Measured Serum Vascular Endothelial Growth Factor Levels Research Articles

Gene polymorphisms of VEGF and VEGFR2 are associated with the severity of Hashimoto's disease and the intractability of Graves' disease, respectively.

Vascular endothelial growth factor (VEGF) is one of main regulators of angiogenesis that functions by binding to its receptors, including VEGF receptor (VEGFR) 2. There are few data available regarding the association between VEGF and VEGFR polymorphisms and the susceptibility to and prognosis of autoimmune thyroid diseases (AITDs). To elucidate this association, we genotyped four functional VEGF and two VEGFR2 polymorphisms and measured serum VEGF levels. In the four functional VEGF polymorphisms, the frequencies of the I carrier and I allele of VEGF -2549 I/D, which has lower activity, were higher in patients with severe HD than in those with mild HD. In the two functional VEGFR2 polymorphisms, the frequency of the rs2071559 CC genotype, which has higher activity, was higher in patients with intractable GD than in controls, and the proportion of GD patients with larger goiters was higher in those with the CC genotype. Moreover, the frequency of the rs1870377 TT genotype with higher activity was higher in patients with intractable GD than in those with GD in remission. Combinations of VEGF and VEGFR2 polymorphisms with stronger interactions were associated with the intractability of GD. Serum VEGF levels were higher in HD and AITD patients than those in controls. In conclusion, VEGF polymorphisms with lower activity were associated with the severity of HD, while VEGFR2 polymorphisms and the combinations of VEGF and VEGFR2 polymorphisms, which have stronger interactions, were associated with the intractability of GD. VEGF and VEGFR2 polymorphisms were associated with HD severity and GD intractability, respectively.

Serum VEGF levels in gastric cancer patients: correlation withclinicopathological parameters

To evaluate the predictive role of the circulating levels of vascular endothelial growth factor (VEGF) in gastric cancer patients. This study is a case-control study. We measured serum VEGF levels of 30 patients aged between 34 and 83 years with gastric cancer and 30 patients without malignant pathology, operated on for benign pathologies, with ages ranging from 18 to 69. Serum levels of VEGF were correlated with the tumor type classification (signet cell adenocarcinoma) and the presence of adjacent tissue invasion. There was also a positive correlation between serum VEGF and carcinoembryonic antigen levels. In gastric cancer patients, serum VEGF levels may provide additional prognostic information for preoperative evaluation of invasion and tumor type.

Higher level of serum vascular endothelial growth factor in type 2 diabetic patients with diabetic retinopathy hospitalized for hyperglycemic state

Vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, and higher levels of intraocular VEGF are observed in patients with active proliferative diabetic retinopathy. Meanwhile, whether serum VEGF level is associated with diabetic retinopathy (DR) or not is controversial. To investigate the significance of serum VEGF levels in diabetic patients with DR, we measured serum VEGF levels in 138 type 2 diabetic patients hospitalized for treatment of a hyperglycemic state, all of whom were not complicated by VEGF-related diseases, such as malignancy, cardiovascular disease or infectious disease. Serum VEGF level was significantly increased in diabetic patients with DR as compared to those without DR. Moreover, multiple regression analysis and stepwise regression analysis revealed that body mass index and presence or absence of DR were associated with serum VEGF level; in particular, the presence of DR was strongly correlated with increased serum VEGF level. Increased serum VEGF level may be closely associated with the presence of DR in type 2 diabetic patients. Whether this conclusion is true for general type 2 diabetic patients is a subject for future investigation because of several limitations of this study, including sample selection bias.

Serum vascular endothelial growth factor is related to systemic oxidative stress in patients with lung cancer

Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.

Low serum VEGF levels are associated with Alzheimer's disease

As vascular endothelial growth factor (VEGF) determines important neurotrophic and neuroprotective actions, we postulated serum VEGF levels could be abnormally low in patients with Alzheimer's disease (AD). We measured serum VEGF levels (VEGF(165) isoform by ELISA) in 51 patients with AD by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria and compared with 66 age- and gender-matched non-demented controls. Patients with AD were stratified into levels of dementia severity by the Clinical Dementia Rating scale. Serum VEGF levels were stratified into upper (>309 pg/ml), middle (207-309 pg/ml), and lower (<207 pg/ml) tertiles. VEGF (-2,578) (rs 699,947) and VEGF (-634) (rs 2,010,963) polymorphisms were genotyped in patients with AD and controls. The mean concentration of VEGF in the serum of patients with AD (215.9 pg/ml, SD 101.5) was significantly lower than that of the controls (308.6 pg/ml, SD 223.9, P = 0.004), and decreased serum VEGF levels were associated with AD in a dose-dependent manner, the lower tertile of serum VEGF levels being associated with a fivefold increased risk for AD when compared with the upper tertile. There was no significant correlation between serum VEGF levels and age, sex, APOE alleles, AD dementia severity nor VEGF gene polymorphisms. Decrease in serum VEGF levels could contribute to the neurodegenerative process in AD.

Increased serum vascular endothelial growth factor levels in microscopic poly angiitis with pulmonary involvement

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the lungs. However, there are little serological markers that predict its prognosis or severity of pulmonary involvement. Vascular endothelial growth factor (VEGF) is an angiogenic mediator, which has been reported to be elevated in systemic vasculitis. In this study, we measured serum VEGF levels in 22 MPA patients with pulmonary involvement. We also investigated VEGF expression in pulmonary cells using flow cytometry analysis. We found that serum VEGF levels in MPA patients were significantly higher than those in respiratory or urinary tract infection. The serum VEGF levels decreased in parallel with the improvement of MPA symptoms. The serum VEGF levels in MPA patients who died within 5 years were significantly higher than those who survived more than 5 years. The sensitivity of VEGF levels to distinguish MPA patient with poor prognosis from those with good prognosis was 90.9%, and specificity was 81.8% (cutoff value = 802.5 pg/ml). The serum VEGF levels showed significant positive correlation with the composite physiological index, which indicates the severity of pulmonary lesion. In flow cytometry analysis, CD11b positive bronchoalveolar lavage fluid cells expressed VEGF. Immunohistochemically, alveolar macrophages, tissue infiltrating inflammatory cells and alveolar epithelial cells stained positive for VEGF. Measurement of serum VEGF levels in MPA might become one of the markers for prognosis and the severity of pulmonary involvement in MPA. VEGF might contribute to the development of pulmonary lesion of MPA.

Evaluation of serum vascular endothelial growth factor (VEGF) levels following trans-arterial chemoembolization (TACE) of hepatic malignancies of gastrointestinal (GI) origin

3087 Background: TACE is an effective modality in the treatment of metastatic or primary hepatic malignancies of GI origin. One outcome from this effective therapy is hypoxia and cell death with tumor necrosis. Inflammation induced by necrotic cells and hypoxia due to the embolization process are potential stimulators of VEGF production. VEGF is a potent angiogenic cytokine, and secretion of this factor can lead to increased tumor angiogenesis, thereby offsetting the goal of therapy. In this study, we measured serum VEGF levels before and after chemoembolization of hepatic malignancies. Additionally, serum uric acid levels are measured as a correlate of tumor necrosis. Methods: 14 patients, 18 years or older, with primary or secondary malignancies confined to the liver, were included. 10 ml of blood was collected from patients before and at various time points following chemoembolization. All blood samples collected were grouped in one of the 5 groups: pre, 24 hr post, early post (>1 day & < 1 week), intermediate post (≥1 week & < 4 weeks), and late post (≥4 weeks). The 14 patients received a total of 24 treatments, and data was analyzed using two-tailed paired T-test. Results: Serum VEGF levels were significantly increased at 24 hr post-TACE (mean increase of 57%, p=.0005). There were increases at the intermediate and late time points, but these differences were not statistically significant when compared to the pre-TACE levels (p=0.074 and 0.067, respectively). At late time points, serum uric acid levels demonstrated a mean increase of 11% (p=0.03). Serum uric acid levels at the other time points were not significantly changed from the pre-TACE levels. Conclusions: Serum VEGF level is increased following TACE for hepatic malignancies of GI origin and may be the result of multiple factors: hypoxia and tumor necrosis. The increased VEGF secretion may stimulate angiogenesis and promote tumor regrowth, suggesting a potential role of combining antiangiogenic therapy with current TACE protocols in the treatment of hepatic malignancies. No significant financial relationships to disclose.

Vascular Endothelial Growth Factor Level as a Prognostic Determinant of Small Cell Lung Cancer in Japanese Patients

To clarify the clinical significance of vascular endothelial growth factor (VEGF) in Japanese patients with small cell lung cancer (SCLC). We measured serum VEGF levels using an enzyme-linked immunosorbent assay in 45 patients with SCLC before treatment and in 38 patients with benign pulmonary disease and in 32 healthy subjects (71 non-malignant subjects). VEGF immunostaining was performed in tissue biopsies obtained from 23 SCLC patients during bronchoscopic examination. Median serum VEGF level was 332 pg/ml in patients with SCLC and 160 pg/ml in non-malignant subjects, respectively. The 95% cut-off level to exclude non-malignant subjects was 500 pg/ml. An elevated VEGF level (>500 pg/ml) was found more frequently in patients with extensive disease of SCLC than in those with the limited disease (p<0.01). A significant positive correlation was found between the serum VEGF level and platelet count in SCLC patients (r=0.389; p=0.0083). Serum VEGF level also correlated with serum lactate dehydrogenase in SCLC patients (r=0.381; p=0.0098). However, it did not correlate with serum neuron-specific enolase and pro-gastrin-releasing peptide level. Patients with the elevated VEGF levels had significantly shorter progression-free time than those with the normal VEGF levels (p<0.05). Patients with the elevated VEGF levels had a significantly shorter overall survival time than those with the normal VEGF levels in univariate survival analysis (p<0.05). Further, the elevated VEGF level remained as a significant determinant of poor survival in multivariate analysis (p<0.01). Serum VEGF level was significantly higher in patients with positive VEGF protein immunoreactivity in tumor tissue in SCLC. Elevated serum VEGF levels were associated with poor outcome in SCLC.

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0-2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0-45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0-49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n = 31, acute phase: 0.0-2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0-146.5 pg/ml, median 26.90 pg/ml; P = 0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs = 0.347, P = 0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P = 0.012 and P = 0.003, respectively) and multivariate (P = 0.037, OR 6.16 and P = 0.0059, OR 7.59, respectively) analyses. Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.