Abstract 3302: Vascular Endothelial Growth Factor Receptor Inhibition Impairs Intracerebral Hemorrhage-induced angiogenesis

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Han-Jin Cui ◽  
Qi-Ting Liu ◽  
Hua-Jun Zhou ◽  
TAO TANG
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Intracerebral Hemorrhage ◽  
Growth Factor Receptor ◽  
Treated Group ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Sham Control ◽  
Receptor Inhibition ◽  
Endothelial Growth Factor

Background and purpose: Our previous work has proved that Intracerebral hemorrhage (ICH) induces angiogenesis, accompanied by upregulation of vascular endothelial growth factor (VEGF) and its receptors. As the most potent mitogen of endothelial cells (ECs), VEGF must bind to its receptor_vascular endothelial growth factor receptor-2, to make it be phosphorylated, which plays the roles in promoting proliferation, migration, survival of ECs. In this study, our purpose is to investigate the effect of VEGF receptor inhibition on angiogenesis after ICH. Method: Fifteen Kunming mice were randomly divided into 3 groups, including sham control (n=5), ICH group (n=5), and SU5416-treated group (n=5). ICH model was induced by injection collagenase type VII into right globus pallidus stereotaxically. SU5416-treated group was injected by SU5416 (10 mg/kg per dose) intraperitoneally after ICH induction. Intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) was used to label new-born ECs. Neurological severity score (NSS), corner turn test and foot-fault test were used to investigate the neurological function at 1d, 3d and 7d following the surgery. Angiogenesis and the level of p-VEGFR-2 were evaluated at 7d by immunohistochemistry. Results: At 1d, there is no difference between the two ICH-induced groups in NSS, corner turn test, foot-fault test; at 3d and 7d, the NSS in ICH group is significantly lower than that of SU5416-treated group ( P <0.05), and the times for right-turn and foot-fault in ICH group are notably fewer than those of SU5416-treated group ( P <0.05). At 7d, no expression of p-VEGFR-2 was detected in sham control animals, while the expression of p-VEGFR-2 in ICH group is notably higher than that in SU5416-treated group ( P <0.05); and the expression of p-VEGFR-2 is located in vWF-immunoreactive ECs; there is no BrdU-labeled nuclear in vessels observed in sham-control mice, but BrdU-labeled nuclei in vessels in ICH group are remarkably more than those in SU5416-treated group ( P <0.05). Conclusions: Activation of VEGFR-2 is an important mechanism for angiogenesis after ICH, which is related with the recovery of neurological behavioral function.

scholarly journals Correlation of vascular endothelial growth factor and vascular endothelial growth factor receptor-1 levels in serum and thyroid nodules with histopathological and radiological variables

2019 ◽  
Vol 11 (01) ◽  
pp. 051-057 ◽  
Author(s):  
Gurkan Haytaoglu ◽  
Fatih Kuzu ◽  
Dilek Arpaci ◽  
Ayfer Altas ◽  
Murat Can ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Thyroid Nodules ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Needle Aspiration ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Number Of Patients ◽  
Endothelial Growth Factor

Abstract BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) is a major cytokine in angiogenesis and has a role on aggressivity of various tumors. The expression of VEGF has been shown to increase in differential thyroid cancer. The aim of the study was to evaluate serum and intranodular VEGF (nVEGF) and VEGF receptor-1 (VEGFR-1) levels in patients with thyroid nodules and their relevance to ultrasonographic and pathological results. MATERIALS AND METHODS: A total of eighty patients were included in the study. Thyroid fine-needle aspiration biopsies were performed, and the levels of serum and nVEGF and VEGFR-1 were measured. Any possible correlations between serum and nVEGF, VEGFR-1, and biochemical/radiological variables were investigated. RESULTS: There were no significant differences between serum VEGF (sVEGF), nVEGF, sVEGFR-1, nVEGFR-1 levels, number of nodules, size of nodules, and benign and malignant ultrasonographic features. sVEGF and nVEGF were higher in malignant or suspicious nodules than that in benign nodules, but did not reach statistical significance (P > 0.05). sVEGFR-1 and nVEGFR-1 levels were higher in hyperthyroid patients than that in euthyroid patients (P < 0.05 and P = 0.003, respectively). nVEGFR-1 level was higher in hypothyroid patients than that in euthyroid patients (P = 0.016). sVEGF level was found to be higher in hyperactive nodules than that in others. Both sVEGFR-1 (P = 0.008) and nVEGF levels (P = 0.01) significantly increased with increasing age. nVEGFR-1 decreased with increasing body mass index (BMI) (P = 0.004). CONCLUSIONS: Our study showed the relationships of sVEGF, nVEGF, sVEGFR-1, and nVEGFR-1 levels with age, gender, BMI, and hyperthyroidism. To determine the role of VEGF/VEGFR-1 in thyroid nodules, further studies are required with a large number of patients.

T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 501-501
Author(s):  
Thai Huu Ho ◽  
Robert Charles Gagnon ◽  
Yuan Liu ◽  
F. Stephen Hodi ◽  
Sabina Signoretti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
T Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Treated Group ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Cell Repertoire ◽  
Endothelial Growth Factor

501 Background: Reports have demonstrated an inverse relationship between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway suggesting that T cell repertoires may impact response to VEGFR blockade. We evaluated the association between clinical outcomes and T cell repertoire in metastatic RCC patients receiving a front-line anti-VEGFR, pazopanib. Methods: Pre-treatment RCC tumors were analyzed from VEG105192, a phase III study of mRCC patients randomized (2:1) to pazopanib (paz) 800 mg daily vs placebo (pbo) for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. Using the Adaptive Biotechnologies immunoSEQ Assay, we assessed TCR clonality, a measure of total repertoire represented by expanded clones, and entropy, a measure of evenness and diversity. PD-L1 was evaluated by immunohistochemistry (IHC) H-Scores. The goal of the study was to determine if the repertoire of T cell clones was associated with progression-free survival as a clinical endpoint. Results: In the cohort with available tissue, the median PFS was 10.8 and 5.5 months (mos) for paz and pbo, respectively. TCRB (n = 114) and TCRG (n = 43 pbo, 109 paz) clonality ranged from 0-0.31 and 0-0.98, and entropy from 1-12.1 and 0-10.37, respectively. TCRB and TCRG entropy were highly correlated (Spearman’s R = 0.92, n = 114). Samples from the pbo-treated group with higher TCRG entropy, defined as the top 25th percentile, were associated with an improved median PFS (12.8 months) when compared to the lower 75th percentile (3.1 months, P = 0.023); similar trends were seen for TCRB entropy. Neither entropy nor clonality was associated with maximal reduction in tumor volume in the paz-treated group. PD-L1 H-scores were not associated with entropy or clonality (P > 0.05). Conclusions: Our data suggests that RCC samples with higher entropy are associated with a favorable prognosis. Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study. Clinical trial information: NCT00334282.

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

2015 ◽  
Vol 113 (02) ◽  
pp. 329-337 ◽  
Author(s):  
Peter W. Hewett ◽  
Takeshi Fujisawa ◽  
Samir Sissaoui ◽  
Meng Cai ◽  
Geraldine Gueron ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Carbon Monoxide ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Sprouting Angiogenesis ◽  
Endothelial Growth Factor

SummaryCarbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor-reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

scholarly journals 224 Vascular endothelial growth factor receptor inhibition induces vascular dysfunction via redox-sensitive processes

Heart ◽  
2017 ◽  
Vol 103 (Suppl 5) ◽  
pp. A145.1-A145
Author(s):  
Karla Bianca Neves ◽  
Francisco J Rios ◽  
Augusto C Montezano ◽  
Lucas Van Der Mey ◽  
Carmine Savoia ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Dysfunction ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Receptor Inhibition ◽  
Endothelial Growth Factor
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