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https://www.readbyqxmd.com/read/28714916/targeting-of-tumor-neovasculature-with-grb-vegf121-a-novel-cytotoxic-fusion-protein
#1
REVIEW
Khalid A Mohamedali, Michael G Rosenblum
Angiogenesis is a critical process in numerous diseases, and intervention in neovascularization has therapeutic value in several disease settings, including ocular diseases, arthritis, and in tumor progression and metastatic spread. Various vascular targeting agents have been developed, including those that inhibit growth factor receptor tyrosine kinases, blocking antibodies that interfere with receptor signal transduction, and strategies that trap growth factor ligands. Limited anti-tumor efficacy studies have suggested that the targeted delivery of the human pro-apoptotic molecule Granzyme B to tumor cells has significant potential for cancer treatment...
July 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28655794/diffusion-mri-phenotypes-predict-overall-survival-benefitfrom-anti-vegf-monotherapy-in-recurrent-glioblastoma-converging-evidence-from-phase-ii-trials
#2
Benjamin M Ellingson, Elizabeth Gerstner, Marion Smits, Raymond Y Huang, Rivka R Colen, Lauren E Abrey, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Ararat Chakhoyan, Renske Gahrmann, Whitney B Pope, Kevin Leu, Catalina Raymond, Davis C Woodworth, John F de Groot, Patrick Y Wen, Tracy Batchelor, Martin J van den Bent, Timothy F Cloughesy
Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. <br /><br />Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929)...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28651842/sulodexide-prevents-activation-of-the-pla2-cox-2-vegf-inflammatory-pathway-in-human-retinal-endothelial-cells-by-blocking-the-effect-of-age-rage
#3
Giovanni Giurdanella, Francesca Lazzara, Nunzia Caporarello, Gabriella Lupo, Carmelina Daniela Anfuso, Chiara M Eandi, Gian Marco Leggio, Filippo Drago, Claudio Bucolo, Salvatore Salomone
Diabetic retinopathy is characterized by the breakdown of endothelial blood-retinal barrier. We tested the hypothesis that sulodexide (SDX), a highly purified glycosaminoglycan composed of 80% iduronylglycosaminoglycan sulfate and 20% dermatan sulfate, protects human retinal endothelial cells (HREC) from high glucose (HG)-induced damage, through the suppression of inflammatory ERK/cPLA2/COX-2/PGE2 pathway, by blocking the effect of advanced glycation end-products (AGEs). HREC were treated with HG (25mM) or AGEs (glycated-BSA, 2mg/ml) for 48h, with or without SDX (60μg/ml) or aflibercept (AFL, 40μg/ml), a VEGF-trap...
June 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28623721/macrophage-phenotypic-mechanomodulation-of-enhancing-bone-regeneration-by-superparamagnetic-scaffold-upon-magnetization
#4
Suisui Hao, Jie Meng, Yu Zhang, Jian Liu, Xin Nie, Fengxin Wu, Yanlian Yang, Chen Wang, Ning Gu, Haiyan Xu
Macrophages are involved in all phases of scaffold induced tissue regeneration, orchestrating the transition from an inflammatory to regenerative phenotype to guide all other cell types to complete the wound healing process when a tissue defect advances beyond the critical size. Therefore, harnessing macrophages by scaffolds is important for facilitating tissue regeneration in situ. In this work we utilized the superparamagnetic scaffold upon magnetization as a mechanostimulation platform to apply forces directly to macrophages grown in the scaffold, aiming to figure out whether the functions of macrophages related to bone tissue regeneration can be mechanomodulated and to elucidate the underlying mechanisms...
June 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/28607469/pth-1-34-induced-differentiation-and-mineralization-of-mandibular-condylar-cartilage
#5
Mara Heather O' Brien, Eliane Hermes Dutra, Alexandro Lima, Ravindra Nanda, Sumit Yadav
Intermittent Parathyroid Hormone (I-PTH) is the only FDA approved anabolic drug therapy available for the treatment of osteoporosis in males and postmenopausal females. The effects of I-PTH on the chondrogenic lineage of the mandibular condylar cartilage (MCC) are not well understood. To investigate the role of I-PTH on the MCC and subchondral bone, we carried out our studies using 4 to 5 week old triple transgenic mice (Col1a1XCol2a1XCol10a1). The experimental group was injected with PTH (80 μg/kg) daily for 2 weeks, while control group was injected with saline...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594896/zoledronate-suppressed-angiogenesis-and-osteogenesis-by-inhibiting-osteoclasts-formation-and-secretion-of-pdgf-bb
#6
Si-Yong Gao, Guang-Sen Zheng, Lin Wang, Yu-Jie Liang, Si-En Zhang, Xiao-Mei Lao, Kan Li, Gui-Qing Liao
PURPOSE: Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation...
2017: PloS One
https://www.readbyqxmd.com/read/28524152/-vascular-endothelial-growth-factor-inhibitors-in-the-treatment-of-neovascular-age-related-macular-degeneration
#7
I N Dyakov, S K Zyryanov
Neovascular age-related macular degeneration (AMD) is the leading cause of vision loss in older patients. An important role in angiogenesis is played by regulatory mechanisms (an increase in the number of proliferating endothelial and stromal cells and morphological alterations in the vascular network) induced by factors from the vascular endothelial growth factor (VEGF) family. Since 2006, the key treatment of neovascular AMD includes agents that inhibit the activity of VEGF. This review covers the effectiveness and safety of the use of anti-VEGF agents in neovascular AMD patients...
2017: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/28359053/platelets-as-a-novel-source-of-pro-inflammatory-chemokine-cxcl14
#8
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...
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
#9
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
#10
Tobias Zehnder, Aldo R Boccaccini, Rainer Detsch
Biofabrication aims to develop functional, biological constructs using automated processes (additive manufacturing, AM) involving different cell types and biomaterials (Groll  et al 2016  Biofabrication 13001 1-6). 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...
May 11, 2017: Biofabrication
https://www.readbyqxmd.com/read/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#11
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
#12
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
#13
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...
March 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
#14
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 B Atkins
Purpose: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and 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 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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