activity in SpA. However, it probably participates in the ethiopathogenetic process, as it is consumed in these patients.
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Biomarcadores/sangue , Proteína C-Reativa/análise , Componente Amiloide P Sérico/análise , Índice de Gravidade de Doença , Espondilite Anquilosante/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/patologia , Adulto JovemRESUMO
ABSTRACT Objective We wanted to investigate whether there is a relationship between circulating irisin, retinol binding protein-4 (RBP-4), adiponectin and proinflammatory mediators implicated in the development of insulin resistance (IR) in metabolic syndrome (MetS). Subjects and methods In 180 individuals, including controls and patients with MetS, we measured fasting plasma insulin, high sensitivity C-reactive protein (hsCRP), pentraxin-3 (PTX-3), interleukin-33 (IL-33), irisin, RBP-4, and adiponectin using ELISA kits. Results While fasting plasma hsCRP, PTX-3, IL-33, irisin, RBP-4 concentrations were higher, adiponectin levels were lower in patients with MetS than in controls. A correlation analysis revealed that plasma irisin levels were positively associated with MetS components such as waist circumference and waist-hip ratio, low density lipoprotein (LDL) and markers of systemic inflammation such as PTX-3, hsCRP, uric acid, and RBP-4. Adiponectin levels were negatively associated with waist circumference, waist-hip ratio, PTX-3 and LDL. Conclusions Although the precise mechanisms are still unclear, irisin, RBP-4, adiponectin and PTX-3 are hallmarks of the MetS, which is related to low-grade inflammation. It is conceivable that irisin and adiponectin might contribute to the development of MetS and may also represent novel MetS components. Future clinical studies are needed to confirm and extend these data.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Fibronectinas/sangue , Mediadores da Inflamação/sangue , Síndrome Metabólica/sangue , Adiponectina/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Ensaio de Imunoadsorção Enzimática , Biomarcadores/sangue , Estudos de Casos e ControlesRESUMO
Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk to develop HCC increases with the severity of liver inflammation and fibrosis. Long pentraxin 3 (PTX3) is a soluble pattern-recognition receptor produced by phagocytes and nonimmune cells at sites of inflammation or injury. The aim of the present study was to determine the association of PTX3 polymorphisms and its plasma levels with HCC occurrence among patients with HCV. Samples from 524 patients with chronic hepatitis C were evaluated in this study. Two polymorphisms (rs1840680 and rs2305619) in the PTX3 gene were determined by real-time PCR. PTX3 plasma levels were measured by Enzyme-linked Immunosorbent Assay (ELISA). Our data show a significant association between PTX3 polymorphisms and HCC occurrence in univariate and multivariate analysis (P = 0.024). Patients with HCC had higher PTX3 plasma levels compared to individuals with mild or severe fibrosis (P < 0.0001 and P = 0.002, respectively). In addition, PTX3 rs2305619 polymorphism and plasma levels were correlated with Child-Pugh scores B and C in HCC individuals. PTX3 seems to be a risk factor for HCC occurrence in chronic hepatitis C. This is the first study that evaluates PTX3 in the context of hepatitis C.