Deep endometriosis (DE) is the most severe subtype of endometriosis, with the hallmark of lesions infiltrating adjacent tissue. Abnormal vascularisation has been implicated in contributing to endometriosis lesion development in general, and how vascularisation influences the pathogenesis of DE, in particular, is of interest. This systematic review followed the PRISMA guidelines to elucidate and examine the evidence for DE-specific vascularisation. A literature search was performed using MEDLINE, Embase, PubMed, Scopus, Cochrane CENTRAL Library and Europe PubMed Central databases. The databases were searched from inception to the 13 March 2023. A total of 15 studies with 1125 patients were included in the review. The DE lesions were highly vascularised, with a higher microvessel density (MVD) than other types of endometriotic lesions, eutopic endometrium from women with endometriosis and control tissue. Vascular endothelial growth factor, its major subtype (VEGF-A) and associated receptor (VEGFR-2) were significantly increased in the DE lesions compared to superficial endometriosis, eutopic endometrium and control tissue. Progestin therapy was associated with a significant decrease in the MVD of the DE lesions, explaining their therapeutic effect. This review comprehensively summarises the available literature, reporting abnormal vascularisation to be intimately related to the pathogenesis of DE and presents potentially preferential therapeutic targets for the medical management of DE.

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

Bevacizumab is a monoclonal antibody that targets VEGF-A and inhibits tumor angiogenesis. Bevacizumab is approved for the treatment of various cancer, including metastatic colorectal cancer (mCRC), ovarian cancer, lung cancer, and others. Thus, it is widely used in oncology, but contrary to other therapeutic classes, there is still a lack of validating predictive factors for treatment outcomes with these agents. In recent years, the research for factors predictive of anti-VEGF treatments and especially bevacizumab response has been one of the most competitive translational research fields. Herein, we review and present the available literature of the clinical use of biomarkers, pharmacogenomics (PG), and therapeutic drug monitoring (TDM) approaches that can be used for the optimization of bevacizumab use in the era of precision medicine.

Angiogenesis is the process through which new blood vessels are formed from pre-existing vessels and is essential for the growth of all solid tumors. Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis, which is crucial for tumor growth and metastasis. Its inhibition with antiangiogenic drugs is thought to improve delivery of chemotherapy through vascular normalization and disruption of tumor vasculature. Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR)1 and VEGFR2 extracellular domains that binds to VEGF-A, VEGF-B, placental growth factor (PlGF) 1 and 2. Aflibercept has demonstrated preclinical efficacy in different tumor types and exerts its antiangiogenic effects through regression of tumor vasculature, remolding of vasculature, and inhibition of new tumor vessel growth. This review examines the effects of aflibercept on tumor vasculature and on different types of solid tumors, and explores the preclinical and clinical benefits of inclusion aflibercept into anticancer treatment strategies.

Burkitt\'s lymphoma (BL) is a malignancy of B lymphocytes. The rapid growth rate and frequent systemic spread result in most patients presenting with advanced disease at diagnosis. Cerebrospinal fluid cytology is the gold standard (with very high accuracy) for diagnosing BL central nervous system (CNS) metastasis; however, the low sensitivity of this method limits its clinical applications. Here, we report a case of BL with CNS metastasis. The levels of vascular endothelial growth factor (VEGF)-A and VEGF-C in the serum and cerebrospinal fluid were used to evaluate the status of BL remission and recurrence. Comparisons were made between VEGF and the other risk factors used in evaluating CNS metastasis. Although not in strict accordance, VEGF levels mirrored the disease course. Therefore, VEGF may reflect the status of BL CNS metastasis. Understanding the role of VEGF in CNS metastasis may help to improve the staging and risk classification of BL as well as the investigation of targeted therapy.

Rosacea is a common, chronic inflammatory skin disease of poorly understood origin. Based on its clinical features (flushing, chronic inflammation, fibrosis) and trigger factors, a complex pathobiology involving different regulatory systems can be anticipated. Although a wealth of research has shed new light over recent years on its pathophysiology, the precise interplay of the various dysregulated systems (immune, vascular, nervous) is still poorly understood. Most authors agree on 4 major clinical subtypes of rosacea: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. Still, it needs to be elucidated whether these subtypes develop in a consecutive serial fashion or if any subtypes may occur individually as part of a syndrome. Because rosacea often affects multiple family members, a genetic component is also suspected, but the genetic basis of rosacea remains unclear. During disease manifestation and early stage, the innate immune system and neurovascular dysregulation seem to be driving forces in rosacea pathophysiology. Dissection of major players for disease progression and in advanced stages is severely hampered by the complex activation of the innate and adaptive immune systems, enhanced neuroimmune communication, profound blood vessel and possibly lymphatic vessel changes, and activation of almost every resident cell in the skin. This review discusses some of the recent findings and aims to build unifying hypotheses for a modern understanding of rosacea pathophysiology.