Median Vascular Endothelial Growth Factor Level Research Articles

Reappraisal of VEGF in the Pathogenesis of Kawasaki Disease.

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients.

HbA1c and Serum Level of VEGF in Diabetic Retinopathy Patients

Objective: This study aims to determine whether HbA1c level has a correlation with vascular endothelial growthfactor (VEGF) serum level in diabetic retinopathy (DR) patients.Methods: This is an analytical cross-sectional study of patients with DR due to type 2 diabetes, with a purposivesampling technique. Patients were grouped into non-proliferative DR (NPDR) and proliferative DR (PDR). HbA1cand VEGF serum levels were assessed by taking the patient’s venous blood.Results: A total of 82 samples were included, in which the mean HbA1c levels were 8.17% ± 1.91% and the medianVEGF levels were 85.78 ng/L (range 38.23-149.43 ng/L). A total of 23 out of 35 NPDR patients were female (65.7%),while 29 out of 47 PDR patients were male (61.7%). Approximately 61.7% of PDR patients had a DM duration ofmore than 10 years, while 62.9% of NPDR patients had DM duration of less than 10 years. There was an increasein the mean of HbA1c levels in the PDR group compared to NPDR, although it was not statistically significant (p =0.214), and there was no difference in the median VEGF levels of the two groups. Spearman’s correlation analysisrevealed no correlation between HbA1 and VEGF levels in diabetic retinopathy, in both the NPDR and PDRgroups (correlation coefficient 0.183 and -0.022 respectively).Conclusion: No statistically significant correlation was found between HbA1c and VEGF serum levels in diabeticretinopathy patients. In this study poor glycemic control were not proven for their implications for VEGFprogression. VEGF serum levels may not be used as a marker of DR severity.

Antilipidemic ezetimibe induces regression of endometriotic explants in a rat model of endometriosis with its anti-inflammatory and anti-angiogenic effects.

To assess the potential therapeutic role of antilipidemic ezetimibe on endometriosis in an experimental rat model. A standard experimental endometriosis model was created with 18 Whistar-Albino rats, and after 1month, the sizes of the endometriotic explants were measured. The rats were randomized as study and control groups. A total of 1mg/kg/day ezetimibe and 1ml/kg/day saline were administered orally to the study and control groups respectively for 28days. At the end of 28days, the explants were measured again, excised, and sent for histopathologic assessment for expression of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) and number of mast cells. At the end of the study period, the size of the endometriotic explants decreased significantly in the study group; but not in the control group (from 145.3 ± 120.5 to 89.8 ± 60.1 vs 174.72 ± 88.3 to 87.65 ± 27.1 cm3 respectively); however, the amount of post- and pretreatment differences in explant sizes was similar in the groups. The median TNF-α and VEGF levels were significantly lower in the ezetimibe group when compared to the control group (4 [3-4] vs 2 [1-3], p 0.029; 4 [3-4] vs 2 [2-3], p 0.002; respectively). And numbers of mast cells in all uterine layers were also lower in the ezetimibe group. Ezetimibe decreased the size of the endometriotic explants with its anti-inflammatory and anti-angiogenic properties. This agent alone or with combination of other agents may have a potential role in the treatment of endometriosis.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background:Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxiaObjective:The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020.Methods:This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005.Results:The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005).Conclusion:HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

Vascular Endothelial Growth Factor Levels Difference among Hepatocellular Cancer Patients Based on Barcelona Clinic Liver Cancer Staging

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It depends on angiogenesis for growth and metastasis. Vascular endothelial growth factor (VEGF), a growth factor for angiogenesis, is hoped to be a biomarker for the diagnosis of HCC and its development. AIM: The objective of the study is to determine the difference of VEGF levels among HCC patients based on barcelona clinic liver cancer (BCLC) staging. METHODS: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between January and December 2018. Patients aged 18 years or older with HCC were enrolled using consecutive sampling method. Patients with cholangiocarcinoma, hemangioma, and liver metastasis were excluded from the study. The diagnosis of HCC was confirmed by triphasic computed tomography-scanning. Circulating VEGF levels were determined from serum specimen using Quantikine Human VEGF-enzyme-linked immunosorbent assay. All patients were grouped based on BCLC staging. Kruskal Wallis-H test was applied at 95% confidence interval. p &lt; 0.05 was considered significant. RESULTS: Of 60 patients, 47 (78.3%) were male. Mean age of patients was 61.4 (SD11.7) years. Hepatitis B was the most common etiology (70.0%) of HCC. Based on BCLC staging, 25 (41.7%) patients were in stage C. Median VEGF level was 951.25 pg/mL. There was a statistically significant difference in VEGF levels (p = 0.006) where patients in Stage C (1,009.6 pg/mL) and D (1,189.7 pg/mL) had higher VEGF levels compared to those in Stage A (578 pg/mL). CONCLUSION: There was a statistically significant difference of VEGF levels among HCC patients based on BCLC staging.

Prognostic role of plasma level of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor in hepatocellular carcinoma.

BACKGROUNDMost hepatocellular carcinomas (HCCs) are hypervascular, with characteristic features of hepatic arterial supply to the tumor. The factors involved in tumor angiogenesis include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF).AIMTo investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival (OS) and progression-free survival (PFS).METHODSPlasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1, Ang-2, and VEGF. Their associations with clinical characteristics, OS, and PFS were analyzed.RESULTSThe median plasma levels of Ang-1, Ang-2, and VEGF were 3216 pg/mL, 1684 pg/mL, and 26.5 pg/mL, respectively. The plasma level of Ang-2 showed a significant increase from early stage [Barcelona clinic liver cancer (BCLC) A] to intermediate (BCLC B) and advanced stage HCC (BCLC C/D), whereas Ang-1, VEGF, and alpha-fetoprotein (AFP) levels in the plasma did not show any such changes. Multivariable analysis, propensity score-matched analysis, and time-dependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and PFS. Neither Ang-1 nor VEGF was significantly associated with OS or PFS. The neutrophil-to-lymphocyte ratio was an independent factor for OS and PFS. CONCLUSIONThe plasma levels of Ang-2 correlated with liver function, tumor stage, and tumor invasiveness, showing better performance in predicting OS and PFS than AFP, Ang-1, or VEGF.

Cytokine profile in multiple myeloma

BackgroundCytokines play a crucial role in the growth, survival and dissemination of malignant plasma cells in patients of multiple myeloma (MM). We estimated concentrations of five key cytokines: Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Tumor Necrosis Factor- alpha (TNF- α), B-cell activating factor (BAFF), and Receptor Activator of Nuclear Factor-κB ligand (RANKL) in newly diagnosed and relapsed/refractory MM (RRMM). MethodsThe study groups include 68 newly diagnosed and 21 relapsed/refractory (RR) MM patients. 32 out of 68 newly diagnosed MM patients were evaluated for serum cytokine concentrations after their treatment. For survival analysis, the various parameters were studied in relation to both progression free survival (PFS) and overall survival (OS). ResultsThe median serum levels of VEGF, IL-6, BAFF and RANKL were higher in RRMM compared with newly diagnosed patients. However, the difference was significant for BAFF levels (p = 0.04). The median serum levels of VEGF, IL-6, TNF-α, BAFF and RANKL were significantly higher in newly diagnosed and RRMM patients, compared to controls. We also observed lower plasma levels of VEGF (p=<0.0001) and BAFF (p=<0.0001) in BM compartment compared to the levels in serum from peripheral blood of newly diagnosed patients. Significant reduction in the median levels of IL-6, TNF-α, BAFF and RANKL was seen after 4–6 cycles of induction treatment in responders but not in non-responders. On survival analysis, RRMM patients had inferior median OS and PFS compared to that in newly diagnosed MM patients and found to be significantly associated with low haemoglobin representing the more aggressive disease biology in recurrent myeloma. The mean levels of IL-6 were significantly different in patients who died as compared to patients who were alive. ConclusionsThe present study demonstrates that the serum levels of VEGF, IL-6, TNF, BAFF and RANKL are significantly elevated and decrease significantly after treatment. The concentrations of circulating cytokines will reflect those of the bone marrow and could be used for subsequent analyses.

40P - Vascular endothelial growth factor in colorectal cancer pathology, survival and treatment

BackgroundAngiogenesis (the growth of new blood vessels) is important for tumour invasion and metastasis in order for a tumour to grow beyond a few millimetres in size. Vascular endothelial growth factor (VEGF) is thought to be the predominant angiogenic factor in colorectal and other cancers. As a result, numerous studies have looked at VEGF expression in colorectal cancer patients and several therapeutic agents have been trialled that target the VEGF pathway. MethodsVEGF levels were determined in 100 paired tumour and normal colorectal tissue samples (1998-2001) and 75 pre-operative plasma samples (2000-2002) by ELISA. Tissue (pg/mg protein) and plasma VEGF levels (pg/ml) were correlated with the tumour pathology. Survival analysis was performed for disease-free and overall 15-year survival (Kaplan Meier, p<0.05). The study had ethics approval. ResultsVEGF levels were significantly up-regulated in colorectal tumour tissue compared to normal tissue. The median VEGF levels were 288 (range, 30-4,156) pg/mg protein for tumour, 38 (0-833) for normal colon and 90 (0-1,262) pg/ml for pre-operative plasma samples. Tumour levels of VEGF correlated with the tumour depth, differentiation and whether the tumour had undergone lymphatic invasion e.g. well differentiated, 230 (79-1,348), moderate 392 (30-4,156) and poorly differentiated 685 (88-2,612)pg/mg protein. Plasma VEGF levels significantly correlated with tumour differentiation and vascular invasion,e.g. 211 (14-889) vascular invasion and 80 (0-785)pg/ml, no vascular invasion. The 15-year survival status for patients with tissue samples was 30% were alive and well, 1% was alive with recurrence and 69% had died. For the 75 plasma patients; 27% patients were alive and well with the remaining 67% having died. VEGF levels in plasma but not tissue samples significantly correlated with both disease-free and overall 15-year survival, with patients with low plasma VEGF levels having a better survival outcome (p<0.05, Kaplan Meier). ConclusionsVEGF levels in both colorectal tumour tissue and pre-operative plasma samples correlated with the tumour pathology. However, only pre-operative plasma VEGF levels correlated with disease-free and overall 15-year survival. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Correlations of serum VEGF and MMP-2 levels with CLM in CRC patients and effects of TACE on their expressions.

To investigate the correlations of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) levels with colorectal liver metastasis (CLM) in patients with colorectal cancer (CRC), and determine the effects of transhepatic arterial chemoembolization (TACE) on their expressions. A total of 110 CRC patients treated in the department of interventional radiology of our hospital from May 2013 to May 2016 were randomly enrolled. All patients received treatment of TACE after surgery. During surgery, 10 mL venous blood was taken, and the protein levels of VEGF and MMP-2 in serum were detected via enzyme-linked immunosorbent assay (ELISA). The correlations of VEGF and MMP-2 levels with clinicopathological features of patients were analyzed. The values of VEGF and MMP-2 in predicting CLM were analyzed using the receiver operating characteristic (ROC) curve. Moreover, changes in serum VEGF and MMP-2 levels in CRC patients were analyzed before TACE, and at 1 and 6 months after TACE. The median VEGF and MMP-2 levels in serum of CRC patients were 64.8 ng/mL and 114.4 ng/mL, respectively, which were significantly higher than those in healthy control group (5.3 ng/mL and 6.8 ng/mL) (p<0.05). The expressions of VEGF and MMP-2 in serum of CRC patients were correlated with the depth of tumor infiltration, Dukes' staging, CLM and lymph node metastasis (p<0.05). Logistic regression analyses showed that the expression levels of VEGF and MMP-2 were positively correlated with CLM (p<0.05). The ROC curve revealed that the sensitivity, specificity and accuracy of serum VEGF in the diagnosis of CLM were 62.2%, 78.5% and 80.2%, respectively. The sensitivity, specificity and accuracy of serum MMP-2 in the diagnosis of CLM were 68.9%, 85.5% and 82.2%, respectively. The serum VEGF levels in CRC patients before TACE, and at 1 and 6 months after TACE were (64.8±58.8) ng/mL, (43.1±27.3) ng/mL and (24.8±12.3) ng/mL, respectively, showing a downward trend (p<0.05). The serum MMP-2 levels in CRC patients before TACE, and at 1 and 6 months after TACE were (114.4±136.2) ng/mL, (73.4±58.5) ng/mL and (39.6±30.4) ng/mL, respectively, also indicating a reducing trend (p<0.05). The levels of VEGF and MMP-2 in portal vein serum of CRC patients can be used as effective indexes for judging the prognosis of CRC and predicting CLM. Patients with high expression of VEGF and MMP-2 should be actively treated with TACE after surgery to improve the survival rate.

Comparative analysis of serum and tumor vascular endothelial growth factor, insulin-like growth factor 1, matrix metalloproteinase 7 levels in patients with ovarian cancer

Aim: To perform a comparative analysis with simultaneous measurement of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF1) and matrix metalloproteinase 7 (MMP7) in serum samples taken from healthy women and ovarian cancer patients; to perform association of these markers with their expression in primary tumors depending on clinical, morphological and biochemical characteristics of the disease and its prognosis. Materials and methods: We assessed 54 treatment-naive patients with ovarian cancer aged from 23 to 74 years (mean ± SD, 53.2 ± 1.9), being at various FIGO stages of the disease. The control group consisted of 120 healthy women of matched age and reproductive status, in whom serum biomarker levels were studied. Patient survival was assessed by the Kaplan-Meier method, with survival curves compared with log-rank test. All analyses were done with “STATISTICA” and SPSS software. Results: Serum VEGF levels in ovarian cancer patients were significantly (p 505 pg/ml (upper quartile in the control). With 505 pg/ml taken as a threshold, the test had sensitivity of 79.6% and specificity of 75%. Another cut-off value of serum VEGF level between the patients with ovarian cancer and the control group (510 pg/ml) was derived from ROC curves and 75% sensitivity and 78.2% specificity. No acceptable cut-off value for serum IGF1 to differentiate between the patients with ovarian cancer and the controls could be obtained from the ROC curves. Serum MMP7 levels in the patients with ovarian cancer were significantly higher than those in the control group (Mann-Whitney test p < 0.0001). With ROC curves, the best sensitivity to specificity ratio for MMP7 value of 4.6 ng/ml was obtained to differentiate between the patients with ovarian cancer and the controls (sensitivity 83.3%, and specificity 81%). The variance analysis did not reveal any association between serum VEGF, IGF1 and MMP7 and age of patients with ovarian cancer, tumor histology, concomitant somatic and gynecological diseases, and CA-125 levels. Serum VEGF and IGF1 levels did not correlate with the stage of ovarian cancer, in contrast to MMP7, whose levels were significantly higher in stages IIIc–IV. The median VEGF level significantly increased as the degree of differentiation decreased from 510 to 622 pg/ml (p < 0.002), while median IGF1, on the contrary, decreased from 219 to 116 pg/ml (p < 0.0001). There was a direct correlation between serum and tumor VEGF levels in ovarian cancer patients (r = 0.65, p < 0.0001). On the contrary, there was an inverse correlation between serum and tumor IGF1 levels (r = -0.68, p < 0.0001). Serum and tumor MMP7 levels remained unrelated to each other. Tumor VEGF, IGF1 and MMP7 content was unrelated to the age of the patients, their reproductive status, presence of concomitant somatic and gynecological diseases, histology of ovarian cancer, and serum CA-125 levels. VEGF levels in the tumor were not associated with the stage of ovarian cancer, but in patients with initial stages Ia and Ib stages MMP7 values significantly lower (2.1 ng/mg protein) compared to those in stages IIIc and IV (6.1 and 4.7 ng/mg protein, respectively, p < 0.05). Similar pattern was noted for IGF1: tumor IGF1 values in the patients with stages Ia–Ib were significantly lower (0.5 ng/mg protein) than those with stages IIIc–IV (median, 1.3–1.4 ng/mg protein). A significant increase in both serum and tumor VEGF levels was detected in the patients with ovarian cancer with decreased degree of differentiation. On the contrary, tumor IGF1 levels, but not serum ones, were significantly increased from 0.6 to 1.4 ng/ml in the patients with poorly differentiated ovarian cancer. MMP7 tumor expression did not depend on the degree of its differentiation. Serum VEGF levels above 700 pg/ml and tumor levels of above 590 ng/mg protein should be considered as unfavorable prognostic factors in patients with ovarian cancer.

Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in children with brain tumors.

Angiogenesis is the process of new vessel formation originating from the existing vascular network. It plays an important role in the growth and spread of malignancies, including brain tumors. The process of angiogenesis is characterized by increased expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and by the release of their soluble forms into circulation. The aim of the study was to evaluate serum levels of VEGF and bFGF in children with malignant and benign brain tumors. The study group (group N) included 106 children diagnosed with brain tumors. The children in group N were classified according to tumor pathology into 3 subgroups: N1 (n = 63): patients with malignant tumors, excluding anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM); N2 (n = 25): patients with benign tumors; and N3 (n = 18): patients with high grade gliomas (AA and GBM). VEGF and bFGF were determined by ELISA in blood samples before the initiation of chemotherapy. VEGF and bFGF levels were compared within the subgroups in relation to tumor grading and the extent of surgery. The median VEGF in patients with brain tumors was significantly higher than in the control group. The median levels of VEGF and bFGF in subgroup N1 were significantly higher than in the control group. The differences in VEGF and bFGF concentrations between the subgroups in relation to the extent of tumor resection were not significant. Significantly higher plasma VEGF levels in children with brain neoplasms may reflect enhanced angiogenesis in the tumors.

Endothelial dysfunction in the pathogenesis of pre-eclampsia in Ghanaian women

BackgroundPre-eclampsia (PE) remains a disease of theories despite extensive research into its etiology. Alteration in the production of vascular endothelial growth factor (VEGF), a biomarker of endothelial dysfunction, is associated with pre-eclampsia although conflicting reports have been reported. The aim of the study was to determine and compare maternal serum levels of VEGF among pre-eclamptics, normotensive non pregnant and pregnant women.This was a cross-sectional study involving 100 women with pre-eclampsia, 102 women with normotensive pregnancy and 75 normotensives who were not pregnant. The study was carried out at Korle Bu Teaching Hospital (KBTH) from April to June in 2011. Basic socio-demographic and obstetric data were obtained by means of structured questionnaire. Following venesection, about 5mls of blood was sampled from the participants for the various tests. Enzyme Linked Immunosorbent Assay was used to determine the maternal serum levels of free VEGF. Data analysis was performed using SPSS version 20.ResultsSignificant reduction in median serum levels of free VEGF was seen in both, normal pregnant [84.06 pg/ml (IQR: 78.90–99.67)] and pre-eclamptic women [4.71 pg/ml, (IQR: 3.41–7.93)] compared to the non-pregnant (395.85 pg/ml, IQR 234.93–625) with p < 0.001; the reduction was far greater in the pre-eclamptic group compared to that of normotensive pregnant group (p < 0.001). Early-onset pre-eclampsia had significantly more severe reduction in free VEGF levels (3.89, IQR: 2.60–5.67 pg/ml) compared to that of late onset PE (5.23, IQR: 3.78–16.97 pg/ml) with p<0.001 indicating a severer endothelial damage in former.ConclusionsEndothelial dysfunction contributes significantly to the pathogenesis of pre-eclampsia as demonstrated by profound decrease in maternal serum VEGF levels in PE compared to normotensive pregnancy and non-pregnancy state. The pathophysiology of early-onset pre-eclampsia may be partly explained by marked reduction in free serum VEGF levels with resultant severe endothelial dysfunction.

Associations between circulating endostatin levels and vascular organ damage in systemic sclerosis and mixed connective tissue disease: an observational study.

IntroductionSystemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are chronic immune-mediated disorders complicated by vascular organ damage. The aim of this study was to examine the serum levels of the markers of neoangiogenesis: endostatin and vascular endothelial growth factor (VEGF), in our unselected cohorts of SSc and MCTD.MethodsSera of SSc patients (N = 298) and MCTD patients (N = 162) from two longitudinal Norwegian cohorts were included. Blood donors were included as controls (N = 100). Circulating VEGF and endostatin were analyzed by enzyme immunoassay.ResultsMean endostatin levels were increased in SSc patients 93.7 (37) ng/ml (P < .001) and MCTD patients 83.2 (25) ng/ml (P < .001) compared to controls 65.1 (12) ng/ml. Median VEGF levels were elevated in SSc patients 209.0 (202) pg/ml compared to MCTD patients 181.3 (175) pg/ml (P = .017) and controls 150.0 (145) pg/ml (P < .001). Multivariable analysis of SSc subsets showed that pulmonary arterial hypertension (coefficient 15.7, 95 % CI: 2.2–29.2, P = .023) and scleroderma renal crisis (coefficient 77.6, 95 % CI: 59.3–100.0, P < .001) were associated with elevated endostatin levels. Multivariable analyses of MCTD subsets showed that digital ulcers were associated with elevated endostatin levels (coefficient 10.5, 95 % CI: 3.2–17.8, P = .005). The risk of death increased by 1.6 per SD endostatin increase (95 % CI: 1.2–2.1, P = .001) in the SSc cohort and by 1.6 per SD endostatin increase (95 % CI: 1.0–2.4, P = .041) in the MCTD cohort after adjustments to known risk factors.ConclusionsEndostatin levels were elevated in patients with SSc and MCTD, particularly SSc patients with pulmonary arterial hypertension and scleroderma renal crisis, and MCTD patients with digital ulcers. Elevated endostatin levels were also associated with increased all-cause mortality during follow-up in both groups of patients. We propose that endostatin might indicate the degree of vascular injury in SSc and MCTD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0756-5) contains supplementary material, which is available to authorized users.

Serum VEGF and PGF may be significant markers in prediction of severity of preeclampsia

Objective: The aim of this study evaluate the value of vascular endothelial growth factor (VEGF) and placental growth factor (PGF) serum levels in prediction of preeclampsia, severity and onset time of the disease.Methods: Twenty five placentas of pregnant women diagnosed with preeclampsia (15 severe preeclampsia, 10 mild preeclampsia) and peripheral venous blood samples were collected. The placental and serum levels of VEGF and PGF were measured.Results: VEGF level was significantly higher in cases and the optimal cut-off point was calculated as 600.5 to differentiate the cases and the controls, with 64% sensitivity and 100% specificity. There was a significant increase in median serum level of VEGF in severe cases compared to the mild cases and the controls. The optimal cut-off point for VEGF was calculated as 673.5 to differentiate mild and severe cases, with 93.3% sensitivity and 90% specificity. Whereas, PGF was significantly lower in severe cases than that in the mild cases and controls. The optimal cut-off point for PGF was calculated as 16.1 to differentiate mild and severe cases, with 66.7% sensitivity and 100% specificity.Conclusion: VEGF and PGF may be significant markers in prediction of severity of preeclampsia, and VEGF may also be valuable in prediction of preeclampsia.

Influence of serum VEGF levels on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer.

To explore the influence of serum vascular endothelial growth factor (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. A total of 37 patients diagnosed with cervical cancer by biopsy were selected and treated with concurrent chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted before treatment to assess VEGF levels, and its relationships with clinicopathological features and short-term therapeutic effects were analyzed. The median VEGF level in 37 patients before treatment was 647.15 (393.35~1125.16) pg/ mL. Serum VEGF levels in patients aged <50 years, in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with lymph node metastasis and tumor size>4 cm were significantly increased (P<0.05). The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size and serum VEGF level before treatment were independent risk factors affecting the therapeutic outcome, and the higher the level of serum VEGF, the worse the prognosis when tumor size>4 cm. Some 56.8% of patients manifested with myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with hepatic and renal injury during the treatment. Serum VEGF level may reflect the degree of malignancy of cervical cancer and predict therapeutic effect, which is of great importance to cancer diagnosis and prognosis.

Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy.

To determine the effects of laser photocoagulation on serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble angiopoietin receptor Tie-2 (Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes mellitus (T2DM) and proliferative diabetic retinopathy (PDR). We also explored the role of the Ang/Tie system in PDR. 160 patients with T2DM, including 50 patients with non-diabetic retinopathy (NDR), 58 patients with non-proliferative diabetic retinopathy (NPDR), and 52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure. The median levels of Ang-2 and VEGF in serum were significantly higher in the NPDR group (4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group (2.67 ng/mL and 159.8 pg/mL, respectively, P<0.01), with the highest level in the PDR group (6.26 ng/mL and 531.2 pg/mL, respectively, P<0.01). The median level of Ang-1 was significantly higher in the NPDR group (10.77 ng/mL) compared to the NDR group (9.31 ng/mL) and the PDR groups (9.54 ng/mL) (P<0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups (1.49 vs 2.69 and 2.90, both P<0.01). The median level of Tie-2 was not significantly different among three groups (P>0.05). Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups (both P<0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased (both P<0.05), whereas serum Ang-1 level and Ang-1/Ang-2 ratio were weakly increased (P>0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group, however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups. Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2DM patients with PDR.

Urinary VEGF and PGE2 levels and the association with arsenical metabolites in copper-smelting workers

ObjectivesTo examine vascular endothelial growth factor (VEGF) and PGE2 levels in urine from the copper smelting workers exposed to arsenic and analyse the relationships between urinary VEGF or PGE2 level...

Distinct peritoneal fluid ghrelin and leptin in infertile women with endometriosis and their correlation with interleukin-6 and vascular endothelial growth factor

Objective: The objective of the present study was to evaluate the levels of leptin, ghrelin, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in peritoneal fluid in patients with endometriosis and infertility, and study their correlation.Design and setting: This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility and/or pain at a tertiary care hospital. Based upon laparoscopic and histopathological findings, patients were categorized as with endometriosis and no endometriosis. Of the 50 patients with infertility (age 23–41 years), 19 had endometriosis while 31 had no endometriosis. The markers were assessed using ELISA kits.Results: The median levels of leptin in patients with endometriosis (10.20 ng/mL) were higher (p = 0.04) and median levels of ghrelin in patients with endometriosis (150.4 pg/mL) were lower (p = 0.037) versus patients with no endometriosis (5.07 ng/mL and 229.6 pg/mL, respectively). The median levels of IL-6 and VEGF in patients with endometriosis were not different between the groups. The correlation analyses showed that leptin levels and IL-6 were positively correlated (p = 0.0001).Conclusions: The results suggest that ghrelin and leptin might play a key role in pathophysiology of endometriosis, and leptin is associated with inflammation in endometriosis.

Predictive value of tumor recurrence using urinary vascular endothelial factor levels in patients receiving radiation therapy for Glioblastoma Multiforme (GBM)

BackgroundGlioblastoma Multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Standard of care includes maximal resection followed by chemoradiotherapy. Tumors need adequate perfusion and neovascularization to maintain oxygenation and for removal of wastes. Vascular endothelial growth factor (VEGF) is a well characterized pro-angiogenic factor. We hypothesized that the increases in urinary VEGF levels would occur early in the course of tumor recurrence or progression. We examine the feasibility of collecting and analyzing urinary VEGF levels in a prospective, multi-institutional trial (Radiation Therapy Oncology Group, RTOG, 0611) as well as the role of VEGF as a marker of tumor recurrence.MethodWe evaluated VEGF levels in urine specimens collected post-operatively, at the conclusion of radiation therapy (RT) and one month following RT. Urinary VEGF levels were correlated with tumor progression at one year. VEGF levels were measured by enzyme-linked immunosorbant assay in urine specimens and normalized to urinary creatinine levels. Sample size was determined based on a 50% 1-year recurrence rate. With a sensitivity and specificity of 80%, the expected 95% confidence interval was (0.69, 0.91) with 100 patients. A failure was defined as documented disease progression, recurrence or death before one year.Results202 patients were enrolled between February-2006 and October-2007. Four patients were ineligible as they did not receive RT. Of the remaining 198 patients, 128 had all three samples collected. In this group, 35 patients (27.3%) did not progress, 89 (69.5%) had progression and 4 (3.1%) died without evidence of progression. Median VEGF levels at baseline were 52.9 pg/mg Cr (range 0.2- 15,034.4); on the last day of RT, 56.6 (range 0–2,377.1); and at one month follow-up, 70.0 (range 0.1-1813.2). In patients without progression at 1-year, both baseline VEGF level and end of RT VEGF level were lower than those of patients who progressed: 40.3 (range 0.2-350.8) vs. 59.7 (range 1.3-15,034.4) and 41.8 (range 0–356.8) vs. 69.7 (range 0–2,377.1), respectively. This did not reach statistical significance. Comparison of the change in VEGF levels between the end of RT and one month following RT, demonstrated no significant difference in the proportions of progressors or non-progressors at 1-year for either the VEGF increased or VEGF decreased groups.ConclusionUrine can be collected and analyzed in a prospective, multi-institutional trial. In this study of patients with GBM a change in urinary VEGF levels between the last day of RT and the one month following RT did not predict for tumor progression by one year.

Phase2 study of bevacizumab with carboplatin–paclitaxel for non-small cell lung cancer with malignant pleural effusion

Vascular endothelial growth factor (VEGF) is involved in non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE), but little is known regarding the efficacy of bevacizumab (Bev) with carboplatin-paclitaxel (CP) for NSCLC with MPE. Chemotherapy-naive non-SQ NSCLC patients with MPE were eligible to participate. Pleurodesis before chemotherapy was not allowed. In the first cycle, the treated patients received only CP to prevent Bev-induced wound healing delayed after chest drainage. Subsequently, they received 2-6 cycles of CP with Bev. Patients who completed more than 4 cycles of CP and Bev without disease progression or severe toxicities continued to receive Bev alone as a maintenance therapy. The primary end point was overall response, although an increase in MPE was allowed in the first cycle. The VEGF levels in plasma and MPE were measured at baseline, and the VEGF levels in plasma were measured after 3 cycles of chemotherapy. Between September 2010 and June 2012, 23 patients were enrolled. The overall response rate was 60.8%; the disease control rate was 87.0%. Sixteen patients received maintenance therapy, following a median of 3 cycles. Median progression-free and overall survival times were 7.1months (95% confidence interval [CI], 5.6-9.4months) and 11.7months (95% CI, 7.4-16.8months), respectively. Most patients experienced severe hematological toxicities, including ≥grade 3 neutropenia; none experienced severe bleeding events. The MPE control rate improved on combining CP with Bev (CP, 78.3%; CP with Bev, 91.3%; P=0.08). The median baseline VEGF level in MPE was 1798.6 (range 223.4-35,633.4) pg/mL. Plasma VEGF levels significantly decreased after 3 chemotherapy cycles (baseline, 513.6±326.4pg/mL, post-chemotherapy, 25.1±14.1pg/mL, P<0.01). CP plus Bev was effective and tolerable in chemotherapy-naïve non-squamous NSCLC patients with MPE.