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International Ophthalmology Jun 2024Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO).
METHODS
This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups.
RESULTS
At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections.
CONCLUSION
Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications.
TRIAL REGISTRATION INFORMATION
The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).
Topics: Humans; Retinal Vein Occlusion; Ranibizumab; Male; Female; Dexamethasone; Intravitreal Injections; Macular Edema; Prospective Studies; Drug Implants; Visual Acuity; Middle Aged; Angiogenesis Inhibitors; Glucocorticoids; Tomography, Optical Coherence; Treatment Outcome; Aged; Drug Therapy, Combination; Follow-Up Studies
PubMed: 38913192
DOI: 10.1007/s10792-024-03158-x -
Frontiers in Immunology 2024The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC).
BACKGROUD
The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC).
METHODS
A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs).
RESULTS
The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group.
CONCLUSIONS
PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.
Topics: Humans; Endostatins; Male; Female; Lung Neoplasms; Middle Aged; Retrospective Studies; Aged; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Staging; Carcinoma, Squamous Cell; Adult; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 38911862
DOI: 10.3389/fimmu.2024.1413204 -
ACS Omega Jun 2024Increasing evidence indicates that peripheral blood vessels play a pivotal role in regulating tumor growth with the presence of new blood vessels facilitating tumor...
Increasing evidence indicates that peripheral blood vessels play a pivotal role in regulating tumor growth with the presence of new blood vessels facilitating tumor growth and metastasis. Nevertheless, the impact of specific molecule-mediated angiogenesis on the tumor immune microenvironment (TIME) and individual prognosis of uterine corpus endometrial carcinoma (UCEC) remains uncertain. The transcriptome information on 217 prognostic angiogenesis-related genes was integrated, and the angiogenesis patterns of 506 UCEC patients in The Cancer Genome Atlas (TCGA) cohort were comprehensively evaluated. We identified five angiogenic subtypes, namely, EC1, EC2, EC3, EC4, and EC5, which differed significantly in terms of prognosis, clinicopathological features, cancer hallmarks, genomic mutations, TIME patterns, and immunotherapy responses. Additionally, an angiogenesis-related prognostic risk score (APRS) was constructed to enable an individualized comprehensive evaluation. In multiple cohorts, APRS demonstrated a powerful predictive ability for the prognosis of UCEC patients. Likewise, APRS was confirmed to be associated with clinicopathological features, genomic mutations, cancer hallmarks, and TIME patterns in UCEC patients. The predictability of APRS for immune checkpoint inhibitor (ICI) therapy was also salient. Subsequently, the expression levels of four angiogenesis-related hub genes were verified by qRT-PCR, immunohistochemistry, and single-cell sequencing data analysis. The effects of four representative genes on angiogenesis were validated by Wound-Healing and Transwell assays, tube formation assay in vitro, and tumor xenograft model in vivo. This study proffered a new classification of UCEC patients based on angiogenesis. The established APRS may contribute to individualized prognosis prediction and immunotherapy selections that are better suited for UCEC patients.
PubMed: 38911819
DOI: 10.1021/acsomega.4c03034 -
Veterinary World May 2024Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been... (Review)
Review
Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.
PubMed: 38911075
DOI: 10.14202/vetworld.2024.1052-1072 -
Journal of Scleroderma and Related... Jun 2024Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue...
Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.
PubMed: 38910594
DOI: 10.1177/23971983241256250 -
Yonsei Medical Journal Jul 2024Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and... (Comparative Study)
Comparative Study
PURPOSE
Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib.
MATERIALS AND METHODS
We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias.
RESULTS
Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, =0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, =0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank =0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank =0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all >0.05).
CONCLUSION
Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
Topics: Humans; Nivolumab; Carcinoma, Hepatocellular; Phenylurea Compounds; Pyridines; Sorafenib; Liver Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Adult; Progression-Free Survival
PubMed: 38910299
DOI: 10.3349/ymj.2023.0263 -
International Ophthalmology Jun 2024In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular...
OBJECTIVE
In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage.
METHODS
A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging.
RESULTS
The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51).
CONCLUSION
Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.
Topics: Humans; Intravitreal Injections; Retrospective Studies; Male; Female; Middle Aged; Angiogenesis Inhibitors; Adult; Vascular Endothelial Growth Factor A; Visual Acuity; Retinal Hemorrhage; Tomography, Optical Coherence; Fluorescein Angiography; Eye Injuries; Treatment Outcome; Bevacizumab; Ranibizumab; Fundus Oculi; Follow-Up Studies
PubMed: 38909337
DOI: 10.1007/s10792-024-03168-9 -
Scientific Reports Jun 2024Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting...
Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting angiogenesis, are promising candidates in cancer treatment. We propose AAPL, a sequence-based predictor to identify AAPs with machine learning models of improved prediction accuracy. Each peptide sequence was transformed to a vector of 4335 numeric values according to 58 different feature types, followed by a heuristic algorithm for feature selection. Next, the hyperparameters of six machine learning models were optimized with respect to the feature subset. We considered two datasets, one with entire peptide sequences and the other with 15 amino acids from peptide N-termini. AAPL achieved Matthew's correlation coefficients of 0.671 and 0.756 for independent tests based on the two datasets, respectively, outperforming existing predictors by a range of 5.3% to 24.6%. Further analyses show that AAPL yields higher prediction accuracy for peptides with more hydrophobic residues, and fewer hydrophilic and charged residues. The source code of AAPL is available at https://github.com/yunzheng2002/Anti-angiogenic .
Topics: Machine Learning; Angiogenesis Inhibitors; Peptides; Algorithms; Amino Acid Sequence; Humans
PubMed: 38909149
DOI: 10.1038/s41598-024-65062-9 -
International Ophthalmology Jun 2024To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal...
PURPOSE
To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal injections of conbercept.
METHODS
A total of 86 eyes from 86 patients received intravitreal conbercept in a 1 + PRN regimen. After the initial injection, patients were followed for 12 months. They were categorized into two groups based on their 12-month visual acuity change: those who achieved greater than a one-line improvement in BCVA (improved group; n = 65) and those who experienced a one-line or lesser improvement or a decrease in BCVA (non-improved group; n = 21).
RESULTS
Over the 12-month period, the mean BCVA in the improved group significantly improved from 0.82 to 0.41 LogMAR. In the non-improved group, BCVA changed from 1.24 to 1.09 LogMAR. Similarly, the mean CRT decreased from 426.21 μm at baseline to 251.56 μm at 12 months in the improved group, and from 452.47 to 382.45 μm in the non-improved group. Multivariable logistic regression analyses revealed that older age (OR 1.287; 95% CI 1.019-1.625; P = 0.034), poorer baseline BCVA (OR 6.422; 95% CI 1.625-25.384; P = 0.008), the presence of subfoveal CNV (OR 4.817; 95% CI 1.242-18.681; P = 0.023), and organized interlacing patterns of CNV morphology (OR 5.593; 95% CI 1.397-22.392; P = 0.015) emerged as independent risk factors correlated with worsened visual prognosis following intravitreal conbercept injections.
CONCLUSIONS
Conbercept demonstrates significant efficacy and safety in treating PM-CNV. Key factors influencing visual recovery post-treatment include older age, poorer baseline BCVA, the presence of subfoveal CNV, and organized interlacing patterns of CNV morphology.
Topics: Humans; Choroidal Neovascularization; Intravitreal Injections; Male; Myopia, Degenerative; Female; Recombinant Fusion Proteins; Middle Aged; Visual Acuity; Prognosis; Tomography, Optical Coherence; Fluorescein Angiography; Retrospective Studies; Follow-Up Studies; Adult; Aged; Treatment Outcome; Angiogenesis Inhibitors; Fundus Oculi
PubMed: 38907787
DOI: 10.1007/s10792-024-03177-8 -
Cell Communication and Signaling : CCS Jun 2024Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating...
Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.
Topics: Humans; Animals; Human Umbilical Vein Endothelial Cells; Mice; Mitochondria; DNA-Directed RNA Polymerases; Diabetic Retinopathy; Mice, Inbred C57BL; Cell Proliferation; Neovascularization, Pathologic; Male; Neovascularization, Physiologic; Cell Movement; Apoptosis; Angiogenesis
PubMed: 38907279
DOI: 10.1186/s12964-024-01712-9