Higher Serum Vascular Endothelial Growth Factor Levels Research Articles

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

We sought to clarify the musculoskeletal ultrasound (MSUS) findings and serum concentrations of cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica (GC-R PMR). Patients with PMR admitted to Nagasaki University Hospital (n = 41) were enrolled. MSUS of both shoulder joints was performed in 36 patients. Patients’ sera were analyzed for cytokines/growth factors using multiplex assay kits. We examined the cases of 17 males and 24 females (median age 70 years). There were 27 GC-R patients and 14 non-GC-R patients. PD signals were detected in significantly more GC-R patients (65.2%) than non-GC-R patients (23.1%) (p = 0.035). The median serum level of vascular endothelial growth factor (VEGF) was significantly higher in the GC-R group at 871.4 pg/mL than the non-GC-R group (422.8 pg/mL) (p = 0.03) and significantly higher in the PD-positive versus PD-negative patients (p = 0.04). A multivariate analysis revealed that a high serum VEGF level was an independent variable contributing to GC resistance (p = 0.017, odds ratio: 10.34). These results suggest that a high serum VEGF level is a biomarker of GC resistance in PMR, which might be explained by PD-positive neovascularization in inflamed joints of PMR.

Serum Vitamin D Levels and Vascular Endothelial Growth Factor in Patients with Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Diabetes Mellitus (DM) is the most common noncommunicable disease and the fifth leading cause of death worldwide. Recent research has demonstrated that low Vitamin D levels and high Vascular Endothelial Growth Factor (VEGF) in middle-aged and elderly populations represent a risk factor for Type 2 Diabetes Mellitus (T2DM). Aim: To estimate the Vitamin D and VEGF levels in study subjects with T2DM and healthy controls and to correlate the Vitamin D level and VEGF with HbA1c % in study subjects with T2DM. Materials and Methods: A cross-sectional study was undertaken from October 2014 to November 2016 at the Department of Medicine in collaboration with the Department of Biochemistry, Bangalore Medical College and Research Institute, Bangalore. The study included 50 T2DM subjects on oral hypoglycaemic agents for five years and 50 age and sexmatched healthy controls selected randomly from the general population. In all the study subjects, Random Blood Glucose (RBG), LFT, Renal Function Test (RFT), HBA1c, serum Vitamin D, and serum VEGF were estimated. Student t-test and Chisquare/Fisher-Exact test were used to find the significance of study parameters between cases and controls. Multivariate logistic regression analysis was done to assess the risk factors for DM. Results: The mean age of the cases was 50.9±9.7 years and of controls was 49.76±7.7 years. Among the 50 cases, 19 (38%) were men and 31 (62%) were women. Among the 50 controls, 27 (54%) were men and 23 (46%) were women. The mean Body Mass Index (BMI) among cases was 27.21±4.59 and in controls was 24.82±2.63 (p-value=0.0016). The mean serum 25(OH) Vitamin D levels in cases were 11.39±3.32 ng/mL and in controls were 28.06±11.14 ng/mL (p-value <0.001). The mean serum VEGF levels in cases were 97.52±16.96 pg/mL and in controls were 56.37±17.74 pg/mL (p-value <0.001). Conclusion: The present study found that subjects with T2DM have lower serum 25(OH) Vitamin D levels and higher serum VEGF levels than those without T2DM. Serum Vitamin D decreases and serum VEGF-A levels increase with increasing HbA1c%, correlating with vascular complications.

Serum VEGF levels as a predictor of recurrence in patients with advanced‑stage esophageal squamous cell carcinoma following curative esophagectomy followed by chemotherapy or concurrent radiotherapy.

The present study evaluated serum levels of vascular endothelial growth factor (VEGF) as a predictor of recurrence in patients with advanced-stage esophageal squamous cell carcinoma (ESCC) following curative esophagectomy followed by chemotherapy or concurrent radiotherapy. Patients with locally advanced resectable ESCC underwent R0 esophagectomy followed by chemotherapy or concurrent radiotherapy as an adjuvant. Serum VEGF levels in 173 patients, including 57 patients with recurrent disease, and 183 healthy controls were determined using a Luminex assay. The results demonstrated that the serum VEGF levels were significantly higher in 57 patients with locally advanced resectable ESCC at recurrence compared with the levels at pre-treatment (P<0.001). The patients with recurrence exhibited significantly higher serum VEGF levels during chemotherapy or concurrent radiotherapy than patients with no recurrence (P<0.05). Patients with low serum VEGF levels had a significantly longer survival time than those with high serum VEGF levels prior to treatment (P<0.01). The median survival times were 70 and 25 months in patients with locally advanced resectable ESCC with serum VEGF levels <161.75 and ≥161.75 pg/ml following treatment, respectively (P<0.01). Compared with patients with VEGF levels <147 pg/ml following treatment, patients with locally advanced resectable ESCC with VEGF levels ≥147 pg/ml had a significantly higher risk of recurrence (P<0.01). Patients with low serum VEGF levels (<147 pg/ml) had significantly higher recurrence-free survival rates than those with high serum VEGF levels (≥147 pg/ml) following treatment (P<0.01). The findings of the present study demonstrate that serum VEGF levels are a potential predictor of recurrence and of the treatment outcomes of chemotherapy or concurrent radiotherapy in patients with locally advanced resectable ESCC.

Peculiarities of serum levels of vascular growth factor and its receptors in dialysis patients

Recent research has shown that VEGF may influence the condition and survival of patients with chronic kidney disease (CKD), including those treated with dialysis procedures. Identifying the value of this factor is important to uncover the mechanisms of CKD progression and improve treatment strategies.&#x0D; The present study aimed to determine the mean serum levels of vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and their correlations with pro-inflammatory cytokines (TNF-α, MCP-1, IL -6, IL -8) in dialysis patients stratified by dialysis modality and Carnivit use.&#x0D; Methods. In this prospective cohort study, serum levels of VEGF, VEGF-R, and proinflammatory cytokines were determined in 41 hemodialysis (HD) patients (group 1) and 14 peritoneal dialysis (PD) patients (group 2), 28 of whom were treated with Carnivit. The assay was performed with the enzyme immunoassay "SunRise TouchScreen" using IBL International (Germany) test systems. The limits of normal values (reference range) were determined based on the results of a study with 20 conditionally healthy individuals.&#x0D; Results. All included patients had significantly higher serum levels of VEGF compared to healthy donors (p=0.006); a significant increase in this mediator was observed in both HD and PD treated subjects (p=0.002 and p=0.007, respectively). Carnivit treatment resulted in a significant decrease (p=0.023) in this mediator to normal levels in all patients. Subgroup analysis showed a significant decrease in VEGF (p=0.016) and VEGF-R (p=0.005) in HD patients after therapy. Mean concentrations of growth factor in HD patients (p=0.098) and PD patients (p=0.160) did not differ from those of healthy subjects.&#x0D; A positive correlation was observed between serum levels of VEGF and its receptors in the studied patients both before and after treatment (p &lt; 0.0001).&#x0D; A direct correlation between IL -8 and VEGF and VEGF-R was observed in HD patients and an inverse correlation between MCP-1 and VEGF-R was observed in PD patients. After Carnivit treatment, the correlation between serum levels of IL -8 and VEGF-R (0.782, p=0.01) and between VEGF and VEGF-R (0.770, p=0.01) remained in group 1 and between VEGF and VEGF-R (0.829, p=0.03) in group 2.&#x0D; Conclusion. Increased concentrations of VEGF and its receptors were detected in the blood of dialysis patients, with a positive correlation between them and the pro-inflammatory IL -8. Treatment with Carnivit resulted in a significant decrease in cytokines with the maintenance of the balance between vascular growth factor and its receptors, which we consider a positive effect for the inhibition of inflammation with the progression of endothelial dysfunction.

Serum levels of angiogenesis-related factors in patients with psoriasis.

Psoriasis is characterized by increased dermal vascularity, indicating that aberrant angiogenesis is associated with the pathogenesis of psoriasis. Data on angiogenesis-related factors in psoriasis patients are limited. We explored serum levels of angiogenesis-related factors in patients with psoriasis, and investigated their association with clinical severity and laboratory data. Psoriasis patients visiting our hospital from April 2013 to April 2018 and healthy controls were included in this study. Serum levels of angiopoietin-1, fibroblast growth factor (FGF)-basic, epidermal growth factor (EGF), platelet endothelial cell adhesion molecule (PECAM)-1, placental growth factor, and vascular endothelial growth factor (VEGF) were measured by LEGENDplex. Serum samples obtained from 10 healthy controls, 18 patients with psoriasis vulgaris (PsV), 24 patients with psoriatic arthritis (PsA), and 13 patients with generalized pustular psoriasis (GPP) were analyzed. The serum angiopoietin-1 level was elevated in the PsV, PsA, and GPP patients. GPP patients had a higher serum VEGF level than healthy controls. In contrast, serum levels of EGF and PECAM-1 were lower in the PsV, PsA, and GPP patients than in healthy controls. The serum FGF-basic level was lower in the PsA and GPP patients than in healthy controls. Serum levels of FGF-basic in PsA and GPP patients, PECAM-1 in PsA patients, and VEGF in GPP patients became closer to the respective levels in healthy controls after systemic therapy. The serum FGF-basic level was positively correlated with the psoriasis area and severity index and the number of circulating eosinophils in GPP patients. The serum VEGF level was correlated positively with the serum C-reactive protein (CRP) level and erythrocyte sedimentation rate, and negatively with the serum albumin level in GPP patients. In conclusion, our exploratory study revealed that psoriasis affects serum levels of certain angiogenesis-related factors. Some of these factors could be biomarkers of treatment outcomes, clinical severity, and systemic inflammation.

Serum Levels of Vascular Endothelial Growth Factor, Platelet Activating Factor and Eosinophil-Derived Neurotoxin in Chronic Spontaneous Urticaria-A Pilot Study in Adult Patients.

Chronic spontaneous urticaria (CSU) is a skin disease characterized by the presence of wheals, angioedema, or both for at least 6 weeks. Although, CSU is often regarded as autoimmune in nature, its etiology is not fully explained and interactions between various small molecules are still taken under account. The aim of this research was to investigate the mean serum concentration of vascular endothelial growth factor (VEGF), platelet activating factor (PAF), and eosinophil-derived neurotoxin (EDN) in relation to the disease activity and pruritus intensity in adult patients with CSU. Fifteen patients with CSU and 15 healthy subjects participated in this pilot study. Blood samples were taken to examine the mean serum levels of VEGF, PAF, and EDN by the enzyme-linked immunosorbent assay test (ELISA). The Urticaria Activity Score (UAS7) and The Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that VEGF, PAF, and EDN concentrations were higher in patients with CSU compared with those of the control group, but only for VEGF it was statistically significant (p = 0.008). However, levels of all investigated cytokines were not significantly correlated neither with the disease activity nor with the pruritus intensity. Our results showed higher serum levels of VEGF, PAF, and EDN among CSU patients which may highlight a functional role of these cytokines in the disease’s pathogenesis. In contrast, VEGF, PAF, or EDN might not be useful to reflect the severity of symptoms.

Increased Vascular Endothelial Growth Factor Serum Level and the Role of +936C/T Gene Polymorphism in Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p < 0.001), with a positive correlation with the 6MWT outcome. No significant difference was observed in the VEGF serum levels between VEGF +936C/T genotypes. There was no difference in the VEGF +936C/T genotype between COPD patients and healthy subjects (chi2 test p = 0.92, OR = 1.04, 95%CI = 0.41–2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12–4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.

Serum Vascular Endothelial Gowth Factor Correlates with Hasford Score in Chronic Myeloid Leukemia.

Introduction and Aim Increased angiogenesis in BM is one of the characteristics of chronic myeloid leukemia (CML) implicated in its progression. Vascular endothelial growth factor (VEGF) one of the most potent regulator of angiogenesis is increased in CML. The prognostic impact of serum VEGF in CML is largely unknown with sparse literature from India. So the present study aimed to measure serum VEGF levels in different phases of CML and to assess its prognostic significance using Hasford score. Methods Forty Ph + patients of CML were enrolled in the study. Complete clinical history and physical examination was done. Hemogram was done by Beckman Coulter LH 500. Peripheral smear (Wright's stain) was done by microscopy. Serum VEGF (plain vial) using ELISA was calculated. Statistical analysis was performed using SPSS software version 20. Results The mean serum VEGF levels were significantly higher in patients than in controls (p < 0.0001). The patients in accelerated/blast phase demonstrated significantly higher levels of serum VEGF (mean 151pg/mL) than those in the chronic phase (mean 90.87pg/mL) (p = 0.02). Serum VEGF levels showed a significant positive correlation with the overall Hasford prognostic score (p = 0.023). Conclusion Serum VEGF levels can serve as an independent prognostic marker in CML patients irrespective of phase of CML. Also, S. VEGF levels can be used to monitor patients on imatinib therapy and identify those who might benefit from antiangiogenesis therapy. However, larger studies are needed with a larger number of patients in different phases of CML to validate our findings and thus pave the way for future research.

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis.

BackgroundSarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis.ObjectivesThe aim of our study was to determine the association of these markers’ serum levels on lung function and the patients’ quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis.Methods54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King’s Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay.ResultsBetween 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores.ConclusionsAmong patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with bevacizumab for advanced non-squamous non-small-cell lung cancer patients with gradual progression on EGFR-TKI treatment: A cohort study.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve outcomes of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, acquired resistance inevitably emerges and remains a major challenge. The present study aimed to evaluate the efficacy of EGFR-TKIs plus bevacizumab in advanced non-squamous NSCLC patients with gradual progression on EGFR-TKIs.Advanced non-squamous EGFR-mutated NSCLC patients with gradual progression on EGFR-TKIs were administered bevacizumab while EGFR-TKIs were continued until disease progression occurred. Tumor lesions were assessed, and blood samples were collected at the start of the combination treatment and every 6 weeks until disease progression.Among the 15 included patients, there were no grade 3 or higher adverse events (AEs). Partial response (PR) and stable disease (SD) were achieved in 1 and 13 patients, respectively, with an objective response rate (ORR) of 6.7% and a disease control rate (DCR) of 93.3%. The median progression-free survival 2 (PFS2), defined as the time from the initiation of combination treatment to disease progression, was 5.0 (95% confidence interval [CI]: 4.0–6.0) months. Additionally, Spearman correlation analysis revealed that PFS2 was positively correlated with the serum vascular endothelial growth factor (VEGF) level at baseline (r = 0.7212, P = .0234). Patients with high baseline serum VEGF levels showed a better median PFS2 than those with low baseline serum VEGF levels (5.5 months vs 3.6 months, P = .0333).EGFR-TKIs plus bevacizumab led to a durable prolongation of PFS in non-squamous NSCLC patients with gradual progression on EGFR-TKIs. This therapeutic regimen was well tolerated and could be a promising strategy for these patients. Serum VEGF could be a potential biomarker to predict a subset of patients who are likely to benefit from EGFR-TKIs combined with bevacizumab.

Higher level of acute serum VEGF and larger infarct volume are more frequently associated with post-stroke cognitive impairment

Serum vascular endothelial growth factor (VEGF) and infarct volume detected by brain imaging have been associated with stroke outcome. However, the relationship of these two variables with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between acute serum VEGF levels and infarct volume with PSCI in ischemic stroke patients. Fifty-six first-ever ischemic stroke patients who were hospitalized in Dr. Sardjito General Hospital Yogyakarta, Indonesia were prospectively recruited. Serum VEGF level was taken on day 5 of stroke onset and measured by ELISA. Infarct volume was calculated manually from head CT scan by expert radiologist. PSCI was assessed after 3 months follow up by using Montreal Cognitive Assessment-Indonesian version (MoCA-INA). We performed a ROC curve analysis to determine the cut-off point of VEGF level and infarct volume. Multivariate logistic regression analysis was performed to measure the contribution of VEGF level and infarct volume to PSCI after controlling covariates (demographic and clinical data). The mean age of PSCI and non-PSCI patients was 61.63% ± 8.47 years and 58.67% ± 9.01 years, respectively (p = 0.221). No differences observed for vascular risk factors, infarct location, and NIHSS in both groups. Multivariate logistic regression showed that patients with higher VEGF level alone (≥519.8 pg/ml) were 4.99 times more likely to have PSCI than those with lower VEGF level (OR = 4.99, 95% CI = 1.01-24.7, p = 0.048). In addition, patients with larger infarct volume alone (≥0.054 ml) were also more frequently associated with PSCI (OR = 7.71, 95% CI = 1.39-42.91, p = 0.019). Acute ischemic stroke patients with higher serum VEGF level (≥519.8 pg/ml) and larger infarct volume (≥0.054 ml) were more likely to have PSCI 3 months after stroke. These findings may contribute to predict PSCI earlier and thus better prevention strategy could be made.

Role of Serum Vascular Endothelial Growth Factor (VEGF) as a Potential Biomarker of Response to Immune Checkpoint Inhibitor Therapy in Advanced Melanoma: Results of a Pilot Study.

Background: The development of biomarkers predictive of response to immune checkpoint inhibitor (ICI) therapies in advanced melanoma is an area of great interest in oncology. Our study evaluated the potential role of serum vascular endothelial growth factor (VEGF) as a predictive biomarker of clinical benefit and response to treatment with ICIs.Methods: Pre-treatment peripheral blood samples were obtained from advanced melanoma patients undergoing ICI therapy as monotherapy or in combination at two tertiary care hospitals in Western Australia. Serum VEGF levels were correlated with response to therapy and survival outcomes.Results: Serum VEGF samples were collected from a total of 130 patients treated with ICI therapy (pembrolizumab 73, ipilimumab 15, and ipilimumab/nivolumab combination 42). Median serum VEGF level was significantly higher in the non-responders (82.15 pg/mL) vs. responders (60.40 pg/mL) in the ipilimumab monotherapy cohort (P < 0.0352). However, no difference was seen in VEGF levels between non-responders and responders in pembrolizumab and ipilimumab/nivolumab treated patients.Conclusions: The results of our study confirm previous observations that that high pre-treatment serum VEGF levels in advanced melanoma patients may predict poor response to ipilimumab. However, serum VEGF is not predictive of outcome in patients treated with anti-PD-1 agents alone or in combination with ipilimumab.

Vascular endothelial growth factor in systemic lupus erythematosus in correlations with disease activity and nailfold capillaroscopic changes

BackgroundAngiogenesis plays a role in the pathogenesis of systemic lupus erythematosus (SLE). Both serum vascular endothelial growth factor (VEGF) and capillaroscopic abnormalities may reflect intensity of microcirculatory changes in the course of SLE.AimsTo quantify serum VEGF level and its correlation with microvascular changes, assessed by nailfold capillaroscopy (NFC), and possible relationship with SLE activity.Patients and methodsA total of 90 patients with SLE were subjected to detailed medical history and clinical examination and assessment of disease activity using the SLE Disease Activity Index score and organ damage using Systemic Lupus International Collaborating Clinics/ American College of Rheumatology damage index. Laboratory investigations were done including autoantibodies [anti-nuclear antibody, anti-DNA, anti-cardiolipin (immunoglobulin G and immunoglobulin M), and lupus anticoagulant]. VEGF serum level was measured using enzyme-linked immunosorbent assay. NFC examination was done for recognition of NFC abnormalities.ResultsSerum VEGF level was elevated in the entire study group (mean of 831±572 ng/l), with a statistically highly significant correlation with Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index and SLE Disease Activity Index score of disease activity (r=0.349, P=0.001, and r=0.897, P<0.001, respectively), together with a significant positive correlation with the presence of nephritis (P=0.002), positive anti-double-stranded DNA (P≤0.001), and consumed C3 and C4 (P≤0.001), which are laboratory markers indicating lupus activity. Moreover, a higher serum VEGF level was associated with severe NFC changes with a statistically highly significant positive correlation with the capillary width (r=0.561, P<0.001), capillary length (r=0.411, P<0.001), and mean capillary density (r=0.308, P=0.003).ConclusionIncreased serum VEGF level and progression of NFC score had been directly related to lupus activity and internal organ involvement, especially nephritis.

High Serum VEGF Level in Erdheim-Chester Disease: Correlation with Cardiovascular Involvement and Response to Treatment

Context - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by tissue infiltration of CD68 (+), CD1a (-) histiocytes in various organs. It has been classified as a myeloid neoplasia since the discovery of the RAS-RAF-MEK-ERK pathway alterations. Angiogenesis displays an important role in neoplastic and inflammatory process. Vascular Endothelial Growth Factor (VEGF) is a major proangiogenic factor. VEGF is expressed by many tumor cells, and was found to be expressed by Langerhans histiocytic cells. Mechanisms of cardiovascular involvement in ECD are still not clear, however we hypothesize that VEGF may contribute to the development of lesions of ECD. We further hypothesize that VEGF serum level could help distinguish different profiles of patients and study their response to treatment. Patients and Methods - We conducted a retrospective study in patients with ECD seen in the French National Reference Center for Histiocytoses of the Pitié-Salpêtrière Hospital. These patients had histologically confirmed ECD and were included in the study if they had at least one determination of serum VEGF. Serum VEGF level was assessed by ELISA and considered high when above a concentration of 500pg/mL. Evaluation of cardiac and vascular involvements was based on cardiac magnetic-resonance imaging and CT-angiography of the aorta as often as possible, and replaced by other imaging modalities when they were contraindicated. Results - We screened 254 patients of whom 231 had had at least one determination of VEGF serum level. Serums VEGF were high in 122 out of 231 patients (52.8%). Patients with a high serum VEGF level had more frequently a vascular involvement of ECD (68.8% vs 48.6%, p=0.001), especially signs of a "coated aorta" (47.5% vs 33%, p=0.025). Cardiac involvement was also more prevalent in patients with high serum VEGF level (59% vs 41.2%, p=0.007). Notably, coronary arteries were twice as frequently affected (28.7% vs 14.7%, p=0.010). BRAF status was not significantly different between patients with high or low levels of VEGF. VEGF level were not correlated to the presence of an inflammatory syndrome (evaluated on CRP elevation). At first determination, median serum VEGF among patients with high levels was 850pg/mL (SD 682.22). Under treatment, we observed a decrease of the serum VEGF level. Among 68 patients with a serum VEGF level determination at 12 months, the concentration of VEGF decreased significantly (mean difference 305.4, p&lt;10-6), reaching a median of 507pg/mL (SD 552.58) at 12 months. Conclusion - Cardiovascular involvement is frequent and prognostically relevant in ECD. Evaluation of ECD clinical course and response to treatment is still challenging, and repeated imaging is often necessary. VEGF serum level could help distinguish patients with cardiovascular profile and contribute to follow up under treatment. Comprehension of the role of VEGF and the possible impact of anti-VEGF treatment will benefit from a study of VEGF and VEGF-receptor expression in lesions of ECD patients. Disclosures No relevant conflicts of interest to declare.

Correlations of serum homocysteine, VEGF and gastrin 17 with gastric cancer and precancerous lesions.

To investigate the correlations of Homocysteine (Hcy), vascular endothelial growth factor (VEGF), and serum gastrin 17 (G17) with gastric cancer and precancerous lesions. A total of 56 patients with gastric cancer (gastric cancer group) and 53 patients with precancerous lesions (precancerous lesion group) admitted to Heze Municipal Hospital from January 2017 to October 2018 were selected, and 50 healthy subjects undergoing the physical examination in the same period were selected as control group. The levels of serum Hcy, VEGF, and G17 in the three groups were compared, and the relations of each index with clinicopathological characteristics of gastric cancer were analyzed. The levels of serum Hcy, VEGF-A, VEGF-C, VEGF-D, and G17 in gastric cancer group and precancerous lesion group were higher than in control group, and those in gastric cancer group were higher than in precancerous lesion group (p<0.05). Besides, the high expression levels of serum Hcy, VEGF, and G17 had evident correlations with the tumor-node-metastasis (TNM) stage, Lauren type, infiltration depth, and lymph node metastasis of gastric cancer (p<0.05). Hcy, VEGF, and G17 can exhibit different levels of expressions in precancerous lesions. They are also highly expressed in gastric cancer. Besides, they are involved in the occurrence and development of gastric cancer and can be regarded as crucial indexes with clinical significance for the differential diagnosis of gastric cancer and precancerous lesions in the early stage.

Serum Vascular Endothelial Growth Factor in Egyptian Obese Women with Insulin Resistance.

BACKGROUND:Obesity is a major factor in the development of several sub-clinical anomalies. Insulin resistance (IR) is associated with obesity. Vascular endothelial growth factor (VEGF) plays a significant role in inflammation and vascular neogenesis. However the precise relationships of its levels with clinical, lipid, and metabolic profiles are unknown.AIM:This study aimed to examine the association between serum VEGF concentrations with IR risk and metabolic and lipid parameters in obese women.METHODS:Serum VEGF, metabolic biomarkers and anthropometry were measured in 83 obese women with IR and 50 healthy women. Fat distributions in the abdominal, subcutaneous and visceral area were assessed. Homeostasis model assessment for insulin resistance index (HOMA-IR) was calculated. For analytical purposes, VEGF levels were categorised into three tertiles groups.RESULTS:Obese women with IR showed significantly higher levels of serum VEGF as compared with the control group. Moreover, obese women in the highest VEGF tertile had significantly higher values of obesity indices, visceral fat index, abnormal lipid levels and HOMA-IR compared to with those in the lower tertile.CONCLUSION:Elevated VEGF levels are associated with IR and high visceral fat index in obese women which in turn increased the risk for metabolic complications.

Serum Vascular Endothelial Growth Factor Levels in Asthmatic Children

Background: Bronchial asthma is a heterogeneous disease, which is usually characterized by chronic airway inflammation. Asthma is a global problem with 300 million affected individuals. Angiogenesis has been recognized as an essential step in the development and maintenance of airway inflammation and tissue remodeling. Vascular endothelial growth factor plays a key role in both the physiological and pathophysiological forms of angiogenesis. Aim of the present study was to measure serum levels of vascular endothelial growth factor in asthmatic children to assess its relation with asthma severity. Subjects and Methods: This study was conducted on two groups, group A: 30 asthmatic children and group B: 20 healthy children of matched age and sex. Serum vascular endothelial growth factor (VEGF) levels were measured by ELISA. Results: There was no significant difference between asthmatic and control groups as regard age, sex and weight. There was significant increase in serum VEGF levels in asthmatic group than control group. There was negative correlation between VEGF serum levels and pulmonary function tests. There was positive correlation between serum VEGF levels and asthma severity. Conclusion: There were higher levels of serum VEGF in asthmatic patients than healthy control. Serum VEGF was higher in those with moderate and severe asthma than those with mild disease.

Serum Vascular Endothelial Growth Factor Levels in Asthmatic Children

Background: Bronchial asthma is a heterogeneous disease, which is usually characterized by chronic airway inflammation. Asthma is a global problem with 300 million affected individuals. Angiogenesis has been recognized as an essential step in the development and maintenance of airway inflammation and tissue remodeling. Vascular endothelial growth factor plays a key role in both the physiological and pathophysiological forms of angiogenesis. Aim of the present study was to measure serum levels of vascular endothelial growth factor in asthmatic children to assess its relation with asthma severity. Subjects and Methods: This study was conducted on two groups, group A: 30 asthmatic children and group B: 20 healthy children of matched age and sex. Serum vascular endothelial growth factor (VEGF) levels were measured by ELISA. Results: There was no significant difference between asthmatic and control groups as regard age, sex and weight. There was significant increase in serum VEGF levels in asthmatic group than control group. There was negative correlation between VEGF serum levels and pulmonary function tests. There was positive correlation between serum VEGF levels and asthma severity. Conclusion: There were higher levels of serum VEGF in asthmatic patients than healthy control. Serum VEGF was higher in those with moderate and severe asthma than those with mild disease.

A Meta-Analysis of Vascular Endothelial Growth Factor for Nasopharyngeal Cancer Prognosis.

Background: Vascular endothelial growth factor (VEGF) has been reported to serve as a promising prognostic marker in several cancers. This meta-analysis aims to assess the prognostic significance of VEGF in nasopharyngeal cancer (NPC).Methods: We conducted a systematic literature search of PubMed, Embase, and the Cochrane Library for observational studies published until June, 2018 to identify observational studies on the prognostic effect of tissue VEGF expression or serum VEGF level on the survival of NPC. The primary outcome measure assessed was overall survival (OS). The secondary outcomes included disease-free survival (DFS) or progression-free survival (PFS). Summary hazard ratio (HR) and its 95% confidence interval (95% CI) were derived using a random-effects model.Results: Out of 840 retrieved citations, 16 studies inclusive of 1,345 patients were included in the analysis of tissue VEGF expression and cancer survival. The pooled HRs for OS and DFS in patients with high VEGF expression were 2.07 (95% CI: 1.32–3.25) and 5.99 (95% CI: 2.66–13.48), respectively, with significant heterogeneity between studies (I2 = 79.1% for OS and 50.2% for DFS). Tissue high VEGF expression was not significantly associated with short RFS, PFS, or MFS. Five studies also investigated the prognostic effect between serum VEGF level and patient survival and found that high serum VEGF level was significantly associated with short OS for patients with NPC (HR 2.47, 95% CI 1.16–5.28), but not with short PFS (HR 1.47, 95% CI 0.92–2.35).Conclusions: Determination of tissue VEGF expression and serum VEGF level have the potential to serve as biomarkers and add prognostic information in NPC. Prospective analyses of associated data on VEGF expression and serum VEGF level in large NPC cohorts could be further conducted to advance our understanding of the relationship between VEGF and NPC outcomes.

Association of rs6921438 A

BackgroundGenome-wide association studies (GWAS) have identified common variants at the Vascular-Endothelial-Growth-Factor (VEGF) gene locus, which appear to be associated with plasma VEGF concentrations. These factors are among the major risk factors for cardiovascular disease and metabolic syndrome (MetS). We have investigated the association between serum VEGF concentrations and a VEGF genetic variant (rs6921438 A<G) in 852 patients with or without MetS, defined according to International-Diabetes-Federation (IDF) criteria, recruited from the Mashhad Stroke and Heart Atherosclerotic Disorders cohort and their possible relationships with cardio-metabolic risk-factors and diet. MethodsIn total of 852 individuals, genotyping was performed using polymerase-chain-reaction and restriction-fragment-length-polymorphisms. Serum VEGF level was determined in 122 subjects using the EV 3513 cytokine biochip array. Anthropometric and biochemical characteristics, including fasting blood glucose and lipid profile evaluated by univariate and multivariate analyses. The association of the polymorphism with serum VEGF level and its interaction with dietary intake in association with the essential determinants of cardiovascular risk factors were assessed. ResultsAs would be expected, patients with MetS had markedly higher body mass index, waist-circumference, serum total cholesterol, triglyceride, hs-CRP and blood pressure, and lower concentrations of HDL-C, compared to non-MetS individuals (P < 0.05). The association between the rs6921438 single nucleotide polymorphism (SNP) and the presence of MetS and individual features of MetS were not statistically significant. Interestingly we observed a significant association between high serum VEGF levels with the GG and GA genotypes in the individuals with MetS, compared to the wild-type genotype, which was also associated with dietary fat intake. ConclusionOur findings show an association between a VEGF gene polymorphism with serum VEGF concentrations and dietary fat intake, but there was no association with the presence of MetS.