Aptamers targeting vascular endothelial growth factor molecular regulation as potential therapists

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Molecular Regulation ◽  
Dna Aptamers ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Anti Vegf ◽  
Short Period ◽  
Wide Range ◽  
Endothelial Growth Factor

The discovery of vascular endothelial growth factor (VEGF) and its vital biological function has changed our knowledge of vasculogenesis and angiogenesis, while introducing a new strategy to the anticancer arsenal: this protein's specialized inhibition. Discovering VEGF's molecular regulation as well as developing revolutionary therapeutic strategies that directly or indirectly target VEGF is an outstanding case study that demonstrates the relevance of basic research in directing innovation and translational medicine. Following FDA approval of pegaptanib for AMD therapy, nucleic acid-based aptamers were discovered and developed. In an efficient bench-to-bedside process, a spate of new aptamers targeting a range of targets were discovered in a short period as high-potential therapists. Anti-VEGF DNA-based aptamers were the most significant. Standard SELEX processes were utilized to find most anti-VEGF DNA aptamers, while some of them employed alternate and upgraded SELEX-based techniques. After identifying the best oligonucleotide sequences, the highest affinity aptamers were further refined for target binding and/or activity. Synthesizing and evaluating the parent aptamer's structural analogs was utilized to find strategies to boost performance. Despite aptasensor success in a wide range of signal transduction approaches, which also allow extremely low detection limits, more work has to be done to construct meaningful and easy-to-use VEGF aptasensors for point-of-care diagnostics. In actuality, most published Aptasensors have only been evaluated in vitro, and it is vital to broaden their use to future in vivo situations and difficult clinical data. Creating high-affinity anti-VEGF DNA aptamers paves the path for additional diagnostic and therapeutic application research. Given the biological complexity of VEGF signaling, pharmacological combination therapies can significantly improve conventional anticancer treatments. These can be combined with VEGF signaling suppression to give more effective therapy and avoid resistance, which is frequent in cancer.

scholarly journals Screening auf Frühgeborenenretinopathie – die wichtigsten Änderungen in der neuen deutschen Leitlinie 2020

2021 ◽  
Author(s):  
Jeany Q. Li ◽  
Ulrich Kellner ◽  
Birgit Lorenz ◽  
Andreas Stahl ◽  
Tim U. Krohne
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Retinopathy Of Prematurity ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Zone Ii ◽  
Endothelial Growth Factor ◽  
Rop Screening

Zusammenfassung Hintergrund Durch Verbesserungen in der neonatologischen Versorgung von Frühgeborenen und die Entwicklung neuer Behandlungsmöglichkeiten der Frühgeborenenretinopathie („retinopathy of prematurity“ [ROP]) haben sich die Anforderungen an das ROP-Screening seit der Veröffentlichung der letzten Fassung der deutschen Leitlinie zum ROP-Screening im Jahr 2008 verändert. Auf Grundlage aktueller Studiendaten wurde die Leitlinie in 2020 grundlegend überarbeitet und in einer aktualisierten Fassung veröffentlicht. Ziel Dieser Artikel fasst die wichtigsten Änderungen in der neuen Leitlinie zusammen. Ergebnisse Die Altersgrenze für einen Screeningeinschluss wurde für Kinder ohne zusätzliche Risikofaktoren auf ein Gestationsalter von unter 31 Wochen gesenkt. Die Mindestdauer für eine Sauerstoffsupplementation, die einen Einschluss in das Screening bei Frühgeborenen erforderlich macht, wurde auf über 5 Tage angehoben. Eine Behandlung bei ROP in Zone II kann nun schon bei jedem Stadium 3 mit Plus-Symptomatik unabhängig von der Anzahl der betroffenen Uhrzeiten erfolgen. Für die Nachkontrollen nach Anti-VEGF („vascular endothelial growth factor“)-Therapie wurden Kriterien zur Frequenz und Dauer definiert. Das verbindliche Dokument für diese und weitere neue Empfehlungen ist die Leitlinie selber. Schlussfolgerungen Die Empfehlungen der Leitlinie ermöglichen eine zuverlässige Identifikation von Kindern mit ROP-Risiko für den Einschluss in das Screening und eine rechtzeitige Erkennung fortgeschrittener Krankheitsstadien für die Therapieeinleitung, um so Erblindung durch ROP zu verhindern.

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.

scholarly journals Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival

2021 ◽  
Author(s):  
Takao Kamai ◽  
Toshiki Kijima ◽  
Toyonori Tsuzuki ◽  
Akinori Nukui ◽  
Hideyuki Abe ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Cell Death ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Primary Tumors ◽  
Anti Vegf ◽  
Programmed Cell Death 1 ◽  
Endothelial Growth Factor

Abstract Background Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both. Methods In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody. Results Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival. Conclusions Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.

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.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration

2016 ◽  
Vol 235 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Tomoaki Shiba ◽  
Mao Takahashi ◽  
Izumi Yoshida ◽  
Hikari Taniguchi ◽  
Tadashi Matsumoto ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protective Factor ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Vascular Endothelial ◽  
Cumulative Number ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

scholarly journals Malignant peritoneal mesothelioma. Is there a new treatment?

Rare Tumors ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 150-152
Author(s):  
Kakil Ibrahim Rasul ◽  
David J Kerr
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Peritoneal Mesothelioma ◽  
Vascular Endothelial ◽  
Malignant Peritoneal Mesothelioma ◽  
Anti Vegf ◽  
Alternative Approach ◽  
New Treatment ◽  
Endothelial Growth Factor

The authors report a novel, alternative approach to treat malignant peritoneal mesothelioma (MPeM) targeting, vascular endothelial growth factor (VEGF) using anti-VEGF (bevacizumab) chemotherapy combination.

Tractional retinal detachment (‘crunch’ phenomenon) from intravitreal anti-vascular endothelial growth factor injection in central retinal vein occlusion

2021 ◽  
Vol 14 (4) ◽  
pp. e240506
Author(s):  
Albert John Bromeo ◽  
Amadeo Veloso ◽  
Sweet Jorlene Lerit ◽  
Myron Carlo Gomez
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Retinal Detachment ◽  
Central Retinal Vein Occlusion ◽  
Vascular Endothelial ◽  
Tractional Retinal Detachment ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Endothelial Growth Factor ◽  
Central Retinal Vein

Tractional retinal detachment is an uncommon complication of intravitreal anti-vascular endothelial growth factor (VEGF) injection wherein the drug triggers tractional retinal detachment as a result of fibrovascular membrane contraction. We present a case of a 42-year-old hypertensive woman diagnosed with chronic central retinal vein occlusion on both eyes. The right eye had total retinal detachment and neovascular glaucoma, while the left eye had retinal neovascularisation. Panretinal photocoagulation and intravitreal anti-VEGF injection was started on the left eye. However, she was lost to follow-up. She returned 4 months later with extensive tractional retinal detachment involving the macula on the left eye. She subsequently underwent vitrectomy with endolaser and silicone oil tamponade on the left eye. The anti-VEGF ‘crunch’ results from regression of fibrovascular proliferation with a concurrent increase in fibrosis, resulting in worsening retinal traction. With the widespread use of anti-VEGF agents, ophthalmologists need to be aware of this vision-threatening complication.

scholarly journals Real world evidence on 5661 patients treated for macular oedema secondary to branch retinal vein occlusion with intravitreal anti-vascular endothelial growth factor, intravitreal dexamethasone or macular laser

2020 ◽  
pp. bjophthalmol-2020-315836 ◽  
Author(s):  
Richard Gale ◽  
Maria Pikoula ◽  
Aaron Y Lee ◽  
Spiros Denaxas ◽  
Catherine Egan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Visual Acuity ◽  
Growth Factor ◽  
Macular Oedema ◽  
Branch Retinal Vein Occlusion ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Intravitreal Dexamethasone ◽  
Endothelial Growth Factor

Background/aimsClinical trials suggest anti-vascular endothelial growth factor is more effective than intravitreal dexamethasone as treatment for macular oedema secondary to branch retinal vein occlusion. This study asks if ‘real world’ data from a larger and more diverse population, followed for a longer period, also support this conclusion.MethodsData collected to support routine care at 27 NHS (National Health Service) Trusts between February 2002 and September 2017 contained 5661 treatment-naive patients with a single mode of treatment for macular oedema secondary to branch retinal vein occlusion and no history of cataract surgery either during or recently preceding the treatment. Number of treatment visits and change in visual acuity from baseline was plotted for three treatment groups (anti-vascular endothelial growth factor (anti-VEGF), intravitreal dexamethasone, macular laser) for up to 3 years.ResultsMean baseline visual acuity was 57.1/53.1/62.3 letters in the anti-VEGF/dexamethasone/macular laser groups, respectively. This changed to 66.72 (+9.6)/57.6 (+4.5)/63.2 (+0.9) at 12 months. Adequate numbers allowed analysis at 18 months for all groups (66.6 (+9.5)/56.1 (+3.0)/60.8 (-1.5)) and for anti-VEGF at 36 months (68.0, +10.9) Mean number of treatments were 5.1/1.5/1.2 at 12 months, 5.9/1.7/1.2 at 18 months for all three groups and 10.3 at 36 months for anti-VEGF.ConclusionsVisual acuity improvements were higher and more sustained with anti-VEGF. Higher treatment burden occurred with anti-VEGF but this reduced over 36 months. Patients with better vision at baseline than those in the clinical trials maintained high levels of vision with both anti-VEGF and dexamethasone.

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