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Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.

BackgroundCongenital diaphragmatic hernia (CDH) is a cause of significant morbidity. CDH is the most common neonatal diagnosis requiring extracorporeal membrane oxygenation (ECMO).MethodsWe compared the different characteristics of ECMO and non-ECMO patients with CDH in a case-control study. Data were extracted from the Kids' Inpatient Database. Records from 2006 to 2016 were used. Patients

Pathologic retinal neovascularization is a potentially blinding consequence seen in many common diseases including diabetic retinopathy, retinopathy of prematurity, and retinal vaso-occlusive diseases. This study investigates epithelial membrane protein 2 (EMP2) and its role as a possible modulator of angiogenesis in human retinal pigment epithelium (RPE) under hypoxic conditions. To study its effects, the RPE cell line ARPE-19 was genetically modified to either overexpress EMP2 or knock down its levels, and RNA sequencing and western blot analysis was performed to confirm the changes in expression at the RNA and protein level, respectively. Protein expression was evaluated under both normoxic conditions or hypoxic stress. Capillary tube formation assays with human umbilical vein endothelial cells (HUVEC) were used to evaluate functional responses. EMP2 expression was found to positively correlate with expression of pro-angiogenic factors HIF1α and VEGF at both mRNA and protein levels under hypoxic conditions. Mechanistically, EMP2 stabilized HIF1α expression through downregulation of von Hippel Lindau protein (pVHL). EMP2 mediated changes in ARPE-19 cells were also found to alter the secretion of a paracrine factor(s) in conditioned media that can regulate HUVEC migration and capillary tube formation in in vitro functional angiogenesis assays. This study identifies EMP2 as a potential mediator of angiogenesis in a human RPE cell line. EMP2 levels positively correlate with pro-angiogenic mediators HIF1α and VEGF, and mechanistically, EMP2 regulates HIF1α through downregulation of pVHL. This study supports further investigation of EMP2 as a promising novel target for therapeutic treatment of pathologic neovascularization in the retina.

Purpose: Investigate risk factors for short term reactivation of retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) therapy and determine safety and efficacy of repeat injections., Methods: Retrospective chart review study of patients screened for ROP as inpatients between 2013-2023 who received IVR within the UCLA healthcare system. Primary outcomes were rates and timing of short term ROP reactivation, defined as repeat worsening of ROP to stage 2 or 3 before 52 weeks postmenstrual age (PMA), as well as risk factors for reactivation. Other outcomes included adverse events and rates of reactivation after a second intravitreal injection., Results: 82 eyes of 43 patients received primary IVR 0.25mg/0.025cc for type 1 ROP. 13 patients (22 eyes) (30.2% of patients, 26.8% of eyes) developed short term reactivation an average of 7.2±1.7 weeks after treatment. Increased reactivation risk was associated with zone I disease (OR 6.23, 95% CI 1.35-28.7, p=0.019), lower PMA at 1st injection (OR 1.64, 95% CI 1.19-2.26; p=0.003), and lower gestational age at birth (OR 1.80, 95% CI 1.04-3.13, p=0.037). Of the 13 patients that received repeat injections, 5 required laser treatment for a second reactivation (11.6% of patients receiving IVR). No eyes developed retinal vascular occlusion, endophthalmitis or cataract., Conclusion: Repeat injections may be required after primary IVR for aggressive ROP. Repeat IVR treatment for ROP is effective and poses few ophthalmic adverse events, though additional reactivation remains a risk., Competing Interests: Financial Disclosures: The authors have no conflicts of interest to declare.

Purpose: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization., Methods: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed., Results: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss., Conclusions: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.