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Aflibercept placental growth factor

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
Laura Kowalczuk, Alexandre Matet, Ali Dirani, Alejandra Daruich, Aude Ambresin, Irmela Mantel, Richard F Spaide, Natacha Turck, Francine Behar-Cohen
PURPOSE: To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. METHODS: Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography...
December 20, 2016: Retina
E Al Kahtani, Z Xu, S Al Rashaed, L Wu, A Mahale, J Tian, E B Abboud, N G Ghazi, I Kozak, V Gupta, J F Arevalo, E J Duh
PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays an important role in experimental models of diabetic retinopathy and retinal neovascularization. We aimed to investigate whether vitreous levels of PlGF correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and bevacizumab treatment. We also analysed PDR membranes to confirm the presence of the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control study: undiluted vitreous fluid samples were obtained from 28 active PDR patients without preoperative bevacizumab treatment, 21 active PDR patients with preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control patients...
November 25, 2016: Eye
Tine Van Bergen, Bart Jonckx, Lieve Moons, Jean H M Feyen, Ingeborg Stalmans
PURPOSE: The complementary effects of mitomycin-C (MMC) and anti-placental growth factor (PlGF) therapy were explored and compared to the combined administration of MMC and aflibercept. Additionally, the effect of PlGF (inhibition) on IOP was investigated, since aqueous PlGF is known to be upregulated in glaucoma patients. METHODS: In the trabeculectomy mouse model, intracameral injection(s) of the PlGF inhibitor (5D11D4) were compared to MMC or aflibercept and to the combination of both compounds...
August 1, 2016: Investigative Ophthalmology & Visual Science
Takuji Torimura, Hideki Iwamoto, Toru Nakamura, Mitsuhiko Abe, Yu Ikezono, Fumitaka Wada, Takahiko Sakaue, Hiroshi Masuda, Osamu Hashimoto, Hironori Koga, Takato Ueno, Hirohisa Yano
BACKGROUND & AIM: Aflibercept known as ziv-aflibercept in the United States is a soluble decoy receptor of both vascular endothelial growth factor (VEGF) receptor-1 and -2 known to inhibit the binding of VEGF and placental growth factor (PlGF) to VEGF receptor-1 and -2. Here, we analyzed the mechanisms of the antitumor effects of aflibercept in mouse hepatoma models. METHODS: In in vitro studies, we determined the effects of aflibercept on human umbilical vein cell (HUVEC) proliferation and bone marrow (BM) cell differentiation to endothelial progenitor cells (EPCs)...
July 2016: Neoplasia: An International Journal for Oncology Research
Alessandra Puddu, Roberta Sanguineti, Carlo Enrico Traverso, Giorgio L Viviani, Massimo Nicolò
PURPOSE: The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro...
August 4, 2016: European Journal of Ophthalmology
Keegan A Harkins, Mary Haschke, Diana V Do
Diabetic macular edema (DME) is an accumulation of fluid in the central retina, secondary to vascular-leakage from diabetic vascular damage. DME and other ophthalmic sequela of diabetes are the leading cause of blindness in 20 to 74-year-olds. The development of VEGF-inhibitors (anti-VEGF) has revolutionized DME treatment improving the clinician's ability to remove excess fluid from the macula, improving visual-acuity. Aflibercept is an anti-VEGF agent made of a recombinant fusion protein (consisting of VEGF receptors 1 and 2 extracellular domains) fused with the Fc-portion of human-IgG1, which binds both VEGF isoforms A and B, and placental growth factor...
May 2016: Immunotherapy
Yoko Nomura, Makoto Kaneko, Kanjiro Miyata, Yutaka Yatomi, Yasuo Yanagi
PURPOSE: To confirm the formation of a drug-growth factor complex and investigate the effects of three VEGF inhibitors in the activation of platelets. METHODS: Growth factors and individual drugs were mixed and incubated. Scattered light intensity was measured by dynamic light scattering (DLS) to monitor the formation of drug-growth factor complex. Blood samples were obtained from 16 subjects (5 AMD patients and 11 healthy volunteers). Platelets obtained from the platelet-rich fraction by centrifugation were washed and resuspended in HEPES/Tyrode buffer...
December 2015: Investigative Ophthalmology & Visual Science
François Ghiringhelli, Julie Vincent, Françoise Beltjens, Leila Bengrine, Sylvain Ladoire
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF). This molecule binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, preventing them from activating their respective receptors. Aflibercept is used for the treatment of metastatic colorectal cancer (mCRC) in association with irinotecan. For reasons that remain to be elucidated, the addition of aflibercept to irinotecan-based chemotherapy increases the incidence of grade 3-4 diarrhea...
December 2015: Investigational New Drugs
Alfredo García-Layana, Marta S Figueroa, Javier Araiz, José M Ruiz-Moreno, Francisco Gómez-Ulla, Luis Arias-Barquet, Nicholas Reiter
A formulation of aflibercept for intravitreal injection (Eylea) is approved for the treatment of patients with exudative age-related macular degeneration (AMD). Aflibercept has a significantly higher affinity for Vascular endothelial growth factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials showed this drug achieves improved results in patients with exudative AMD similar to those obtained with monthly ranibizumab, using a bimonthly treatment regimen after a loading dose of three intravitreal injections, which translates to less use of healthcare resources...
October 2015: Drugs & Aging
Maximilian Pfau, Heidi Fassnacht-Riederle, Matthias D Becker, Nicole Graf, Stephan Michels
PURPOSE: After 48 months, unresolved macular edema secondary to central retinal vein occlusion (CRVO) is present in more than half of the patients treated with ranibizumab/bevacizumab. Switching therapy to aflibercept, a more recent vascular endothelial growth factor-A (VEGF-A) inhibitor, as well as VEGF-B and placental growth factor inhibitor, might improve the clinical outcome in patients with CRVO who respond insufficiently to ranibizumab/bevacizumab. METHODS: The presented study is a retrospective analysis of CRVO patients (n = 13) responding insufficiently to ranibizumab and/or bevacizumab (requiring treatment every 6 weeks or more frequently)...
2015: Ophthalmic Research
Sobha Sivaprasad, A Toby Prevost, James Bainbridge, Rhiannon Tudor Edwards, David Hopkins, Joanna Kelly, Phil Luthert, Caroline Murphy, Jayashree Ramu, Negin Sarafraz-Shekary, Joana Vasconcelos, Beverley White-Alao, Philip Hykin
INTRODUCTION: Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation...
September 14, 2015: BMJ Open
Vincenzo Ricci, Monica Ronzoni, Teresa Fabozzi
Angiogenesis is the process through which new blood vessels are formed from pre-existing vessels and is essential for the growth of all solid tumors. Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis, which is crucial for tumor growth and metastasis. Its inhibition with antiangiogenic drugs is thought to improve delivery of chemotherapy through vascular normalization and disruption of tumor vasculature. Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR)1 and VEGFR2 extracellular domains that binds to VEGF-A, VEGF-B, placental growth factor (PlGF) 1 and 2...
December 2015: Critical Reviews in Oncology/hematology
Yahiya Y Syed, Kate McKeage
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF), a key regulator of angiogenesis. It binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, and, thus, prevents them from binding to and activating their cognate receptors. In the USA and EU, intravenously administered aflibercept in combination with an infusion of leucovorin, fluorouracil and irinotecan (FOLFIRI) is approved for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after treatment with an oxaliplatin-containing regimen...
August 2015: Drugs
Yi-Ryeung Park, Sung Kun Chung
PURPOSE: To examine the inhibitory effect of topical aflibercept [vascular endothelial growth factor (VEGF) trapR1R2] on corneal neovascularization (NV) in rabbits. METHODS: Corneal NV was induced in 24 eyes of 12 rabbits. Seven days after a silk suture in the corneal stroma, the rabbits were divided into 4 groups of 6 eyes each. Two groups were treated with topical aflibercept at 2 different concentrations: 2 mg/0.5 mL (0.1%, group 1) and 2 mg/5 mL (0.01%, group 2)...
October 2015: Cornea
Claus Zehetner, Nikolaos E Bechrakis, Martin Stattin, Rudolf Kirchmair, Hanno Ulmer, Martina T Kralinger, Gerhard F Kieselbach
PURPOSE: Placental growth factor (PlGF) has been implicated as a contributor to resistance against anti-VEGF therapy. The purpose of the present study was to analyze the systemic levels of PlGF, VEGF-A, and VEGF-B in patients with neovascular age-related macular degeneration (AMD) after treatment with aflibercept, ranibizumab, or bevacizumab. METHODS: Totals of 19 patients were treated with intravitreal aflibercept, 19 with ranibizumab, and 18 with bevacizumab. The cytokine levels were measured by ELISA just before the injection, and 7 days and 1 month thereafter...
May 2015: Investigative Ophthalmology & Visual Science
Valeria Tarallo, Sandro De Falco
Angiogenesis is a complex biological phenomenon essential for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process but in several pathological conditions, angiogenesis results abnormal with either excessive or insufficient proliferation of blood vessels. The pro-angiogenic members of VEGF family, VEGF-A, VEGF-B and placental growth factor (PlGF), and the related receptors, VEGFR-1 and VEGFR-2, have a central and decisive role in pathological angiogenesis...
July 2015: International Journal of Biochemistry & Cell Biology
F Cabrera López
Aflibercept is a new anti-vegf drug that, unlike ranibizumab and bevacizumab blocks both vegf-A and placental growth factor. Moreover, it binds with much greater strength and affinity to human VEGF-A165 than other endogenous vegf receptors, conferring it with a more extended effect and allowing a lower frequency of intravitreal injections. This facilitates the adoption of fixed treatment regimens other than monthly or individual regimens such as "treat and extend". Aflibercept is indicated for the treatment of neovascular (exudative) age-related macular degeneration (ARMD), visual alteration due to macular edema secondary to central retinal vein occlusion (CRVO) and visual alteration due to diabetic macular edema (DME)...
March 2015: Archivos de la Sociedad Española de Oftalmología
J R Azanza Perea, B Sádaba
Aflibercept is a fusion protein whose chemical structure combines the constant fraction of any IgG with a variable fraction constructed with fundamental parts of VEGF receptors. Consequently, it is able to bind to various VEGF as well as to placental growth factor (PIGF), which has been related to a possible synergistic effect in efficacy. The affinity of this drug is higher than that of ranibizumab and bevacizumab. Moreover, it has an intraocular antiinflammatory effect. Intravitreal administration leads to the presence of traces of the drug in plasma but the concentrations are so reduced that the presence of systemic adverse effects, including arterial hypertension, is practically nil...
March 2015: Archivos de la Sociedad Española de Oftalmología
Luis Arias Barquet
Angiogenesis is the process through which new blood vessels are formed, based on preexisting vessels, and is the paradigm of diseases such as cancer and exudative ageassociated macular degeneration (ARMD). Several proangiogenic factors have been identified, such as vascular endothelial growth factor (VEGF), especially VEGF-A, which activates endothelial cells and promotes cell proliferation, migration, and an increase in vascular permeability. VEGF is also involved in the etiopathogenesis of other retinal diseases, such as diabetic macular edema and macular edema secondary to retinal vein occlusion...
March 2015: Archivos de la Sociedad Española de Oftalmología
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