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Targeting fluorescent nanodiamonds to vascular endothelial growth factor receptors in tumor
摘要： The increased expression of vascular endothelial growth factor (VEGF) and its receptors is associated with angiogenesis in a growing tumor, presenting potential targets for tumor-selective imaging by way of targeted tracers. Though fluorescent tracers are used for targeted in vivo imaging, the lack of photostability and biocompatibility of many current fluorophores hinder their use in several applications involving long-term, continuous imaging. To address these problems, fluorescent nanodiamonds (FNDs), which exhibit infinite photostability and excellent biocompatibility, were explored as fluorophores in tracers for targeting VEGF receptors in growing tumors. To explore FND utility for imaging tumor VEGF receptors, we used click-chemistry to conjugate multiple copies of an engineered single-chain version of VEGF site-specifically derivatized with trans-cyclooctene (scVEGF-TCO) to 140 nm FND. The resulting targeting conjugates, FND-scVEGF, were then tested for functional activity of the scVEGF moieties through biochemical and tissue culture experiments and for selective tumor uptake in Balb/c mice with induced 4T1 carcinoma. We found that FND-scVEGF conjugates retain high affinity to VEGF receptors in cell culture experiments and observed preferential accumulation of FND-scVEGF in tumors relative to untargeted FND. Microspectroscopy provided unambiguous determination of FND within tissue by way of the unique spectral shape of nitrogen-vacancy induced fluorescence. These results validate and invite the use of targeted FND for diagnostic imaging and encourage further optimization of FND for fluorescence brightness.
关键词： Vascular Endothelial Growth Factor,Oncology,Targeted Fluorescence Imaging,Nanodiamond,Angiogenesis
更新于2025-11-21 11:24:58
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Effect of Anti-vascular Endothelial Growth Factor Antibody on the Survival of Cultured Retinal Ganglion Cells
摘要： Purpose: To investigate the effects of anti-vascular endothelial growth factor (VEGF) antibody on the survival of retinal ganglion cell (RGC)-5 cells differentiated with staurosporine under oxidative stress. Methods: We used real-time polymerase chain reaction and Western blot to confirm the expression of VEGF, VEGF receptor (VEGFR)-1 and VEGFR-2 in RGC-5 cells differentiated with staurosporine for 6 hours. The differentiated RGC-5 cells were treated with 800 μM hydrogen peroxide (H2O2) for 24 hours to induce oxidative stress. Then, the survival rate of RGC-5 was confirmed by lactate dehydrogenase assay at each concentration (0, 0.01, 0.1, and 1 mg) using bevacizumab as the anti-VEGF antibody. The expression of VEGF, VEGFR-1, and VEGFR-2 was confirmed using real-time polymerase chain reaction. Results: VEGF, VEGFR-1, and VEGFR-2 were all expressed in differentiated RGC-5 cells. When RGC-5 cells were simultaneously treated with bevacizumab and 800 μM H2O2, survival of RGC-5 decreased with bevacizumab concentration. VEGF expression in RGC-5 cells increased with increasing concentration of bevacizumab. Similar patterns were observed for VEGFR-1 and VEGFR-2, but the degree of increase was smaller than that for VEGF. Conclusions: When bevacizumab was administered to differentiated RGC-5 cells, the cell damage caused by oxidative stress increased. Therefore, given these in vitro study results, caution should be exercised with bevacizumab treatment.
关键词： Oxidative stress,RGC-5,Retinal ganglion cell,Anti-vascular endothelial growth factor,Bevacizumab
更新于2025-09-23 15:22:29
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In Vivo 3D Imaging of Retinal Neovascularization Using Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Imaging
摘要： The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes.
关键词： PAM,VEGF,multimodal imaging,optical coherence tomography,photoacoustic microscopy,retinal neovascularization,vascular endothelial growth factor,OCT
更新于2025-09-23 15:22:29
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MicroRNA-9 inhibits retinal neovascularization in rats with diabetic retinopathy by targeting vascular endothelial growth factor A
摘要： Diabetic retinopathy (DR) is a leading cause of adult visual impairment and loss. This study aims to explore the effects of microRNA‐9 (miR‐9) on retinal neovascularization during DR by targeting the vascular endothelial growth factor A (VEGFA). DR rat models were successfully established. Retinal microvascular endothelial cells (RMECs) of DR rats were isolated and treated with miR‐9 mimic, miR‐9 inhibitor or small interfering RNA (siRNA)‐VEGFA. The expressions of miR‐9, VEGFA, and cluster of differentiation 31 (CD31) of the rats’ tissues and cells were examined. The targeting relationship between miR‐9 and VEGFA was testified. The tubule formation, the cell proliferation and the periodic distribution and apoptosis were evaluated after transfection. In the retinal tissues of DR rats, miR‐9 expression decreased while the expression of VEGFA and CD31 increased. Notably, miR‐9 targeted and inhibited VEGFA expression. In response to the treatment of miR‐9 mimic and siRNA‐VEGFA, a reduction was identified in CD31 expression, tubule formation, and proliferation of RMECs and cell ratio in the S phase, but an increase was observed in apoptosis rate of RMECs. The treatment of miR‐9 inhibitor reversed the manifestations. Our study demonstrated that miR‐9 could inhibit retinal neovascularization of DR and tubule formation, and promote apoptosis in RMECs by targeting VEGFA.
关键词： retinal microvascular endothelial cells,diabetic retinopathy,vascular endothelial growth factor A,microRNA‐9,retinal neovascularization
更新于2025-09-23 15:21:21
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Efficacy of aflibercept on exudative age-related macular degeneration in patients exhibiting complete ranibizumab resistance and tachyphylaxis
摘要： Purpose: The present study compared the efficacy of aflibercept for neovascular age-related macular degeneration (NV-AMD) in patients with complete ranibizumab resistance and tachyphylaxis. Methods: Forty-four eyes of 38 neovascular age-related macular degeneration patients were evaluated. Eyes were divided into a complete resistance group (n=23 eyes) and tachyphylaxis group (n=21 eyes). Results: After three injections, eight (38.1%) patients in the tachyphylaxis group and nine (39.1%) in the complete resistance group presented with macular dryness. After the first injection of aflibercept, the mean visual acuity improved significantly in the tachyphylaxis group (p=0.018) but remained unchanged in the complete resistance group (p=0.37). There was a non-significant trend towards improved mean visual acuity in both groups after the second and third injections relative to the acuity at the final visit for ranibizumab treatment. In the tachyphylaxis group, the presence of subfoveal pigmented epithelium detachment (PED) decreased significantly after intravitreal aflibercept treatment. Conclusions: Although treatment with aflibercept yielded generally positive anatomical results in both groups, no significant increase in visual acuity was achieved.
关键词： Tachyphylaxis,Ranibizumab,Angiogenesis inhibitors,Vascular endothelial growth factor A,Macular degeneration
更新于2025-09-23 15:21:21
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Serum VEGF and Ang-2 Levels in Infants Before and After Laser Treatment for Retinopathy of Prematurity
摘要： Objectives: To investigate VEGF and Ang-2 level changes in the systemic circulation after laser photocoagulation in premature infants with ROP. Methods: Eleven infants (4 girls and 7 boys) had serum levels determined for VEGF and Ang-2, collected 1 day prior to and 7 days after ROP laser therapy. Serum levels of VEGF and Ang-2 were quantified by enzyme-linked immunosorbent assay (ELISA). Results: Serum VEGF levels were significantly lower at 7 days after laser therapy compared to that at 1 day prior to laser therapy (p ? 0.045). Serum Ang-2 levels increased significantly at 7 days after laser therapy compared with that at 1 day prior to laser therapy (p ? 0.046). Conclusions: Serum VEGF levels in patients with ROP were suppressed and Ang-2 levels elevated significantly after laser therapy. The results suggest that changes in VEGF and Ang-2 serum levels may reflect regression and treatment of ROP.
关键词： angiopoietin 2,premature infants,serum levels,Retinopathy of prematurity,vascular endothelial growth factor
更新于2025-09-23 15:19:57
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Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes
摘要： Purpose: To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD) with anti-VEGF agents. Materials and methods: We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes. Results: A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71%) maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (-96.6 μm), and 56% of patients maintained dry retinas. Conclusion: Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients.
关键词： visual acuity,vascular endothelial growth factor,choroidal neovascularization,age-related macular degeneration
更新于2025-09-19 17:15:36
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Foreground Detection with Deeply Learned Multi-Scale Spatial-Temporal Features
摘要： The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer.
关键词： combination therapy,vascular endothelial growth factor,dihydrofolate reductase,bladder cancer,Pralatrex,Palbociclib Isethionate
更新于2025-09-19 17:15:36
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Is there still a role of macular laser treatment in branch retinal vein occlusion in the era of intravitreal injections?
摘要： We aimed to evaluate whether macular laser still has a role in the treatment of macular oedema (MO) caused by branch retinal vein occlusion (BRVO) and provide an overview of recent studies on commonly available treatment options. A literature search was last conducted in PubMed on 26 February 2019, limited to human randomized controlled trials published in English since 2008. Seventeen articles addressing 13 trials were included in this assessment. In trials evaluating intravitreal corticosteroid and macular laser, triamcinolone was non-inferior to laser in regard to visual acuity (VA) and central retinal thickness (CRT) outcomes. Combination treatment of dexamethasone and laser resulted in better VA and lower CRT after 6 months. In trials evaluating vascular endothelial growth factor (VEGF) inhibitors versus macular laser treatment, or sham and rescue laser, better VA and CRT of VEGF inhibition treatment was consistently reported. Results of combination treatment versus VEGF inhibition monotherapy were inconsistent, with four of six studies reporting comparable outcomes and injection burden. Study comparison was affected by considerable differences in study design and inadequate reporting of laser protocol and rescue laser. Studies evaluating angiostatic treatment as monotherapy largely report the use of rescue laser, indicating that some patients would benefit from supplemental laser treatment even in the era of intravitreal therapy. Thus, we suggest further studies on optimal design of combination therapy prioritizing longer follow-up time to sufficiently evaluate the delayed effect of laser.
关键词： vascular endothelial growth factor,branch retinal vein occlusion,review,corticosteroid,macular oedema,randomized controlled trials,macular laser
更新于2025-09-19 17:13:59
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Low-level laser therapy induces human umbilical vascular endothelial cell proliferation, migration and tube formation through activating the PI3K/Akt signaling pathway
摘要： Low-level laser therapy (LLLT) has been recognized as a light therapy that may be used for tissue regeneration, inflammation reduction, and pain relief. We intended to evaluate the effects of LLLT on the proliferation, migration, and tube formation of HUVECs as well as their related mechanisms. HUVECs were exposed to laser irradiation under different laser parameters (irradiation dose, interval and power intensity) in order to choose the optimal parameters, which were determined by the increase in proliferation of HUVECs as follows: irradiation dose of 4.0 J/m2, interval time of 12 h and 6 times in total. The HUVEC proliferation, migration, and tube formation, and levels of angiogenesis-related genes (HIF-1α, eNOS and VEGFA) were examined following LLLT. As suggested by the obtained data, LLLT (1.0, 2.0 and 4.0 J/m2) increased the HUVEC proliferation, migration, and tube formation in dose-and time-dependent manner, accompanied with increases in the levels of HIF-1α, eNOS, and VEGFA. Furthermore, the regulatory mechanism regarding the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was explored, phosphorylation levels of PI3K and Akt proteins were assessed by Western blot assay, which showed the enhancement of phosphorylation of PI3K, Akt, and mTOR by LLLT. The inhibitor for the PI3K/Akt axis was used to verify the involvement of PI3K/Akt signaling pathway. The obtained results suggested that the inhibition of the PI3K/Akt signaling pathway attenuated the effects of LLLT on proliferation, migration, and angiogenesis of HUVECs. In conclusion, LLLT promotes the proliferation, migration, and angiogenesis of HUVECs via activation of the PI3K/Akt signaling pathway.
关键词： Vascular endothelial growth factor,Low-level laser therapy,PI3K/Akt signaling pathway,Migration,Angiogenesis
更新于2025-09-16 10:30:52