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Christopher E Anderson, L Lee Hamm, Gem Batuman, Damodar R Kumbala, Chung-Shiuan Chen, Swapna G Kallu, Ravi Siriki, Shilpa Gadde, Myra A Kleinpeter, N Kevin Krane, Eric E Simon, Jiang He, Jing Chen
BACKGROUND: There are limited data on the associations of circulating angiogenic factors with chronic kidney disease (CKD). We investigate the associations of circulating vascular endothelial growth factor (VEGF)-A, angiopoietin-1, angiopoietin-1/VEGF-A ratio, VEGF receptor 1 (VEGFR-1), VEGFR-2, and pentraxin-3 with CKD. METHODS: We recruited 201 patients with CKD and 201 community controls without CKD from the greater New Orleans area. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1...
May 21, 2018: BMC Nephrology
Gilda Varricchi, Stefania Loffredo, Maria Rosaria Galdiero, Giancarlo Marone, Leonardo Cristinziano, Francescopaolo Granata, Gianni Marone
Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. During adulthood, angiogenesis and lymphangiogenesis are activated at sites of tumor growth, tissue injury and remodeling, and chronic inflammation. Vascular endothelial growth factors (VEGFs), angiopoietin (ANGPTs) and a multitude of additional signaling molecules play distinct roles in the modulation of angiogenesis/lymphangiogenesis. VEGFs and ANGPTs activate specific tyrosine kinase receptor (e...
May 17, 2018: Current Opinion in Immunology
Ju Yang, Jing Yan, Baorui Liu
In addition to the crucial role in promoting the growth of tumor vessels, vascular endothelial growth factor (VEGF) is also immunosuppressive. VEGF can inhibit the function of T cells, increase the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and hinder the differentiation and activation of dendritic cells (DCs). Recent studies have investigated the role of antiangiogenic agents in antitumor immunity, especially in recent 3 years. Therefore, it is necessary to update the role of targeting VEGF/VEGFR in antitumor immunity...
2018: Frontiers in Immunology
Shunsuke Shibao, Ryo Ueda, Katsuya Saito, Ryogo Kikuchi, Hideaki Nagashima, Atsuhiro Kojima, Hiroshi Kagami, Eriel Sandika Pareira, Hikaru Sasaki, Shinobu Noji, Yutaka Kawakami, Kazunari Yoshida, Masahiro Toda
Object: Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas...
April 20, 2018: Oncotarget
Yang Kyung Cho, Eun Young Shin, Hironori Uehara, Balamurali Ambati
PURPOSE: To investigate the anti(lymph)angiogenic and anti-inflammatory effects of 0.5% timolol maleate in a murine corneal suture model. METHODS: Corneal neovascularization and lymphangiogenesis were compared in groups of mice that underwent corneal suture and were subsequently administered a subconjunctival injection of 0.5% timolol maleate, dexamethasone, or phosphate-buffered saline (PBS). Immunohistochemical staining and analysis were performed in each group...
May 14, 2018: Journal of Ocular Pharmacology and Therapeutics
Han Jo Kim, Moo-Jun Baek, Dong Hyun Kang, Sang-Cheol Lee, Sang Byung Bae, Kyu Taek Lee, Namsu Lee, Hyungjoo Kim, Dongjun Jeong, Tae Sung Ahn, Moon Soo Lee, Dae Sik Hong, Jong-Ho Won
PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010...
April 2018: Annals of Coloproctology
Andrea Casadei Gardini, Luca Faloppi, Giuseppe Aprile, Oronzo Brunetti, Chiara Caparello, Jody Corbelli, Luchino Chessa, Daniele Bruno, Giorgio Ercolani, Alessandro Leonetti, Giorgio de Stefano, Nunzia Farella, Francesco Giuseppe Foschi, Arianna Lanzi, Vincenzo Dadduzio, Giorgia Marisi, Gianluca Masi, Francesca V Negri, Flavia Pagan, Daniele Santini, Emanuela Scarpi, Marianna Silletta, Nicola Silvestris, Emiliano Tamburini, Davide Tassinari, Caterina Vivaldi, Umberto Vespasiani Gentilucci, Vittorina Zagonel, Lorenzo Calvetti, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
Introduction Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS...
December 1, 2017: Tumori
Paulina Kozakiewicz, Ludmiła Grzybowska-Szatkowska
Despite the development of standard therapies, including surgery, radiotherapy and chemotherapy, survival rates for head and neck squamous cell carcinoma (HNSCC) have not changed significantly over the past three decades. Complete recovery is achieved in <50% of patients. The treatment of advanced HNSCC frequently requires multimodality therapy and involves significant toxicity. The promising, novel treatment option for patients with HNSCC is molecular-targeted therapies. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib), vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or vascular endothelial growth factor receptor (VEGFR) inhibitors (sorafenib, sunitinib and vandetanib) and inhibitors of phosphatidylinositol 3-kinase/serine/threonine-specific protein kinase/mammalian target of rapamycin...
May 2018: Oncology Letters
Kurt Ballmer-Hofer, Caroline A C Hyde, Thomas Schleier, Dragana Avramovic
Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) is the main mediator of angiogenic signaling in endothelial cells and a primary responder to VEGF. VEGF dependent VEGFR-2 activation regulates endothelial cell migration and proliferation, as well as vessel permeability. VEGF is presented as an antiparallel homodimer, and its binding to VEGFR-2 brings two receptors in close proximity. Downstream signaling is triggered by receptor dimerization, kinase activation, and receptor internalization. Our aim was to further investigate allosteric inhibition using binders targeting extracellular subdomains 4⁻7 of VEGFR-2 as an alternative to existing anti-angiogenic therapies, which rely on neutralizing VEGF or blocking of the ligand-binding site on the receptor...
May 1, 2018: International Journal of Molecular Sciences
Ya-Ru Wen, Jun-Hua Yang, Xiao Wang, Zhi-Bin Yao
Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-β clearance. This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain. First, human lymphatic endothelial cells were treated with 100 ng/mL recombinant human vascular endothelial growth factor-C (rhVEGF-C) protein...
April 2018: Neural Regeneration Research
Rie Imamaki, Kazuko Ogawa, Yasuhiko Kizuka, Yusuke Komi, Soichi Kojima, Norihiro Kotani, Koichi Honke, Takashi Honda, Naoyuki Taniguchi, Shinobu Kitazume
Most of the angiogenesis inhibitors clinically used in cancer treatment target the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway. However, the current strategies for treating angiogenesis have limited efficacy. The issue of how to treat angiogenesis and endothelial dysfunction in cancer remains a matter of substantial debate. Here we demonstrate a glycosylation-dependent regulatory mechanism for tumor angiogenesis. St6gal1-/- mice, lacking the α2,6-sialylation enzyme, were shown to exhibit impaired tumor angiogenesis through enhanced endothelial apoptosis...
May 2, 2018: Oncogene
S Sh Gapizov, L E Petrovskaya, L N Shingarova, E V Svirschevskaya, D A Dolgikh, M P Kirpichnikov
Endothelial cells play a major role in the development of inflammation and neoangiogenesis in cancer and chronic inflammatory diseases. In 3D cultures, cells are under conditions that closely resemble those existing in healthy and disease-stricken human organs and tissues. Therefore, the development of a 3D model based on the Ea.hy926 endothelial cell line is an urgent need in molecular and cellular biology. Cell cultivation on an anti-adhesive substrate under static conditions was shown to lead to the formation of spheroids (3D cultures)...
January 2018: Acta Naturae
L Muratori, S Gnavi, F Fregnan, A Mancardi, S Raimondo, I Perroteau, S Geuna
Vascular endothelial growth factor (VEGF) represents one of the main factor involved not only in angiogenesis and vasculogenesis but also in neuritogenesis, VEGF plays its function acting via different receptors: VEGF receptor1 (VEGFR-1), VEGF receptor2 (VEGFR-2), VEGF receptor3 (VEGFR-3) and co-receptors Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). This study reports on the first in vivo analysis of the expression of VEGF and VEGF family molecules in peripheral nerve degeneration and regeneration: for this purpose, different model of nerve lesion in rat were adopted, the median nerve crush injury and the median nerve transaction followed or not by end-to end microsurgical repair...
April 30, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Cristina M Failla, Miriam Carbo, Veronica Morea
Vascular endothelial growth factor receptor (VEGFR)-1 exists in different forms, derived from alternative splicing of the same gene. In addition to the transmembrane form, endothelial cells produce a soluble VEGFR-1 (sVEGFR-1) isoform, whereas non-endothelial cells produce both sVEGFR-1 and a different soluble molecule, known as soluble fms-like tyrosine kinase (sFlt)1-14. By binding members of the vascular endothelial growth factor (VEGF) family, the soluble forms reduce the amounts of VEGFs available for the interaction with their transmembrane receptors, thereby negatively regulating VEGFR-mediated signaling...
April 27, 2018: International Journal of Molecular Sciences
Jiaqing Xiong, Lifang Liu, Kui Li, Weixia Zhang, Jiaxin Nie
To investigate the relationship between the Notch signaling pathway and expression of vascular relevant factors in rabbit deep II degree burn model.
 Methods: A total of 120 New Zealand white rabbits were randomly divided into a block group, a model group, and a control group. The block group was injected 2 mg/kg γ-secretase inhibitor (GSI) once a day at 1 d before the model establishment, and 1-14 d after the deep II degree burns model establishment. The model group were injected physiological saline at the same time...
March 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Grazia Maugeri, Agata Grazia D'Amico, Daniela Maria Rasà, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two related peptides acting as neurotransmitters/neuromodulators in central and peripheral nervous system. They are also involved in cancer showing a controversial role. Particulary, they are implicated in neuroblastoma differentiation (NB). This pediatric tumor can evolve to a malignant metastatic disease or spontaneously regress towards a benign form, known as ganglioneuroblastoma/ganglioneuroma. A negative hallmark of neoplasia progression is represented by hypoxic microenvironment...
April 17, 2018: Neuropeptides
Ibrahim Abdullah Al Balawi, Rashid Mir, F M Abu-Duhier
Aim: VEGF gene polymorphisms can induce either increase or inhibition of VEGF secretion, with altered promoter activity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breast carcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene with breast cancer risk in Saudi women. Methodology: Genotyping of the VEGF-gene variation (-2578A>C) was performed using the amplification refractory mutation system PCR. We investigated the association of VEGF gene variants with different clinicopathological features of breast cancer patients...
April 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
J Su, Z Q Li, S Cui, L H Ji, K X Chai, H Geng, X J Ma, Y Z Yang, Z Z Bai, R L Ge
Objective: This study was aimed at investigating the levels and relationships of vascular endothelial growth factor (VEGF) and its receptor(VEGFR) in the bone marrow mononuclear cells (MNC) of chronic mountain sickness (CMS). Methods: A total of 34 patients with CMS and 30 controls residing at altitudes of 3 000-4 500 m were recruited for this study. The levels of VEGF, VEGFR1 and VEGFR2 in bone marrow MNC were detected by flow cytometry technique and RT-qPCR. Results: The percentage of VEGFR2 positive cells in the bone marrow MNC of CMS were higher than that of the controls[20...
April 10, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Chloe J Peach, Viviane W Mignone, Maria Augusta Arruda, Diana C Alcobia, Stephen J Hill, Laura E Kilpatrick, Jeanette Woolard
Vascular endothelial growth factor-A (VEGF-A) is a key mediator of angiogenesis, signalling via the class IV tyrosine kinase receptor family of VEGF Receptors (VEGFRs). Although VEGF-A ligands bind to both VEGFR1 and VEGFR2, they primarily signal via VEGFR2 leading to endothelial cell proliferation, survival, migration and vascular permeability. Distinct VEGF-A isoforms result from alternative splicing of the Vegfa gene at exon 8, resulting in VEGFxxx a or VEGFxxx b isoforms. Alternative splicing events at exons 5⁻7, in addition to recently identified posttranslational read-through events, produce VEGF-A isoforms that differ in their bioavailability and interaction with the co-receptor Neuropilin-1...
April 23, 2018: International Journal of Molecular Sciences
Daniel Escorsim Machado, Jamila Alessandra Perini, Erika Menezes de Mendonça, Jessica Ristow Branco, Karina Cristina Rodrigues-Baptista, Jessica Alessandra-Perini, Jair Machado Espíndola-Neto, Thiago Alves Dos Santos, Wagner Santos Coelho, Luiz Eurico Nasciutti, Mauro Sola-Penna, Patricia Zancan
The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200 mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group...
April 21, 2018: Molecular and Cellular Endocrinology
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