Mean Vascular Endothelial Growth Factor Level Research Articles

Level of Vascular Endothelial Growth Factor in Aqueous Humor and Surgical Results of Ahmed Glaucoma Valve Implantation in Patients With Neovascular Glaucoma

To determine the associations between the levels of growth factors in aqueous humor and the surgical outcomes of Ahmed glaucoma valve implantation in patients with neovascular glaucoma (NVG). From 19 NVG eyes of 19 patients, a sample of aqueous humor was taken just before Ahmed glaucoma valve implantation. Levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, and TGF-beta2 in aqueous humor aspirates were measured using a sandwich enzyme-linked immunosorbent assay method. When the postoperative intraocular pressures were >or=21 mm Hg with or without antiglaucoma medications at 2 successive visits or when any other surgical interventions were needed to lower intraocular pressure, that surgery was considered a failure. After patients were classified into success versus failure groups, the levels of the growth factors between the 2 groups was compared. The cumulative probability of success according to Kaplan-Meier analysis was also determined. Mean postoperative follow-up period was 40.9+/-19.6 months and cumulative probability of success was 43% at 57 months after surgery. Mean VEGF level in the failure group was higher than that of the success group (P=0.014). However, there was no statistical difference in the levels of TGF-beta1, TGF-beta2, and protein between 2 study groups (all P>0.05). The level of VEGF in aqueous humor was significantly higher in the failure group after the Ahmed glaucoma implantation compared with the success group. Our results imply that VEGF may play a role in determining surgical success after Ahmed valve implantation in patients with NVG.

Serum VEGF increases in diabetic polyneuropathy, particularly in the neurologically active symptomatic stage

To identify the relationship between vascular endothelial growth factor (VEGF) and diabetic polyneuropathy (DPN). Two hundred and twenty diabetic patients participated, 113 with DPN and 107 without DPN. All patients were also classified according to the four stages of DPN (no neuropathy: stage 0; asymptomatic neuropathy: stage 1; symptomatic neuropathy: stage 2; disabling neuropathy: stage 3). Serum VEGF concentration was measured using an enzyme-linked immunosorbent assay (ELISA) and levels between the patients with and without DPN and also between the different stages of DPN, were compared. The mean serum VEGF level in all patients was 264.6 +/- 218.8 pg/ml. The mean serum VEGF level was higher in patients with DPN (310.1 +/- 224.3 pg/ml) than in the patients without DPN (216.5 +/- 204.0 pg/ml, P = 0.0014). Serum VEGF was higher in the 'symptomatic' stage (stage 2, 364.8 +/- 225.9 pg/ml) in comparison with the 'asymptomatic' (stage 1, 256.7 +/- 224.4 pg/ml, P = 0.015) and 'disabling' (stage 3, 180.3 +/- 109.4 pg/ml, P = 0.042) stages. The mean serum VEGF level in patients with diabetic retinopathy (261.1 +/- 210.6 pg/ml) and in patients with diabetic nephropathy (241.5 +/- 185.7 pg/ml) was not increased. The serum VEGF level is increased in patients with DPN, particularly in patients in the neurologically active 'symptomatic' stage.

Changes in vascular endothelial growth factor, angiopoietins, and Tie-2 levels with G-CSF stimulation in healthy donors

The roles of vascular endothelial growth factor (VEGF), Tie-2, and angiopoietins in the mobilization of the hematopoietic stem cells (HSCs) in humans are not yet clearly understood. In order to elucidate mechanisms of HSC mobilization from their niches, we aimed to investigate the effects of mobilization with granulocyte colony-stimulating factor to the levels of VEGF, Tie-2, and angiopoietins 1 and 2 in the allogeneic HSC transplantation donors. Soluble VEGF, Tie-2, angiopoietin 1 and angiopoietin 2 levels were studied in 20 healthy allogeneic HSC transplantation donors before (from peripheral blood) and 5 days after mobilization (from apheresis material). Mean VEGF level in the postmobilization apheresis sample was significantly higher compared to baseline premobilization peripheral blood (t test, p < 0.001). In contrast, mean Tie-2 level in the postmobilization aphaeresis sample was significantly lower compared to baseline premobilization peripheral blood (t test, p = 0.01). Angiopoietin 1 and angiopoietin 2 levels did not differ between baseline and postmobilization samples. A significant rise in VEGF level after mobilization suggests stimulation of the angiogenesis. A significant fall in Tie-2 level suggests suppression of the angiopoietin 1/Tie-2 signaling, leading to release of HSC from the hematopoietic niches and mobilization to the peripheral blood.

Vascular endothelial growth factor gene polymorphisms and serum levels in Behçet’s disease

Vascular endothelial growth factor (VEGF) is important for angiogenesis and inflammation, both of which are codependent and contribute to the pathophysiology of Behçet's disease (BD). In this report, we sought to investigate whether the selected VEGF polymorphisms [-634 C/G, +936 C/T and an 18 bp insertion/deletion (I/D) at -2549 of the VEGF promoter region] are associated with susceptibility and severity of BD in the Tunisian population. One hundred and thirty-five Tunisian BD patients and 157 healthy controls were recruited. The VEGF gene was genotyped by polymerase chain reaction followed by digestion with restriction endonucleases. VEGF serum levels of BD patients and healthy controls were measured by enzyme-linked immunosorbent assay. We found no association between the VEGF polymorphisms and the susceptibility to BD. However, when data were analysed according to the presence of each symptom, we found a positive association between VEGF 18 bp I/D polymorphism and ocular involvement as well as BD severity. Indeed, among the BD patients, the frequency of the 18 bp I/I genotype was less in patients with ocular inflammation (6.1% vs 24.6%, P = 0.007) and in patients with severe BD (9.2% vs 21.4%, P = 0.0014). Moreover, the mean serum VEGF level was considerably higher in BD patients (P < 0.01) than in healthy controls. We suggest that VEGF gene polymorphisms may be involved in the development of the ocular BD as well as the severity of the disease.

Serum vascular endothelial growth factor levels in patients with medullary thyroid carcinoma

High levels of vascular endothelial growth factor (VEGF) have been reported in patients with cancers of different origins. There are no data comparing serum VEGF levels of medullary thyroid carcinoma (MTC) patients with that of the healthy subjects. We tried to assess whether serum VEGF concentration in MTC patients is correlated with tumour extension and whether this marker might be used to further refine the selection of candidates for future therapies with receptor tyrosine kinase inhibitors. Sera from 57 individuals divided into five groups: group I, healthy individuals (n=14); group II, MTC patients in remission (n=10); group III, MTC patients with residual disease (n=12); group IV, MTC patients with loco-regional disease (n=11) and group V, MTC patients with distant metastases (n=10) were analysed for serum VEGF and calcitonin (CT) levels. Analysis of serum VEGF did not disclose significant differences among the five groups. Mean serum VEGF level of patients with distant metastases was not significantly different from that observed in healthy individuals (319.4+/-49.78 vs 313.7+/-43.13 ng/l). Serum VEGF levels correlated positively with serum CT (r=0.4891; P=0.0394) for CT values below 2500 ng/l whereas there was no correlation for CT values above this threshold. Serum VEGF levels in MTC patients are not significantly different from those found in healthy individuals and did not correlate with the extension of disease.

UFT and its metabolite γ-butyrolactone (GBL) inhibit angiogenesis induced by vascular endothelial growth factor in advanced cervical carcinoma

The aim of this study was to evaluate the potential role of UFT and its metabolite gamma-butyrolactone (GBL) for inhibition of angiogenesis induced by vascular endothelial growth factor (VEGF) in advanced cervical carcinoma by the determination of serum GBL and VEGF, and by immunohistochemical staining to assess VEGF protein expression, before and after UFT therapy. The subjects were 35 patients with an advanced cervical carcinoma and five healthy volunteers between 2002 and 2003 at Hiroshima University Hospital, under informed consent. The patients received two courses of oral fluoropyrimidine (UFT) therapy at a dose of 600 mg/day for 5 and 2 days off treatment. Serum GBL and VEGF was measured before and after UFT therapy by the gas chromatography mass spectrometry and ELISA-kit in 22 patients and five healthy volunteers, respectively. Immunohistochemical detection of VEGF protein was done in 35 cervical cancers. Results The mean serum GBL level before and after UFT therapy was 21.9 +/- 2.3 and 79.3 +/- 6.2 ng/ml, respectively, and it was significantly increased after UFT administration (P < 0.0001). The mean serum VEGF level before and after UFT therapy was 95.3 +/- 28.1 and 67.5 +/- 11.2 pg/ml, respectively, and it was decreased by UFT administration. In 20 out of 33 (66.6%) patients who were detected with VEGF protein, VEGF protein expression was decreased by UFT therapy. The Delta GBL value (GBL after UFT--GBL before UFT therapy) showed a significant inverse correlation with Delta VEGF value (VEGF after therapy--VEGF before therapy) (r2 = 0.940). Our findings suggest that UFT and its metabolite GBL inhibit angiogenesis induced by VEGF to have an antitumor effect on cervical cancer.

Serum Levels of Vascular Endothelial Growth Factor (VEGF) as a Prognostic Factor in Renal Cell Carcinoma

Purpose: Vascular endothelial growth factor (VEGF) is recognized as a potent constituent of the vascularization and growth of solid tumors. We assessed the serum levels of VEGF and we evaluated its correlation to the clinicopathologic findings and clinical outcome of patients with renal cell carcinoma (RCC). Materials and Methods: Serum samples were collected before surgery from patients with RCC. The levels of serum VEGF were assessed by using quantitative enzyme immunoassay. Comparison of the serum VEGF level with the tumor stage, grade, cell type and clinical outcome was performed, and the survival rate between the RCC patients above and below the mean VEGF level was evaluated. Results: The mean follow-up was 5.1 years. The serum VEGF level was significantly higher in the patients with RCC (mean: 497pg/ml) than that in the controls (mean: 211pg/ml) (p<0.001). The serum VEGF level was correlated with the tumor size, the pathologic T stage and the clinical stage and histologic nuclear grade, but not with the histologic subtype. Patients with a lower VEGF level (<497pg/ml) showed longer survival (p=0.0207 on univariate analysis, p=0.04 on multivariate analysis). Conclusions: Our study indicated that the serum VEGF level was significantly correlated with the clinical or pathologic stage, the nuclear grade and adverse survival. These results suggest that the serum VEGF level could be a comparable prognostic factor to the tumor stage and grade. (Korean J Urol 2007;48:1219-1223) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs

Patients with critically ischemic limbs due to maintenance hemodialysis and diabetes are increasing in number markedly in Japan. The difficulty of treating critically ischemic limbs is well recognized. Despite active medication and surgical therapy, many critically ischemic limbs are amputated. Ninety-two patients with critically ischemic limbs were treated by transplantation of autologous peripheral blood stem cells (PBSCs). The stem cells were mobilized into the peripheral blood by administration of granulocyte colony stimulating factor (G-CSF). The mobilized mononuclear cells were separated by an apheresis technique using a centrifuge. The separated mononuclear cells contained approximately 4.0 x 10(7) CD34-positive cells. The collected cell suspension was divided into aliquots of 0.5-1.0 ml and transplanted into the muscle of ischemic limbs at 50-70 transplantation points. At 1.5 months after PBSC transplantation, a strong immunostaining of CD34-positive cells and factor VIII, as well as capillary formation, was observed in the muscles into which stems cells had been transplanted. In each patient tested, the serum vascular endothelial growth factor (VEGF) level increased after stem cell transplantation; the mean VEGF level increased by 176%. Of 11 diabetic patients (DM) who were not receiving hemodialysis (HD), there were no amputees regardless of their Fontaine classification. Of 19 patients in the HD(+)DM(-) category, there were no amputations in Fontaine stage I, II, and III patients, whereas three limbs and one toe were amputated in Fontaine stage IV patients. Of 13 patients in the HD(-)DM(+) category, none of the Fontaine stage I, II, or III patients underwent amputation, but six Fontaine stage IV patients underwent amputation. Of 49 patients in the HD(+)DM(+) category, 38 (78%) were classified as Fontaine stage IV, 71% (27/38) of whom had a toe or a limb amputated. In nine patients over 80 years of age, one toe and one limb were amputated. Nondiabetic, nondialyzed patients with ischemic limbs are strongly indicated for stem cell transplantation regardless of Fontaine classification. Therapeutic angiogenesis is effective for critically ischemic limbs resulting from hemodialysis and diabetes until Fontaine stage III, but is of limited effectiveness for stage IV cases.

Association of Elevated Levels of Vascular Endothelial Growth Factor in Obstructive Sleep Apnea Syndrome with Patient Age rather than with Obstructive Sleep Apnea Syndrome Severity

Background: Although certain studies report high levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of systemic hypoxia on circulating VEGF remains controversial. Objectives: To study the association of serum VEGF and OSAS in a large group of patients. Methods: One hundred patients with OSAS (mean age 58.1 ± 12.4 years, mean body mass index 30.6 ± 5.4 kg/m²) were tested for serum VEGF levels, and the findings were correlated with the severity of OSAS, as determined by the apnea-hypopnea index (AHI) on the basis of polysomnography and background data. Results: The mean AHI was 40.0 ± 21.2 (range 10–106). Mean minimal oxygen saturation was 80.6 ± 11.7% (range 43–98%) and mean time of oxygen saturation under 90% was 50.0 ± 75.0 min (range 0–300 min). The mean VEGF level was 445.2 ± 289.8 pg/ml in the study group (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8 ± 64.4 10³/ml and the mean VEGF/platelet ratio was 1.95 ± 1.40 pg/10⁶. There was no association of VEGF or VEGF/platelets with the severity of OSAS. However, both factors showed a significant correlation with patient age (r = 0.224, p = 0.01 and r = 0.425, p = 0.01, respectively). Age was the only parameter to significantly predict VEGF and VEGF/platelets on multivariate analysis (R² = 0.713, p = 0.001 and R² = 0.844, p = 0.001, respectively). Conclusion: The elevation of serum VEGF in OSAS is not associated with the severity of the disease, but it is associated with patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS, and its age-dependent increase might partly explain the reduced mortality in elderly OSAS patients.

Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects

Background: We previously demonstrated efficacy and impact on serum vascular endothelial growth factor (VEGF) for metronomic cyclophosphamide (C) and methotrexate (M) in patients with breast cancer. New metronomic schedules were investigated.Patients and methods: Patients with advanced breast cancer were randomized to receive oral C (50mg daily) and M (2.5mg twice daily on days 1 and 4) (arm A) or the same regimen plus thalidomide (200mg daily) (arm B).Results: The mean VEGF level decreased from 378.9 (± 274.4) pg/ml at baseline to 305.9 (± 203.6) pg/ml at 2 months (P < 0.001), with similar change with respect to baseline in both arms. In 171 evaluable patients we observed three complete remissions (CR) in both arms A and B, 15 partial remission (PR) in arm A and seven in arm B, for an overall response of 20.9% [95% confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8% to 20.6%) in arm B. The clinical benefit (CR + PR + SD ≥ 24 weeks) was 41.5% for both arms. Toxicity was generally mild. Higher neurological toxicity (2% versus 60%; P < 0.0001) and constipation (8% versus 51%; P < 0.0001) was observed in arm B.Conclusions: Metronomic low-dose CM induced a drop in VEGF, and was effective and minimally toxic. The addition of thalidomide did not improve results.

Elevated Oxidative Stress and Reciprocal Reduction of Vascular Endothelial Growth Factor Levels With Severity of COPD

The prevalent theory concerning the pathogenesis of COPD is that it is an imbalance between oxidants and antioxidants. However, it has been reported that a decrease in vascular endothelial growth factor (VEGF) might affect the pathogenesis of COPD. Therefore, this study was designed to examine the differences between oxidative stress and VEGF levels, and the severity of COPD. Controlled cross-sectional analysis. University hospital. Twelve healthy control subjects and 57 COPD patients were included in this study. These COPD patients were divided into four groups based on the Global Initiative for Chronic Obstructive Lung Disease classification (mild COPD, 14 patients; moderate COPD, 15 patients; severe COPD, 16 patients; very severe COPD, 12 patients). Inflammatory markers, degree of oxidative stress, and VEGF levels were examined in sputum samples from all subjects. Nitrogen oxide levels in induced sputum were significantly higher in COPD patients than in healthy control subjects, and they increased with increases in the severity of COPD. In contrast, peroxynitrite inhibitory activity decreased with increases in the severity of COPD. Therefore, the mean (SD) peroxynitrite stress (ie, the nitrogen oxide level/peroxynitrite inhibitory activity ratio) steeply increased with increases in the severity of COPD (mild COPD: 8.4; SD, 1.5; p = 0.02; moderate COPD: 10.8; SD, 1.4; p < 0.0001; severe COPD: 14.5; SD, 2.5; p < 0.0001; very severe COPD: 18.3; SD, 4.1; p < 0.0001) compared with that of healthy control subjects. VEGF levels in induced sputum reciprocally decreased with severity of COPD (mild COPD: 1,360 pg/mL; SD, 800 pg/mL; p = 0.97; moderate COPD: 1,180 pg/mL; SD, 760 pg/mL; p = 0.50; severe COPD: 650 pg/mL; SD, 450 pg/mL; p = 0.007; very severe COPD: 480 pg/mL, SD, 240 pg/mL; p = 0.002). In addition, peroxynitrite inhibitory activity in COPD patients exhibited an accelerated decline from the mean VEGF level in healthy control subjects. Elevated oxidative stress levels and a reciprocal reduction of VEGF levels in induced sputum were prominent with increases in the severity of COPD. Thus, epithelial cell injury mediated by oxidative stress may induce the decrease in lung VEGF levels, resulting in the promotion of the development of COPD.

Serum levels of vascular endothelial growth factor in patients undergoing prostate biopsy for suspicion of prostate cancer

Objectives To analyze the correlation between serum levels of vascular endothelial growth factor (VEGF) and biopsy findings in patients with a suspicion of prostate cancer. Methods Serum levels of VEGF were measured on frozen, archival serum obtained before prostate biopsy in 47 patients with clinical and/or biologic suspicion of prostate cancer. VEGF-A levels were measured using an enzyme-linked immunosorbent assay. Results The prostate biopsies showed cancer in 27 patients (group 1) and benign tissue in the remaining 20 patients (group 2). No statistically significant difference was found between the two groups in age, digital rectal examination findings, total prostate-specific antigen (PSA) levels, free PSA levels, and complexed PSA levels. The mean prostate volume was significantly lower in group 1 (45.5 g versus 53.9 g; P = 0.04), and the mean percentage of free PSA (free PSA/total PSA) was significantly lower in group 1 (11.3% versus 19%; P = 0.0003). Serum VEGF-A levels were not significantly different between the two groups. The mean VEGF level was 90.6 pg/mL in group 1 and 107.9 pg/mL in group 2 ( P = 0.55). Multivariate analysis showed that VEGF-A levels were not predictive of prostate cancer. Conclusions Our findings suggest that serum VEGF-A is not helpful to predict prostate cancer in patients with clinical and/or biologic suspicion of prostate cancer.

Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder

Angiogenesis is essential for tumor growth and progression and is mediated by positive and negative regulators of vessel growth. Since angiogenic mediators found in patient serum have been postulated to reflect the angiogenic potential of a malignant tumor, we investigated the angiogenic activity in the serum of patients with transitional cell carcinoma (TCC). The data were correlated to tumor characteristics and the clinical course of the patients. Eighty-one patients with transitional cell carcinoma and 53 control persons were included in the study. Preoperative serum samples were collected and both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were quantified by ELISA. Additionally, the serum evoked proliferative activity on human umbilical vein endothelial cells (HUVEC) was evaluated. Data were compared to the clinical course of the patients. Serum of tumor patients significantly enhanced the proliferative capacity of HUVEC, compared to cells grown in standard culture medium (p = 0.0032), but not when compared to serum from control persons. Serum from patients with superficial TCC and well differentiated tumors induced a significantly higher angiogenic response (ANG(hi)) than serum from patients with poorly differentiated and invasive carcinomas (ANG(lo); p = 0.037). VEGF level of ANG(hi) serum was 384.22 +/- 247.76 pg/ml (n = 37) which significantly differed from mean VEGF level detected in ANG(lo) serum (247.72 +/- 211.93 pg/ml, n = 42; p = 0.019). Similarly, mean bFGF levels were 9.58 +/- 5.91 pg/ml in ANG(hi) serum versus 5.74 +/- 3.52 pg/ml) in ANG(lo) serum (p = 0.0043). A negative correlation was established between VEGF/bFGF serum concentration and patient prognosis. The experiments demonstrate a positive correlation between VEGF and bFGF serum level and endothelial proliferation in vitro. The inverse relationship between angiogenic activity and tumor stage might disclose information about angiogenesis and tumor progression in TCC.

Angiogenic cytokines in serum and cutaneous lesions of patients with polyarteritis nodosa

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are angiogenic cytokines, that have been reported to elevate serum levels in patients with collagen diseases such as systemic sclerosis and dermatomyositis as well as in those with inflammatory bowel diseases. In this study, the serum levels of bFGF and VEGF were measured by using enzyme-linked immunosorbent assay in 20 patients with polyarteritis nodosa (PAN; 5 with systemic PAN and 15 with cutaneous PAN) and in 20 control subjects. We also investigated the expression of bFGF and VEGF in cutaneous lesions of patients by using immunohistochemical methods. Basic FGF was undetectable in the serum of control subjects, but detectable levels were found in 4 of 5 patients with classical PAN and 3 of 15 patients with cutaneous PAN. The serum bFGF level in these patients with systemic PAN was significantly elevated in comparison with that in healthy control subjects. The VEGF level was 178 +/- 41 pg/mL in the serum of healthy individuals. The mean VEGF level in patients with systemic or cutaneous PAN was significantly higher than that in healthy controls. Serum bFGF and VEGF levels in patients with systemic PAN were significantly elevated in comparison with those having cutaneous PAN. Immunohistochemical studies showed elevated bFGF expression on damaged endothelial cells in necrotizing vasculitis lesions. Elevated expression of bFGF was also observed on fibroblasts around the vasculitis. Some of the infiltrating cells around vasculitis lesions expressed VEGF. The study was small. Serum bFGF and VEGF levels may be useful markers of the disease activities of PAN.

Significance of vascular endothelial growth factor and epidermal growth factor in development of papillary thyroid cancer

Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis and increases vascular permeability. Epidermal growth factor (EGF) induces proliferation of epidermal cells and stimulates epidermal migration. Increased VEGF and EGF expression have been associated with poor clinical outcome in many malignancies. Several recent reports have shown overexpression of VEGF and EGF in papillary thyroid cancer (PTC). The study aimed to determine the intensity of expression of VEGF and EGF in patients with PTC and to find any correlation between the intensity of the expression and staging of the disease at the moment of surgery The study comprised a group of 48 consecutive patients with PTC who underwent radical surgery. The group consisted of 11, 25, eight and four patients at pT1N0M0, pT2N0M0, pT3N1M0 and pT4N1M0 stages, respectively. The control group was composed of 20 healthy bone marrow transplant donors, age-, gender- and BMI-matched with PTC patients. The immuno-chemiluminescence enzyme linked immunoassay (ELISA) method was used to determine the expression and level of VEGF and EGF in serum samples. Patients' characteristics, serum levels of VEGF and EGF, final histology and pTNM were analysed. The mean serum level of VEGF and EGF was remarkably higher in PTC patients than in controls. A negative correlation between staging in pTNM classification and the mean serum VEGF level (r=-0.5168; P<0.05) as well as a positive correlation between staging in pTNM classification and the mean serum EGF level (r=0.6104; P<0.05) in PTC patients was observed. Both VEGF and EGF play an important role in PTC growth. However, the intensity of their expression is variable, depending on the stage of the disease. The highest intensity of VEGF expression is characteristic for low-stage T1N0M0 disease, whereas the highest intensity of EGF expression is more often found at locally advanced pT3 and pT4N1M0 stages of the disease. Further long-term follow-up studies are required to demonstrate the prognostic value of VEGF and EGF in PTC, particularly in identification of patients with expected poor prognosis or shorter recurrence-free survival.

The circulating levels of VEGF, MMP-2 and ET-1 and their relationship in preeclampsia

PREECLAMPSIA HYUN JOO SEOL, MIN JEONG OH, KYUNG JOO LEE, JEONG A KWON, JAE KWAN LEE, HAI JOONG KIM, Korea University Medical Center, Obstetrics and Gynecology, Seoul, South Korea, Pochon CHAUniversity Medical Center, Obstetrics and Gynecology, Seoul, South Korea, Korea University Medical Center, Laboratory Medicine, Seoul, South Korea OBJECTIVE: In myographic studies, an incubation of myometrial resistance vessels from normal pregnant women with vascular endothelial growth factor (VEGF) resulted in a reduction of endothelium-dependent relaxation. VEGF has been known to upregulate endothelin-converting enzyme-1 (ECE-1), a key enzyme for endothelin-1(ET-1)[1-21] processing. However, matrix metalloproteinase-2 (MMP-2) can also cleave big endothelin-1 and yield more potent ET-1[1-32]. The aim of this study was to investigate the circulating levels of VEGF, MMP-2 and ET-1 and their relationship in preeclampsia. STUDY DESIGN: Blood samples were obtained from 40 pregnant women with (n = 20) and without (n = 20) preeclampsia before labor. The serum concentrations of VEGF, MMP-2 and plasma ET-1 were measured by ELISA. The results were analyzed using Mann-Whitney U test and linear regression analysis. RESULTS: The median values of maternal age, parity, gestational age at the time of blood sampling were similar in both groups. Systolic and diastolic pressures were significantly higher in the preeclampsia group than in the control group and birth weight of newborns was higher in the control group than the preeclampsia group (3.09G 0.72 vs 2.27G 0.75 kg, P! .0001) Compared to the control group, the preeclampsia group had higher levels of VEGF, MMP-2, ET-1 (mean VEGF level, 2.39 G 0.75 vs 0.28 G 0.14ng/ml, P ! .001; mean MMP-2 level, 31.99 G 6.05 vs 11.8 G 11.75ng/ml, P ! .001; mean ET-1 level, 43.54 G 13.92 vs 14.83 G 5.77 pg/ml, P ! .0001). In addition, there were significant positive correlations among them. (VEGF and MMP-2, r = 0.91, P ! .0001; MMP-2 and ET-1, r = 0.780, P ! .0001; VEGF and ET-1, r = 0.671, P ! .0001). CONCLUSION: The circulating VEGF, MMP-2, ET-1 levels are elevated in preeclampsia patients and there were significant positive correlations among them. These findings suggest that VEGF-induced, endothelium-dependent inhibition of vasorelaxation might be mediated by increased ET-1 via MMP-2 S34 SMFM Abstracts

Vascular endothelial and basic fibroblast growth factor serum levels in patients with Behçet's disease.

Behçet's disease (BD) is a systemic vasculitis of unknown aetiology. Its pathogenesis is related to endothelial cell dysfunction, humoral immune defects, and immune system dysregulation. The aim of this study was to investigate the possible role of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of BD. We also investigated whether disease activity, age, or duration of BD correlates with VEGF and bFGF. We studied 33 patients and 20 healthy controls. Vascular endothelial growth factor and bFGF serum levels were measured by enzyme-linked immunosorbent assay. We measured acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean serum VEGF level was significantly higher in patients with BD (398.8+/-222.2 pg/ml) than the control group (193.0+/-122.4 pg/ml) (P=0.002). The levels were similar in both active and inactive BD (P=0.675) but did not correlate with disease duration, CRP, ESR, or age (P>0.05 for each). The bFGF was below detection limits in 18 of 33 patients with BD and ten of 20 controls, and its mean serum level was higher in BD patients (42.4+/-76.9 pg/ml) than controls (29.0+/-9.1 pg/ml), but this difference was not statistically significant (P=0.232). The bFGF levels were similar in both active and inactive BD (P=0.09) and, in patients, correlated with disease duration and CRP (r=0.58, P=0.02; r=-0.57, P=0.02, respectively) but not with ESR or age (P>0.05 for each). Vascular endothelial growth factor may be more important in the pathogenesis of BD than bFGF. Neither growth factor is an activity criterion or inflammatory marker in BD.

Vascular Endothelial Growth Factor Levels in Active Pulmonary Tuberculosis

Vascular endothelial growth factor (VEGF) is a mediator with potent angiogenic, mitogenic, and vascular permeability-enhancing activities that are specific for endothelial cells. Intense angiogenesis has been found in active pulmonary tuberculosis lesions. To determine whether active pulmonary tuberculosis is associated with increased serum levels of VEGF compared with inactive tuberculosis and VEGF levels in healthy subjects, and to assess the changes in serum VEGF levels before and after therapy. Prospective clinical study. Chest clinic of a university hospital, Eskisehir, Turkey. Serum VEGF levels of 44 patients with active pulmonary tuberculosis, 24 patients with inactive pulmonary tuberculosis, and 20 healthy subjects were determined. VEGF levels were increased in active pulmonary tuberculosis patients (mean [+/- SD] VEGF level, 598.03 +/- 298.25 pg/mL) compared to both inactive pulmonary tuberculosis patients (mean VEGF level, 296.98 +/- 115.31 pg/mL) and control subjects (mean VEGF level, 339.67 +/- 74.65 pg/mL). The increase in VEGF level observed in patients with active tuberculosis was statistically significant when compared with levels in two other groups (p < 0.001 for both). Serum VEGF levels were statistically different before treatment and after treatment in 10 patients who were observed from diagnosis to the end of treatment (p < 0.01). Increased serum VEGF levels may be an indicator of active pulmonary tuberculosis, since levels were higher in patients with active pulmonary tuberculosis and were lower after successful treatment. The role of VEGF-mediated angiogenesis in the pathogenesis and progression of pulmonary tuberculosis lesions should be further elucidated.

Circulating levels of vascular endothelial growth factor in patients with oral squamous cell carcinoma

Abstract. Angiogenesis is a crucial step in tumour growth, progression, and metastasis. Recently, many angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is thought to be one such angiogenic factor and is also thought to be a selective mitogen for vascular endothelial cells. The present study was designed to determine the circulating levels of VEGF in human oral squamous cell carcinoma (OSCC) and to investigate its correlation with the clinicopathologic features and prognosis. The study consisted of 10 healthy volunteers and 31 patients with OSCC. A quantitative sandwich enzyme immunoassay technique was used to measure the concentrations of VEGF in the sera. The data obtained from the experiment were analysed with independent-samples t-test. The mean concentrations of serum VEGF were 148.80±64.17 pg · ml −1 (range, 59–231 pg · ml −1) in normal controls and 567.97±338.17 pg · ml −1 (range, 136–1892 pg · ml −1) in OSCC group. Statistical analysis showed that the mean VEGF level in sera of OSCC patients was significantly higher than that in healthy controls ( P< 0.001). The serum VEGF levels of OSCC patients correlated with condition of nudal metastasis ( P< 0.05) and clinical stage ( P< 0.05) but not with sex ( P> 0.05) and degree of differentiation ( P> 0.05). Our study showed that OSCC was associated with significantly elevated serum VEGF concentration. Higher level of serum VEGF also correlated with lymph node metastasis and clinical stage of OSCC. Determination of serum VEGF concentration may be helpful to distinguish OSCC patients from the normal individuals.

Serum endostatin correlates with progression and prognosis of non-small cell lung cancer

The relationship between non-small cell lung cancer and platelet counts, serum levels of vascular endothelial growth factor (VEGF) and endostatin, is unclear. Platelet counts and serum VEGF and endostatin levels were measured preoperatively in 99 patients with non-small cell lung cancer, and the relationship between these factors and clinicopathological features, including prognosis, was examined. Mean serum VEGF level was slightly higher in patients than in healthy subjects ( P=0.23). Mean serum endostatin level was 42.4±40.4 ng/ml in patients compared to 16.3±10.3 ng/ml in healthy subjects ( P=0.0003). Serum endostatin levels were significantly higher in patients with involvement greater than T2 or stage IB, compared to other patients. Platelet count and serum endostatin level greater than the median were associated with poor prognosis. Our results suggested that platelet count and serum endostatin level may be useful markers for non-small cell lung cancer.