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Vegf trap

Ingunn Holen, Diane V Lefley, Sheila E Francis, Sarah Rennicks, Steven Bradbury, Robert E Coleman, Penelope Ottewell
BACKGROUND: We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in breast cancer cells that metastasise to bone compared with cells that do not. We have now investigated the functional role of IL-1 by blocking IL-1R signalling with the clinically licensed antagonist, anakinra. METHODOLOGY: 6-week old female BALB/c mice received a subcutaneous or intra-venous injection of MDA-MB-231-IV or MCF7 cells...
September 27, 2016: Oncotarget
Eliane H Dutra, Mara H O' Brien, Alexandro Lima, Zana Kalajzic, Aditya Tadinada, Ravindra Nanda, Sumit Yadav
OBJECTIVES: To evaluate the cellular and matrix effects of botulinum toxin type A (Botox) on mandibular condylar cartilage (MCC) and subchondral bone. MATERIALS AND METHODS: Botox (0.3 unit) was injected into the right masseter of 5-week-old transgenic mice (Col10a1-RFPcherry) at day 1. Left side masseter was used as intra-animal control. The following bone labels were intraperitoneally injected: calcein at day 7, alizarin red at day 14 and calcein at day 21. In addition, EdU was injected 48 and 24 hours before sacrifice...
2016: PloS One
Amir Soltani, Eugene Haydn Walters, David W Reid, Shakti Dhar Shukla, Kaosia Nowrin, Chris Ward, H Konrad Muller, Sukhwinder Singh Sohal
BACKGROUND: This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD). METHODS: Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months. Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Wonseok Kang, Joon Seok Lim, Mi-Suk Park, Gou Young Koh, Honsoul Kim
PURPOSE: Hepatic malignancies can easily develop resistance to antiangiogenic therapy, but the underlying mechanism remains poorly understood. This study explores whether antiangiogenic therapy influences the tumor vascular network and/or the vessels feeding the hepatic tumor. METHODS: Mice implanted with Lewis lung carcinoma (LLC) cells were subcutaneously injected 3 times (once every other day starting 1 week after LLC implantation) with either an antiangiogenic agent [vascular endothelial growth factor (VEGF)-Trap] or control agent (bovine serum albumin) at a dose of 25 mg/kg before performing angiography...
September 20, 2016: Journal of Vascular Research
Pei-Xin Lai, Chung-Wein Chen, Shih-Chun Wei, Tzu-Yu Lin, Hong-Jyuan Jian, Irving Po-Jung Lai, Ju-Yi Mao, Pang-Hung Hsu, Han-Jia Lin, Wen-Shyong Tzou, Shiow-Yi Chen, Scott G Harroun, Jui-Yang Lai, Chih-Ching Huang
Angiogenesis is the process of formation of new blood vessels, which is essential to human biology, and also plays a crucial role in several pathologies such as tumor growth and metastasis, exudative age-related macular degeneration, and ischemia. Vascular endothelial growth factor (VEGF), in particular, VEGF-A165 is the most important pro-angiogenic factor for angiogenesis. Thus, blocking the interaction between VEGFs and their receptors is considered an effective anti-angiogenic strategy. We demonstrate for that first time that bovine serum albumin-capped graphene oxide (BSA-GO) exhibits high stability in physiological saline solution and possesses ultrastrong binding affinity towards VEGF-A165 [dissociation constant (Kd) ∼3 × 10(-12) M], which is at least five orders of magnitude stronger than that of high-abundant plasma proteins such as human serum albumin, fibrinogen, transferrin, and immunoglobulin G...
December 2016: Biomaterials
Ling Cen, Yu Jiang, Xiuwen Zhang, Hongying Chao, Rong Xiao, Wenmin Han, Tao Chen, Xuzhang Lu
OBJECTIVE: To assess the correlation of cytogenetic changes with serum vascular endothelial growth factor (VEGF) and serum tartrate resistant acid phosphatase (TRacp-5b) levels among elderly patients with multiple myeloma (MM). METHODS: Chromosomal changes were analyzed with a modified culturing method in the presence of IL-6. Serum levels of VEGF and TRacp-5b were determined with enzyme-linked immunosorbent assays (ELISA). RESULTS: Among the 60 MM patients, chromosomal abnormalities were found in 27 cases, including 22 with numerical abnormalities and 15 with structural abnormalities...
October 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Allison F O'Neill, Lei Qin, Patrick Y Wen, John F de Groot, Annick D Van den Abbeele, Jeffrey T Yap
Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered...
August 30, 2016: Journal of Neuro-oncology
Andrea Rossi, Sebastien Gauvrit, Michele Marass, Luyuan Pan, Cecilia B Moens, Didier Y R Stainier
The mechanisms that allow cells to bypass anti-VEGFA therapy remain poorly understood. Here we use zebrafish to investigate this question and first show that vegfaa mutants display a severe vascular phenotype that can surprisingly be rescued to viability by vegfaa mRNA injections at the one-cell stage. Using vegfaa mutants as an in vivo test tube, we found that zebrafish Vegfbb, Vegfd and Pgfb can also rescue these animals to viability. Taking advantage of a new vegfr1 tyrosine kinase deficient mutant, we determined that Pgfb rescues vegfaa mutants via Vegfr1...
August 24, 2016: Blood
Yumiko Yamauchi, Shigeharu Ueki, Yasunori Konno, Wataru Ito, Masahide Takeda, Yuka Nakamura, Junko Nishikawa, Yuki Moritoki, Ayumi Omokawa, Tomoo Saga, Makoto Hirokawa
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study...
December 2016: Cytokine
Dong Li, Jiejun Shi, Yanhua Du, Kaiming Chen, Zhenping Liu, Bing Li, Jie Li, Fei Tao, Hua Gu, Cizhong Jiang, Jianmin Fang
Tumor cells become resistant after long-term use of anti-VEGF (vascular endothelial growth factor) agents. Our previous study shows that treatment with a VEGF inhibitor (VEGF-Trap) facilitates to develop tumor resistance through regulating angiogenesis-related genes. However, the underlying molecular mechanisms remain elusive. Histone modifications as a key epigenetic factor play a critical role in regulation of gene expression. Here, we explore the potential epigenetic gene regulatory functions of key histone modifications during tumor resistance in a mouse Lewis lung carcinoma (LLC) cell line...
2016: PloS One
Dawei Zhang, Yongjun Huang, Zongwen Huang, Rongkai Zhang, Honggang Wang, Dong Huang
BACKGROUND Osteoclast formation is closely related to the immune system. FTY720, a new immunosuppressive agent, has some functions in immune regulation. Its main active ingredients become FTY-720P in vivo by phosphorylation modification. The objective of this study was to determine the effects of FTY-720 with various concentrations on osteoclasts in vitro. MATERIAL AND METHODS RAW264.7 cells and bone marrow-derived mononuclear phagocytes (BMMs) were treated with RANKL to obtain osteoclasts in vitro. To investigate the role of FTY-720 in osteoclast formation, trap enzyme staining was performed and the number of osteoclasts was counted...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Gilbert Deray, Nicolas Janus, Blandine Aloy, Vincent Launay-Vacher
During the last decade, inhibitors of the vascular endothelial growth factor (VEGF) were developed for the treatment of cancer. Many anti-VEGF are available but the issue is still the same: to inhibit the effect of the VEGF on their receptors. There are two main classes, depending on the mechanism of action by blocking the binding of the ligand on the receptor (VEGF trap or monoclonal antibody) or by affecting directly the receptor (tyrosine kinase inhibitor [TKI], monoclonal antibody directed against the VEGF receptor)...
July 2016: Bulletin du Cancer
Rosario Amato, Martina Biagioni, Maurizio Cammalleri, Massimo Dal Monte, Giovanni Casini
PURPOSE: Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. METHODS: Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants...
June 1, 2016: Investigative Ophthalmology & Visual Science
Yi Zhu, Yuan Wu, Yu Liang, Wenfu Tan, Zhuoran Liu, Jianhua Xiao
INTRODUCTION: The aim of this study is to determine whether regulation of the expression level of fms-like tyrosine kinase-4 (Flt-4) is related to osteoclast differentiation. MATERIAL AND METHODS: Osteoclast formation and differentiation of mouse bone marrow cells and RAW264.7 cells were performed. To induce osteoclast differentiation, RANKL (50 ng/ml) with or without vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D) was added to mouse bone marrow cells and RAW264...
June 1, 2016: Archives of Medical Science: AMS
Sang Jun Park, Yewon Choi, Young Mi Na, Hye Kyoung Hong, Ji Yeon Park, Kyu Hyung Park, Jae Yong Chung, Se Joon Woo
Purpose: We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model. Methods: Aflibercept was injected intravitreally in 21 eyes from New Zealand White rabbits. The eyes were enucleated 1, 24, 48, 120, 216, 360, and 720 hours (1, 2, 5, 9, 15, and 30 days, respectively) after injection and immediately frozen at -80°C. The concentrations of aflibercept in the vitreous, aqueous humor, and retina/choroid were determined by performing an indirect enzyme-linked immunosorbent assay, and analyzed to understand the pharmacokinetic properties of the drug...
May 1, 2016: Investigative Ophthalmology & Visual Science
Xiao-Feng Li, Chun-Chun Xue, Yong-Jian Zhao, Shao-Dan Cheng, Dong-Feng Zhao, Qian-Qian Liang, Lin Chen, Qiang Wang, Sheng Lu, Qi Shi, Yong-Jun Wang, Bing Shu
STUDY DESIGN: Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice which show intervertebral disc (IVD) degeneration. OBJECTIVE: To clarify the pathological changes in lumbar IVD degeneration in Opg KO mice. SUMMARY OF BACKGROUND DATA: Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration...
May 18, 2016: Spine
Farzana Sharmin, Casey McDermott, Jay Lieberman, Archana Sanjay, Yusuf Khan
Autografts have been shown to stimulate osteogenesis, osteoclastogenesis and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics...
May 7, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Dong Li, Kun Xie, Longzhen Zhang, Xuejing Yao, Hongwen Li, Qiaoyu Xu, Xin Wang, Jing Jiang, Jianmin Fang
Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect...
July 28, 2016: Cancer Letters
Niamh Hallinan, Stephen Finn, Sinead Cuffe, Shereen Rafee, Kenneth O'Byrne, Kathy Gately
Fibroblast growth factors (FGFs) regulate a plethora of biological functions, in both the embryonic and adult stages of development, binding their cognate receptors and thus activating a variety of downstream signalling pathways. Deregulation of the FGF/FGFR signalling axis, observed in multifarious tumor types including squamous non-small cell lung cancer, occurs through genomic FGFR alterations that drive ligand-independent receptor signalling or alterations that support ligand-dependent activation. Mutations are not restricted to the tyrosine kinase domain and aberrations appear to be tumor type dependent...
May 2016: Cancer Treatment Reviews
Maria Waizel, Annekatrin Rickmann, Björn R Blanke, Katharina Wolf, Sara Kazerounian, Peter Szurman
PURPOSE: To study the visual outcome and change in central macular thickness (CMT) in patients with neovascular age-related macular degeneration (AMD) who were previously treated with aflibercept (VEGF Trap-Eye, Eylea) and were subsequently switched to bevacizumab (Avastin). METHODS: In this observational analysis, 19 eyes initially treated with at least 3 injections of bevacizumab after initial treatment with at least 3 injections of aflibercept are reported. Outcome measures were Snellen visual acuity (best-corrected visual acuity (BCVA) and CMT measured by spectral-domain optical coherence tomography...
August 4, 2016: European Journal of Ophthalmology
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