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1.
Ther Drug Monit ; 46(3): 321-331, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38723115

BACKGROUND: Pazopanib, an anti-angiogenic multitarget tyrosine kinase inhibitor, has been approved for the treatment of metastatic renal cell carcinoma and soft tissue sarcoma. However, its recommended dose does not always produce consistent outcomes, with some patients experiencing adverse effects or toxicity. This variability is due to differences in the systemic exposure to pazopanib. This review aimed to establish whether sufficient evidence exists for the routine or selective therapeutic drug monitoring of pazopanib in adult patients with approved indications. METHODS: A systematic search of the PubMed and Web of Science databases using search terms related to pazopanib and therapeutic drug monitoring yielded 186 and 275 articles, respectively. Ten articles associated with treatment outcomes or toxicity due to drug exposure were selected for review. RESULTS: The included studies were evaluated to determine the significance of the relationship between drug exposure/Ctrough and treatment outcomes and between drug exposure and toxicity. A relationship between exposure and treatment outcomes was observed in 5 studies, whereas the trend was nonsignificant in 4 studies. A relationship between exposure and toxicity was observed in 6 studies, whereas 2 studies did not find a significant relationship; significance was not reported in 3 studies. CONCLUSIONS: Sufficient evidence supports the therapeutic drug monitoring of pazopanib in adult patients to improve its efficacy and/or safety in the approved indications.


Angiogenesis Inhibitors , Carcinoma, Renal Cell , Drug Monitoring , Indazoles , Kidney Neoplasms , Pyrimidines , Sarcoma , Sulfonamides , Indazoles/therapeutic use , Humans , Sulfonamides/therapeutic use , Sulfonamides/pharmacokinetics , Pyrimidines/therapeutic use , Pyrimidines/pharmacokinetics , Drug Monitoring/methods , Carcinoma, Renal Cell/drug therapy , Sarcoma/drug therapy , Kidney Neoplasms/drug therapy , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacokinetics
2.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Article En | MEDLINE | ID: mdl-38724487

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.


Bevacizumab , Child Development , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/physiopathology , Retinopathy of Prematurity/surgery , Male , Female , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Child, Preschool , Cross-Sectional Studies , Child , Child Development/drug effects , Child Development/physiology , Infant, Newborn , Infant, Premature , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Motor Skills/physiology , Intravitreal Injections
3.
Nat Prod Res ; 38(11): 1918-1923, 2024 Jun.
Article En | MEDLINE | ID: mdl-38739564

Blumea eriantha D.C is a weed from Asteraceae family and is reported to have anticancer activity. The essential oil from the aerial parts was extracted by steam distillation method with the yield of 0.36%. Through GC-MS analysis of the oil, seventeen compounds could be identified by comparing with linear retention indices with the library. Out of the seventeen compounds ß-Caryophylline oxide was isolated by column chromatography with gradient elution and the structure was determined through FT-IR, MS, 1HNMR, 13 C NMR and DEPT. The oil was evaluated for its effect on angiogenesis using Chorioallantoic Membrane Assay (CAM Assay). The concentration dependent antiangiogenic effect was observed with IC 50 value of 19.28 ppm.


Angiogenesis Inhibitors , Asteraceae , Gas Chromatography-Mass Spectrometry , Oils, Volatile , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/chemistry , Asteraceae/chemistry , Animals , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/blood supply , Plant Components, Aerial/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Molecular Structure , Spectroscopy, Fourier Transform Infrared , Polycyclic Sesquiterpenes
5.
Int Ophthalmol ; 44(1): 225, 2024 May 15.
Article En | MEDLINE | ID: mdl-38748185

PURPOSE: To evaluate the importance of the status of posterior vitreous in eyes with endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: The absence or existence of posterior vitreous detachment (PVD) was elicited in 23 eyes of 23 patients with injection related endophthalmitis, during pars plana vitrectomy (PPV) and compared with 24 control eyes of 24 patients who received intravitreal anti-VEGF without any complication. RESULTS: Thirtten (54.2%) out of 24 patients in the control group had full PVD, whereas only 2 (9.5%) out of 23 eyes in endophthalmitis group (p < 0.001) had full PVD. In all eyes without PVD, posterior vitreous was inducted to be detached at least from optic nerve and macular area without any iatrogenic tear. CONCLUSION: The absence of PVD is a factor that increases the risk of endophthalmitis after intravitreal injections. Uncomplicated separation of the posterior vitreous from the retina in PPV contributes to better prognosis.


Angiogenesis Inhibitors , Endophthalmitis , Intravitreal Injections , Vascular Endothelial Growth Factor A , Vitrectomy , Vitreous Detachment , Humans , Endophthalmitis/etiology , Endophthalmitis/diagnosis , Endophthalmitis/epidemiology , Intravitreal Injections/adverse effects , Male , Female , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Risk Factors , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Middle Aged , Vitrectomy/adverse effects , Vitrectomy/methods , Vitreous Body , Ranibizumab/administration & dosage , Ranibizumab/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Aged, 80 and over
6.
Bioorg Chem ; 147: 107405, 2024 Jun.
Article En | MEDLINE | ID: mdl-38696843

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.


Macular Degeneration , Peptides, Cyclic , Receptors, CCR3 , Animals , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemical synthesis , Macular Degeneration/drug therapy , Macular Degeneration/pathology , Mice , Receptors, CCR3/antagonists & inhibitors , Receptors, CCR3/metabolism , Humans , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/chemical synthesis , Angiogenesis Inhibitors/chemistry , Molecular Structure , Structure-Activity Relationship , Mice, Inbred C57BL , Dose-Response Relationship, Drug , Apoptosis/drug effects , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/pathology , Choroidal Neovascularization/metabolism , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/pathology , Angiogenesis
7.
Vestn Oftalmol ; 140(2): 112-120, 2024.
Article Ru | MEDLINE | ID: mdl-38742507

Diabetic macular edema (DME) is a degenerative disease of the macular area in diabetes mellitus and can lead to vision loss, disability, and significantly reduced quality of life. Faricimab is the only bispecific antibody for DME therapy that targets two pathogenic pathways (Ang-2 and VEGF-A). PURPOSE: This study comparatively evaluates the clinical and economic feasibility of faricimab and other angiogenesis inhibitors in patients with DME. MATERIAL AND METHODS: This article analyzed literature on the efficacy and safety of intravitreal injections (IVI) of ranibizumab 0.5 mg, aflibercept 2 mg, and faricimab 6 mg. A model of medical care was developed for patients with DME receiving anti-angiogenic therapy. Pharmacoeconomic analysis was performed using cost minimization and budget impact analysis (BIA) methods. Modeling time horizon was 2 years. The research was performed from the perspective of the healthcare system of the Russian Federation. RESULTS: The efficacy and safety of faricimab in a personalized regimen (up to one IVI in 16 weeks) are comparable to those of aflibercept and ranibizumab, administered in various regimens. The use of faricimab is associated with the lowest number of IVIs. Over 2 years, the maximum costs of drug therapy were associated with the use of ranibizumab (about 914 thousand rubles), while the minimum costs were associated with the use of faricimab (614 thousand rubles). The reduction in inpatient care costs with faricimab therapy was 36% compared to aflibercept (216 and 201 thousand rubles in inpatient and day hospitals, respectively) and 82% compared to ranibizumab (486 and 451 thousand rubles in inpatient and day hospitals, respectively). BIA demonstrated that the use of faricimab will reduce the economic burden on the healthcare system by 11.3 billion rubles (9.8%) over 2 years. CONCLUSION: The use of faricimab is a cost-effective approach to treatment of adult patients with DME in Russia.


Angiogenesis Inhibitors , Diabetic Retinopathy , Economics, Pharmaceutical , Macular Edema , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Humans , Macular Edema/drug therapy , Macular Edema/etiology , Macular Edema/economics , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/economics , Russia , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/administration & dosage , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Intravitreal Injections , Ranibizumab/administration & dosage , Ranibizumab/economics , Cost-Benefit Analysis , Antibodies, Bispecific/economics , Antibodies, Bispecific/administration & dosage , Treatment Outcome
8.
BMC Cancer ; 24(1): 614, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773427

OBJECTIVE: Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival. RESULTS: General patient information between the two groups showed no significant differences (P > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group (P < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group (P < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group (P < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group (P < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group (P < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group (P < 0.05). CONCLUSION: In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.


Angiogenesis Inhibitors , Angiogenic Proteins , Carcinoma, Hepatocellular , Liver Neoplasms , Neovascularization, Pathologic , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Middle Aged , Male , Female , Aged , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacology , Angiogenic Proteins/metabolism , Adult , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Lactones/therapeutic use , Lactones/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Angiogenesis
9.
Sci Rep ; 14(1): 11681, 2024 05 22.
Article En | MEDLINE | ID: mdl-38778065

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 µm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.


Visual Acuity , Humans , Male , Female , Aged , Japan , Retrospective Studies , Aged, 80 and over , Visual Acuity/drug effects , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/administration & dosage , Macular Degeneration/drug therapy , Macular Degeneration/pathology , Intravitreal Injections , Middle Aged , Tomography, Optical Coherence
11.
Nutrients ; 16(9)2024 Apr 25.
Article En | MEDLINE | ID: mdl-38732529

The Mediterranean diet, renowned for its health benefits, especially in reducing cardiovascular risks and protecting against diseases like diabetes and cancer, emphasizes virgin olive oil as a key contributor to these advantages. Despite being a minor fraction, the phenolic compounds in olive oil significantly contribute to its bioactive effects. This review examines the bioactive properties of hydroxytyrosol and related molecules, including naturally occurring compounds (-)-oleocanthal and (-)-oleacein, as well as semisynthetic derivatives like hydroxytyrosyl esters and alkyl ethers. (-)-Oleocanthal and (-)-oleacein show promising anti-tumor and anti-inflammatory properties, which are particularly underexplored in the case of (-)-oleacein. Additionally, hydroxytyrosyl esters exhibit similar effectiveness to hydroxytyrosol, while certain alkyl ethers surpass their precursor's properties. Remarkably, the emerging research field of the effects of phenolic molecules related to virgin olive oil on cell autophagy presents significant opportunities for underscoring the anti-cancer and neuroprotective properties of these molecules. Furthermore, promising clinical data from studies on hydroxytyrosol, (-)-oleacein, and (-)-oleocanthal urge further investigation and support the initiation of clinical trials with semisynthetic hydroxytyrosol derivatives. This review provides valuable insights into the potential applications of olive oil-derived phenolics in preventing and managing diseases associated with cancer, angiogenesis, and atherosclerosis.


Angiogenesis Inhibitors , Olive Oil , Phenols , Phenylethyl Alcohol , Olive Oil/chemistry , Humans , Phenols/pharmacology , Angiogenesis Inhibitors/pharmacology , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/pharmacology , Diet, Mediterranean , Atherosclerosis/prevention & control , Atherosclerosis/drug therapy , Cyclopentane Monoterpenes , Neoplasms/prevention & control , Neoplasms/drug therapy , Catechols/pharmacology , Aldehydes/pharmacology , Animals , Antineoplastic Agents/pharmacology , Anti-Inflammatory Agents/pharmacology
12.
BMC Pediatr ; 24(1): 301, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704544

BACKGROUND: We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. CASE PRESENTATION: The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. CONCLUSIONS: Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.


Angiogenesis Inhibitors , Bevacizumab , Fluorescein Angiography , Intravitreal Injections , Laser Coagulation , Retinal Neovascularization , Retinopathy of Prematurity , Humans , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Infant, Newborn , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Female , Laser Coagulation/methods , Retinal Neovascularization/etiology , Retinal Neovascularization/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Combined Modality Therapy
13.
Drug Dev Res ; 85(3): e22195, 2024 May.
Article En | MEDLINE | ID: mdl-38704831

We investigated the angiogenesis-modulating ability of noscapine in vitro using osteosarcoma cell line (MG-63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG-63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real-time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG-63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG-63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG-63 cells and zebrafish embryos. Therefore, noscapine may prevent MG-63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions.


Hemodynamics , Neovascularization, Pathologic , Noscapine , Zebrafish , Animals , Humans , Noscapine/pharmacology , Cell Line, Tumor , Hemodynamics/drug effects , Neovascularization, Pathologic/drug therapy , Angiogenesis Inhibitors/pharmacology , Hypoxia , Cell Movement/drug effects , Embryo, Nonmammalian/drug effects , Osteosarcoma/drug therapy , Angiogenesis
14.
Article En | MEDLINE | ID: mdl-38701802

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.


Bevacizumab , Carcinoma, Squamous Cell , Eye Neoplasms , Horse Diseases , Horses , Animals , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Horse Diseases/drug therapy , Female , Carcinoma, Squamous Cell/veterinary , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Eye Neoplasms/veterinary , Eye Neoplasms/drug therapy , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Corneal Stroma/drug effects , Corneal Stroma/pathology
15.
Cancer Treat Rev ; 127: 102749, 2024 Jun.
Article En | MEDLINE | ID: mdl-38714074

Cancer cells merely exist in isolation; rather, they exist in an intricate microenvironment composed of blood vessels, signalling molecules, immune cells, stroma, fibroblasts, and the ECM. The TME provides a setting that is favourable for the successful growth and survivance of tumors. Angiogenesis is a multifaceted process that is essential for the growth, invasion, and metastasis of tumors. TME can be visualized as a "concert hall," where various cellular and non-cellular factors perform in a "symphony" to orchestrate tumor angiogenesis and create "Havoc" instead of "Harmony". In this review, we comprehensively summarized the involvement of TME in regulating tumor angiogenesis. Especially, we have focused on immune cells and their secreted factors, inflammatory cytokines and chemokines, and their role in altering the TME. We have also deciphered the crosstalk among various cell types that further aids the process of tumor angiogenesis. Additionally, we have highlighted the limitations of existing anti-angiogenic therapy and discussed various potential strategies that could be used to overcome these challenges and improve the efficacy of anti-angiogenic therapy.


Neoplasms , Neovascularization, Pathologic , Tumor Microenvironment , Humans , Neovascularization, Pathologic/pathology , Neoplasms/pathology , Neoplasms/blood supply , Neoplasms/drug therapy , Animals , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacology , Angiogenesis
16.
Invest Ophthalmol Vis Sci ; 65(5): 26, 2024 May 01.
Article En | MEDLINE | ID: mdl-38758639

Purpose: In diabetic macular edema (DME), hyper-reflective foci (HRF) has been linked to disease severity and progression. Using an automated approach, we aimed to investigate the baseline distribution of HRF in DME and their co-localization with cystoid intraretinal fluid (IRF). Methods: Baseline spectral-domain optical coherence tomography (SD-OCT) volume scans (N = 1527) from phase III clinical trials YOSEMITE (NCT03622580) and RHINE (NCT03622593) were segmented using a deep-learning-based algorithm (developed using B-scans from BOULEVARD NCT02699450) to detect HRF. The HRF count and volume were assessed. HRF distributions were analyzed in relation to best-corrected visual acuity (BCVA), central subfield thickness (CST), and IRF volume in quartiles, and Diabetic Retinopathy Severity Scores (DRSS) in groups. Co-localization of HRF with IRF was calculated in the central 3-mm diameter using the en face projection. Results: HRF were present in most patients (up to 99.7%). Median (interquartile range [IQR]) HRF volume within the 3-mm diameter Early Treatment Diabetic Retinopathy Study ring was 1964.3 (3325.2) pL, and median count was 64.0 (IQR = 96.0). Median HRF volumes were greater with decreasing BCVA (nominal P = 0.0109), and increasing CST (nominal P < 0.0001), IRF (nominal P < 0.0001), and DRSS up to very severe nonproliferative diabetic retinopathy (nominal P < 0.0001). HRF co-localized with IRF in the en face projection. Conclusions: Using automated HRF segmentation of full SD-OCT volumes, we observed that HRF are a ubiquitous feature in DME and exhibit relationships with BCVA, CST, IRF, and DRSS, supporting a potential link to disease severity. The spatial distribution of HRF closely followed that of IRF.


Diabetic Retinopathy , Macular Edema , Subretinal Fluid , Tomography, Optical Coherence , Visual Acuity , Humans , Macular Edema/metabolism , Macular Edema/diagnosis , Macular Edema/diagnostic imaging , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/diagnosis , Tomography, Optical Coherence/methods , Visual Acuity/physiology , Male , Female , Middle Aged , Subretinal Fluid/metabolism , Aged , Angiogenesis Inhibitors/therapeutic use , Algorithms , Intravitreal Injections
17.
Med Oncol ; 41(6): 144, 2024 May 08.
Article En | MEDLINE | ID: mdl-38717574

Peganum harmala has been extensively employed in Algerian traditional medicine practices. This study aimed to explore the impact of n-butanol (n-BuOH) extract sourced from Peganum harmala seeds on cell proliferation, cell migration, and angiogenesis inhibition. Cytotoxic potential of n-BuOH extract was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide) assay against human breast adenocarcinoma MCF-7 cells, cell migration was determined using scratch assay, and anti-angiogenic effect was evaluated through macroscopic and histological examinations conducted on chick embryo chorioallantoic membrane. Additionally, this research estimated the phytochemical profile of n-BuOH extract. Fifteen phenolic compounds were identified using Ultra-performance liquid chromatography UPLC-ESI-MS-MS analysis. In addition, the n-BuOH extract of P. harmala exhibited potent antioxidant and free radical scavenging properties. The n-BuOH extract showed potent cytotoxicity against MCF-7 cell with an IC50 value of 8.68 ± 1.58 µg/mL. Furthermore, n-BuOH extract significantly reduced migration. A strong anti-angiogenic activity was observed in the groups treated with n-BuOH extract in comparison to the negative control. Histological analysis confirmed the anti-angiogenic effect of the n-BuOH extract. This activity is probably a result of the synergistic effects produced by different polyphenolic classes.


Angiogenesis Inhibitors , Cell Movement , Peganum , Phenols , Plant Extracts , Humans , Cell Movement/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Peganum/chemistry , Chick Embryo , Phenols/pharmacology , Phenols/analysis , Angiogenesis Inhibitors/pharmacology , MCF-7 Cells , Animals , Cell Proliferation/drug effects , Phytochemicals/pharmacology , Phytochemicals/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/blood supply
18.
Toxicon ; 243: 107742, 2024 May 28.
Article En | MEDLINE | ID: mdl-38705486

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.


Angiogenesis Inhibitors , Bothrops , Cell Proliferation , Crotalid Venoms , Lung Neoplasms , Animals , Humans , Angiogenesis Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Cell Proliferation/drug effects , Phospholipases A2/pharmacology , Cell Movement/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Vascular Endothelial Growth Factor A/metabolism , A549 Cells , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Neovascularization, Pathologic/drug therapy , Reactive Oxygen Species/metabolism , Venomous Snakes
19.
Int Ophthalmol ; 44(1): 216, 2024 May 05.
Article En | MEDLINE | ID: mdl-38705908

PURPOSE: To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. METHODS: In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. RESULTS: Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. CONCLUSION: Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.


Angiogenesis Inhibitors , Bevacizumab , Endophthalmitis , Intravitreal Injections , Visual Acuity , Humans , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Endophthalmitis/diagnosis , Endophthalmitis/etiology , Retrospective Studies , Male , Female , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Aged , Middle Aged , Aged, 80 and over , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Macular Edema/drug therapy , Macular Edema/diagnosis , Macular Edema/etiology , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/complications , Follow-Up Studies , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy
20.
Vestn Oftalmol ; 140(2. Vyp. 2): 7-15, 2024.
Article Ru | MEDLINE | ID: mdl-38739125

PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.


Angiogenesis Inhibitors , Biometry , Intraocular Pressure , Intravitreal Injections , Tomography, Optical Coherence , Humans , Male , Intraocular Pressure/drug effects , Intraocular Pressure/physiology , Female , Tomography, Optical Coherence/methods , Aged , Biometry/methods , Angiogenesis Inhibitors/administration & dosage , Anterior Eye Segment/diagnostic imaging , Anterior Eye Segment/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Tonometry, Ocular/methods , Middle Aged , Macular Degeneration/drug therapy , Macular Degeneration/diagnosis , Treatment Outcome
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