Angiogenesis Signaling in Retinoblastoma: Prognostic and Therapeutic Applications.

To the editor, We read with great interest the study by She-Juan An et al., which showed that posttreatment plasma VEGF levels associated with the overall survival of patients with advanced non-small-cell lung cancer treated with bevacizumab plus chemotherapy. In this study, before and 6 weeks after treatment, vascular endothelial growth factor (VEGF) levels measured. Also, this study showed that low posttreatment VEGF levels associated with better overall survival (OS) [1]. We have some insights for this decrease in serum VEGF levels. VEGF circulating in the blood of patients with cancer may be derived from various sources, as depicted in Fig. 1. Circulating levels of VEGF are dependent on the amount released from tumor cells (Fig. 1A) and/or platelets activated at the tumor-vessel endothelium. Activated platelets release VEGF (Fig. 1B), and platelet consumption causes increased levels of thrombopoietin, which in turn stimulates megakaryopoiesis and platelet production in the bone marrow. Newly produced platelets are larger in size than those produced during steady-state thrombopoiesis, and therefore contain an elevated amount of VEGF (Fig. 1C). Finally, host immune cells as macrophages that infiltrate tumor tissues can be an additional source of VEGF (Fig. 1 D) [2]. Serum VEGF levels have also been found to correlate with platelet count in a mixed population of metastatic cancers and renal cancer, and some investigators have also stated that VEGF should be corrected for platelet counts. To correct for variation in platelet counts between patients, it has been proposed that the concentration of VEGF per platelet (pg/10) can be calculated by dividing the serum VEGF concentration (pg/ml) by the platelet count (910/ml) [3]. In the study, She-Juan An et al., mean VEGF levels decreased from 81.5 pg/ml to 50.5 pg/ml after 6 weeks of treatment (P = 0.08), with a mean reduction of 31 pg/ml in overall. The relationship of the plasma VEGF levels with OS and progression-free survival (PFS), the patients were divided in the two groups based on their median VEGF value. The OS differed significantly between the low and high posttreatment VEGF levels (25.6 months vs. 13.4 months, P = 0.0284). No other relationship was found with plasma VEGF levels. It is known that most cytotoxic chemotherapeutics decrease the platelet count. In this study, thrombocytopenia was developed in 27.3% patients treated with bevacizumab plus chemotherapy. The association between VEGF levels and thrombocytopenia was not reported. Also, it is possible that platelet counts decreased with chemotherapy, but remained within normal limits. Because platelet counts before and after therapy has not been reported, the possible contribution of platelets on the decreasing VEGF levels remains obscure. We believe that the decrease in serum VEGF levels may at least in part be due to decreased platelet counts secondary to chemotherapy, and plasma VEGF levels may not accurately reflect the truth all the time before correcting the VEGF levels for platelet counts. M. A. N. Şendur S. Aksoy (&) Ş. Yaman Z. Arik N. Y. Ozdemir N. Zengin Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey e-mail: saksoy07@yahoo.com

Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis. Physical exercise improves learning and memory abilities by increasing the levels of several growth factors in the hippocampus. One growth factor, vascular endothelial growth factor (VEGF), is primarily produced in the muscles and not only increases in the periphery during exercise but can also cross the blood-brain barrier. The aim of this study is to investigate the effects of regular aerobic chronic exercise on different types of muscle fibers and the relationships between learning/memory and muscle induced-VEGF. Following a one-week adaptation period, male rats underwent treadmill training at a speed of 8 m/min for 30 min daily, 3 days a week for 6 weeks. Memory functions were evaluated using the Morris water maze. VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were measured in type 1 and type 2 muscle fibers and VEGF levels were also measured in the hippocampus. Exercise positively affected both learning and memory and also increased VEGF levels in both muscle fiber types. Muscle VEGF levels positively correlate with hippocampal learning and hippocampal VEGF levels. Exercise reduced both SOD and MDA levels in type 1 and type 2 muscle fibers, whereas GPx levels decreased only in type 2 muscle fibers. Our findings suggest that regular aerobic exercise elevates VEGF levels and diminishes oxidative stress in both fiber types. Exercise-induced VEGF levels in both type 1 and 2 muscle fibers appear to be associated with the positive effect of exercise on learning and memory function and is accompanied by an increase in VEGF levels in the hippocampus. Further research is needed to elucidate the exact mechanism by which fiber type-specific VEGF mediates hippocampal neurogenesis and angiogenesis.

5554 Background: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are commonly over- expressed in OC and may correlate with poor prognosis. EGFR mutations, although rare, have recently been reported in ovarian cancer. We examined these factors for prognostic value in the setting of treatment with BE. Results of a phase II trial of BE in recurrent OC pts have previously been reported; there were 1 CR and 1 PR among 13 patients. The trial was closed to accrual due to 2 bowel perforations. Methods: Pretreatment plasma VEGF, urine VEGF, and serum VEGFR2 levels are available on 9, 8, and 8 pts to date. VEGF levels were determined using an ELISA (R& D Systems, Minneapolis, MN). Tumor from 8 pts: 1(CR), 1 (PR), 5 (SD), 1 (PD) was available for immunohistochemical analysis for EGFR. Genomic DNA was successfully isolated from 6 paraffin embedded tumor specimens. EGFR exons 18 to 21 were amplified by PCR using primary and secondary PCR primer pairs. PCR products were purified and submitted for DNA sequencing against forward and reverse primers (analyzed with Sequencher). Results: Mean baseline plasma VEGF level was 107.6 pg/ml (range, 52–198 pg/ml). For analysis, we combined CR+PR+SD versus PD. Wilcoxon rank-sum test was used to compare baseline plasma VEGF levels, urine VEGF and serum VEGFR2 between the two response groups. There were no significant differences between response and baseline VEGF levels (p=0.39), urine VEGF (p=0.56), and VEGFR2 (p=0.56) respectively. The pt with prolonged CR (18 mos) had the highest baseline VEGF level. Cox proportional hazards regression models was used to look at the association between overall survival (OS) and VEGF levels. There was no significant relationship between (OS) and baseline plasma VEGF (p= 0.38), urine VEGF (p=0.33) or serum VEGFR2 (p=0.63) respectively. No EGFR mutations were found in exon 19 (n=4) or exon 21 (n=6). EGFR expression is being evaluated. Conclusions: Our results indicate that there were no significant relationship between response or OS and baseline VEGF or VEGFR2 levels in our treated pts. The study was supported by NCI Grant N01-CM-17102. [Table: see text]

Objective To determine the intraocular levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in patients with neovascular glaucoma (NVG) and to evaluate the relationship between probable clinical diathesis and associated levels. Methods Experimental study. Fifty-four NVG eyes of 54 patients and 10 fresh healthy donor eyes for corneal transplantation as controls were selected. The levels of VEGF and PDGF in aqueous humor and vitreous liquid aspirates from them were measured. Of the 54 eyes, 17 had central retinal vein occlusion (CRVO), 22 had diabetic retinopathy (DR), 4 had retinal vasculitis (Eales disease),4 had retinal detachments (RD) and 7 had unidentified NVG (NA). Among them, the number of NVG cases with iris neovascularization grades Ⅰ , Ⅱ, Ⅲ and Ⅳ were 17, 12, 13 and 12, respectively,and 36 eyes were treated with prophylactic retinal photocoagulation and/or cryotherapy. The levels of VEGF and PDGF were measured using an enzyme-linked immunosorbent assay (ELISA) method. The differences in VEGF and PDGF levels between the NVG and control groups were analyzed with a Mann-Whitney U test. The differences in the various primary causes, in the iris neovascularization grades and between the prophylactic-treated and untreated groups were analyzed with ANOVA, LSD-t and independent samples t test, respectively. The correlation analysis between VEGF and PDGF levels in each group were checked with a Pearson test. Results The free VEGF and PDGF concentrations in aqueous humor from NVG patients were (926.3±223.5)ng/L and (226.2±81.5)ng/L and the concentrations in vitreous liquid were (1096.1±235.9)ng/L and (375.3±141.5)ng/L, which were higher than concentrations in normal control eyes (aqueous humor: ZVEGF=-4.993, ZPDGF=-4.891, vitreous liquid: ZVEGF=-4.991, ZPDGF=-4.992, all P=0.000). The free VEGF concentrations in aqueous humor and vitreous liquid from NVG secondary to CRVO were higher than those in the NA group (aqueous humor: t=1.746, P=0.033; vitreous liquid: t=1.917, P=0.027). There were no differences in VEGF between CRVO, DR, Eales, and RD eyes. The PDGF concentrations in aqueous humor and vitreous liquid from NVG with diabetic retinopathy (DR) were higher than the concentrations in NVG secondary to Eales disease (aqueous humor: t=1.697, P=0.043; vitreous liquid: t=1.762, P=0.038).There were no statistical differences between VEGF in aqueous humor and vitreous liquid among the various iris neovascularization grades. The vitreal PDGF level in iris neovascularization grade Ⅳ was higher than that in grade Ⅲ (t=1.740, P=0.049). The VEGF and PDGF concentrations in aqueous humor and vitreous liquid in NVG with previous retinal photocoagulation and/or cryotherapy were lower than those in non-intervention NVG (aqueous humor: ZVEGF=2.945, PVEGF=0.003; tPDGF=3.199,PPDGF=0.002; vitreous liquid:ZVEGF=3.165, PVEGF=0.002; tPDGF=2.984, PPDGF=0.004). Correlation analysis showed that there was a positive correlation between the VEGF and PDGF levels in aqueous humor (r=0.305, P=0.025) and vitreous liquid (r=0.303, P=0.026). In NVG secondary to CRVO, the VEGF level in vitreous liquid was positively correlated with PDGF (r=0.503, P=0.040), while the VEGF level in aqueous humor from NVG with DR was positively correlated with PDGF (r=0.462, P=0.030).Conclusion VEGF and PDGF levels are related to primary causes of NVG and iris neovascularization grading, and their release may be inhibited after retinal photocoagulation and/or cryotherapy in NVG eyes. Key words: Glaucoma,neovascular; Vascular endothelial growth factors; Platelet-derived growth factor; Neovascularization; Laser therapy

13030 Background: In non-small cell lung cancer (NSCLC), sensitivity to gefitinib is associated with activating mutations of the epidermal growth factor receptor (EGFR). Tumor samples obtained for diagnosis of NSCLC are limited and often unsuitable for analysis of mutations. Other biomarkers are thus needed. We previously reported that serum vascular endothelial growth factor (VEGF) levels were significantly lower in responders to gefitinib than non-responders. To assess levels of circulating VEGF as a predictive and prognostic marker of gefitinib treatment in NSCLC patients, we examined the associations between plasma VEGF levels before gefitinib treatment and clinical outcome. Methods: Eighty four NSCLC patients treated with gefitinib were enrolled into this investigation. Plasma VEGF levels were measured in blood samples before gefitinib administration. Patients were grouped according to VEGF level around a cut-off of 80.7 pg/ml, based on results from normal controls. Response to gefitinib was judged using RECIST guidelines. Time to progression (TTP) and overall survival (OS) following gefitinib treatment were calculated using Kaplan-Meier methods. Groups were compared using log-rank test. We evaluated the immunohistochemical expression of VEGF and EGFR mutations in tumor samples from 37 patients. Results: Response rate was significantly higher with low VEGF level than with high VEGF level (p = 0.0010). Multivariate analysis for response to gefitinib including sex, histology, smoking status, performance status and plasma VEGF level identified only low VEGF level as predictive of response to gefitinib. Low VEGF level was also correlated with prolonged median TTP (4.1 months vs. 1.1 months, p = 0.0081) and OS (11.1 months vs. 5.4 months, p = 0.0290). Multivariate analysis for survival revealed low VEGF level as associated with prolonged TTP (p = 0.0081) and OS (p = 0.0708). Plasma VEGF level was not associated with either VEGF expression or EGFR mutations of tumor tissue. Conclusions: Our results suggest that plasma VEGF levels before gefitinib treatment are predictive of response to gefitinib and prognostic of patients who receive gefitinib. [Table: see text]

Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia-induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9), angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor-β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker. Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006-2008. Vitreous samples were collected before the start of the conventional 3-ppp vitrectomy. Vitreous MMP-2 and MMP-9, Ang-1 and Ang-2, VEGF, EPO and TGFβ1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls. Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP-2 (p = 0.0015), totalMMP-2 (p = 0.0011), proMMP-9 (p = 0.00001), totalMMP-9 (p < 0.00001), Ang-2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFβ1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang-2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9). The main new finding is that the intravitreal concentrations of Ang-2 correlated significantly with MMP-9, VEGF, EPO and TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically.

Vascular endothelial growth factor and nitric oxide are both related to tumor progression. This study was designed to measure preoperative plasma vascular endothelial growth factor and nitrite levels in patients with colorectal cancer to evaluate their clinical applications as tumor markers. In total, 279 patients with primary colorectal cancer and 20 patients with hemorrhoids (as a control) were included in this study. Plasma vascular endothelial growth factor was measured by quantitative, solid-phase, enzyme-linked immunosorbent assay (R&D Systems), whereas nitrite was measured by a high-performance liquid chromatographic method. The vascular endothelial growth factor (mean, 220.6 pg/ml, P < 0.005) and nitrite (mean, 29.4 microM, P = 0.043) levels of patients with cancer were significantly higher than those of controls (mean vascular endothelial growth factor, 67 pg/ml; mean nitrite, 23 microM). Preoperative plasma vascular endothelial growth factor levels were positively correlated with tumor stage, T class, M class, and tumor size (Spearman correlation, P < 0.01), but were not associated with gender, N class, tumor location, histology type, or grade. There were no statistical differences in nitrite levels among different groups of patients with cancer. Higher vascular endothelial growth factor levels also were correlated with leukocytosis, elevated carcinoembryonic antigen, and a higher platelet count. The positive rates of vascular endothelial growth factor elevation (>148.6 pg/ml) compared with carcinoembryonic antigen elevation were 36.9 to 14.6 percent in Stage I, 60.9 to 33 percent in Stage II, 62.9 to 48.7 percent in Stage III, and 86 to 70.2 percent in Stage IV, respectively. The overall positive rate of vascular endothelial growth factor elevation also was higher than that of carcinoembryonic antigen elevation (63 percent for vascular endothelial growth factor vs. 42.5 percent for carcinoembryonic antigen, P = 0.016). More than one-half of the patients without carcinoembryonic antigen elevation still had elevated vascular endothelial growth factor levels. The combined assessment using vascular endothelial growth factor and carcinoembryonic antigen was superior to individual assessment using vascular endothelial growth factor or carcinoembryonic antigen. In node-negative tumor, the patients with vascular endothelial growth factor elevation had worse disease-free survival than those without vascular endothelial growth factor elevation (P = 0.0367). There was no association of vascular endothelial growth factor elevation with survival in patients with node-positive tumor. Plasma vascular endothelial growth factor is a useful complementary tumor marker; however, synchronous measurement of white blood cells, platelets, and carcinoembryonic antigen is suggested in the clinical application of vascular endothelial growth factor to colorectal cancer.

Background Bronchial asthma is an inflammatory disease of the airways that is associated with airway remodeling. The vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9 (MMP-9) is a major proteolytic enzyme that induces bronchial remodeling in asthma. However, there is no data available on the possible role of the VEGF or on the potential relationship between the VEGF and MMP-9 in acute asthma. Therefore, the VEGF was studied to determine whether or not it participates in airway inflammation during acute asthma. An additional aim of this study was to determine whether or not the VEGF levels correlated with the MMP-9 levels in the sputum of acute asthma patients. Methods Both the VEGF and MMP-9 levels were measured by an enzyme immunoassay and zymographic analysis in the sputum of patients with either stable asthma or with acute asthma. The VEGF and MMP-9 levels were also evaluated during a spontaneous asthma attack. Results The VEGF levels were significantly higher in the sputum of acute asthmatic patients than in either the stable patients the control subjects. The VEGF levels in the sputum during asthma exacerbation were significantly higher than those on the remission days, and those levels decreased after decreased after asthma therapy. In acute asthmatic patients, the VEGF levels in the sputum correlated with the number of neutrophils and eosinophils. In addition, a significant correlation was established between the VEGF and MMP-9 levels in the sputum. Conclusion These results suggest that VEGF overproduction is associated with airway inflammation during acute asthma and is related to the MMP-9 function.

We explored the effect of astaxanthin on vascular endothelial growth factor in the aqueous humor, by measuring vascular endothelial growth factor levels and oxidation-related parameters, including O2•− scavenging activity, H2O2 level, and total hydroperoxide level in the aqueous humor, obtained from 35 patients before and after astaxanthin administration. We evaluated the relationship between vascular endothelial growth factor and the oxidation-related parameters as well as the patient’s diabetic status, age, and sex. Vascular endothelial growth factor levels did not change significantly but O2•− scavenging activity and total hydroperoxide level significantly (p<0.05) increased and decreased, respectively. Both pre- and post- astaxanthin intake, vascular endothelial growth factor and total hydroperoxide levels were positively correlated (Pearson: r = 0.42, p<0.05; r = 0.55, p<0.01, respectively). Analysis of vascular endothelial growth factor levels and O2•− scavenging activities gave a negative correlation but only pre-astaxanthin intake (r = −0.37, p<0.05). Differences in levels pre- and post-astaxanthin only showed association between vascular endothelial growth factor and total hydroperoxide (r = 0.49, p<0.01) analyzed by multiple linear regression. Using multivariate analysis, pre-astaxanthin vascular endothelial growth factor level was associated with two factors of total hydroperoxide and O2•− scavenging activity (r = 0.49, p<0.05), and post-astaxanthin vascular endothelial growth factor level with two factors of total hydroperoxide and sex (r = 0.60, p<0.01). Astaxanthin intake may have affected vascular endothelial growth factor level through its antioxidant effects by increasing O2•− scavenging activity and suppressing peroxide production.

Objective : to investigate the levels and clinical associations of vascular endothelial growth factor (VEGF) and its type 2 receptor (VEGFR-2) in patients with systemic sclerosis (SSc). Subjects and methods . The investigation enrolled 46 patients aged 19–77 years with SSc lasting 0.5–24 years. This group included 23 patients with limited cutaneous SSc (lSSc) and 23 with diffuse cutaneous SSc (dSSc). Forced vital capacity (FVC), lung diffusing capacity (LDC), and pulmonary arterial systolic pressure (PASP) were investigated in all the patients. An enzyme immunoassay was used to estimate serum VEGF and VEGFR-2 levels in the patients and 20 healthy individuals who constituted a control group. Results and discussion . The levels of VEGF in the healthy individuals and SSc patients ranged from 0.20 to 264.00 and from 0.02 to 1034.20 pg/ml, respectively. The mean VEGF level in the study group was more than twice that in the control group: 212.35±253.93 and 97.74±71.46 pg/ml, respectively (p=0.032). In dSSc and lSSc, the levels of VEGF were in the range of 0.02–599.80 and 0.02–1034.20 pg/ml, respectively. The VEGF level in lSSc was significantly higher than that in dSSc and averaged 267.11±268.74 and 120.40±141.09 pg/ml, respectively (p=0.012). Nineteen (41%) patients were found to have digital ulcers during examination or in the medical history. The VEGF level in the presence of the ulcers was higher than that in their absence, but this difference was statistically insignificant. PASP was greater than the upper normal limit (30 mm Hg) in 19 (43%) patients. The level of VEGF in PASP <30 and ≥31 mm Hg was in the range of 0.02–363.60 and 0.20–1034.20 pg/ml, respectively. That in elevated PASP was significantly higher than that in normal PASP (p=0.0042). The mean VEGF level in patients with LDC <50% was substantially higher than in those with LDC ≥50% (364.20±381.95 and 128.55±142.70 pg/ml, respectively; p=0.034). FVC <80% of the due value was observed in 11 (26%) of 43 patients. The level of VEGF in these patients was higher than in those with normal FVC, but this difference is statistically insignificant. In SSc patients, the level VEGFR-2 was in the range of 915.7–23 290.0 pg/ml (mean value, 5784.6±4773.8 pg/ml) and much higher than that in the control group (1552.6±272.8 pg/ml) (p<0.0001). There were no differences in the level of VEGFR-2 in the presence and absence of digital ulcers, with normal and elevated PASP, with LDC <50 or ≥50%, and with normal and reduced FVC.Correlation analysis revealed a close direct association between the level of VEGF and PASP (r=0.40; p=0.007). There was also a tendency towards an inverse correlation of LDC with VEGF levels, which was not, however, statistically significant (r=-0.28; p=0.070). Conclusion . The patients with SSc have been found to have higher VEGF and VEGFR-2 levels. Their close association with the clinical manifestations of SSc indicates that the VEGF/VEGFR-2 axis plays a role in the pathogenesis of the disease.

Objective To investigate the correlation of serum interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and lactate dehydrogenase (LDH) levels with the prognosis of gastric cancer patients. Methods From December 2018 to December 2020, 45 patients with gastric cancer treated in our hospital and 50 healthy individuals were assessed for eligibility and recruited. The eligible patients were assigned to an observation group, and the healthy subjects were assigned to a control group. Serum IL-17, LDH, and VEGF levels of the eligible participants were determined by the enzyme-linked immunosorbent assay (ELISA) and biochemical testing. The association of serum IL-7, LDH, and VEGF levels with their pathological characteristics was examined in the observation group. The correlation between serum IL-17 and VEGF was analyzed using the Pearson method, and regression models were established using COX proportional risk to explore the independent risk factors for gastric cancer. Results Gastric cancer was associated with higher levels of IL-17, LDH, and VEGF versus a healthy status (P < 0.05). There was no significant difference in serum IL-17, LDH, and VEGF levels between the two groups of patients with different clinical characteristics (P > 0.05). Higher tumor TNM stages resulted in significantly higher levels of IL-17, LDH, and VEGF (P < 0.05). Serum IL-17 level was positively correlated with VEGF level (P < 0.05). Cox regression multifactorial analysis showed that serum IL-17, LDH, VEGF, and tumor TNM stages could be independent high-risk influencing factors for gastric cancer (P < 0.05). Serum IL-17 was positively correlated with VEGF levels in patients with gastric cancer. Conclusion Serum IL-17, LDH, and VEGF levels in gastric cancer patients are closely correlated with the TNM stage and patients' prognosis, both of which show great potential as effective indicators for evaluating the prognosis of gastric cancer.

Objective To investigate the impact of plasma homocysteine （ Hcy） on type 2 diabetics （ T2DM） patients with diabetic nephropathy （ DN） and diabetic retinopathy （ DR） , and to explore the correlation among the levels of plasma Hcy , vascular endothelial growth factor （VEGF）, homeostasis model assessment of insulin resistance （HOMA-IR）, and insulin resistance （ISI）. Methods A total of 241 cases of diabetes was recruited as subjects according to the 2010 China guideline for type 2 diabetes.The history of smoking, hypertension, duration of diabetes, height, and weight were measured.Fasting blood were collected to analyze the levels of fasting insulin （FINS）, fasting plasma glucose （FPG）, glycated hemoglobin a1c （HbA1c）, plasma Hcy （Rate method）, and VEGF [enzyme-linked immunosorbent assay, ELISA）].Results The age, body mass index （BMI）, the history of hyperten-sion, duration of diabetes, HbA1c, homeostasis model assessment of insulin resistance （HOMA-IR）, microalbuminuria （MAU）, and VEGF were positively correlated with the levels of plasma Hcy or VEGF .The levels of ISI were reduced with the increased levels of Hcy or VEGF.The history of smoking was positively correlated with the VEGF .Spearman correlation analysis demonstrated that the levels of plasma Hcy were positively correlated with the levels of VEGF （ r =0.498 , P <0.01 ） .In the groups of diabetic retinopathy and early diabetic nephropathy , it could find that increased duration of diabetes , increased IR, higher levels of HbA1c and VEGF, and the levels of plasma Hcy≥10μmol/L might be the risk factors of DR （ P <0.05 ） .Only the history of hypertension and high levels of VEGF and Hcy in early DN showed a strong correlation （ P <0.05 ） .Conclusions Spearman correlation analysis demonstrated that the levels of plasma Hcy were positively correlated with the levels of VEGF .Higher levels of Hcy and VEGF might be the risk factors of the early DN and DR.At the same time, lower level of ISI might be the risk factor of DR , but the reduction of ISI might not be the main risk factor of the early DN . Key words: Hyperhomocysteinemia; Diabetic retinopathy; Diabetic nephropathies; Insulin resistance; Endothelial growth fac-tors/biosynthesis

Objective To investigate the relationship between vascular endothelial growth factor (VEGF) levels and eosinophilic inflammatory profiles,and the degree of airway vascular permeability in the asthmatic rats. We evaluated the effect of inhaled dexamethasone on VEGF levels in BALF. Methods Eighteen SD rats were randomly divided into three groups: the control group, the asthma model group and the dexamethasone group. Asthmatic model was established by sensitization and challenge with ovalbumin and rats were inhaled dexamethasone before challenge in dethamethasone group. The VEGF levels, the percentage of eosinophils,the airway vascular permeability index in BALF and the PC50 were examined.Results The VEGF levels,the percentage of eosinophils,the PC50 and the airway vascular permeability index in asthma model group were higher than that in control group( P <0.05 orP <0.01). After 6-week inhaled dexamethasone therapy,the VEGF levels, the percentage of eosinophils, the PC50 and the airway vascular permeability index in dexamethasone group were decreased compared to asthma model group( P<0.05 or P<0.01). The VEGF levels were negatively correlated with PC50, the percentage of eosinophils, the airway vascular permeability index( r = - 0. 68,0. 76,0. 84, P <0. 01). Conclusions The VEGF levels in BALF were increased in asthmatic rats and its levels were associated with airway percentage of EOS,airway responsiveness and airway vascular permeability. These findings provide strong evidence that VEGF may play an important role in pathogenesis of asthma. Key words: Bronchial asthma; Vascular endothelial growth factor

Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy

Objective To investigate the changes and clinical value of serum vascular endothelial growth factor (VEGF) level before,during and after radiotherapy in patients with esophageal carcinoma.Methods The sera of 67 esophageal carcinoma patients and 30 healthy control cases were collected.The VEGF level in serum samples were measured with enzyme-linked immunosorbent assay (ELISA) method.The relations among VEGF level changes,clinical stages and radiotherapy effect were analyzed.Results The VEGF levels of patients with esophagus cancer before,during and after radiotherapy were significantly higher than those in control group ( F =11.65,P ＜ 0.01 ).The VEGF level after radiotherapy was significant lower than that before radiotherapy ( F =10.72,P ＜ 0.01 ).The average VEGF level of patients with T3 and T4 was significantly higher than that of control group ( F =14.10,P ＜ 0.01 ).The average VEGF level of patients with N1 and N2 was significantly higher than that of control group( F =8.64,P ＜0.01).In 62 patients,the serum VEGF level increased in 21 cases but decreased in 41 cases after radiotherapy.With difference in radiotherapy efficiency of 61.90％ and 90.24％,respectively(x2 =6.08,P＜ 0.05).The average VEGF level during and after radiotherapy for 50 cases of CR + PR were significantly lower than that before radiotherapy( F =7.98,P ＜ 0.01 ).Conclusions Monitoring the serum VEGF level of patients with esophagus cancer can help evaluate the radiosensitivity,which has a significance in predicting the prognosis of radiotherapy. Key words: Esophageal carcinoma; Radiotherapy ; Vascular endothelial growth factor