scholarly journals Optimal Efficacy and Safety of Humanized Anti-Scg3 Antibody to Alleviate Oxygen-Induced Retinopathy

2021 ◽  
Vol 23 (1) ◽  
pp. 350
Author(s):  
Ye He ◽  
Hong Tian ◽  
Chang Dai ◽  
Rong Wen ◽  
Xiaorong Li ◽  
...  
Keyword(s):  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Efficacy And Safety ◽  
Oxygen Induced Retinopathy ◽  
Retinal Pathology ◽  
Factor Inhibitor ◽  
Functional Analyses ◽  
Endothelial Growth Factor ◽  
Retinal Disorder ◽  
The U.S

The retinopathy of prematurity (ROP), a neovascular retinal disorder presenting in premature infants, is the leading causes of blindness in children. Currently, there is no approved drug therapy for ROP in the U.S., highlighting the urgent unmet clinical need for a novel therapeutic to treat the disease. Secretogranin III (Scg3) was recently identified as a disease-selective angiogenic factor, and Scg3-neutralizing monoclonal antibodies were reported to alleviate pathological retinal neovascularization in mouse models. In this study, we characterized the efficacy and safety of a full-length humanized anti-Scg3 antibody (hAb) to ameliorate retinal pathology in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, by implementing histological and functional analyses. Our results demonstrate that the anti-Scg3 hAb outperforms the vascular endothelial growth factor inhibitor aflibercept in terms of efficacy and safety to treat OIR mice. Our findings support the development of anti-Scg3 hAb for clinical application.

scholarly journals Bevacizumab (Avegra®) for the treatment of gynecological cancers: joint experience of several centers

2021 ◽  
Vol 16 (4) ◽  
pp. 84-90
Author(s):  
A. G. Kedrova ◽  
S. Е. Krasilnikov ◽  
D. S. Ogay ◽  
Т. A. Maksimenko ◽  
V. I. Voznesenskiy ◽  
...  
Keyword(s):  
Reproductive System ◽  
Additional Treatment ◽  
Clinical Effects ◽  
Vascular Endothelial ◽  
Efficacy And Safety ◽  
Female Reproductive System ◽  
Good Safety Profile ◽  
Factor Inhibitor ◽  
Endothelial Growth Factor ◽  
Joint Experience

Tumors of the female reproductive system are among the five most common cancers in women worldwide. Up to 60 % of these patients require chemotherapy to reduce the risk of recurrence. Currently, an additional treatment option is available for patients with advanced cancers of the female reproductive system, namely vascular endothelial growth factor inhibitor bevacizumab. To assess the efficacy and safety of Avegra®, Russian generic of bevacizumab, we summarized the experience of 5 specialized healthcare institutions that used it for the treatment of 178 patients with tumors of the female reproductive system. The analysis of side effects in 1,074 treatment cycles demonstrated that Avegra® had a good safety profile. Clinical effects of Avegra® were similar to those of the original drug.

scholarly journals Intraokulare Entzündungen bei Brolucizumab-Anwendung

2021 ◽  
Author(s):  
F. G. Holz ◽  
C. Heinz ◽  
A. Wolf ◽  
H. Hoerauf ◽  
U. Pleyer
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Review Committee ◽  
Oder Eine ◽  
Diagnostik Und Therapie ◽  
Factor Inhibitor ◽  
Antientzündliche Therapie ◽  
Endothelial Growth Factor

ZusammenfassungDer VEGF(„vascular endothelial growth factor“)-Inhibitor Brolucizumab ist seit Oktober 2019 in den USA und seit Februar 2020 in Europa zur Behandlung der neovaskulären altersabhängigen Makuladegeneration (nAMD) zugelassen. Grundlage der Zulassung bildeten die randomisierten, doppel-blinden Phase-III-Studien HAWK und HARRIER mit insgesamt 1817 Patienten. Hierbei zeigte Brolucizumab 6 mg (je nach Krankheitsaktivität alle 12 oder alle 8 Wochen verabreicht) eine nichtunterlegene Wirksamkeit in Bezug auf den bestkorrigierten Visus gegenüber Aflibercept 2 mg (alle 8 Wochen verabreicht). Erste Rückmeldungen zum Einsatz von Brolucizumab nach der Marktzulassung in den USA haben einzelne, z. T. schwerwiegende Fälle behandlungsassoziierter intraokularer Entzündungen mit retinaler Vaskulitis und/oder retinaler, vaskulärer Okklusion beschrieben, die teilweise zu einem schweren Visusverlust führten. Die Daten der Zulassungsstudien wurden daraufhin durch ein Safety Review Committee (SRC) unabhängig retrospektiv analysiert. Ziel der vorliegenden Publikation ist es, Anwendern eine Orientierungshilfe aus Autorensicht bei der Therapie einer Brolucizumab-assoziierten intraokularen Entzündung zu bieten. Von zentraler Bedeutung ist hierbei auch eine erweiterte Aufklärung der Patienten über Symptome einer intraokularen Entzündung. Obwohl die Fallserien und die HAWK/HARRIER-Daten es nicht abschließend beantworten, bleiben eine zu späte Detektion, eine unterdosierte antientzündliche Therapie oder eine unbedachte Wiederbehandlung mit Brolucizumab dem Verdacht ausgesetzt, Komplikationen zu verstärken. Ein Stopp der Brolucizumab-Therapie sollte grundsätzlich erfolgen, sobald es nach Gabe des Medikaments zu intraokularen Entzündungen mit oder ohne retinalen Vaskulitiden und oder Gefäßverschluss kam. Abhängig vom Schwerpunkt der Entzündung werden dem Behandler an die Leitlinien und Stellungnahmen angelehnte Empfehlungen für Diagnostik und Therapie dargestellt. Diese Übersichtsarbeit ersetzt nicht die fachgesellschaftlichen Stellungnahmen.

scholarly journals Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

scholarly journals Effect of directly acting anti-viral agents on immunological imprints in chronic HCV-4a patients: interleukin-10 and vascular endothelial growth factor genes expression level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iman S. Naga ◽  
Amel Abdel Fattah Kamel ◽  
Said Ahmed Ooda ◽  
Hadeer Muhammad Fath Elbab ◽  
Rania Mohamed El-Sharkawy
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Factor ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Wide Range ◽  
Chronic Hcv ◽  
Endothelial Growth Factor

Abstract Background Hepatitis C virus infection is a global health challenge with Egypt being one of the highly affected countries. IL-10 has been suggested as a suitable marker to assess necroinflammation and to monitor the progression of liver damage. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor playing a central role in many physiological as well as pathological processes. Several factors can be predictive of the response to treatment and achievement of SVR; some of which are host-related, and others are virus-related. The gene expression of IL-10 and VEGF have multiple effects for treatment response. The aim of the present work was to study the effect of treatment with directly acting agents (DAA) on the expression of VEGF and IL-10 genes in chronic hepatitis C virus-infected Egyptian genotype-4a patients. Twenty-five HCV subjects where evaluated for IL-10 and VEGF gene expression before and after treatment with DAA. Results IL-10 expression was downregulated in 92% of the cases. VEGF expression was heterogeneous showing spreading of values along a wide range with 64% of the cases being downregulated. Conclusion DAAs do not completely reverse the immunological imprints established upon chronic HCV infection.

P0590ADVERSE RENAL OUTCOME FOLLOWING ADMINISTRATION OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN A SINGLE TERTIARY CENTRE IN MALAYSIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maisarah Jalalonmuhali ◽  
Tengku Ain Fathlun Tengku Kamalden ◽  
Nurul 'Ain Sham Ismail ◽  
See Yen Yong ◽  
Wei Ting Teo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Serum Creatinine ◽  
Post Treatment ◽  
Angiogenic Factor ◽  
Renal Outcome ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Abstract Background and Aims Intravenous (IV) anti-vascular endothelial growth factor(VEGF) is a potent anti-angiogenic factor for the treatment of solid tumours. While, intravitreal anti-VEGF injection is used in the treatment for macular and retinal diseases. The effects of IV anti-VEGF agents are well documented to cause hypertension, renal impairment and proteinuria. However only few reports showed the significance of intravitreal anti-VEGF injection causing minimal change disease (MCD) and acute kidney injury (AKI). Hence, this study is to determine the outcome of renal function following intravitreal anti-VEGF injection. Method This is a prospective, cross sectional study recruiting patients from ophthalmology day-care operation theatre that were scheduled for intravitreal anti-VEGF injection in University Malaya Medical Centre (UMMC). On the day of the injection of anti-VEGF, patients’ demographic data (age, gender, medical background, medications), blood pressure, height, weight and investigations for serum creatinine and urine protein creatinine ratio (PCR) were collected. Following these, they will receive the intravitreal anti-VEGF as per schedule. All these patients were given a follow-up within 72hours to reassess blood pressure, serum creatinine and urine PCR. Results A total of 90 patients were recruited. However, 15 patients were subsequently excluded as there was no repeated serum creatinine at 72-hours post treatment. Their mean age was 67.25 ± 10.41. Among all, 3 patients had significance increased in serum creatinine (4%) with significance changed of urine PCR post treatment. Table 1 showed baseline parameters prior to treatment and table 2 was post treatment parameters. Higher serum creatinine and proteinuria pre intravitreal anti-VEGF were identified to have higher OR of 1.018 (95% CI 1.001-1.035) (p=0.043) and OR 1.004 (1.000-1.007) (p=0.025) respectively among those who developed AKI. In assessing the association between higher pre-treatment creatinine and proteinuria (independent variable) and development of AKI (dependent variable) estimated by logistic regression with no AKI as a reference group we found that there were no significance. Conclusion Following intravitreal anti-VEGF administration, there were no significant changes in blood pressure. However, 4% from our cohort had AKI and worsening proteinuria at 72 hours post treatment. These patients had higher serum creatinine and proteinuria prior to treatment. However, our study is underpowered to establish the relationship between intravitreal anti-VEGF and development of AKI. Further study with larger sample size and longer-term outcome is needed.

scholarly journals eNOS-induced vascular barrier disruption in retinopathy by c-Src activation and tyrosine phosphorylation of VE-cadherin

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Takeshi Ninchoji ◽  
Dominic T Love ◽  
Ross O Smith ◽  
Marie Hedlund ◽  
Dietmar Vestweber ◽  
...  
Keyword(s):  
No Synthase ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ocular Diseases ◽  
Oxygen Induced Retinopathy ◽  
No Formation ◽  
Therapy Development ◽  
Endothelial Growth Factor ◽  
Deutsche Forschungsgemeinschaft

Background:Hypoxia and consequent production of vascular endothelial growth factor A (VEGFA) promote blood vessel leakiness and edema in ocular diseases. Anti-VEGFA therapeutics may aggravate hypoxia; therefore, therapy development is needed.Methods:Oxygen-induced retinopathy was used as a model to test the role of nitric oxide (NO) in pathological neovascularization and vessel permeability. Suppression of NO formation was achieved chemically using L-NMMA, or genetically, in endothelial NO synthase serine to alanine (S1176A) mutant mice.Results:Suppression of NO formation resulted in reduced retinal neoangiogenesis. Remaining vascular tufts exhibited reduced vascular leakage through stabilized endothelial adherens junctions, manifested as reduced phosphorylation of vascular endothelial (VE)-cadherin Y685 in a c-Src-dependent manner. Treatment with a single dose of L-NMMA in established retinopathy restored the vascular barrier and prevented leakage.Conclusions:We conclude that NO destabilizes adheren junctions, resulting in vascular hyperpermeability, by converging with the VEGFA/VEGFR2/c-Src/VE-cadherin pathway.Funding:This study was supported by the Swedish Cancer foundation (19 0119 Pj ), the Swedish Research Council (2020-01349), the Knut and Alice Wallenberg foundation (KAW 2020.0057) and a Fondation Leducq Transatlantic Network of Excellence Grant in Neurovascular Disease (17 CVD 03). KAW also supported LCW with a Wallenberg Scholar grant (2015.0275). WCS was supported by Grants R35 HL139945, P01 HL1070205, AHA MERIT Award. DV was supported by grants from the Deutsche Forschungsgemeinschaft, SFB1450, B03, and CRU342, P2.

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