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https://www.readbyqxmd.com/read/28359053/platelets-as-a-novel-source-of-pro-inflammatory-chemokine-cxcl14
#1
Alexander Witte, Madhumita Chatterjee, Florian Lang, Meinrad Gawaz
OBJECTIVE: Platelets are a major source of chemokines. Here, we demonstrate for the first time that platelets express significant amounts of CXCL14 and disclose powerful effects of platelet-derived CXCL14 on monocyte and endothelial migration. METHODS: The expression of CXCL14 in platelets and in the supernatant of activated platelets was analysed by immunoblotting, ELISA, and flow cytometry. The effect of platelet-derived CXCL14 on monocyte migration was evaluated using a modified Boyden chamber...
March 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#2
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly over-expressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1 and VEGF...
March 20, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28266351/biofabrication-of-a-co-culture-system-in-an-osteoid-like-hydrogel-matrix
#3
Tobias Zehnder, Aldo Boccaccini, Rainer Detsch
Biofabrication aims to develop functional, biological constructs using automated processes (additive manufacturing, AM) involving different cell types and biomaterials [1]. As bone tissue is based on the crosstalk between osteoblasts and osteoclasts at least, evaluating cell-cell and cell-material interactions is of interest to understand bone remodeling. There is increasing interest in the role of osteoclasts not only considering bone resorption, but also their influence on the proliferation, migration and differentiation of osteoblasts...
March 7, 2017: Biofabrication
https://www.readbyqxmd.com/read/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#4
Patricia Himmels, Isidora Paredes, Heike Adler, Andromachi Karakatsani, Robert Luck, Hugo H Marti, Olga Ermakova, Eugen Rempel, Esther T Stoeckli, Carmen Ruiz de Almodóvar
Formation of a precise vascular network within the central nervous system is of critical importance to assure delivery of oxygen and nutrients and for accurate functionality of neuronal networks. Vascularization of the spinal cord is a highly stereotypical process. However, the guidance cues controlling blood vessel patterning in this organ remain largely unknown. Here we describe a new neuro-vascular communication mechanism that controls vessel guidance in the developing spinal cord. We show that motor neuron columns remain avascular during a developmental time window, despite expressing high levels of the pro-angiogenic vascular endothelial growth factor (VEGF)...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28133920/dual-targeting-of-vascular-endothelial-growth-factor-and-bone-morphogenetic-protein-9-10-impairs-tumor-growth-through-inhibition-of-angiogenesis
#5
Yuichi Akatsu, Yasuhiro Yoshimatsu, Taishi Tomizawa, Kazuki Takahashi, Akihiro Katsura, Kohei Miyazono, Tetsuro Watabe
Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10...
January 2017: Cancer Science
https://www.readbyqxmd.com/read/28116649/phase-i-trial-of-aflibercept-vegf-trap-with-radiation-therapy-and-concomitant-and-adjuvant-temozolomide-in-patients-with-high-grade-gliomas
#6
Lakshmi Nayak, John de Groot, Jeffrey S Wefel, Timothy F Cloughesy, Frank Lieberman, Susan M Chang, Antonio Omuro, Jan Drappatz, Tracy T Batchelor, Lisa M DeAngelis, Mark R Gilbert, Kenneth D Aldape, Alfred W K Yung, Joy Fisher, Xiaobu Ye, Alice Chen, Stuart Grossman, Michael Prados, Patrick Y Wen
Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen...
January 23, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28031424/the-dart-study-results-from-the-dose-escalation-and-expansion-cohorts-evaluating-the-combination-of-dalantercept-plus-axitinib-in-advanced-renal-cell-carcinoma
#7
Martin H Voss, Rupal S Bhatt, Elizabeth R Plimack, Brian I Rini, Robert S Alter, J Thaddeus Beck, Dawn Wilson, Xiaosha Zhang, Musa Mutyaba, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Shuchi S Pandya, Michael Atkins
PURPOSE: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1 receptor-fusion protein that acts as a ligand trap for bone morphogenetic proteins (BMP) 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27992512/68ga-trap-rgd-3-hybrid-imaging-for-the-in-vivo-monitoring-of-%C3%AE-v%C3%A3-3-integrin-expression-as-biomarker-of-anti-angiogenic-therapy-effects-in-experimental-breast-cancer
#8
Philipp M Kazmierczak, Andrei Todica, Franz-Josef Gildehaus, Heidrun Hirner-Eppeneder, Matthias Brendel, Ralf S Eschbach, Magdalena Hellmann, Konstantin Nikolaou, Maximilian F Reiser, Hans-Jürgen Wester, Saskia Kropf, Axel Rominger, Clemens C Cyran
OBJECTIVES: To investigate 68Ga-TRAP-(RGD)3 hybrid imaging for the in vivo monitoring of αvß3-integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer. MATERIALS AND METHODS: Human breast cancer (MDA-MB-231) xenografts were implanted orthotopically into the mammary fat pads of n = 25 SCID mice. Transmission/emission scans (53 min to 90 min after i.v. injection of 20 MBq 68Ga-TRAP-(RGD)3) were performed on a dedicated small animal PET before (day 0, baseline) and after (day 7, follow-up) a 1-week therapy with the VEGF antibody bevacizumab or placebo (imaging cohort n = 13; therapy n = 7, control n = 6)...
2016: PloS One
https://www.readbyqxmd.com/read/27990354/effect-of-trapping-vascular-endothelial-growth-factor-a-in-a-murine-model-of-dry-eye-with-inflammatory-neovascularization
#9
Jin Woo Kwon, Jin A Choi, Eun Young Shin, Tae Yoon La, Dong Hyun Jee, Yeon Woong Chung, Yang Kyung Cho
AIM: To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. METHODS: We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS)...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27847621/fusion-proteins-for-treatment-of-retinal-diseases-aflibercept-ziv-aflibercept-and-conbercept
#10
REVIEW
João Rafael de Oliveira Dias, Gabriel Costa de Andrade, Eduardo Amorim Novais, Michel Eid Farah, Eduardo Büchele Rodrigues
In the last few years, monoclonal antibodies have revolutionized the treatment of retinal neovascular diseases. More recently, a different class of drugs, fusion proteins, has provided an alternative treatment strategy with pharmacological differences. In addition to commercially available aflibercept, two other drugs, ziv-aflibercept and conbercept, have been studied in antiangiogenic treatment of ocular diseases. In this scenario, a critical review of the currently available data regarding fusion proteins in ophthalmic diseases may be a timely and important contribution...
2016: International Journal of Retina and Vitreous
https://www.readbyqxmd.com/read/27844403/defective-bone-repair-in-c57bl6-mice-with-acute-systemic-inflammation
#11
D A Behrends, D Hui, C Gao, A Awlia, Y Al-Saran, A Li, J E Henderson, P A Martineau
BACKGROUND: Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. QUESTION/PURPOSES: (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? METHODS: Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days...
March 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/27784235/study-in-treatment-of-collagen-induced-arthritis-in-dba-1-mice-model-by-genistein
#12
Yiping Hu, Jinchao Li, Ling Qin, Wenxiang Cheng, Yuxiao Lai, Ye Yue, Peigen Ren, Xiaohua Pan, Peng Zhang
BACKGROUND: This work aimed to evaluate the effects of genistein treatment in Collagen Induced Arthritis (CIA) mouse model. METHODS: CIA was elicited in DBA/1 Mice by an intradermal injection of 100 μL of an emulsion of bovine type II collagen (CII) in isovolumic incomplete Freund's adjuvant (IFA) at the base of the tail. Twenty-one days later, a second injection of CII in IFA was administered at the base of the tail. After the symptoms of arthritis showed in mouse model, we divided animals into two groups according to their clinical symptom scores...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27765923/il-1-drives-breast-cancer-growth-and-bone-metastasis-in-vivo
#13
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...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27723812/cellular-and-matrix-response-of-the-mandibular-condylar-cartilage-to-botulinum-toxin
#14
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
https://www.readbyqxmd.com/read/27703346/inhaled-corticosteroid-normalizes-some-but-not-all-airway-vascular-remodeling-in-copd
#15
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
https://www.readbyqxmd.com/read/27643516/antiangiogenic-therapy-induces-hepatic-tumor-vascular-network-rearrangement-to-receive-perfusion-via-the-portal-vein-and-hepatic-artery
#16
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...
2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27639528/ultrastrong-trapping-of-vegf-by-graphene-oxide-anti-angiogenesis-application
#17
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
https://www.readbyqxmd.com/read/27577203/-correlation-of-cytogenetic-changes-with-vegf-and-tracp-5b-levels-among-60-elderly-patients-with-multiple-myeloma
#18
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
https://www.readbyqxmd.com/read/27576699/demonstration-of-dce-mri-as-an-early-pharmacodynamic-biomarker-of-response-to-vegf-trap-in-glioblastoma
#19
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
https://www.readbyqxmd.com/read/27557946/regulation-of-vegf-signaling-by-natural-and-synthetic-ligands
#20
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
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