scholarly journals Three-Dimensional Cell Metabolomics Deciphers the Anti-Angiogenic Properties of the Radioprotectant Amifostine

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2877
Author(s):  
Theodora Katsila ◽  
Styliani A. Chasapi ◽  
Jose Carlos Gomez Tamayo ◽  
Constantina Chalikiopoulou ◽  
Eleni Siapi ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Three Dimensional ◽  
Drug Repurposing ◽  
Cell Physiology ◽  
Resonance Spectroscopy ◽  
Vascular Endothelial ◽  
Angiogenesis Assay ◽  
Endothelial Growth Factor ◽  
Shed Light ◽  
Cell Metabolomics

Aberrant angiogenesis is a hallmark for cancer and inflammation, a key notion in drug repurposing efforts. To delineate the anti-angiogenic properties of amifostine in a human adult angiogenesis model via 3D cell metabolomics and upon a stimulant-specific manner, a 3D cellular angiogenesis assay that recapitulates cell physiology and drug action was coupled to untargeted metabolomics by liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. The early events of angiogenesis upon its most prominent stimulants (vascular endothelial growth factor-A or deferoxamine) were addressed by cell sprouting measurements. Data analyses consisted of a series of supervised and unsupervised methods as well as univariate and multivariate approaches to shed light on mechanism-specific inhibitory profiles. The 3D untargeted cell metabolomes were found to grasp the early events of angiogenesis. Evident of an initial and sharp response, the metabolites identified primarily span amino acids, sphingolipids, and nucleotides. Profiles were pathway or stimulant specific. The amifostine inhibition profile was rather similar to that of sunitinib, yet distinct, considering that the latter is a kinase inhibitor. Amifostine inhibited both. The 3D cell metabolomics shed light on the anti-angiogenic effects of amifostine against VEGF-A- and deferoxamine-induced angiogenesis. Amifostine may serve as a dual radioprotective and anti-angiogenic agent in radiotherapy patients.

Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis

2021 ◽  
Vol 157 ◽  
pp. 103186
Author(s):  
Avash Das ◽  
Somnath Mahapatra ◽  
Dhrubajyoti Bandyopadhyay ◽  
Santanu Samanta ◽  
Sandipan Chakraborty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Early changes in coronary artery wall structure detected by microcomputed tomography in experimental hypercholesterolemia

2007 ◽  
Vol 293 (3) ◽  
pp. H1997-H2003 ◽  
Author(s):  
Xiang-Yang Zhu ◽  
Michael D. Bentley ◽  
Alejandro R. Chade ◽  
Erik L. Ritman ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Coronary Artery ◽  
Growth Factor ◽  
Three Dimensional ◽  
Wall Structure ◽  
Vascular Endothelial ◽  
Micro Ct ◽  
Artery Wall ◽  
Coronary Artery Wall ◽  
Endothelial Growth Factor

Changes in the structure of the artery wall commence shortly after exposure to cardiovascular risk factors, such as hypercholesterolemia (HC), but may be difficult to detect. The ability to study vascular wall structure could be helpful in evaluation of the factors that instigate atherosclerosis and its pathomechanisms. The present study tested the hypothesis that early morphological changes in coronary arteries of hypercholesterolemic (HC) pigs can be detected using the novel X-ray contrast agent OsO4 and three-dimensional micro-computed tomography (CT). Two groups of pigs were studied after they were fed a normal or an HC (2% cholesterol) diet for 12 wk. Hearts were harvested, coronary arteries were injected with 1% OsO4 solution, and cardiac samples (6-μm-thick) were scanned by micro-CT. Layers of the epicardial coronary artery wall, early lesions, and perivascular OsO4 accumulation were determined. Leakage of OsO4 from myocardial microvessels was used to assess vascular permeability, which was correlated with immunoreactivity of vascular endothelial growth factor in corresponding histological cross sections. OsO4 enhanced the visualization of coronary artery wall layers and facilitated detection of early lesions in HC in longitudinal tomographic sections of vascular segments. Increased density of perivascular OsO4 in HC was correlated with increased vascular endothelial growth factor expression and suggested increased microvascular permeability. The use of OsO4 as a contrast agent in micro-CT allows three-dimensional visualization of coronary artery wall structure, early lesion formation, and changes in vascular permeability. Therefore, this technique can be a useful tool in atherosclerosis research.

390 Characterisation of a Platelet Rich Fibrin Membrane and Formation of an Autologous Fibrin Mesh

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
Joshua Burke ◽  
Jack Helliwell ◽  
Mikolaj Kowal ◽  
David Jayne
Keyword(s):  
Three Dimensional ◽  
Clinical Results ◽  
Vascular Endothelial ◽  
Blood Draw ◽  
Platelet Rich Fibrin ◽  
Fibrin Scaffold ◽  
Surgical Sutures ◽  
Endothelial Growth Factor ◽  
Range Of Values ◽  
Fibrin Membrane

Abstract Aim Platelet-rich fibrin (PRF) is a three-dimensional fibrin scaffold with associated platelets and leukocytes which releases high quantities of growth factors over a sustained period of time. PRF has shown promising clinical results in promoting wound healing and tissue regeneration. The aims of this feasibility study were to establish optimal spinning methods for production of PRF, to quantify the production of vascular endothelial growth factor (VEGF) by PRF and to explore new vehicles of clinical PRF delivery. Method Assessment of optimal production involved comparisons between Protocol 1 (EDTA bottle) and Protocol 2 (no additive) at three different centrifugation forces: 400g, 1000g and 1700g. VEGF production was analysed using ELISA with varied incubation periods and PRF plug segments. Novel methods for PRF delivery were explored using surgical sutures and a Zimmer® Skin Graft Mesher. Results Protocol 2 demonstrated shorter average time to blood draw (9.8s compared to 13.6s) and to centrifuge (25.5s compared to 33.1s) with a decreased range of values. All PRF segments exhibited a positive correlation between incubation time and amount of VEGF produced with the bottom segments producing on average more VEGF. A segment of the fibrin plug was successfully secured on a suture and meshed in a 1:1.5 ratio. Conclusions PRF production can be optimised using blood bottles with no additive and high centrifugation forces. VEGF production by PRF peaks at 120 hours with the bottom PRF segment exhibiting the highest rate of production. The first description of a PRF mesh enables new clinical applications.

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

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