Predictive potential of various plasma inflammation-, angiogenesis-, and extracellular matrix remodeling-associated mediators for intra-amniotic inflammation and/or microbial invasion of the amniotic cavity in preterm labor.

PURPOSE: To determine whether various inflammatory-, angiogenic/anti-angiogenic-, and extracellular matrix remodeling-associated proteins in plasma, alone or in combination with conventional blood-based markers, can predict intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with spontaneous preterm labor (PTL). METHODS: A total of 193 singleton pregnant women with PTL (23-33 weeks) were included in this retrospective cohort study. Plasma samples were obtained at the time of amniocentesis. Amniotic fluid (AF) was cultured for microorganism detection and consequent MIAC diagnosis. IL-6 levels were determined in AF and used to identify IAI (AF IL-6 ≥ 2.6 ng/mL). Endostatin, haptoglobin, IGFBP-2/3, LBP, M-CSF, MMP-2/8, pentraxin 3, PlGF, S100A8/A9, and VEGFR-1 levels were assayed in plasma samples by ELISA. CRP levels and neutrophil-to-lymphocyte ratio (NLR) were measured. RESULTS: Plasma LBP, MMP-8, and S100A8/A9 levels, CRP levels, and NLR were significantly higher, and plasma IGFBP-2 and MMP-2 levels were significantly lower in women with IAI/MIAC than in those without this condition, whereas no baseline variables differed significantly between the two groups. Using a stepwise regression analysis, a noninvasive prediction model for IAI/MIAC was developed, which included plasma LBP, MMP-2, and MMP-8 levels (area under the curve [AUC], 0.785). The AUC for this prediction model was significantly or borderline greater than that of any single factor included in the model. CONCLUSIONS: IGFBP-2, LBP, MMP-2, MMP-8, and S100A8/A9 may represent valuable plasma biomarkers for predicting IAI/MIAC in women with PTL. Combination of LBP, MMP-2, and MMP-8 expression data can significantly improve the predictive potential for IAI/MIAC.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Endostatin a Potential Biomarker for Heart Failure with Preserved Ejection Fraction / Endostatina é um Potencial Biomarcador para a Insuficiência Cardíaca com Fração de Ejeção Preservada

Abstract Background: Endostatin is a circulating endogenous angiogenesis inhibitor preventing neovascularization. Previous studies demonstrated the prognostic value of Endostatin among patients with heart failure with reduced ejection fraction (HFrEF). However, the role of Endostatin among patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. Objective: This study aimed to investigate the association between serum Endostatin levels, natriuretic peptide levels and the severity of left ventricular diastolic dysfunction and the diagnosis of HFpEF. Methods: Endostatin serum concentrations were measured in 301 patients comprising 77 HFpEF patients, 169 patients with asymptomatic left ventricular diastolic dysfunction (ALVDD), and 55 controls with normal cardiac function. Results: Endostatin serum levels were significantly elevated in patients with HFpEF (median/interquartile range 179.0 [159-220]) and ALVDD (163.8 [145.4-191.3]) compared to controls (149.1 [130.6-176.9]), p < 0.001 and p = 0.004, respectively) and significant correlated with N-terminal pro B-type natriuretic peptide (NT-proBNP). Conclusions: This hypothesis-generating pilot study gives first evidence that Endostatin correlates with the severity of diastolic dysfunction and may become a novel biomarker for HFpEF. We hypothesize a rise in Endostatin levels may reflect inhibition of adaptive angiogenesis and adverse cardiac remodeling.

Resumo Fundamentos: A Endostatina é um inibidor circulante endógeno da angiogênese que previne a neovascularização. Estudos anteriores demonstraram o valor prognóstico da Endostatina em pacientes com insuficiência cardíaca com fracção de ejeção reduzida (ICFEr). No entanto, o papel da Endostatina entre os pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEp) permanece incerto. Objetivo: Investigar a associação entre os níveis séricos de Endostatina, níveis de peptídeos natriuréticos e a gravidade de disfunção ventricular esquerda e diastólica e o diagnóstico de ICFEp. Métodos: Mediu-se a concentração sérica de Endostatina em 301 pacientes, compreendendo 77 pacientes com ICFEp, 169 pacientes com disfunção ventricular esquerda assintomática diastólica (DVEAD) e 55 controles com a função cardíaca normal. Resultados: Os níveis de Endostatina no soro foram significativamente elevados em pacientes com ICFEp (mediana / intervalo interquartil 179,0 [159-220]) e DVEAD (163,8 [145,4-191,3]) em comparação com os controles (149,1 [130,6-176,9]), p < 0,001 e p = 0,004, respectivamente) e correlação significativa com o terminal do pro-peptídeo natriurético tipo B (NT-proBNP). Conclusões: Este estudo piloto gerador de hipótese fornece a primeira evidência de que a Endostatina se correlaciona com a gravidade da disfunção diastólica e pode tornar-se um novo biomarcador para ICFEp. Nossa hipótese é de que um aumento nos níveis de Endostatina pode refletir inibição da angiogênese adaptativa e remodelação cardíaca adversa.

Endostatina sérica en preeclampsia y eclampsia / Serum endostatins in pre-eclampsia and eclampsia

Objetivo: Comparar las concentraciones de endostatina sérica en eclámpticas, preeclámpticas y embarazadas normotensas. Materiales y método: Se incluyó a 30 pacientes con preeclampsia leve (grupo A), a 30 pacientes con preeclampsia grave (grupo B) y a 30 pacientes con eclampsia (grupo C ). El grupo control fue seleccionado por tener edad e índice de masa corporal similares a los de los grupos en estudio y consistió en 30 embarazadas sanas (grupo D). Solo se incluyó a pacientes nulíparas. Las muestras de sangre se recolectaron antes del parto y, en los grupos en estudio, inmediatamente después del diagnóstico para la determinación de endostatina sérica. Resultados: Los valores más altos de endostatina se observaron en el grupo de pacientes eclámpticas junto con las preeclámpticas graves. Se encontraron valores más bajos en las preeclámpticas leves. Los grupos en estudio presentaron valores de endostatina significativamente superiores a los controles (p < 0,05). El análisis de regresión lineal mostró que los factores que afectaban significativamente la concentración plasmática de endostatina fueron el ácido úrico y la proteinuria en 24 h (p < 0,05). Conclusión: Las pacientes eclámpticas y preeclámpticas presentan concentraciones de endostatina sérica más altas que las embarazadas normotensas (AU)

Objective: To compare serum endostatin concentrations in eclamptic, pre-eclamptic and normotensive pregnant women. Materials and method: The study included 30 patients with mild preeclampsia (group A), 30 patients with severe pre-eclampsia (group B), and 30 patients with eclampsia (group C). A control group, consisting of 30 healthy pregnant women of similar age and body mass index to the studiy groups, was selected (group D). Only nuliparous patients were included. Blood samples were collected for serum endostatin determination from all patients before delivery, and from the study groups immediately after diagnosis. Results: Higher values of endostatin were observed in eclamptic patients together with severe pre-eclamptic patients. Lower values were found in mild pre-eclamptic patients. The study groups had significantly higher values of endostatin compared with the control group (P<.05). Linear regression analysis, found that factors that significantly affected plasma endostatin concentrations were uric acid and 24-hour proteinuria. Conclusion: The findings of this study showed that eclamptic and pre-eclamptic patients had higher serum endostatin concentrations than normotensive pregnant women (AU)

Primary tumorectomy promotes angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice

PURPOSE: To investigate the effect of primary tumorectomy on angiogenesis and pulmonary metastasis in osteosarcoma-bearing nude mice. METHODS: Osteosarcoma was introduced to nude mice via subcutaneous injection of MG-63 cells. One hundred and eighty osteosarcoma-bearing mice were used equally in 3 parallel experiments. The effect of tumorectomy (TR) on the expression of vascular endothelial growth factor (VEGF) and endostatin was investigated by ELISA. Meanwhile, the effect on angiogenesis was evaluated by Matrigel plug assay, and pulmonary metastasis assessed by calculating the metastatic foci. Sham-operation (SO) and untreated (UT) groups served as controls. RESULTS: The VEGF (TR: 79.55 ± 7.82 pg/mL vs. SO: 110.01 ± 5.69 pg/mL, UT: 123.50 ± 10.41 pg/mL; p < 0.01) and endostatin (TR: 47.09 ± 6.22 ng/mL vs. SO: 117.64 ± 7.39 ng/mL, UT: 126.73 ± 6.55 ng/mL; p<0.01) were down-regulated significantly after tumorectomy, and angiogenesis was significantly promoted simultaneously. The incidence of pulmonary metastatic foci was 80.0% in the TR group, 40.0% in the SO group and 35.0% in the UT group. CONCLUSION: Primary tumorectomy can down-regulate the expression of VEGF and endostatin and promote angiogenesis which leads to the acceleration of pulmonary metastasis. These findings imply that anti-angiogenic treatment can be considered after primary tumorectomy.

Serum endostatin and bFGF as predictive factors in advanced breast cancer patients treated with letrozole

Introduction. To investigate the value of baselineserum levels of VEGF, bFGF, endostatin and theirratio as predictive factors of response to endocrinetherapy in patients with metastatic breast cancer(MBC) and positive ER treated with letrozole aftertamoxifen failure.Materials and method. The serum levels of endostatin,VEGF and bFGF were determined in postmenopausalpatients with progressing MBC fromserum samples obtained before initiation of letrozole.The relation between serum angiogenic factorlevels and TTP was investigated.Results. Seventy-six patients (45.2%) presented ahigh endostatin level (> 24.6 ng/ml), 40% low bFGFlevels (0 pg/ml) and 50.4% low VEGF ( 24.6 ng/ml and bFGF equal 0 pg/mlwas 9.5 months versus 19.5 months in patients withendostatin 0 pg/ml.Conclusions. The baseline levels of bFGF and endostatinare predictive factors of efficacy in patientswith MBC treated with letrozole and can selectgroups with different TTP

No disponible