Guava leaf extract and polyvinylpyrrolidone hydrogel for rabbit oral wounds.

Background: The progress in cancer treatment, including bone malignancies, is associated with advances in molecular biology. Based on the results of a number of studies, treatment of bone sarcomas have been expanded with targeted therapy that uses drugs with targeted actions, including anti-angiogenic and bevacizumab, in particular. It inhibits the binding of a key activator of neoangiogenesis, vascular endothelial growth factor (VEGF), with its receptors type 1 and 2 (Flt-1 and KDR) on the surface of endothelial cells, which results in a decrease in vascularization and in inhibition of tumor growth. Beyond VEGF, other activators of neoangiogenesis have been identified, such as interleukin 16 (IL-16). Aim: To compare baseline serum IL-16 and VEGF in patients with malignant, borderline and benign bone tumors. Materials and methods: Serum IL-16 and VEGF levels was compared in 138 patients with primary bone tumors: benign (n=10); borderline (giant cell bone, n=22); malignant (n=106), aged 14 to 50 years, by immunoenzyme assay (Biosource, USA for IL-16 and R&D, USA for VEGF) before any specific treatment. Bone malignancies were identified as osteosarcoma (n=45, among them 35 typical, 6 parosteal, and 4 periosteal), chondrosarcoma (n=24), Ewing sarcoma (n=27), and undifferentiated pleomorphic sarcoma (n=7) and chordoma (n=3). Results: The rate of IL-16 identification in the serum of bone tumors patients was 93%, with no significant differences depending on the histological structure of the tumor. No association between the size of primary tumors and IL-16 serum levels was found. Overall 3 and 5-year survival of patients with malignant bone tumors with IL-16 serum levels>33 pg/mL was significantly lower than in those IL-16 levels of≤33 pg/mL. Overall 5-year survival in osteosarcoma patients with higher IL-16 serum levels 1.6-fold lower, in Ewing sarcoma patients, 1.7-fold lower, and in chondrosarcoma patients, 1.8-fold lower than that the patients with IL-16 levels of≤33 pg/mL. VEGF levels in bone sarcomas patients were significantly higher than in those with borderline and benign tumors, whereas statistical analysis did not find any significant difference in VEGF levels depending on the histological structure of the primary tumor. Maximal VEGF levels were found in periosteal osteosarcoma, minimal ones, in parosteal osteosarcoma. Overall 3 and 5-year survival of patients with bone malignancies and serum VEGF concentrations above the mean for the group (> 493 pg/mL) was higher than that in the patients with low VEGF levels. Similar results were obtained in osteosarcoma, whereas in Ewing sarcoma and chondrosarcoma higher 3 and 5-year survival rates were observed in patients with serum VEGF levels below 493 pg/mL. Conclusion: These data suggest that IL-16 and VEGF expression could be associated with pathophysiological changes related to growth and metastatic process of bone sarcomas, and may be a subject for further studies to determine the levels of these biomarkers and their predictive value in bone malignancies.

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.

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

Full-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factors

Platelet Rich Fibrin (PRF) is a platelet that contains growth factor, such Vascular Endothelial Growth Factor (VEGF) that not only have implication in inflammation, stimulate tissue healing but also bone regeneration. The aim of this study was to evaluate the effect of combination PRF with bone graft (carbonate apatite) to VEGF level. This research is an experimental study, with consecutive sampling technique. This research was conducted by selecting 20 subjects (12 male, 8 female) which divided into two groups; 10 subjects in the treatment group were given bone graft and PRF application while another 10 subjects in the control group were given only bone graft without PRF application. The measurement of VEGF level was taken by inserting the paper point no.30 into sulcus before the surgery (D0) and one week after surgery (D7). VEGF level was assessed by ELISA method. All collected data were analyzed by using Wilcoxon test with p <0.05, and Mann-Whitney test with p <0.05. The treatment group, VEGF level at D0 was 3.8 pg/ml and D7 was 8,1 pg/ml. The difference in the level of VEGF was 4.3 pg/ml. The average of the control group at D0 was 4.5 pg/ml and D7 was 5.4 pg/ml, obtained the difference in the level of VEGF 0.9 pg/ml. The Mann Whitney Test analysis showed there was a significant difference between the treatment group and the control group with p-value 0.038. PRF with bone graft application influence the increased level of VEGF.

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 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

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&amp; 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]

Background Resveratrol (3,4',5-trihydroxystilbene) (RSV) is one of the main non-flavonoid natural polyphenol compounds. Evidence suggests that RSV has a key role in preventing a variety of pathological processes because of its benefits, including anti-aging, anti-inflammatory, and cardiovascular disease prevention. Vascular endothelial growth factor (VEGF) is responsible for vasculogenesis and angiogenesis, and its expression is influenced by RSV. Vascular nitric oxide (NO) acts to relax smooth muscle cells by preventing thrombogenic processes. It has been shown in vitro and in vivo that RSV is involved in NO metabolism. The aim of this work was evaluate the effects of regular low-dose RSV consumption by determining serum VEGF and NO levels compared to a control group. Methods The study involved 27 clinically healthy individuals, divided into a control group (placebo) and an intervention group, supplemented with 100mg RSV/day. The VEGF levels were determined by slot blot technique and NO levels were determined by spectrophotometry before (T0) and after 30 days (T1) of supplementation. Results The VEGF and NO levels slightly decrease from T0 to T1 moment in both study groups, showing a higher decrease in both parameters in the control group compared to the intervention group, but the variation was not statistically significant. Conclusions Daily supplementation with RSV is associated with benefits at the VEGF level as well as at the vascular level. However, further studies with a larger number of participants are needed to confirm the effects of RSV on VEGF and NO levels.

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.

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.

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]

Purpose: To compare intravitreal bevacizumab (IVB) and steroid activity in an experimental uveitis (EU) model.Materials and methods: EU was induced by intravitreal injection of bovine serum albumin (BSA) at baseline. Rabbits were randomly divided into three groups (n = 8) according to treatment with a single dose of IVB, steroid or saline on day 3. Aqueous humor (AH) samples were collected periodically (baseline and days 1, 3, 10 and 33). Rabbits were sacrified and eyes were enucleated for histopathology on day 33. AH vascular endothelial growth factor (VEGF) levels and histopathological changes were subjected to statistical analysis.Results: VEGF levels increased significantly after BSA injection (day 1) when compared with baseline in all three groups. Mean VEGF levels were 794.46 pg/mL, 777.91 pg/mL and 872 pg/mL for IVB, steroid and control groups, respectively (p = 0.002, p = 0.019 and p = 0.014). Seven days after treatment (day 10), VEGF levels decreased significantly in both treatment groups. Mean VEGF levels were 0 pg/mL, 292 pg/mL and 872 pg/mL, repectively (p < 0.001, p = 0.016 and p = 0.12). On day 33, the VEGF levels and inflammation had returned to baseline levels in both treatment groups, whereas no decrease in inflammation was observed in the control group. The histopathological evaluation revealed a mild congestion in ciliary tissue with a normal retina and choroidea in IVB group, a mild congestion in ciliary tissue with moderate inflammation in the posterior vitreus and a normal retina in steroid group and a severe inflammation in ciliary tissue with moderate inflammation in the retina in control group.Conclusions: These findings suggest that IVB may be used as an alternative to steroid treatment to reduce the acute effects of inflammation in patients with uveitis in whom intraocular steroids are contraindicated.

BackgroundPatients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum. This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms. Since, chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients.Methods14 current smokers with bronchitis type COPD, 17 asymptomatic current smokers with normal spirometry and 16 non-smokers were included in the study. VEGF, IL-8, and TNF-α levels in induced sputum were measured and the correlations between these markers, as well as between VEGF levels and pulmonary function were assessed.ResultsThe median concentrations of VEGF, IL-8, and TNF-α were significantly higher in induced sputum of COPD patients (1,070 pg/ml, 5.6 ng/ml and 50 pg/ml, respectively) compared to nonsmokers (260 pg/ml, 0.73 ng/ml, and 15.4 pg/ml, respectively, p < 0.05) and asymptomatic smokers (421 pg/ml, 1.27 ng/ml, p < 0.05, and 18.6 pg/ml, p > 0.05, respectively). Significant correlations were found between VEGF levels and pack years (r = 0.56, p = 0.046), IL-8 (r = 0.64, p = 0.026) and TNF-α (r = 0.62, p = 0.031) levels both in asymptomatic and COPD smokers (r = 0.66, p = 0.027, r = 0.67, p = 0.023, and r = 0.82, p = 0.002, respectively). No correlation was found between VEGF levels in sputum and pulmonary function parameters.ConclusionVEGF levels are raised in the airways of both asymptomatic and COPD smokers. The close correlation observed between VEGF levels in the airways and markers of airway inflammation in healthy smokers and in smokers with bronchitis type of COPD is suggestive of VEGF as a marker reflecting the inflammatory process that occurs in smoking subjects without alveolar destruction.

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.