ObjectiveTo observe and analyze the influencing factors for the prognosis of anti-vascular endothelial growth factor (VEGF) drug treatment in patients with macular neovascularization (MNV) under 45 years old. MethodsA retrospective clinical case study. A total of 89 MNV patients with 96 eyes who were diagnosed and treated with anti-VEGF drugs in Department of Ophthalmology of The Second Hospital of Lanzhou University from January 2020 to January 2024 were included in the study. The ages of all patients were ＜45 years old. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations; 49 eyes underwent OCT angiography (OCTA) examination. The BCVA examination was carried out using the international standard visual acuity chart and was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. The macular foveal thickness (CMT) was measured using an OCT instrument. The size of the MNV lesion was measured using the software of the OCTA self-contained device. The affected eyes were given intravitreal injection of anti-VEGF drugs once, and then the drugs were administered as needed after evaluation. The follow-up time after treatment was ≥6 months. During the follow-up, relevant examinations were performed using the same equipment and methods as before treatment. The last follow-up was taken as the time point for efficacy evaluation. According to the OCT image characteristics of the MNV lesions, the affected eyes were divided into the fibrous scar group and the non-fibrous scar group, with 52 (54.16%, 52/96) and 44 (45.83%, 44/96) eyes respectively. Comparing the CMT and BCVA at the last follow-up with those at the baseline, the affected eyes were divided into the CMT reduction group, the CMT increase group, the BCVA improvement group and the BCVA reduction group, with 66 (68.75%, 66/96), 30 (31.25%, 30/96) eyes and 74 (77.08%, 74/96), 22 (22.92%, 22/96) eyes respectively. The Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between groups. Logistic regression analysis was used to analyze the independent factors affecting the prognosis of MNV patients. ResultsThere were no statistically significant differences in the age (Z=?0.928) and gender composition ratio (χ2= 0.123) between the fibrous scar group and the non-fibrous scar group (P＞0.05); there were statistically significant differences in the number of eyes with a follow-up time of ≥36 months and ＜36 months (χ2= 3.906, P=0.048); there were statistically significant differences in the size of the MNV lesions (Z=?2.385, P=0.017); there were statistically significant differences in the number of eyes with different vascular network morphologies (χ2=12.936, P=0.001). Before treatment and at the last follow-up, the CMT of the affected eyes was 267.50 (237.25, 311.75) μm and 242.00 (217.25, 275.75) μm respectively; logMAR BCVA was 0.20 (0.10, 0.50) and 0.35 (0.16, 0.60) logMAR respectively. There were statistically significant differences in the CMT and logMAR BCVA before treatment and at the last follow-up (Z=?3.311,?1.984; P=0.001, 0.047). There were statistically significant differences in different ages (Z=?2.284), myopic diopter (χ2=7.437), etiology (χ2=6.956), and disease course (Z=?1.687) between the CMT reduction group and the CMT increase group (P＜0.05). There were statistically significant differences in the number of eyes with different subjective feelings between the BCVA improvement group and the BCVA reduction group (χ2=10.133, P＜0.05). The results of logistic regression analysis showed that the etiology was an independent risk factor for CMT thickening. ConclusionsAge, etiology, myopic diopter, disease course, follow-up time, lesion size and the morphology of the neovascular network are the influencing factors for the prognosis of anti-VEGF drug treatment in MNV patients under 45 years old. The etiology is an independent risk factor for CMT increase.
Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.
Objective To study the time effect of the gene expression of recombinant adeno-associated virus (rAAV) vector co-expressing human vascular endothel ial growth factor 165 (hVEGF165) and human bone morphogenetic protein 7 (hBMP-7) genes so as to lay a theoretical foundation for gene therapy of osteonecrosis. Methods The best multipl icity of infection (MOI) of BMSCs transfected with rAAV was detected by fluorescent cell counting. The 3rd generation rabbit bone mesenchymal stem cells (BMSCs) were transfected with rAAV-hVEGF165-internal ribosome entry site (IRES)-hBMP-7 (experimental group) and green fluorescent protein (GFP) labeled rAAV-IRES-GFP (control group), respectively. The expression of GFP was observed by inverted fluorescent microscope. The expressions of hVEGF165 and hBMP-7 were assessed by RT-PCR assay and Western blot assay in vitro. The transfected cells in 2 groups were prepared into suspension with 5 × 106 cells/mL, and injected into the rabbit thigh muscles of experimental group 1 (n=9) and control group 1 (n=9), respectively. The muscle injected with rAAV-IRES-GFP was sl iced by frozen section method and the expression of GFP protein was observed by inverted fluorescent microscope. The expressions of hVEGF165 and hBMP-7 were assessed by Western blot assay and ELISA assay in vivo. Results The best MOI of BMSCs transfected with rAAV was 5 × 104 v.g/cell. In vitro, the expressions of GFP, hVEGF165, and hBMP-7 genes started at 1 day after transfection, the expressions obviously increased at 14 days after transfection, and the expression maintained the b level at 28 days after transfection. In vivo, the expressions of GFP, hVEGF165, and hBMP-7 genes could be detected at 2 weeks after injection, and b expressions were shown at 6 to 8 weeks after injection. The values of hVEGF165 and hBMP-7 were (248.67 ± 75.58) pg/mL and (4.80 ± 0.61) ng/mL respectively in experimental group 1, and were (32.28 ± 8.42) pg/mL and (0.64 ± 0.42) ng/mL respectively in control group 1; showing significant differences between 2 groups (P lt; 0.05). Conclusion The rAAV-hVEGF165-IRES-hBMP-7 has efficient gene expression ability.
Anti-vascular endothelial growth factor (VEGF) drugs have been widely used in clinic by inhibiting angiogenesis to treat ocular diseases such as malignant tumors and diabetic retinopathy. However, recent studies have shown that intravitreal injection of anti-VEGF drugs may have significant systemic absorption, leading to a series of renal damages such as worsening hypertension, proteinuria, new glomerular disease, and thrombotic microangiopathy. This article reviews the renal toxicity of intravitreal injection of anti-VEGF drugs in the treatment of diabetic retinopathy and other ocular diseases, aiming to provide recommendations for clinicians.
Objective To investigate the effects of cediranib on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway and proliferation, migration and invasion of liver cancer cells. Methods The hypoxia microenvironment was simulated in vitro, and different doses of cediranib were used to intervene the human hepatoma cell HepG2, MTT assay was used to detect the proliferation of human hepatoma cell HepG2, Transwell chamber assay was used to detect the invasion and migration of human hepatoma cell HepG2, tumor formation in nude mice was used to detect the growth of human hepatoma cell HepG2 in vivo, the angiogenesis of tumor tissue and expression level of HIF-1α/VEGF pathway protein were detected by immunohistochemistry. Results Compared with the control group, the proliferation rate, invasion and migration abilities, and the expression of HIF-1α/VEGF pathway proteins of human hepatoma cell HepG2 were significantly decreased in the different concentration of cediranib treatment group (P<0.05), the tumor volume and microvessel formation of tumor tissues in nude mice were significantly reduced (P<0.05). Conclusion Cediranib may inhibit the proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF signaling pathway.
Objective To observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet. MethodsA retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age (Z=－0.447), gender composition (Z=－0.485), logMAR BCVA (t=－1.591), intraocular pressure (t=－0.167) and CMT (t=－1.290) between two groups (P＞0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. ResultsAt baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA (t=4.129) and CMT (t=－0.713) were significantly improved, with statistical significance (P＜0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times (t=－1.275), logMAR BCVA (t=－0.492), intraocular pressure (t=0.351) and CMT (t=－1.783) between the two groups (P＞0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. ConclusionShort-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.
ObjectiveTo detect expressions of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST) tissues and analyze their relationships with clinicopathologic features of patients with GIST.MethodsForty paraffin-embeded specimens of surgical resected GIST from January 2015 to March 2018 in the Pathology Department of Yuhuangding Hospital Affilicated to Qingdao University were retrieved. The expressions of E-cad and VEGF proteins were detected by the immunohistochemical method.ResultsThe positive expression rates of E-cad and VEGF proteins in the GIST tissues were 10.0% (4/40) and 50.0% (20/40), respectively. The positive expression rates of E-cad and VEGF proteins were associated with the tumor diameter, mitotic counts, and risk classification (P<0.05). The positive expression rate of the E-cad was negatively related to that of the VEGF in the GIST tissues (rs=–0.55, P=0.001).ConclusionFrom results of this study, VEGF and E-cad might be related with malignancy of GIST, which might be potential facators in predicting prognosis of GIST.
ObjectiveTo investigate the mechanism of G protein coupled receptor kinase interacting protein 1 (GIT1) affecting angiogenesis by comparing the differentiation of bone marrow mesenchymal stem cells (BMSCs) differentiated into endothelial cells between GIT1 wild type mice and GIT1 gene knockout mice.MethodsMale and female GIT1 heterozygous mice were paired breeding, and the genotypic identification of newborn mice were detected by PCR. The 2nd generation BMSCs isolated from GIT1 wild type mice or GIT1 gene knockout mice were divided into 4 groups, including wild type control group (group A), wild type experimental group (group A1), GIT1 knockout control group (group B), and GIT1 knockout experimental group (group B1). The cells of groups A1 and B1 were cultured with the endothelial induction medium and the cells of groups A and B with normal cluture medium. The expressions of vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3, and phospho-VEGFR-2 (pVEGFR-2), and pVEGFR-3 proteins were detected by Western blot. The endothelial cell markers [von Willebrand factor (vWF), platelet-endothelial cell adhesion molecule 1 (PECAM-1), and vascular endothelial cadherin (VE-Cadherin)] were detected by flow cytometry. The 2nd generation BMSCs of GIT1 wild type mice were divided into 4 groups according to the different culture media: group Ⅰ, primary cell culture medium; group Ⅱ, cell culture medium containing SAR131675 (VEGFR-3 blocker); group Ⅲ, endothelial induction medium; group Ⅳ, endothelial induction medium containing SAR131675. The endothelial cell markers (vWF, PECAM-1, and VE-Cadherin) in 4 groups were also detected by flow cytometry.ResultsWestern blot results showed that there was no obviously difference in protein expressions of VEGFR-2 and pVEGFR-2 between groups; and the expressions of VEGFR-3 and pVEGFR-3 proteins in group A1 were obviously higher than those in groups A, B, and B1. The flow cytometry results showed that the expressions of vWF, PECAM-1, and VE-Cadherin were significantly higher in group A1 than in groups A, B, and B1 (P<0.05), and in group B1 than in groups A and B (P<0.05); but no significant difference was found between groups A and B (P>0.05). In the VEGFR-3 blocked experiment, the flow cytometry results showed that the expressions of vWF, PECAM-1, and VE-Cadherin were significantly higher in group Ⅲ than in groupsⅠ, Ⅱ, and Ⅳ, and in group Ⅳ than in groups Ⅰ and Ⅱ (P<0.05); but no significant difference was found between groups Ⅰ and Ⅱ (P>0.05).ConclusionGIT1 mediates BMSCs of mice differentiation into endothelial cells via VEGFR-3, thereby affecting the angiogenesis.
Objective
To systematically evaluate expression of vascular endothelial growth factor (VEGF) protein in triple negative breast cancer (TNBC) and analyze its correlation between positive expression of VEGF protein and clinicopathologic features of patient with TNBC.
Methods
The published literatures relevant VEGF protein expression in TNBC and its relation to clinicopathologic features of patient with TNBC in China were retrieved by means of CNKI, Wanfang, VIP, China Biomedical, Chaoxing Medalink, PubMed databases, and other search tools. The literatures were independently filtered, extracted, and assessed by two reviewers according to the inclusion criteria and exclusion criteria. The meta-analysis was conducted by using RevMan 5.3 software.
Results
A total of 11 literatures were included and involved 1 838 patients (750 patients in the TNBC group and 1 088 patients in the non-TNBC group). The results of meta-nalysis showed that the positive expression of VEGF protein in the TNBC group was significantly higher than that in the non-TNBC group 〔OR=2.64, 95%CI (2.14, 3.26), P<0.000 01〕 , which was significantly increased in the TNBC patients with positive lymph node or stage Ⅲ–Ⅳ as compared with the negative lymph node or stage Ⅰ–Ⅱ 〔OR=0.30, 95% CI (0.14, 0.46), P=0.000 2; OR=0.43, 95% CI (0.29, 0.62), P<0.000 01〕 . However, the positive expression of VEGF protein was no associated with the age of patients with TNBC or tumor size (P>0.05).
Conclusions
VEGF highly expresses in TNBC and it is expected to be a new therapeutic target. Positive expression of VEGF protein is related to positive lymph node and late TNM stage, and it might be associated with prognosis of patient with TNBC.
Retinal vein occlusion (RVO) is a closely related disease of ophthalmology and systemic diseases. The Expert consensus on clinical diagnosis and treatment path of retinal vein occlusion in China (consensus) emphasizes that etiological diagnosis and treatment should be paid primary attention to, and etiological exploration should be placed in an important position in the diagnosis and treatment path. In addition to etiological treatment, the consensus emphasizes that clinical attention should be paid to the management of anterior segment neovascularization, neovascular glaucoma and macular edema. Especially for patients with short course of central retinal vein occlusion, the occurrence of 100-day glaucoma should be vigilant, and active anti-vascular endothelial growth factor (VEGF) drugs, laser photocoagulation and intraocular pressure treatment should be taken. For the treatment of macular edema, the consensus points out that anti-VEGF drugs and intraocular glucocorticoid sustained-release agents are effective, but the latter should be used cautiously to avoid problems such as high intraocular pressure glaucoma and accelerated cataract formation. For deficient RVO, the consensus defines its concept, defines the time point of treatment when combined with macular edema, and clarifies the applicable conditions of laser therapy.
