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ABSTRACT Purpose: To evaluate early changes after the first antivascular endothelial growth factor injection for macular edema secondary to diabetic retinopathy and retinal vein occlusion and the relationship between longterm outcomes. Methods: The study enrolled patients who received anti-vascular endothelial growth factor injections for treatment-naive macular edema due to retinal vein occlusion and diabetic retinopathy. The central macular thickness was measured at baseline, post-injection day 1, week 2, and month 1, and at the last visit using spectral-domain optical coherence tomography. A good response was defined as a central macular thickness reduction of ≥10% on post-injection day 1. Patients were reassessed at the last visit with regard to treatment response on post-injection day 1 based on the favorable anatomic outcome defined as a central macular thickness <350 µm. Results: In total, 26 (44.8%) patients had macular edema-retinal vein occlusion and 32 (55.2%) had macular edema-diabetic retinopathy. The mean follow-up time was 24.0 (SD 8.5) months. A statistically significant decrease in the central macular thickness was observed in both patients with macular edema-retinal vein occlusion and macular edema-diabetic retinopathy after antivascular endothelial growth factor injection therapy (p<0.001 for both). All patients with macular edema-retinal vein occlusion were good responders at post-injection day 1. All nongood responders at post-injection day 1 belong to the macular edema-diabetic retinopathy group (n=16.50%). The rate of hyperreflective spots was higher in nongood responders than in good responders of the macular edema-diabetic retinopathy group (p=0.03). Of 42 (2.4%) total good responders, one had a central macular thickness >350 µm, whereas 5 (31.2%) of 16 total nongood responders had a central macular thickness >350 µm at the last visit (p=0.003). Conclusion: The longterm anatomical outcomes of macular edema secondary to retinal vein occlusion and diabetic retinopathy may be predicted by treatment response 1 day after antivascular endothelial growth factor injection.
RESUMO Objetivo: Avaliar as alterações precoces após a primeira injeção de anticorpos antifator de crescimento endotelial vascular (anti-VEGF) em casos de edema macular secundário à retinopatia diabética e oclusão da veia da retina e a relação entre essas alterações e o resultado a longo prazo. Métodos: Foram incluídos no estudo pacientes que receberam uma injeção de antifator de crescimento endotelial vascular para edema macular, virgem de tratamento e devido à oclusão da veia retiniana ou a retinopatia diabética. A espessura macular central foi medida no início do tratamento e no 1º dia, 2ª semana e 1º mês após a injeção, bem como na última visita, através de tomografia de coerência óptica de domínio espectral. Definiu-se uma "boa resposta" como uma redução ≥10% na espessura macular central no 1º dia após a injeção. Os pacientes foram reavaliados na última visita com relação à resposta ao tratamento no 1º dia após a injeção, com base em um resultado anatômico favorável, definido como uma espessura macular central <350 µm. Resultado: Foram registrados 26 (44,8%) pacientes com edema macular e oclusão da veia da retina e 32 (55,2%) com edema macular e retinopatia diabética. O tempo médio de acompanhamento foi de 24,0 meses (desvio-padrão de 8,5 meses). Foi observada uma diminuição estatisticamente significativa da espessura macular central após o tratamento antifator de crescimento endotelial vascular tanto em pacientes com edema macular e oclusão da veia retiniana quanto naqueles com edema macular e retinopatia diabética (p<0,001 para ambos). Todos os pacientes com edema macular e oclusão da veia retiniana responderam bem no 1º dia pós-injeção. Todos os que responderam mal no 1º dia pós-injeção pertenciam ao grupo com edema macular e retinopatia diabética (n=16,50%). A presença de manchas hiperrefletivas foi maior nos pacientes que responderam mal do que naqueles que tiveram boa resposta no grupo com edema macular e retinopatia diabética (p=0,03). Um dos 42 (2,4%) pacientes com boa resposta total teve espessura macular central >350 um, enquanto 5 (31,2%) do total de 16 pacientes com resposta ruim apresentaram espessura macular central >350 µm na última visita (p=0,003). Conclusão: O resultado anatômico de longo prazo do edema macular secundário à oclusão da veia retiniana e à retinopatia diabética pode ser previsto pela resposta ao tratamento no 1º dia após a injeção de antifator de crescimento endotelial vascular.
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Abstract Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.
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Objective:To explore the predictability cytokines in aqueous humor affecting optical coherence tomography angiography (OCTA) parameters after anti-vascular endothelial growth factor (VEGF) treatment in patients with polypoidal choroidal vasculopathy (PCV).Methods:A cross-sectional study was carried out.Twenty eyes of 20 patients with PCV were included in Xuzhou First People's Hospital from July 2017 to July 2020.All PCV eyes were treated by intravitreal injection of conbercept (IVC) following 3+ PRN regimen.One hundred μl of aqueous humor was collected before treatment and before the third injection, respectively.Thirteen kinds of cytokines in the aqueous humor were detected with Luminex bead-based multiplex array.The aqueous humor of 16 eyes of 16 cataract patients with age and gender matched were collected in the same way during phacoemulsification surgery as control.The values of center macular thickness (CMT), subretinal fluid height (SRFH), pigment epithelial detachment height (PEDH) and pigment epithelial detachment diameter (PEDD) of the eyes in the PCV group were examined with OCTA system.The target cytokines in aqueous humor affecting OCTA parameter change values (the difference between before and after treatment) was analyzed.This study protocol was approved by an Medical Ethic Committee of Xuzhou First People's Hospital (No.xyyll[2020]27) and complied with Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical invention.Results:The concentration of interleukin-8 (IL-8), Leptin, hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF-2), angiopoietin-2 (Ang-2), endothelin-1 and vascular endothelial growth factor-A (VEGF-A) were significantly higher in aqueous humor of the PCV group before treatment than those in the cataract group (all at P<0.05). After treatment, the concentration of VEGF-A in aqueous humor of the PCV group was significantly lower than that before treatment ( P<0.001). The values of CMT, SRFH, PEDH and PEDD were significantly reduced in comparison with before treatment, showing statistical significances (all at P<0.05). The concentration of VEGF-A in aqueous humor was positively correlated and endothelin-1 in aqueous humor was negatively correlated with the change value of CMT ( r=0.592, -0.485, both at P<0.05). The concentration of IL-8 and HGF were positively correlated with SRFH change value ( r=0.492, 0.466, both at P<0.05). VEGF-A and IL-8 concentraions of aqueous humor before treatment were the risk factor of the change value of CMT and SRFH.Every 1pg/ml increase of baseline VEGF-A, the CMT change value reduced 0.836 μm ( P=0.006), and every 1pg/ml increase of baseline IL-8, the SRFH change value reduced 12.522 μm ( P=0.028). Conclusions:The concentrations of VEGF-A and IL-8 in aqueous humor might predict the CMT and SRFH improvement in PCV eyes after anti-VEGF therapy.
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@#AIM: To quantitatively measure and evaluate the VEGF-A, platelet derived growth factor(PDGF)and pigment epithelium derired factor(PEDF)in the aqueous humor of patients with neovascular glaucoma(NVG). <p>METHODS: Prospectively clinical study. This study involved 23 eyes of 23 patients with advanced NVG and 23 control subjects with age related cataract. Protein concentrations of VEGF-A, PDGF and PEDF in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay(ELISA)tests. <p>RESULTS: The VEGF-A and PDGF concentrations in aqueous humor from NVG patients were(1130.56±69.32)ng/L and(221.95±56.08)ng/L, respectively. Both of them were significantly higher than control subject(226.45±37.46)ng/L,(36.25±7.12)ng/L(<i>P</i><0.01). Aqueous PEDF was significantly lower in the NVG group(195.69±42.00)ng/L than that in controls(497.89±12.52)ng/L(<i>P</i><0.01). However, levels of VEGF-A, PDGF and PEDF in the serum of NVG were(226.45±37.46)ng/L,(29.57±6.31)ng/L and(13.24±1.76)ng/L, respectively, which were similar with control subjects(219±34.89)ng/L,(28.28±7.24)ng/L and(12.96±2.08)ng/L(<i>P</i>>0.05). The concentrations of VEGF-A were closely positive correlated with levels of PDGF in the aqueous humor of patients with NVG(<i>r</i>=0.502, <i>P</i>=0.015). However, the concentrations of VEGF-A were closely negative correlated with levels of PEDF in the aqueous humor of patients with NVG(<i>r</i>=-0.480, <i>P</i>=0.020). <p>CONCLUSION: There were higher levels of VEGF-A and PDGF, and lower level of PEDF in the aqueous humor of patients with NVG. There was a positive correlation between VEGF-A and PDGF, a negative correlation between VEGF-A and PEDF. The combination of anti-VEGF agent, PDGF inhibitor and PEDF may provide a new idea for the treatment of NVG.
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AIM:To study the regulation mechanism of diet containing omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on retinal neovascularization in an oxygen-induced retinopathy (OIR) mouse model.METHODS:Sixty C57BL /6J mice,seven-day-old,were classified into 3 groups:A the normal control group,B the OIR model group,C the ω-3 PUFAs diet group.Each group has twenty mice and separated fed by their lactating mice.The normal control group was fed in a standard atmosphere environment,B,C groups were first fed in a hyper-oxygen atmosphere of (75 ± 2) ％ oxygen percentage for 5d,then continue fed in a standard atmosphere.The ω-3 PUFAs diet group was fed with dose base on their weight by 7.5mg/kg/d.All mice were sacrificed when they were seventeen-day-old,the relative neovascularization areas (NA) were calculated by fluorescein angiography on flat-mounted retina.The number of endothelial cell nuclei breaking through the inner linmiting membrane (ILM) was counted on hematoxylin and eosin-stained retinal section.The ω-3PUFAs/ω-6PUFAs relative amount and ratio was measured by GC-MS in the retina.A real-time PCR and Western Blot method were used to detect the mRNA,peroxisome proliferator-avtivated receptor-γ (RPAR-γ),vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR-2)in the retina.RESULTS:There was a significant different in all groups on the relative neovascularization areas and the number of endothelial cell nuclei breaking through the ILM (FNA =20.45,P＜0.05;FILM =48.66,P＜0.05).NA between Group A and B had a significant difference (t=8.64,P＜0.05),the same between Group C and B (t=8.91,P＜0.05).The cell nuclei breaking through ILM in Group A and B was significantly different (t =38.51,P＜ 0.05),the same in GroupC and B (t=19.86,P＜0.05).For the relative contain in retina of ω-3PUFAs and ω-6PUFAs,there was a significant different among all groups (F=129.86,F=112.44;all P＜0.05).That of Group C was significant different than other two groups(t=23.15,25.42;t=16.43,11.95;P＜0.05).There were significant different among all groups on ω-3PUFAs/ω-6PUFAs ratio,retinal RPAR-γmRNA expression,retinal VEGF-A mRNA expression and VEGFR-2 mRNA expression (Fω-3/6 =10.30,FRPAR-γ =138.24,FVEGF-A =69.12,FVEGFR-2 =52.45;P＜0.05).The ω-3PUFAs/ω-6PUFAs ratio of Group C was higher than that of Group B (P＜0.05).Compared to Group B,on one hand Group C had a higher expression (P＜0.05),on other hand Group C had a lower expression on VEGF-A mRNA and VEGFR-2 mRNA(P＜0.05).CONCLUSION:The diet rich with ω-3 PUFAs uplifts the ω-3PUFAs/ω-6PUFAs ratio and activates RPAR-γ to lower expression of VEGF-A and VEGFR-2 to inhabit oxygen induced retinal neovascularization.
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@#AIM: To study the effects of Shuangdan Mingmu capsule on the expressions of vascular endothelial growth factor-a(VEGF-a), VEGF-b, VEGF-c in the retina of a diabetic rat model. <p>METHODS: Forty male SD rats were divided into Group A(normal group), Group B(model group), Group C(Shuangdan Mingmu group)and Group D(positive control group)10 rats(20 eyes)in each group. A rat model of diabetic retinopathy was established by one-time tail vein injection with STZ(50mg/kg). After modeling for 1wk, the rats were given medicine by gavage. After gavage for 4wk rats were sacrificed, and the expressions of VEGF-a, VEGF-b, VEGF-c in the retina tissues were detected by immunohistochemical method. <p>RESULTS: After gavage for 4wk the average gray values of VEGF-a, VEGF-b and VEGF-c protein in the retina of model group, Shuangdan Mingmu group and positive control group were lower than those of the normal group, and the average optical density were higher than those of the normal group. There was a significant difference between the model group and the normal group(<i>P</i><0.01). The average gray values of VEGF-a, VEGF-b and VEGF-c expression in Shuangdan Mingmu group and positive control group were higher than those in the model group(<i>P</i><0.05)and the average optical density value were lower than those in the model group.(<i>P</i><0.01). <p>CONCLUSION: Shuangdan Mingmu capsule could significantly reduce the expressions of VEGF-a, VEGF-b,VEGF-c in the retina and had a certain protective effect on the retina of rats in the diabetic retinopathy model.
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OBJECTIVES@#To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency.@*METHODS@#The arrhythmia was induced by CaCl₂, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats.@*RESULTS@#The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time.@*CONCLUSIONS@#The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.
Subject(s)
Animals , Rats , Arrhythmias, Cardiac/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Myocardial Ischemia/metabolism , Myocardium/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The renal vascular system is vital for maintaining the normal function of kidney, and vascular endothelial growth factor-A (vEGF-A) participates in the development of renal vascular.system and is associated withvarious kidney diseases. Studies have demonstrated that down-expression of renal vEGF-A can result in reduction of microvascular density in medulla kidney, regional hypoxia, and polycythemia, and further lead to increased haemopoietin. The overexpression of vEGF- A can cause renal fibrosis and cyst formation, promoting the progress of kidney disease. Therefore, regulation of vEGF-A expression may influence the occurrence and development of kidney diseases. This review summarized the role of vEGF-A in the renal vascular system and kidney diseases hoping to provide new therapeutic strategies for kidney diseases.
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ObjectiveToinvestigatethecorrelationbetween-2578C>Apolymorphismofvascular endothelium grow th factor (VEGF) gene and carotid atherosclerosis in Chinese Han population in Shandong, China. Methods A total of 384 subjects aged 45-85 in Chinese Han population in Shandong, China w ere enroled. They were divided into either an increased intima-media thickness (IMT) group ( n=248) or a control group (n=136) according to the vascular ultrasound results. The baseline clinical data, such as the demographic data, vascular risk factors, and blood biochemical indicators in both groups were colected. Polymerase chain reaction w as used to detect the VEGF gene -2578C>A polymorphism genotype and alele. Multivariate logistic regression analysis was used to identify the independent risk factors for increased carotid IMT. Results The proportions of hypertension ( 70.6%vs.59.6%;χ2 =4.793, P=0.032), diabetes (18.4%vs.29.0%; χ2 =5.281, P=0.027), hyperlipidemia ( 45.2%vs.33.1%; χ2 =7.883, P=0.006), previous previous stroke or transient ischemic attack (29.0%vs.16.9%;χ2 =6.294, P=0.009), smoking (35.9%vs.19.9%;χ2 =10.708, P=0.001), as w el as total cholesterol ( 4.82 ±1.25 mmol/L vs.4.57 ± 0.94 mmol/L; t= -2.072, P= 0.039 ), triglyceride ( median, interquartile range; 1.71[0.84-2.22] mmol/L vs.1.53[1.08-2.59] mmol/L;Z= -2.560 P=0.010), low-density lipoprotein cholesterol (2.86 ±1.01 mmol/L vs.2.64 ±0.85 mmol/L; t= -2.407, P= 0.033 ), and high-density lipoprotein cholesterol (1.58 ±0.72 mmol/L vs.1.43 ±0.46 mmol/L;t= -2.183, P=0.030) in the increased IMT group, and there w ere significant differences compared w ith the control group. There w as significant difference in genotype frequency betw een the 2 groups (χ2 =10.131; P=0.006). There w as significant difference in C alele frequency between the increased IMT group and the control group (78.2% vs. 70.2%;χ2 =6.068, P=0.014). Multivariate logistic regression analysis showed that CC genotype (odds ratio 1.132, 95%confidence interval 1.021-2.141;P=0.029) w as an independent risk factor for increased carotid IMT. In 248 patients w ith increased IMT, 213 had at least 1 plaque, 76 (39.6%) of them w ere 1-2, 107 (43.15%) w ere 3-4, and 30 (12.1%) w ere 5-8 in plaque index. There w ere no significant differences in frequencies of genotypes (χ2 =6.766, P=0.149) and alele (χ2 =0.185, P=0.667) in the different plaque index groups. Conclusions -2578 single nucleotide polymorphism in the VEGF gene promoter is associated w ith carotid atherosclerosis, and C al ele may be its genetic susceptibility factor in Chinese Han population in Shandong, China.
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Objective To explore the molecular mechanism of S100A9-induced secretion of vascular endothelial growth factor-A (VEGF-A)by monocytes.Methods Peripheral blood specimen were collected from healthy individuals undergoing physical exami-nation and the CD14 + monocytes were purified by using immunomagnetic beads and the expression of the receptor for advanced gly-cation endproducts (RAGE)was detected by flow cytomertry.In vitro CD14 + monocytes were stimulated by S100A9,and anti-RAGE antibody or NK-κB signal pathway inhibitor were pre-incubated for 1 hour and then stimulated by S100A9,the levels of VEGF-A were detected by using enzyme-linked immunosorbent assay.Results The high level of RAGE was expressed by isolated CD14 + monocytes,after S100A9 stimulation,the secretion of VEGF-A by CD14 + monocytes was significantly increased in a dose and time dependent manner.However,the inducing VEGF-A was significantly decreased(P <0.01 ),while pre-treated with anti-RAGE antibody or NK-κB inhibitor (P <0.01).Conclusion S100A9 inducing the secretion of VEGF-A by monocytes and is de-pended on RAGE-NK-κB signal pathway,suggesting that S100A9 might promote angiogenesis.
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PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. MATERIALS AND METHODS: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: non-ulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. RESULTS: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. CONCLUSIONS: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.
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Humans , DNA, Complementary , Dyspepsia , Endoscopy , Helicobacter pylori , Inflammation , Intercellular Signaling Peptides and Proteins , Peptic Ulcer , Reverse Transcriptase Polymerase Chain Reaction , RNA , Stomach Neoplasms , Up-Regulation , Urease , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth FactorsABSTRACT
BACKGROUND: The aim of this in vitro study was to determine the effect of zoledronate, which is frequently used to treat osteoporosis, on osteoarthritis by analyzing zoledronate-induced expression of vascular endothelial growth factor-A (VEGF-A) in chondrocytes and synovial cells. METHODS: After chondrocytes and synovial cells were separated and cultured, zoledronate was added, and VEGF-A and pigment epithelium-derived factor (PEDF) expression were quantified by real-time polymerase chain reaction and Western blotting. RESULTS: There was no significant difference in the expression of VEGF-A mRNA in chondrocytes between the zoledronate group and the control group on the 8th day of culture. The expression of both VEGF-A and PEDF mRNA in synovial cells was significantly decreased in the zoledronate group (P<0.05). CONCLUSIONS: Zoledronate decreases the expression of VEGF-A in synovial cells and may affect the development and progression of osteoarthritis.
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Blotting, Western , Chondrocytes , Osteoarthritis , Osteoporosis , Real-Time Polymerase Chain Reaction , RNA, Messenger , Vascular Endothelial Growth Factor AABSTRACT
Background: Decorin is an extracellular matrix, multifunctional small proteoglycan molecule in tumor stroma that has been shown to be modulator of angiogenesis. No clinical data is available so far on decorin expression and survival outcome of oral cancer. Aim: The aim of the present study was to examine molecular and phenotypic expression of two angiogenesis modulators viz. decorin and vascular endothelial growth factor-A (VEGF-A) in human potentially malignant oral lesions (PMOLs) and oral squamous cell carcinomas (OSCC) in relation to clinico-pathological variables and survival outcome. Materials and Methods: Tissue biopsies were obtained from 72 PMOLs, 108 OSCC and 52 healthy controls. The PMOLs included cases of leukoplakias and oral submucous fi brosis. Immunohistochemistry was performed using antibodies against decorin, VEGF-A and CD-31. Messenger-ribonucleic acid (mRNA) expression was analyzed by using real-time polymerase chain reaction. Results: Cytoplasmic staining of decorin was observed in the basal layer of epithelium in 53 (73.61%) cases of PMOLs and in peritumoral stroma in 55 (50.92%) cases of OSCC. None of the cases showed nuclear expression of decorin. Decorin expression both at phenotypic and molecular level was found to be down-regulated from PMOLs to OSCC. Lymph node metastasis and reduced decorin expression independently correlated with overall survival in OSCC. VEGF-A expression had no signifi cant impact on survival outcome. Conclusion: Micro vessel density and VEGF-A expression were signifi cantly associated with reduced decorin expression in tumor stroma suggesting, decorin as angiogenic modulator in OSCC. Down-regulation of decorin expression and the presence of lymph node metastasis were adverse factor independently affecting overall survival in OSCC.
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Objective To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1 α),vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor-D (VEGF-D)in hypoxic environment as well as the relationship between HIF-lα and VEGF-D.Methods Human esophageal cancer cell line EC9706 was cultured under hypoxia environment for 6,12 and 24 h,the cell radiosensitivity was evaluated by survival curve.HIF-1 α siRNA was constructed and transfected into human EC9706 cells.Protein expressions of HIF-1 α,VEGF-A and VEGF-D were analyzed by Western blot before and after RNA interference.Results EC9706 cells under hypoxia showed radioresistance with a SF2 of 0.62 higher than that of normoxic cells of 0.43.Moreover,the protein expressions of HIF-1α,VEGF-A and VEGF-D were all increased (F =205.24,227.88,130.55,P ＜0.05) due to hypoxia treatment.On the contrary,after HIF-1α siRNA transfer,the protein expressions of HIF-1α,VEGF-A and VEGF-D in EC9706 cells were not influenced by hypoxia treatment.Conclusions EC9706 cells in hypoxic environment was radioresistance,and the upexpressions of HIF1α,VEGF-A and VEGF-D may be involved.
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The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.
Subject(s)
Adult , Animals , Female , Humans , Male , Middle Aged , Rats , Asthma/blood , Cell Line , Epithelial Cells , Gene Expression/drug effects , Isocyanates/toxicity , Occupational Diseases/blood , Toluene 2,4-Diisocyanate/toxicity , Vitamin D-Binding Protein/bloodABSTRACT
There has been emergence of evidence suggesting that specific variants of the vascular en-dothelia growth factor (VEGF) family, based on their ability to regulate angiogenesis, would be pivotal in the pathogenesis of endometriosis. This study was aimed at determining whether high levels of VEGF-A could be found in the serum and peritoneal fluid (PF) of patients with endometriosis. VEGF-A levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum and PF from 46 pa-tients with surgically confirmed endometriosis, and 40 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. The results showed the mean VEGF-A levels were significantly higher in the serum and PF of patients with endometriosis than in the controls. The VEGF-A levels in the serum and PF of patients with severe endometriosis (stages Ⅲ-Ⅳ) were significantly higher than in those with minimal endometriosis (P<0.001). It was concluded that endometriosis was associated with significant modulation in the levels of circulating VEGF-A.
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BACKGROUND: Vascular endothelial growth factor (VEGF)-C and VEGF-D are novel growth factors that regulate lymphatic vessel growth. This study was designed to examine whether the expression of three VEGF family members, VEGF-A, VEGF-C and VEGF-D are associated with the clinicopathologic parameters, especially with lymph node metastasis, in advanced gastric carcinomas. METHODS: Immunohistochemical staining was performed for VEGF-A, VEGF-C, and VEGF-D in the surgically resected specimens from 102 patients with advanced gastric carcinoma. The mRNA expressions of the three VEGF family members were assessed in 16 cases of tumor tissues and their corresponding non-neoplastic tissues. RESULTS: Of the 102 gastric carcinomas, 74 (73%), 82 (80%), and 34 (33%) cases showed cytoplasmic immunoreactivity for VEGF-A, VEGF-C and VEGF-D, respectively. Both VEGF-A and VEGF-C expressions were associated with lymphatic invasion and lymph node metastasis (p0.05). In the tumor tissue, VEGF-C mRNA expression was greater, while VEGF-D mRNA expression was lower than in the nonneoplatic tissue adjacent to the tumor. CONCLUSIONS: VEGF-A and VEGF-C may play important roles for the lymphatic spread of gastric carcinoma. We suggest that neutralizing both VEGF-A and VEGF-C may be reguired to block lymph node metastasis.