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https://www.readbyqxmd.com/read/29161763/quantifying-the-relationship-between-inhibition-of-vegfr-2-drug-induced-blood-pressure-elevation-and-hypertension
#1
Teresa Collins, Kelly Gray, Michal Bista, Matt Skinner, Christopher Hardy, Haiyun Wang, Jerome T Mettetal, Alexander R Harmer
BACKGROUND AND PURPOSE: Several anti-angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15-60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off-target activity at VEGFR-2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR-2 off-target potency into blood pressure elevation would be useful in development of novel TKIs. EXPERIMENTAL APPROACH: We sought to quantify the relationship between VEGFR-2 inhibition and blood pressure elevation for a range of kinase inhibitors...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29158262/the-epac-rap1-pathway-prevents-and-reverses-cytokine-induced-retinal-vascular-permeability
#2
Carla J Ramos, Chengmao Lin, Xuwen Liu, David A Antonetti
Increased retinal vascular permeability contributes to macular edema, a leading cause of vision loss in eye pathologies such as diabetic retinopathy, age-related macular degeneration, and central retinal vein occlusions. Pathological changes in vascular permeability are driven by growth factors such as VEGF and by pro-inflammatory cytokines such as TNF-α. Identifying the pro-barrier mechanisms that block vascular permeability and restore the blood-retinal barrier (BRB) may lead to new therapies. The cAMP-dependent guanine nucleotide exchange factor EPAC promotes exchange of GTP in the small GTPase Rap1...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29153696/dysregulation-of-circulating-autoantibodies-against-vegf-a-vegfr-1-and-plgf-in-preeclampsia-a-role-in-placental-and-vascular-health
#3
Kjartan Moe, Harald Heidecke, Ralf Dechend, Anne Cathrine Staff
OBJECTIVES: Preeclampsia is a state of antiangiogenesis, with high levels of maternal circulating sVEGFR-1 (soluble vascular endothelial growth factor receptor 1, also named sFlt1) and low levels of PlGF (placenta growth factor). Various autoantibodies have been detected in preeclamptic patients. We hypothesize that circulating autoantibodies against VEGF-A (AA-VEGF-A), VEGFR-1 (AA-VEGFR-1) and PlGF (AA-PlGF) are present in preeclamptic women, with different levels from pregnant women with normotensive pregnancies...
October 2017: Pregnancy Hypertension
https://www.readbyqxmd.com/read/29151304/egfr-kras-and-braf-mutational-profiles-of-female-patients-with-micropapillary-predominant-invasive-lung-adenocarcinoma
#4
(no author information available yet)
Background/aim: This study aimed to analyze EGFR, KRAS, and BRAF mutations in females with micropapillary predominant invasive lung adenocarcinoma and their relationships with immunohistochemical and clinicopathological patterns.Materials and methods: A total of 15 females with micropapillary lung adenocarcinoma were selected. Mutational analysis of the EGFR, KRAS, and BRAF genes was carried out. Information regarding the demographic data, tumor size, treatment, and survival time for each patient was collated, and the predominant cell type, secondary architectural growth patterns, psammoma bodies, necrosis, and visceral pleural and angiolymphatic invasions were evaluated...
November 13, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29150606/loss-of-hif-1%C3%AE-in-natural-killer-cells-inhibits-tumour-growth-by-stimulating-non-productive-angiogenesis
#5
Ewelina Krzywinska, Chahrazade Kantari-Mimoun, Yann Kerdiles, Michal Sobecki, Takayuki Isagawa, Dagmar Gotthardt, Magali Castells, Johannes Haubold, Corinne Millien, Thomas Viel, Bertrand Tavitian, Norihiko Takeda, Joachim Fandrey, Eric Vivier, Veronika Sexl, Christian Stockmann
Productive angiogenesis, a prerequisite for tumour growth, depends on the balanced release of angiogenic and angiostatic factors by different cell types within hypoxic tumours. Natural killer (NK) cells kill cancer cells and infiltrate hypoxic tumour areas. Cellular adaptation to low oxygen is mediated by Hypoxia-inducible factors (HIFs). We found that deletion of HIF-1α in NK cells inhibited tumour growth despite impaired tumour cell killing. Tumours developing in these conditions were characterised by a high-density network of immature vessels, severe haemorrhage, increased hypoxia, and facilitated metastasis due to non-productive angiogenesis...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146618/management-of-adverse-events-associated-with-cabozantinib-therapy-in-renal-cell-carcinoma
#6
REVIEW
Manuela Schmidinger, Romano Danesi
Cabozantinib was recently approved for the treatment of advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Cabozantinib is a multikinase inhibitor targeting VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. A 60-mg daily dose led to improved overall survival and progression-free survival (PFS) versus everolimus in advanced RCC patients as a second- or later-line treatment in the METEOR trial...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29143774/disrupting-vegf-vegfr1-interaction-de-novo-designed-linear-helical-peptides-to-mimic-the-vegf13-25-fragment
#7
Beatriz Balsera, M Ángeles Bonache, Marie Reille-Seroussi, Nathalie Gagey-Eilstein, Michel Vidal, Rosario González-Muñiz, María Jesús Pérez de Vega
The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein-protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX⁵ARNX⁸AAX(12)N-NH₂), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1)...
October 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29140979/ginsenoside-rg3-inhibits-angiogenesis-in-a-rat-model-of-endometriosis-through-the-vegfr-2-mediated-pi3k-akt-mtor-signaling-pathway
#8
Yang Cao, Qing Ye, Mengfei Zhuang, Shuwu Xie, Ruihua Zhong, Jingang Cui, Jieyun Zhou, Yan Zhu, Tingting Zhang, Lin Cao
OBJECTIVE: This study aimed to investigate the link between the inhibitory effect of ginsenoside Rg3 on the ectopic endometrium growth and the VEGFR-2-mediated PI3K/Akt/mTOR signaling pathway, a mechanism known to inhibit angiogenesis and induce ectopic endometrial cell apoptosis. MATERIALS AND METHODS: A model of endometriosis was established by allotransplantation in rats. The rats were randomly divided into 5 groups: the ginsenoside Rg3 low-dose group (group A,5mg/kgBW/d of ginsenoside Rg3), the ginsenoside Rg3 high-dose group (group B, 10mg/kgBW/d of ginsenoside Rg3), the gestrinone group (group C, 0...
2017: PloS One
https://www.readbyqxmd.com/read/29137038/quantification-of-stat3-and-vegf-expression-for-molecular-diagnosis-of-lymph-node-metastasis-in-breast-cancer
#9
Yujuan Chen, Ya Liu, Yu Wang, Wen Li, Xiaolu Wang, Xuejuan Liu, Yao Chen, Chibin Ouyang, Jing Wang
BACKGROUND: Axillary lymph node metastasis is associated with increased risk of regional recurrence, distant metastasis, and poor survival in breast malignant neoplasm. Expression of signal transducer and activator of transcription 3 (STAT3) is significantly associated with tumor formation, migration, and invasion in various cancers. In addition, vascular endothelial growth factor (VEGF) expression could promote angiogenesis and increase the risk of tumorigenesis. To determine correlations among STAT3 expression, VEGF, and clinicopathological data on lymph node involvement in breast cancer patients after surgery...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29128359/ubiquitin-c-terminal-hydrolase-l1-plays-a-key-role-in-angiogenesis-by-regulating-hydrogen-peroxide-generated-by-nadph-oxidase-4
#10
In-Kang Song, Hyun Jung Kim, Venkataraman Magesh, Kong-Joo Lee
Ubiquitin C-terminal hydrolase-L1 (UCH-L1), which catalyzes the hydrolysis of ubiquitin esters and amides, is highly expressed in brain. Recently, UCH-L1 has been found to increase cancer cell migration and invasion by modulating hydrogen peroxide generated by NADPH oxidase 4 (NOX4). Because angiogenesis is also mediated by hydrogen peroxide, we explored the role of UCH-L1 in angiogenesis in human umbilical vein endothelial cells (HUVECs). Silencing UCH-L1 suppressed tubule formation in HUVECs, indicating that UCH-L1 promotes angiogenesis in vitro...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29113263/artesunate-inhibits-proliferation-and-invasion-of-mouse-hemangioendothelioma-cells-in-vitro-and-of-tumor-growth-in-vivo
#11
Ning Wang, Hongxia Chen, Yinping Teng, Xionghui Ding, Huan Wu, Xianqing Jin
Artesunate has been demonstrated to be a novel potential antitumor agent in numerous studies. However, its efficacy in infantile hemangioma is unknown. The aim of the present study was to investigate the role of artesunate in the control of vascular tumor biological behavior and molecular mechanism using mouse hemangioendothelioma endothelial (EOMA) cells and a nude mouse model. Cell viability, apoptosis and invasion were determined by an MTT assay, flow cytometric analysis and Transwell invasion assay, respectively...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29104145/the-dual-effects-of-a-novel-peptibody-on-angiogenesis-inhibition-and-m2-macrophage-polarization-on-sarcoma
#12
Xiaoqing Zhu, Jiali Yang, Yanfeng Gao, Chunjing Wu, Lili Yi, Guodong Li, Yuanming Qi
Inhibition of the VEGF/VEGF receptor (VEGFR) and angiopoietin-2 (Ang-2)/TEK receptor tyrosine kinase (Tie-2) pathway is a potential target for tumor angiogenesis. We previously showed that a peptide AS16 which dually inhibits VEGFR/Ang-2 could reduce the tumor growth and decrease the number of microvessels in tumor. However, its short circulating half-life in the serum limits its clinical applications. In this study, as an effort to prolong the short in vivo half-life of AS16, we designed a fusion protein containing peptide AS16 and an IgG Fc fragment...
November 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29103026/effect-of-minocycline-on-vascular-proliferation-after-corneal-alkaline-burn-a-mechanism-study
#13
Haijun Wu, Xin Dai, Hui Li, Chunying Lv
Impairment of vision or blindness always occurs in the progress of corneal neovascularization (CNV). CNV may cause corneal graft rejection at corneal transplant status. Thus, intervention of CNV is of concern to clinical treatment. Given minocycline was reported with inhibiting effect on CNV, our study was focused on specific effect of minocycline on CNV after corneal alkaline burn. Seventy-five male Sprague Dawley rats were randomly assigned into three groups with an equal number (25). Sodium hydroxide (NaOH) solution was used to establish corneal alkaline burn model...
October 20, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29095088/vegf-a121a-binding-to-neuropilins-a-concept-revisited
#14
Sarvenaz Sarabipour, Feilim Mac Gabhann
All known splice isoforms of vascular endothelial growth factor A (VEGF-A) can bind to the receptor tyrosine kinases VEGFR-1 and VEGFR-2. We focus here on VEGF-A121a and VEGF-A165a, two of the most abundant VEGF-A splice isoforms in human tissue (1) , and their ability to bind the Neuropilin co-receptors NRP1 and NRP2. The Neuropilins are key vascular, immune, and nervous system receptors on endothelial cells, neuronal axons, and regulatory T cells respectively. They serve as co-receptors for the Plexins in Semaphorin binding on neuronal and vascular endothelial cells, and for the VEGFRs in VEGF binding on vascular and lymphatic endothelial cells, and thus regulate the initiation and coordination of cell signaling by Semaphorins and VEGFs...
November 2, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29095068/pro-angiogenic-gene-expression-is-associated-with-better-outcome-on-sunitinib-in-metastatic-clear-cell-renal-cell-carcinoma
#15
Benoit Beuselinck, Annelies Verbiest, Gabrielle Couchy, Sylvie Job, Aurélien de Reynies, Clément Meiller, Maarten Albersen, Virginie Verkarre, Evelyne Lerut, Arnaud Méjean, Jean-Jacques Patard, Brigitte Laguerre, Nathalie Rioux-Leclercq, Patrick Schöffski, Stéphane Oudard, Jessica Zucman-Rossi
OBJECTIVES: Clear-cell renal cell carcinomas (ccRCC) are characterized by hyper-vascularization and can respond to vascular endothelial growth factor receptor (VEGFR) inhibitors such as sunitinib. We aimed to study the predictive value of the expression of genes in the hypoxia induced factor (HIF) - vascular endothelial growth factor (VEGF) - VEGFR-pro-angiogenic pathway in metastatic ccRCC (m-ccRCC) patients treated with sunitinib and the correlation between the expression of these genes and the molecular ccrcc-classification, the expression of genes involved in the immune-suppressive microenvironment and Von Hippel-Lindau (VHL) - and Polybromo-1 (PBRM1) - mutational status...
November 2, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29080796/2vascular-endothelial-growth-factor-mediates-ceramide-1-phosphate-stimulated-macrophage-proliferation
#16
Alberto Ouro, Lide Arana, Maziar Riazy, Peng Zhang, Ana Gomez-Larrauri, Urs Steinbrecher, Vincent Duronio, Antonio Gomez-Muñoz
The bioactive sphingolipid ceramide 1-phosphate (C1P) regulates cell division in a variety of cell types including macrophages. However, the mechanisms involved in this action are not completely understood. In the present work we show that C1P stimulates the release of vascular endothelial growth factor (VEGF) in RAW264.7 macrophages, and that this growth factor is essential for stimulation of cell proliferation by C1P. The stimulation of VEGF release was dependent upon activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB-1 also known as Akt-1), and mitogen-activated protein kinase-kinase (MEK)/extracellularly regulated kinase-2 (ERK-2) pathways, as inhibition of these kinases with selective pharmacological inhibitors or with specific gene silencing siRNA, abrogated VEGF release...
October 25, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29076133/effects-of-vascular-endothelial-growth-factors-and-their-receptors-on-megakaryocytes-and-platelets-and-related-diseases
#17
REVIEW
Jin-Gang Yang, Li-Li Wang, Dong-Chu Ma
It is well known that vascular endothelial growth factors (VEGFs) and their receptors (vascular endothelial growth factor receptors, VEGFRs) are expressed in different tissues, and VEGF-VEGFR loops regulate a wide range of responses, including metabolic homeostasis, cell proliferation, migration and tubuleogenesis. As ligands, VEGFs act on three structurally related VEGFRs (VEGFR1, VEGFR2 and VEGFR3 [also termed FLT1, KDR and FLT4, respectively]) that deliver downstream signals. Haematopoietic stem cells (HSCs), megakaryocytic cell lines, cultured megakaryocytes (MKs), primary MKs and abnormal MKs express and secrete VEGFs...
October 26, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29074083/anti-angiogenic-activity-and-mechanism-of-a-chemically-sulfated-natural-glucan-from-phellinus-ribis
#18
Yuhong Liu, Jiazhen Xu, Aizhen Zong, Jihui Wang, Yuguo Liu, Wei Jia, Juan Jin, Guangling Yan, Yongqing Zhang
A sulfated polysaccharide named PRP-S16 was obtained by sulfation of a glucan from Phellinus ribis using the chlorosulfonic acid method. PRP-S16 could significantly block the formation of new vessels in chicken chorioallantoic membrane (CAM). It could also inhibit the proliferation, migration, and tube formation and significantly reduced the mRNA expression of vascular endothelial growth factor (VEGF) in EA.hy926 endothelial cells. Western blotting indicated that PRP-S16 down regulated the protein expression of VEGF and VEGF receptor-1 (VEGFR-1), and inhibited the phosphorylation of VEGFR-2, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK1/2) in EA...
October 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29073598/expression-of-vegfr-2-during-liver-regeneration-after-partial-hepatectomy-in-a-bioluminescence-mouse-model
#19
Patrick Hamid Alizai, Lea Bertram, Daniela Kroy, Julia Kummer, Anne Andert, Ulf Peter Neumann, Tom Florian Ulmer, Athanassious Fragoulis
BACKGROUND: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). METHODS: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day...
October 26, 2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/29069758/transcriptional-factor-oct4-promotes-esophageal-cancer-metastasis-by-inducing-epithelial-mesenchymal-transition-through-vegf-c-vegfr-3-signaling-pathway
#20
Chunguang Li, Maoling Zhu, Xiaoli Lou, Chunying Liu, Hezhong Chen, Xuejing Lin, Weidan Ji, Zhigang Li, Changqing Su
The octamer-binding transcription factor 4 (OCT4) can promote cancer proliferation and metastasis. Esophageal carcinoma (ECC) harbors different quantities of OCT4-positive cancer cells. These cells are highly malignant and prone to metastasis; however, the mechanism remains unknown. In this study, we found that OCT4 enhances vascular endothelial growth factor C (VEGF-C) promoter activity to promote VEGF-C expression and activates VEGF receptor 3 (VEGFR-3) in ECC cells, thereby inducing cancer cell epithelial-mesenchymal transition (EMT)...
September 22, 2017: Oncotarget
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