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.

Prognostic roles of endostatin, matrix metalloproteinase-2 and 9 and tissue inhibitors of metalloproteinase-1 in advanced non-small cell lung cancer

Background and aim of the work: Previous studies verified that Endostatin, matrix metalloproteinase [MMP] -2 and -9, in addition to tissue inhibitors of metalloproteinase [TIMP] -1 may play a crucial role in prognosis of non-small cell lung cancer [NSCLC]. In this study we will investigate the changes in the pretreatment serum levels of these factors and to evaluate their clinical implication in patients with advanced non-small cell lung cancer [NSCLC]

Patients and methods: Pretreatment serum samples were collected from 25 patients and 10 control healthy individuals. The levels of Endostatin, MMP-2, MMP-9, and TIMP-1 were measured using a sandwich enzyme immunoassay kit

Results: The pretreatment serum levels of Endostatin and TIMP1 were significantly elevated and correlated with their stages and survival [P< 0.05], where, the serum level of Endostatin in healthy subjects was 81.20 +/- 23.99 ng/ml and in patients with NSCLC was 354.40 +/- 164.01 ng/ml. The serum level of TIMP1 in healthy subjects was 1.49 +/- 0.29 ng/ml and in patients with NSCLC was 2.96 +/- 0.58 ng/ml. The serum level of MMP2 and 9 were non-significantly decreased in serum of NSCLC patients [P > 0.05], where the serum activity of MMP2 in healthy subjects was 0.14 +/- 0.03 ng/ml and in patients with NSCLC was 0.09 +/- 0.03% and the serum activity of MMP9 in healthy subjects was 0.13 +/- 0.019 ng/ml and in patients with NSCLC was 0.10 +/- 0.03%

Conclusions: Our results indicated that the circulating levels of Endostatin, and TIMP-1 in patients with NSCLC may be valuable future tools for treatment planning and monitoring of treatment, however, these blood tests need to be standardized and validated in large-scale prospective clinical trials

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.

Clinical significance of vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma

Despite the progress in early diagnosis of liver cancer, its prognosis remains poor. Tumor angiogenesis is critical to both growth and metastasis of hepatocellular carcinoma [HCC], and has drawn much attention in recent years. Details regarding serum levels of proangiogenic and antiangiogenic growth factors controlling this process could be obtained by studying serum levels of vascular endothelial growth factor [VEGF] and endostatin respectively. Accordingly, the aim of the present study was to evaluate the clinical significance of serum levels of VEGF and endostatin in patients with HCC and their possible role in metastatic spread. The study was conducted on 25 patients with HCC and 15 age and sex matched healthy controls. The patient group was subdivided into 10 patients with metastatic spread and 15 patients with localized tumors without evidence of any metastasis. Results of the present study revealed that VEGF was significantly higher in HCC patients with and without metastasis when compared to the control group [P<0.01 and P<0.05, respectively]. Furthermore, levels of VEGF were significantly higher in the metastatic group than the non- metastatic one [P<0.05]. In contrast, there was no statistical significant difference in endostatin levels between any of the studied groups [P>0.05]. Moreover, the correlation between serum levels of VEGF and endostatin did not reach statistical significance [P> 0.05]. Our data shows that serum VEGF levels in HCC patients is directly associated with metastasis and recurrence of tumors and increases gradually with the progression of disease. Therefore, the serum VEGF level in HCC patients appears to reflect the disease potential activity of vascular invasion and is a possible marker for metastasis. On the other hand, the unelevated levels of endostatin point to that the angiogenic response is more prominent than the anti-angiogenic response in liver metastasis. These findings support the rationale for anti- angiogenesis therapy in these patients. Thus the role of endostatin as anti -angiogenic factor may be preserved for therapeutic not diagnostic use. However, further investigation is required to elucidate the effectiveness of this promising tool in order to achieve anti-angiogenic properties