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.

Effects of insulin-like growth factor-1 on random pattern skin flap survival in rats

ABSTRACT PURPOSE: To investigate the effects of pharmacological delay with insulin-like growth factor-1 (IGF-1) on skin flap survival. METHODS: Thirty Sprague-Dawley rats were submitted to dorsal skin flap (3x9 cm). Seven days before the surgery, the animals were subdivided into three groups of 10 rats. In group 1 (controls), no injection was done. Seven days before the elevation, saline had been injected to the marked skin flap area in group 2 (sham group), and group 3 (experimental group) underwent a pharmacological delay with subcutaneous IGF-1 injections. On the seventh postoperative day, flap area was analyzed for survival. Tissue samples were obtained for histological and biochemical evaluations. RESULTS: Survival rates were 43.55 ± 16%, 21.40 ± 8%, and 43.12 ± 14% in groups 1, 2, and 3, respectively. Differences between group 2 and other groups were statistically significant. No significant difference was detected between all three groups for tissue or plasma vascular endothelial growth factor (VEGF) levels. There was no significant histological difference between groups. CONCLUSION: Although a single injection of insulin-like growth factor-1 (IGF-1) did not significantly increase flap survival, its wound healing features are still encouraging and further meticulously planned studies, especially with repeated applications or controlled-release methods, and combinations with binding protein are required.

Clinical significance of TGF alpha, TGF beta1 and VEGF in sera of Egyptian patients with breast cancer

Breast cancer [BC] is the most prevalent cancer among women and affects approximately one million women worldwide each year and it is the most prevalent cancer among Egyptian women and constitutes 29% of National Cancer Institute cases. This study was designed to determine the crucial role of TGF-alpha, TGF-beta1and VEGF in patients with Breast carcinoma. Serum level of TGF-alpha, TGF-beta1 and VEGF were determined by ELISA in 51 patients with preoperative and postoperative primary [BC], as well as 30 healthy female persons. This study showed that the TGF-alpha, TGF-beta1 and VEGF levels were significantly high [p = 0.001] in patients with primary breast cancer compared to control healthy female group. Meanwhile the levels of these growth factors did show significant decrease after treatment. This study revealed that serum levels of TGF-alpha, TGF-beta1 and VEGF in patients with breast cancer could be useful biomarkers for prognosis of such type of malignancy

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION: Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors. METHODS: Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes. RESULTS: In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549 ± 161 vs. 2156 ± 202/mm², respectively). CONCLUSION: Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats.

Serum vascular endothelial growth factor in hepatocellular carcinoma: correlation to portal vein thrombosis and other disease characteristics

Vascular endothelial growth factor [VEGF] is the most potent angiogenic factor known so far and it plays an important role in tumor biology. Elevated level of VEGF has been associated with poor prognosis in many cancers; however significance in hepatocellular carcinoma is still controversial. Was to evaluate serum VEGF level in hepatocellular carcinoma patients with or without portal vein thrombosis [PVT] compared to liver cirrhosis patients and healthy subjects and to study possible relation of other clinical and laboratory findings to VEGF level. Serum VEGF level was measured in 20 cirrhotic patients complicated with HCC and PVT, 20 cirrhotic patients complicated with HCC with no portal vein thrombosis, another 20 cirrhotic patients matched for Child-Pugh score 20 he1thy subjects matched for age and sex. VEGF level was compared across different groups, its level was evaluated hug to tumour size, Okuda stage, Child-Pugh class and etiology of liver disease. Serum VEGF was not significantly different between HCC patients with or without PVT, neither a significant as found between HCC patients and liver cirrhosis patients. Yet VEGF level was significantly higher in all cases of liver cirrhosis compared to control subjects. No significant relation was found between serum VEGF level and any of: tumour size, Okuda stage. Alpha fetoprotein, Child-Pugh class or etiology of liver disease. VEGF level is elevated in patients with liver cirrhosis even prior to the emergence HCC

Prognostic value of TNF alpha mRNA and VEGF mRNA expression in patients with chronic hepatitis C geno-type-4, with and without cirrhosis and hepatocellular carcinoma to predict disease outcome

The study aimed to clarify whether vascular endothelial growth factor mRNA [VEGF mRNA] and TNF alpha mRNA in the HCC tissues on top of HCV with and without cirrhosis obtained from specimens after curative hepatic resection has a prognostic value and recurrence predictive value compared to other tumor criteria. A total of 160 patients were studied. The preoperative laboratory, radiological and staging to patients was done. Using in situ hybridization technique, VEGF mRNA and TNF alpha mRNA were determined in liver tissues of, 10 controls, 50 with HCC, 50 with HCV without cirrhosis and 50 HCV with cirrhosis. The results showed that in HCC cases there was positive correlation between increasing age, loss of weight, INR and AFP but not in other cases of CHC with or without cirrhosis. AFP, vascular invasion, encapsulation, tumor size and grade and platelet count were related to patients outcome and recurrence of tumor after follow up of most cases for 3 years. The expression of VEGF in liver tissues was proportional to progress of viral hepatitis to cirrhosis with more expression in cases progressed to malignant changes. More expression of VEGF in HCC was more evident with intense expression in cases with Vascular and capsular invasion and higher level of AFP. Expression of TNF alpha mRNA and VEGF mRNA shows increasing expression with positive correlation to progression of viral hepatitis to cirrhosis with more positive with cases developed HCC

Predictive Significance of Serum IL-6, VEGF, and CRP in Gastric Adenoma and Mucosal Carcinoma before Endoscopic Submucosal Dissection / 대한소화기학회지

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is commonly used for radical resection of gastric adenoma and mucosal cancer, but there is about 30% of discrepancy rate between the histology of the endoscopic biopsy and that of the resecwas to clarify the clinical significance of IL-6, VEGF, CRP before ESD. METHODS: We investigated the correlation between serum IL-6, VEGF, CRP level and discrepancy rate of gastric neoplastic lesions (10 low-grade dysplasias, 18 high-grade dysplasias, and 25 early gastic cancers). RESULTS: Serum levels of IL-6 in gastric adenoma and mucosal cancer patients were significantly higher than in healthy controls (p<0.05). Especially, serum IL-6 level of high-grade dysplasia patient was significantly higher than low-grade dysplasia and mucosal cancer patients, and the positive rate, sensitivity, and negative predictive value of serum IL-6 levels were higher in high-grade dysplasia patient compared to low-grade dysplasia patient and mucosal cancer patient. Serum levels of VEGF in patients with gastric adenoma and mucosal cancer were significantly higher than healthy controls (p<0.01). Serum levels of CRP in patients with mucosal cancer were significantly higher than in the controls (p<0.05), and the positive rate, sensitivity, and positive predictive value of serum CRP levels were higher in high-grade dysplasia and mucosal cancer patients compared to low-grade dysplasia patient. CONCLUSIONS: Serum levels of IL-6, VEGF, and CRP in patients with gastric neoplastic lesions were significantly higher than healthy controls, especially, serum IL-6 level of high grade dysplasia patient was significantly higher than low-grade dysplasia and mucosal cancer patients.

Vascular endothelial growth factor as an indicator of severity of diabetic retinopathy

To evaluate vascular endothelial growth factor [VEGF] as an indicator of severity in diabetic retinopathy. The study included 120 patients divided equally into 3 groups [proliferative diabetic retinopathy [PDR] group, non proliferative diabetic retinopathy [NPDR] group and non diabetics control group]. Vitreous and blood samples were collected from all patients. VEGF concentrations were determined using enzyme linked immuno-sorbent assay and correlated with retinopathy grading. Vitreous concentrations were statistically significant higher than serum concentrations in both retinopathy groups with strong positive correlation [r = 0.927 at p < 0.001 in PDR and r = 0.646 at p < 0.001 in NPDR]. Serum and vitreous VEGF concentrations in diabetics were statistically significant higher than control group [p<0.01]. Both increased with the progression of retinopathy. Very mild NPDR patients had the lowest vitreous concentration [mean = 20.33 ng / ml] but still higher than controls [mean = 4.53 ng / ml]. PDR patients with tractional detachment had the highest vitreous concentration [mean = 225.18 ng / ml]. VEGF concentrations were statistically significant higher in NPDR patients with maculopathy than NPDR patients without maculopathy. There is a strong direct positive correlation between VEGF concentrations and retinopathy grading

Cytokines and growth factors in Duchene muscular dystrophy patients

Dystrophin deficiency associated with Duchene muscular dystrophy [DMD] results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of cytokine and growth factors. Most of the current researches test for such cytokines and growth factors in tissue biopsies, which is an invasive technique. Of the present study is to investigate whether cytokines and growth factors, as indicators of inflammatory response, can be detected in blood of DMD patients as non-invasive technique. Accordingly the cytokine tumor necrosis factor alpha [TNF TNF-alpha], as well as the growth factors basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF] were measured in blood of 24 boys with DMD diagnosed clinically and at the molecular level versus 20 age matching healthy boys. Showed a significant increases in TNF-alpha [30.2 +/- 9.5 vs. 3.6 +/- 0.9 pg/ml] and bFGF [21.7 +/- 10.3 vs. 4.75 +/- 2.2 pg/ml.], while VEGF was significantly decreased [190 +/- 115 vs. 210 +/- 142 pg/ml] in blood of DMD patients compared to controls. Results provide further proof that inflammatory response is associated with DMD pathogenesis and favours the use of biomarkers in blood of such patients as a non invasive technique

Molecular study of vascular endothelial growth factor gene in Iranian patients after myocardial infarction

Stimulation of collateral artery growth [arteriogenesis] and/or capillary network growth [angiogenesis] would be beneficial to the patients with myocardial infarction. To understand the central role of vascular endothelial growth factor [VEGF] in biological angiogenesis, we performed molecular analysis of the VEGF gene in patients afflicted with acute myocardial infarction [AMI]. Forty patients with AMI were divided into two groups according to the presence or absence of created collateral blood vessels in ischemic myocardial region. In these patients we also evaluated the possible relationship of plasma levels of VEGF and its growing ability of new blood vessels. The molecular characterisation of VEGF gene may highlight the presence of natural genomic variants which could facilitate the formation of new vessels in the ischemic area. The genomic analysis of VEGF gene did not reveal any mutations in the coding region, but showed the presence of four and one single nucleotide substitutions in the intronic region and 5'UTR respectively. The C to T nucleotide transition at position -7 of 5'UTR is located in a potential binding site for Sp-1 transcription factor, which could probably affect the VEGF gene transcription. The molecular study of VEGF gene showed that its coding region is highly conserved. Therefore, variations of angiogenesis could be due to the regulatory elements participating in this mechanism

Assessment of the clinical significance of serum vascular endothelial growth factor and matrix metalloproteinase-9in patients with hepatrcellular carcinoma

The pre-therapeutic serum levels of VEGF and MMP-9 were studied in patients with HCC, cirrhotic patients and in healthy subjects by an ELISA assay to elucidate the relationship between serum VEGF, MMP-9 levels and clinicopathological characteristics of HCC. The serum VEGF and MMP-9 were significantly elevated in HCC patients with macroscopic portal vein invasion and with metastasis as compared to HCC patients with neither invasion nor metastasis. Serum VEGF showed a significant difference between HCC patients with tumor size > 5 cm and < 5 cm, however serum MMP-9 did not vary with tumor size. It was concluded that the portal vein invasion and metastasis in HCC is a complex process involving multiple factors including VEGF-mediated angiogenesis and MMP-9 induced degradation of extracellular matrix. The pre-therapeutic serum VEGF and MMP-9 in HCC might be candidate biomarkers reflecting the disease potential for vascular invasion and metastasis, serum VEGF being a superior biomarker as it correlated also with tumor size

Serum concentration of vascular endothelial growth factor [VEGF] in non complicated type II diabetes mellitus and its relation to the degree of diabetic control

This study detremined the serum level of Vascular Endothelial Growth Factor VEGF in non-complicated type II diabetes mellitus and searched for a relationship between it and the degree of diabetic control. The serum level of VEGF was measured using an Enzyme ImmunoAssay in twenty eight patients with uncomplicated type II diabetes mellitus and in ten healthy non-diabetic subjects. The diabetic patients had serum level of VEGF significantly higher than these in controls [P < 0.001], and there was significantly positive correlation between serumlevels of VEGF and the degree of diabetic control particularly HbA1. In conclusion; the results of this study suggested that circulating VEGF is not specific for diabetic vascular complications and chronic hyperglycaemia may be one of the factors regulating VEGF induction and supposed that the elevated VEGF production under high glucose conditions may play role in the accelerated vascular disease observed in diabetes mellitus