scholarly journals DCE-MRI in Glioma, Infiltration Zone and Healthy Brain to Assess Angiogenesis: A Biopsy Study

2021 ◽  
Author(s):  
Vera C. Keil ◽  
Gerrit H. Gielen ◽  
Bogdan Pintea ◽  
Peter Baumgarten ◽  
Angeliki Datsi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kinetic Parameters ◽  
Low Grade ◽  
Normal Brain ◽  
Vascular Endothelial ◽  
Dce Mri ◽  
Vascular Growth Factor ◽  
Significant Difference ◽  
Prognostic Groups ◽  
Prognostic Group

Abstract Purpose To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma. Methods 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters. Results All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. Ktrans, kep and ve were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in Ktrans (p = 0.007) and ve (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones. Conclusion The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.

scholarly journals The VAD Scheme versus Thalidomide plus VAD for Reduction of Vascular Endothelial Growth Factor in Multiple Myeloma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Gan-Lin He ◽  
Duo-Rong Xu ◽  
Wai-Yi Zou ◽  
Sui-Zhi He ◽  
Juan Li
Keyword(s):  
Multiple Myeloma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
Vascular Endothelial ◽  
China National Knowledge Infrastructure ◽  
Significant Difference ◽  
Endothelial Growth Factor

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52–518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21–1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28− -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60–-39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08–377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.

scholarly journals De-novo multilayering in fibrovascular pigment epithelial detachment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manoj Soman ◽  
Jay U. Sheth ◽  
Asmita Indurkar ◽  
Padmanabhan Meleth ◽  
Unnikrishnan Nair
Keyword(s):  
De Novo ◽  
Median Number ◽  
Final Visit ◽  
Low Grade ◽  
Vascular Endothelial ◽  
Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Significant Difference ◽  
Endothelial Growth Factor

AbstractThis study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED—LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED—LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays

2001 ◽  
Vol 100 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Funmi M. BELGORE ◽  
Andrew D. BLANN ◽  
Gregory Y. LIP
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Plasma Levels ◽  
Biological Significance ◽  
Growth Factor Receptor ◽  
Soluble Form ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. VEGF interacts with the endothelium via two membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell media; however, its biological significance is still unknown, with limited data on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for detecting free and VEGF-complexed sFlt-1, which were tested in accordance with standard validation and assessment methodologies employed in commercial settings. The intra-and inter-assay coefficients of variation are < 5% and 10% respectively, and results are highly reproducible. Applying these ELISAs in a clinical setting, we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40 patients with cardiovascular disease and 40 healthy controls. Median (interquartile range) plasma levels of VEGF in patients were significantly greater than controls [403 pg/ml (158–925 pg/ml) versus 113 pg/ml (33–231 pg/ml), P ⩽ 0.05]. Free sFlt-1 was significantly lower in patients compared with controls [8 ng/ml (2–22 ng/ml) versus 21 ng/ml (10–73 ng/ml), P ⩽ 0.05]. There was no significant difference in the levels of complexed sFlt-1 between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal, despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by ELISA may represent the majority of circulating VEGF, and justifies the measurement of plasma VEGF as an indicator of circulating VEGF levels. Furthermore, these results suggest that circulating sFlt-1 may serve as a selective inhibitor of VEGF activity, and that this regulatory mechanism may be altered by pathological conditions.

scholarly journals Assessment of Vascular Endothelial Growth Factor in Fresh versus Frozen Platelet Rich Plasma

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Nada Hosny ◽  
Fikry Goubran ◽  
Basma BadrEldin Hasan ◽  
Noha Kamel
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Calcium Gluconate ◽  
Platelet Rich Plasma ◽  
Vascular Endothelial ◽  
High Concentration ◽  
Significant Difference ◽  
Growth Factor Release ◽  
Endothelial Growth Factor ◽  
Vegf Release

Platelet rich plasma (PRP) is hemoconcentration with platelets concentration above baseline values and high concentration of many growth factors. The aim of this study was to assess freezing effect on vascular endothelial growth factor (VEGF) release from PRP using two different activation methods to simplify its use in different clinical applications. PRP was prepared using two-centrifugation steps method from 12 qualified blood donors. VEGF concentrations were measured in fresh PRP and after freezing/thawing for one and three weeks with two methods of activation using (i) calcium gluconate and (ii) calcium gluconate and thrombin. Platelets count was significantly increased compared to baseline whole blood values in all fresh and frozen PRP samples (p value was <0.05). No significant difference was found between VEGF concentrations after activating fresh and frozen-thawed PRP samples for one and three weeks by calcium alone or calcium with thrombin, and also no significant difference was found when freezing period was extended from one to three weeks. Our results showed that platelets count does not correlate with variable levels of VEGF. PRP could be prepared once and preserved frozen for at least three weeks for the next treatment sessions and activation with thrombin addition to calcium will not augment the growth factor release.

Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma

2014 ◽  
Vol 14 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Shawn L. Hervey-Jumper ◽  
Hugh J. L. Garton ◽  
Darryl Lau ◽  
David Altshuler ◽  
Douglas J. Quint ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Perioperative Complications ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Extent Of Resection ◽  
Receptor Expression ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

Object Vascular endothelial growth factor (VEGF) is the major proangiogenic factor in many solid tumors. Vascular endothelial growth factor receptor (VEGFR) is expressed in abundance in pediatric patients with medulloblastoma and is associated with tumor metastasis, poor prognosis, and proliferation. Gadolinium enhancement on MRI has been suggested to have prognostic significance for some tumors. The association of VEGF/VEGFR and Gd enhancement in medulloblastoma has never been closely examined. The authors therefore sought to evaluate whether Gd-enhancing medulloblastomas have higher levels of VEGFR and CD31. Outcomes and survival in patients with enhancing and nonenhancing tumors were also compared. Methods A retrospective analysis of patients with enhancing, nonenhancing, and partially enhancing medulloblastomas was performed. Primary end points included risk stratification, extent of resection, and perioperative complications. A cohort of 3 enhancing and 3 nonenhancing tumors was selected for VEGFR and CD31 analysis as well as microvessel density measurements. Results Fifty-eight patients were analyzed, and 20.7% of the medulloblastomas in these patients were nonenhancing. Enhancing medulloblastomas exhibited strong VEGFR1/2 and CD31 expression relative to nonenhancing tumors. There was no significant difference in perioperative complications or patient survival between the 2 groups. Conclusions These results suggest that in patients with medulloblastoma the presence of enhancement on MRI may correlate with increased vascularity and angiogenesis, but does not correlate with worse patient prognosis in the short or long term.

Vascular growth factors play critical roles in kidney glomeruli

2015 ◽  
Vol 129 (12) ◽  
pp. 1225-1236 ◽  
Author(s):  
Luigi Gnudi ◽  
Sara Benedetti ◽  
Adrian S. Woolf ◽  
David A Long
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Kidney Diseases ◽  
Glomerular Disease ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Vascular Growth ◽  
Vascular Growth Factor ◽  
And Function ◽  
Endothelial Growth Factors

Kidney glomeruli ultrafilter blood to generate urine and they are dysfunctional in a variety of kidney diseases. There are two key vascular growth factor families implicated in glomerular biology and function, namely the vascular endothelial growth factors (VEGFs) and the angiopoietins (Angpt). We present examples showing not only how these molecules help generate and maintain healthy glomeruli but also how they drive disease when their expression is dysregulated. Finally, we review how manipulating VEGF and Angpt signalling may be used to treat glomerular disease.

scholarly journals Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Fluorescence Imaging ◽  
Low Grade ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Neoplastic Tissue ◽  
Fluorescence Measurements ◽  
Significant Difference ◽  
Quantitative Fluorescence

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

scholarly journals The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

2013 ◽  
Vol 40 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Wenhao Wu ◽  
Yongji Tian ◽  
Hong Wan ◽  
Yongmei Song ◽  
Junhua Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Clinicopathological Characteristics ◽  
Current Treatment ◽  
Brainstem Glioma ◽  
Low Grade ◽  
Normal Brain ◽  
Ki 67 ◽  
Significant Difference ◽  
The Relationship ◽  
Brain Tissues

Background:The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.Methods:This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.Results:Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.Conclusions:Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

scholarly journals Additive Value of Dynamic FDOPA PET/CT for Glioma Grading

2021 ◽  
Vol 8 ◽  
Author(s):  
Antoine Girard ◽  
Pierre-Jean Le Reste ◽  
Alice Metais ◽  
Nibras Chaboub ◽  
Anne Devillers ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Kinetic Parameters ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Time To Peak ◽  
Positron Emission ◽  
Pet Ct ◽  
Significant Difference

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas.Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC).Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min−1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP).Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.

Prognostic importance of vascular endothelial growth factor and its receptors in the uterine sarcoma

2005 ◽  
Vol 15 (2) ◽  
pp. 329-336 ◽  
Author(s):  
S. Arita ◽  
F. Kikkawa ◽  
H. Kajiyama ◽  
K. Shibata ◽  
M. Kawai ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Staining Intensity ◽  
Uterine Sarcoma ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Uterine Smooth Muscle ◽  
Significant Difference ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P = 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P = 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.

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