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https://www.readbyqxmd.com/read/28971631/intravitreal-ziv-aflibercept-clinical-effects-and-economic-impact
#1
Sumit Randhir Singh, Avantika Dogra, Michael Stewart, Taraprasad Das, Jay Chhablani
During the past decade, drugs that inhibit the actions of vascular endothelial growth factor (VEGF) have become standard-of-care treatment for a variety of chorioretinal vascular conditions. The off-label, intravitreal use of ziv-aflibercept (Zaltrap) has provided clinicians with an additional cost-effective drug. The commercial preparation of ziv-aflibercept contains the same aflibercept (VEGF-trap) molecule as Eylea but has a much higher osmolarity (1000 mOsm/kg vs 300 mOsm/kg). Initial concerns regarding cytotoxicity and long-term safety of intravitreal ziv-aflibercept have been largely negated after a series of publications failed to identify adverse ocular and systemic side effects...
October 3, 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28965804/neutralization-of-placental-growth-factor-as-a-novel-treatment-option-in-diabetic-retinopathy
#2
Tine Van Bergen, Tjing-Tjing Hu, Isabelle Etienne, Geert E Reyns, Lieve Moons, Jean H M Feyen
The current standard of care in clinical practice for diabetic retinopathy (DR), anti-vascular endothelial growth factor (VEGF) therapy, has shown a significant improvement in visual acuity. However, treatment response can be variable and might be associated with potential side effects. This study was designed to investigate inhibition of placental growth factor (PlGF) as a possible alternative therapy for DR. The effect of the anti-PlGF antibody (PL5D11D4) was preclinically evaluated in various animal models by investigating different DR hallmarks, including inflammation, neurodegeneration, vascular leakage and fibrosis...
September 28, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28834531/maxillary-sinus-elevation-surgery-with-chronos-and-autogenous-bone-graft-immunohistochemical-assessment-of-runx2-vegf-trap-and-osteocalcin
#3
Rodrigo Dos Santos Pereira, Fernanda Brasil Boos, Luis Fernado Gorla, Idelmo Rangel Garcia, Roberta Okamoto, Eduardo Hochuli-Vieira
The purpose of this study was to evaluate a composite graft of ChronOS, a beta-tricalcium phosphate (β-TCP), mixed 1:1 with an autogenous bone graft in human maxillary sinus augmentation. A total of 12 maxillary sinuses were grafted with an autogenous bone graft (control group), and 9 maxillary sinuses were grafted with ChronOS mixed 1:1 with an autogenous bone graft (test group). After 6 months, biopsy samples were obtained concurrent to the placement of dental implants and were subjected to histomorphometric and immunohistochemical analyses for Runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), tartrate-resistant acid phosphatase, and osteocalcin...
August 23, 2017: International Journal of Periodontics & Restorative Dentistry
https://www.readbyqxmd.com/read/28818671/incidence-and-risk-of-cardiotoxicity-in-cancer-patients-treated-with-targeted-therapies
#4
REVIEW
Matteo Santoni, Federico Guerra, Alessandro Conti, Alessandra Lucarelli, Silvia Rinaldi, Laura Belvederesi, Alessandro Capucci, Rossana Berardi
BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL)...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28736316/early-actions-of-anti-vascular-endothelial-growth-factor-vascular-endothelial-growth-factor-receptor-drugs-on-angiogenic-blood-vessels
#5
Basel Sitohy, Sunghee Chang, Tracey E Sciuto, Elizabeth Masse, Mei Shen, Peter M Kang, Shou-Ching Jaminet, Laura E Benjamin, Rupal S Bhatt, Ann M Dvorak, Janice A Nagy, Harold F Dvorak
Tumors induce their heterogeneous vasculature by secreting vascular endothelial growth factor (VEGF)-A. Anti-VEGF/VEGF receptor (VEGFR) drugs treat cancer, but the underlying mechanisms remain unclear. An adenovirus expressing VEGF-A (Ad-VEGF-A(164)) replicates the tumor vasculature in mice without tumor cells. Mother vessels (MV) are the first angiogenic vessel type to form in tumors and after Ad-VEGF-A(164). Multiday treatments with a VEGF trap reverted MV back to normal microvessels. We now show that, within hours, a single dose of several anti-VEGF drugs collapsed MV to form glomeruloid microvascular proliferations (GMP), accompanied by only modest endothelial cell death...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28655794/diffusion-mri-phenotypes-predict-overall-survival-benefit-from-anti-vegf-monotherapy-in-recurrent-glioblastoma-converging-evidence-from-phase-ii-trials
#6
Benjamin M Ellingson, Elizabeth R Gerstner, Marion Smits, Raymond Y Huang, Rivka 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 de Groot, Patrick Y Wen, Tracy T Batchelor, Martin J van den Bent, Timothy F Cloughesy
Purpose: 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.Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate phase II clinical trials were included: (i) cediranib (NCT00035656); (ii) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); (iii) cabozantinib (XL184-201; NCT00704288); (iv) aflibercept (VEGF Trap; NCT00369590); and (v) bevacizumab or lomustine (BELOB; NTR1929)...
October 1, 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
#7
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...
October 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28524152/-vascular-endothelial-growth-factor-inhibitors-in-the-treatment-of-neovascular-age-related-macular-degeneration
#8
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/28262664/motor-neurons-control-blood-vessel-patterning-in-the-developing-spinal-cord
#9
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/28116649/phase-i-trial-of-aflibercept-vegf-trap-with-radiation-therapy-and-concomitant-and-adjuvant-temozolomide-in-patients-with-high-grade-gliomas
#10
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/27847621/fusion-proteins-for-treatment-of-retinal-diseases-aflibercept-ziv-aflibercept-and-conbercept
#11
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/27643516/antiangiogenic-therapy-induces-hepatic-tumor-vascular-network-rearrangement-to-receive-perfusion-via-the-portal-vein-and-hepatic-artery
#12
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/27576699/demonstration-of-dce-mri-as-an-early-pharmacodynamic-biomarker-of-response-to-vegf-trap-in-glioblastoma
#13
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...
December 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27362259/profiling-analysis-of-histone-modifications-and-gene-expression-in-lewis-lung-carcinoma-murine-cells-resistant-to-anti-vegf-treatment
#14
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
https://www.readbyqxmd.com/read/27318610/-renovascular-effects-of-antiangiogenic-drugs
#15
REVIEW
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
https://www.readbyqxmd.com/read/27286364/vegf-as-a-survival-factor-in-ex-vivo-models-of-early-diabetic-retinopathy
#16
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
https://www.readbyqxmd.com/read/27258433/intraocular-pharmacokinetics-of-intravitreal-aflibercept-eylea-in-a-rabbit-model
#17
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
https://www.readbyqxmd.com/read/27079204/response-to-bevacizumab-after-treatment-with-aflibercept-in-eyes-with-neovascular-amd
#18
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
https://www.readbyqxmd.com/read/26578446/first-year-visual-acuity-outcomes-of-providing-aflibercept-according-to-the-view-study-protocol-for-age-related-macular-degeneration
#19
RANDOMIZED CONTROLLED TRIAL
James S Talks, Andrew J Lotery, Faruque Ghanchi, Sobha Sivaprasad, Robert L Johnston, Nishal Patel, Martin McKibbin, Clare Bailey, Sajjad Mahmood
PURPOSE: Aflibercept has the potential advantage of reducing capacity problems by allowing 2 monthly visits for patients with neovascular macular degeneration (nAMD) compared with monthly pro re nata regimens that are the most commonly used in the United Kingdom. This study aimed to report the visual outcomes achieved in routine clinical practice using the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) protocol at 1 year and compare with trials data and other real-world reports...
February 2016: Ophthalmology
https://www.readbyqxmd.com/read/26492090/phase-i-dose-escalation-and-pharmacokinetic-study-of-intravenous-aflibercept-in-combination-with-docetaxel-cisplatin-and-5-fluorouracil-in-patients-with-advanced-solid-malignancies
#20
MULTICENTER STUDY
Rastislav Bahleda, Jackie Baker, Christophe Massard, Sirish M Gadgeel, Jane E Rogers, Hassan Izzedine, Eric Deutsch, Jeana L Garris, Akbar Khan, Emmanuelle Boelle, Sylvie Assadourian, Jean-Charles Soria, Jaffer A Ajani
PURPOSE: This phase I study (EudraCT No. 2006-001177-25) investigated aflibercept, a vascular endothelial growth factor decoy receptor protein (VEGF Trap), in combination with docetaxel, cisplatin, and 5-fluorouracil in patients with advanced solid tumors. PATIENTS AND METHODS: Patients received 2, 4, or 6 mg/kg of intravenous aflibercept with docetaxel 75 mg/m2, cisplatin 75 mg/m2, and 5-fluorouracil 750 mg/m2 in 3-week cycles until disease progression or unacceptable toxicity...
2016: Oncology
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