The rubeosis of the iris is a serious complication especially in diabetic retinopathy and retinal veins occlusion. Cytokines, especially the vascular growing factor (VEGF), are responsible for the forming of new vessels. The treatment that inhibits the effect of the VEGF presents new possibilities in the neovascular diseases treatment. Bevacizumab (Avastin) is an anti-VEGF antibody that blocks all forms of VEGF-A. In three eyes with proliferative diabetic retinopathy and neovascularization of the iris and the anterior chamber angle, the dose of 1.25 mg of Avastin was applied intravitrealy. Just one week after the application of the drug, the decrease of the leakage on the iris, and the total disappearance of the neovascularization in three weeks were visible on the fluorescein angiogram. The recurrence of the neovascularization was found in one eye after three months and the treatment had to be repeated. Nine months after the second application, the disease is stabilized without the neovascularization. The intraocular pressure was elevated in two eyes before the application of Avastin, and was refractive to the treatment. After the disappearance of the neovascularization, the intraocular pressure was normalized and it was possible to terminate the antiglaucomatous therapy. The bevacizumab intravitreal treatment of the neovascularization of the iris and the anterior chamber angle was proved to be efficient, the neovascularization disappeared and the intraocular pressure was normalized. There were no side effects after the bevacizumab applications in any of our patients.

• MeSH
• bevacizumab MeSH
• diabetická retinopatie komplikace   MeSH
• glaukom neovaskulární komplikace   farmakoterapie   MeSH
• humanizované monoklonální protilátky MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nemoci duhovky komplikace   farmakoterapie   MeSH
• patologická angiogeneze farmakoterapie   MeSH
• vaskulární endoteliální růstový faktor A imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• bevacizumab MeSH
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH
• vaskulární endoteliální růstový faktor A MeSH

PURPOSE: To evaluate the possibility to treat the chorioidal neovascularisation in angioid streaks with the help of Bevacizumab. Chorioidal neovascularisation is here the main reason responsible for destroying the vision and affects about 70-85% of patients with this disease. MATERIAL AND METHODS: 50 years old woman with 2 weeks anamnesis of worsening of vision on left eye. She claims deformed view in the middle of the visual field and mild decrease of visual acuity. BCVA was 0.9 and examination with Amsler grid showed line distorsion in the central part. After fundus examination, angiography and OCT we set diagnosis: angioid streaks complicated by subfoveal chorioidal neovascularisation. We proposed patient treatment with intravitreal Bevacizumab and subsequently started the therapy. RESULTS: One week after bevacizumab application, patient claims vanishing of vision distortion. In four weeks metamorphopsis completely disappeared and BCVA reached 1.2. OCT and FAG showed less leakage. After initial improvement and 7 months of stand still there comes again to vision deterioration (BCVA 0.7). We were obliged to reinject 1.25 mg of Bevacizumab and VA improved to 0.9 and also the deformation was less. Three months after second injection VA was again decreased and patient was treated with third injection. Patient is followed up for period of 12 months with mild deformation of picture and VA 0.7. It was not observed any side effect of treatment. CONCLUSIONS: The treatment of the chorioidal neovascularisation in angioid streaks is another possibility with the help of Bevacizumab.With this treatment can be delayed the devastation of VA with subfoveal neovascularization. It seems that the treatment is only temporally and during the 12 months follow up came to a few relapse.

• MeSH
• bevacizumab MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• neovaskularizace choroidey farmakoterapie   MeSH
• vaskulární endoteliální růstový faktor A imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• bevacizumab MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze MeSH
• monoklonální protilátky MeSH
• vaskulární endoteliální růstový faktor A MeSH

BACKGROUND: Diabetic retinopathy is a serious sight-threatening complication which is manifested by excessive angiogenesis in diabetic patients. AIM: We hypothesize that cultured Rhesus monkey retinal endothelial cells (RhRECs) respond to high glucose with a change in cell proliferation and vascular endothelial growth factor (VEGF) secretion. MATERIALS AND METHODS: In our study, 20 000 cells per well were treated without glucose or with 5.5 mM, 18.5 mM and 30 mM glucose for 24 hours. Viable cells were counted using trypan blue dye exclusion method. VEGF concentrations were measured in cell media by ELISA method. RESULTS: The number of viable cells incubated with 5.5 mM glucose increased significantly by 53.7% after 24 hours. In comparison, the number of viable cells decreased by 2.8% at 18.5 mM of glucose and by 20.4% at 30 mM of glucose after 24 hours of incubation. In contrast to this effect of glucose on the number of viable cells, a significant increase in VEGF levels (pg/mL) in the cell media with a glucose concentration of 0 mM compared to 5.5 mM of glucose was found. VEGF secretion in cell medium with 18.5 and 30 mM of glucose increased non-significantly in comparison with euglycemic levels. CONCLUSION: Our results show that viability of retinal endothelial cells and VEGF release are highly responsive to changes in glucose concentration. Such glucose-induced changes in retinal endothelial cells may negatively impact the integrity of the microvasculature in the diabetic retina leading to angiogenesis and microaneursym.

• Klíčová slova
• VEGF, diabetic retinopathy, glucose, retina, retinal endothelial cell,
• MeSH
• diabetická retinopatie patologie   patofyziologie   MeSH
• ELISA MeSH
• endoteliální buňky cytologie   MeSH
• glukosa metabolismus   farmakologie   MeSH
• Haplorrhini MeSH
• hyperglykemie komplikace   MeSH
• kultivované buňky MeSH
• lidé MeSH
• proliferace buněk účinky léků   fyziologie   MeSH
• referenční hodnoty MeSH
• retina cytologie   MeSH
• senzitivita a specificita MeSH
• vaskulární endoteliální růstový faktor A analýza   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• glukosa MeSH
• vaskulární endoteliální růstový faktor A MeSH

The issue of macular retinal degeneration is one of the key areas of ophthalmology. Recent advances in the targeted delivery of vascular endothelial growth factor (VEGF) suppressants have significantly impacted the patient's prognosis in the form of a significant deceleration in disease progression. Some of the drugs have gradually found their use in other indications (central retinal vein occlusion or diabetic macular edema). The following text gives a brief look at the physiology of VEGF, but not only in the eye, but throughout the human body, particularly in the context of adverse effects resulting from systemic inhibition of its effects.

• Klíčová slova
• VEGF, adverse effects, aflibercept, bevacizumab, pegaptanib, pharmacokinetics, ranibizumab, vascular endothelial growth factor,
• MeSH
• bevacizumab terapeutické užití   MeSH
• diabetická retinopatie * farmakoterapie   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• makulární edém * farmakoterapie   etiologie   MeSH
• ranibizumab terapeutické užití   MeSH
• receptory vaskulárního endoteliálního růstového faktoru terapeutické užití   MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• bevacizumab MeSH
• inhibitory angiogeneze MeSH
• ranibizumab MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• rekombinantní fúzní proteiny MeSH
• vaskulární endoteliální růstový faktor A MeSH

AIM: The aim of this paper is to present clinical experience with the therapy of retinal juxtapapillary hemangioma using the intravitreal application of anti-VEGF substance (bevacizumab) and photodynamic therapy (PDT) with verteporfine (Visudyne). MATERIAL AND METHODS: The authors present a case of a 34 years old male patient with diagnosed retinal hemangioma localized on the optic disc. Subjectively, the patient noticed decrease of vision, and during the clinical examination, the edema in the macula region spreading from the hemangioma with hard exsudates was found; the best-corrected visual acuity (BCVA) was 4/20 (0.2). RESULTS: First, the patient was treated by intravitreal applications of bevacizumab; after the first application, the edema from the macula subsided, and the best-corrected visual acuity improved to 4/12 (0.33). After one month of the first application, a recurrence of the edema occurred and other two injections of bevacizumab were applied; despite this treatment, further worsening of the exsudation from the hemangioma and worsening of the BCVA to 4/32 (0.125) occurred. Subsequently, one session of photodynamic therapy with verteporfine was held. After this therapy, the finding on the posterior ocular pole was stabilized; the BCVA was 4/40 (0.1). Even one year after the PDT therapy, no recurrence was present. CONCLUSION: According to our experience, the PDT with Visudyne appears as promising therapy method of juxtapapillary capillary hemangiomas. The PDT decreases the leaking of the fluid from hemangioma and decreases the size of hemangioma.

• MeSH
• bevacizumab MeSH
• dospělí MeSH
• fluoresceinová angiografie MeSH
• fotochemoterapie metody   MeSH
• fotosenzibilizující látky terapeutické užití   MeSH
• fundus oculi MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• kapilární hemangiom diagnóza   farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• nádory sítnice diagnóza   farmakoterapie   MeSH
• optická koherentní tomografie MeSH
• porfyriny terapeutické užití   MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   MeSH
• verteporfin MeSH
• zraková ostrost MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• bevacizumab MeSH
• fotosenzibilizující látky MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze MeSH
• porfyriny MeSH
• vaskulární endoteliální růstový faktor A MeSH
• verteporfin MeSH

Vascular endothelial growth factor-A (VEGF-A) is a growth factor and pluripotent cytokine that promotes angiogenesis in cancer cells, transitioning to an angiogenic phenotype. The binding of VEGF-A protein to VEGF receptors (VEGFR-1 and VEGFR-2) initiates a cascade of events that stimulates angiogenesis by facilitating the migration and enhancing the permeability of endothelial cells. The proximal promoter of the VEGF gene encompasses a 36-base pair region (from -85 to -50) that can form a stable G-quadruplex (G4) structure in specific conditions. The activity of the VEGF promoter is reliant on this structure. During cancer progression, the VEGF-A G4 succumbs to cellular pressure and fails to maintain a stable structure. This shifts the balance to form a duplex structure, increasing the transcription rate. Earlier research has tried to develop small-molecule ligands to target and stabilise G4, demonstrating the possibility of suppressing VEGF expression. However, they either lack specificity or toxic. Peptides, on the other hand, are significantly less studied as G4 binders. Here, we designed a peptide that successfully binds and stabilises the VEGF-A G4 while reducing its gene expression. This further alters the expression fate of the VEGF-A signalling cascade and blocks angiogenesis in cancer cells. We employed high-resolution nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulation to elucidate the chemical details of G4-peptide interaction. In addition, we used qPCR and western blot techniques to investigate the expression pattern of the molecules implicated in the VEGF-A signalling cascade. The study explores the intricate relationship between peptides and quadruplex structures, revealing valuable insights that can improve the design of pharmacophores targeting the dynamic quadruplex structure. The results of our study are encouraging, opening possibilities for advancements in, the characterisation and optimisation of peptides as G-quadruplex ligands in view of their potential therapeutic uses.

• Klíčová slova
• G‐quadruplex, VEGF‐A, angiogenesis, cancer, peptide,
• MeSH
• angiogeneze MeSH
• G-kvadruplexy * účinky léků   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• patologická angiogeneze * farmakoterapie   metabolismus   MeSH
• peptidy * chemie   farmakologie   MeSH
• promotorové oblasti (genetika) MeSH
• simulace molekulární dynamiky MeSH
• vaskulární endoteliální růstový faktor A * metabolismus   genetika   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• peptidy * MeSH
• vaskulární endoteliální růstový faktor A * MeSH

The aim of the study was to determine whether VEGF, TPS, TK or Endostatin determination in tissue cytosol may have some additional value in distinguishing among different types of thyroid lesions. These markers were chosen as representatives of the 2 main pathways (angiogenesis and proliferation) involved in thyroid diseases. VEGF is the most potent angiogenic promoter and Endostatin plays an opposing role. Thymidine kinase (TK) is a marker of DNA synthesis and TPS, cytokeratin 18 fragments, is a marker of the rate of proliferation. We determined qualitatively all four markers in tissue extracts: cytosol from 157 tissue specimens (93 goitre, 12 Hashimoto's thyroiditis, 39 adenomas and 13 carcinomas). In 6 cases we were able to compare both normal and pathological tissue samples from a single patient. Statistically significant differences were found in the measured markers, but outliers were present in all groups. This fact does not permit their use in differential diagnosis. The highest levels of all markers were reached in adenomas, being higher than in carcinomas, probably explained by the higher overall metabolic rate in adenomas.

• MeSH
• cytosol metabolismus   MeSH
• endostatiny metabolismus   MeSH
• lidé MeSH
• nemoci štítné žlázy metabolismus   MeSH
• štítná žláza metabolismus   MeSH
• thymidinkináza metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endostatiny MeSH
• thymidinkináza MeSH
• vaskulární endoteliální růstový faktor A MeSH

UNLABELLED: Primary graft failure occurs 15 to 30 % of the time after transplantation. Although there have been improvements in preserving the lungs in good condition, there have not been studies on the regulation of transcription factors. METHODS: We carried out an experimental study involving lung transplantation to indirectly evaluate reactive oxygen species (ROS) production and VEGF expression by competitive blockade of HIF-1alpha with chetomin. There were 5 groups: Group-1: Lung blocks were perfused with 0.9 % SSF, immediately harvested, and preserved. Group-2 (I-T): Immediate transplantation and then reperfusion for 1 h. Group-3 (I-R): Lung blocks were harvested and preserved in LPD solution for 6 h and reperfused for 1 h. Group-4 (DMSO): Lung blocks were treated for 4 h with DMSO, preserved for 6 h and transplanted to a receptor treated with DMSO. Group-5 (chetomin): Lung blocks were treated for 4 h with chetomin, preserved for 6 h and transplanted to a receptor treated with chetomin. ROS, mRNA, and protein levels of HIF-1alpha and EG-VEGF were determined. RESULTS: The DMSO and chetomin groups had significantly lower ROS levels. Compared with those in the I-R group, the chetomin group exhibited the lowest level of HIF-1alpha. CONCLUSIONS: Addition of chetomin to the donor and the receptor results in a significant reduction in HIF-1A, VEGF and ROS.

• MeSH
• disulfidy MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus   MeSH
• indolové alkaloidy MeSH
• krysa rodu Rattus MeSH
• plíce metabolismus   účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• transplantace plic * MeSH
• vaskulární endoteliální růstový faktor A * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chetomin MeSH Prohlížeč
• disulfidy MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa * MeSH
• Hif1a protein, rat MeSH Prohlížeč
• indolové alkaloidy MeSH
• reaktivní formy kyslíku * MeSH
• vascular endothelial growth factor A, rat MeSH Prohlížeč
• vaskulární endoteliální růstový faktor A * MeSH

Vascular endothelial growth factor-A165 (VEGF-A165) and fibroblast growth factor-2 (FGF-2) are currently used for the functionalization of biomaterials designed for tissue engineering. We have developed a new simple method for heterologous expression and purification of VEGF-A165 and FGF-2 in the yeast expression system of Pichia pastoris. The biological activity of the growth factors was assessed in cultures of human and porcine adipose tissue-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs). When added into the culture medium, VEGF-A165 stimulated proliferation only in HUVECs, while FGF-2 stimulated the proliferation of both cell types. A similar effect was achieved when the growth factors were pre-adsorbed to polystyrene wells. The effect of our recombinant growth factors was slightly lower than that of commercially available factors, which was attributed to the presence of some impurities. The stimulatory effect of the VEGF-A165 on cell adhesion was rather weak, especially in ADSCs. FGF-2 was a potent stimulator of the adhesion of ADSCs but had no to negative effect on the adhesion of HUVECs. In sum, FGF-2 and VEGF-A165 have diverse effects on the behavior of different cell types, which maybe utilized in tissue engineering.

• Klíčová slova
• adult stem cells, basic fibroblast growth factor (bFGF), cell adhesion, cell proliferation, endothelial cells, heterologous expression, recombinant vascular endothelial growth factor (VEGF), regenerative medicine, tissue engineering, vascular replacements,
• MeSH
• buněčná adheze účinky léků   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   metabolismus   MeSH
• fibroblastový růstový faktor 2 chemie   genetika   farmakologie   MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• lidé MeSH
• prasata MeSH
• proliferace buněk účinky léků   MeSH
• rekombinantní proteiny chemie   farmakologie   MeSH
• vaskulární endoteliální růstový faktor A chemie   genetika   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH
• rekombinantní proteiny MeSH
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč

Vascular endothelial growth factor (VEGF) has been identified as a major promoter of the development of choroidal neovascularization in age-related macular degeneration. The development of choroidal neovascularization can be slowed by preventing the binding of vascular endothelial growth factor to cellular VEGF receptor-2 present on vascular endothelial cells, which represents the major proangiogenic stimulus. Advances in the development of anti-VEGF therapy have led to significant improvement in visual acuity outcomes in recent years that neovascular age-related macular degeneration can no longer be considered an incurable disease. Despite its many advantages, the current standard of care, which is the frequent application of VEGF blockers to the vitreous, is a significant burden on both the patient and the healthcare system. This review is aim on a new brolucizumab molecule (also known as RTH 258 or formerly ESBA 1008). The article focuses on the molecular aspects of the drug and an overview of the basic preclinical and clinical studies that were performed during drug development. Brolucizumab is a single chain fragment of a humanized monoclonal antibody with a molecular weight of 26 kDa that inhibits VEGF-A. Preclinical animal studies have shown good penetration of the molecule through the retina with minimal systemic exposure. The SEE study (phase 1/2) demonstrated safety and tolerability after drug administration. The OSPREY (phase 2) study demonstrated the same efficacy of brolucizumab on visual acuity in the 8-week dosing regimen compared to aflibercept. In the same study, patients were also pilot tested in a 12-week dosing regimen. The HAWK and HARRIER studies (phase 3) demonstrated the efficacy of the drug at a dose of 6 mg in a 12-week dosing schedule in 55.6 % and 51 % of patients, respectively.

• Klíčová slova
• ARMD, CNV, anti-VEGF, brolucizumab, vascular growth factor,
• MeSH
• endoteliální buňky MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze * terapeutické užití   MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• vaskulární endoteliální růstový faktor A * antagonisté a inhibitory   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• brolucizumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze * MeSH
• vaskulární endoteliální růstový faktor A * MeSH