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Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
Monocytes constitute the dominant population among circulating cells expressing VEGFR2. Some pro-angiogenic monocytes express the angiopoietin receptor Tie2 and are called Tie2-expressing monocytes (TEMs). However, the existence of such specific pro-angiogenic subtypes of monocytes is somewhat controversial. The so-called circulating EPCs, when isolated by older adhesion and culture-based methods, were found to be largely of monocytic origin—a subpopulation of monocytes that, when stimulated by VEGF, produce endothelial cell phenotypes in culture. In such cultures, the “early outgrowth” endothelial progenitors include monocytes and T cells, and their formation is strictly dependent on the presence of monocytes. But the cells are nonetheless strongly supportive of angiogenesis and have been named “circulating angiogenic cells” (CACs) by some authors and are likely to overlap with BMDCs, as described in Section 5.2.4.4.
Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
The metastatic process is initiated by the intravasation of tumor cells into blood or lymph vessel lumina to give rise to CTCs. Tumor cells migrate towards the vessel wall in response to chemotactic signals originating from the tumor microenvironment and then must penetrate across the vessel wall. These compose the two key stages of intravasation [751]. Some cancers use micro-anatomical structural sites, such as ‘tumor microenvironment of metastasis (TMEM)' or ‘CSF1/EGF (colony-stimulating factor 1/epidermal growth factor) paracrine signaling pathway', for cell intravasation and subsequent dissemination [751, 752]. These sites have been discovered in both human and murine mammary carcinomas and are composed of three types of cells, a perivascular macrophage, an endothelial cell, and a tumor cell expressing the actin-regulatory protein, mammalian-enabled (MENA), and are in direct physical contact with each other [752–754]. TMEM sites provide a safe passage for migratory cancer cells to intravasate and disseminate to secondary sites by inducing and controlling the local and transient dissociation of endothelial cell junctions at the TMEM [752]. Localized vascular endothelial growth factor-A (VEGF-A) released from the angiopoietin receptor TIE2 expressing TMEM-bound macrophages mediates TMEM-dependent vascular permeability [752]. This is seen in breast cancer where cells disseminate through TIE2/MENACalc/MENAINV-dependent intravasation sites, and these have become clinically validated prognostic markers of metastasis in patients [752]. Moreover, in residual breast cancers of patients treated with neoadjuvant therapy, there may be an increased risk of metastatic dissemination owing to chemotherapy-induced TMEM activity [752]. Other mechanisms of intravasation have been observed or postulated including cooperative intravasation, (where clusters of tumor cells surrounded by the elements of the vessel wall intravasate), vasculogenic mimicry-associated intravasation (where vascular channels are formed by neoplastic cells), as well as the newly hypothesized ‘tumor cell intravasation associated with extrusion', ‘intravasation of tumor cells fusing with macrophages', and ‘intravasation associated with trogocytosis' (means ‘gnaw' or ‘nibble' in Greek, and necessitate “one cell nipping bits off another” [755]) [751].
ANGPTL3: a novel biomarker and promising therapeutic target
Published in Journal of Drug Targeting, 2019
Shuang Jiang, Guo-Hui Qiu, Neng Zhu, Zhe-Yu Hu, Duan-Fang Liao, Li Qin
ANGPTL3 is a member of the ANGPTL protein family, which contains a group of eight proteins (ANGPTL1 to ANGPTL8). ANGPTL protein family shares structural similarity to the angiopoietin protein family including an N-terminal signal peptide (SP), an N-terminal coiled-coil domain (CCD), a linking region and a C-terminal fibrinogen-like domain (FLD) (Figure 1) [1]. However, there are still some structural differences between ANGPTL and angiopoietin family. For example, ANGPTL3 contains the four conserve cysteines implicated in the intramolecular disulphide bonds of the FLD, while it does not contain the two other cysteines that are found within the FLD of other angiopoietins. Consequently, ANGPTL3 forms noncovalent rather than disulphide-linked oligomers. Because of structural differences, ANGPTL3 do not bind to the angiopoietin receptor tyrosine kinase receptor (Tie) 1 or Tie2 [1,2].
Whole-exome screening for primary congenital glaucoma in Lebanon
Published in Ophthalmic Genetics, 2023
Nadine J. Makhoul, Zahi Wehbi, Dalia El Hadi, Baha Noureddine, Rose-Mary Boustany, Christiane Al-Haddad
The angiopoietin receptor TEK (tunica interna endothelial cell kinase) is a receptor tyrosine kinase that regulates vascular homeostasis through phosphorylation (17). In the eye, this receptor is highly expressed in the endothelium of Schlemm’s Canal (17). Heterozygous novel/rare protein-altering mutations in TEK occurred in 10 of 189 families with PCG. It was evident that TEK gene dosage was critical for proper development of aqueous humor outflow pathways and Schlemm’s canal (17). A different disease-causing variant of TEK discovered in an African patient with PCG highlights the value of whole-exome sequencing in detecting these variants (66). In 2021, TEK mutations causing PCG in Chinese patients, with one variant (p.R1003H) of the tyrosine kinase domain characterized as an activating mutation were described. Most cases were males, and the affection was mostly bilateral (67). This correlates with LTBP2/ANGPT1/TEK mutations in a male patient in this cohort. A second unilaterally affected patient (p.T693I) was female. This patient had a homozygous missense mutation in exon 13 of TEK. Although this variant is found almost exclusively in the African/African American cohort in gnomAD (50 out of 51/152174 alleles), it is reported here for the first time as occurring in a homozygous state causing a milder variant, which is counter-intuitive. This suggests this variant might be following an autosomal recessive pattern rather the expected dominant mode of inheritance of the TEK gene. The patient underwent a trabeculectomy with a final vision of 20/100 and well controlled IOP.
Blue rubber bleb nevus syndrome of the orbit and gastrointestinal tract
Published in Orbit, 2020
Stephen C. Dryden, Adrianna E. Eder, Andrew G. Meador, James C. Fleming, Brian T. Fowler
A 14-year-old female with a history of blue rubber bleb nevus syndrome (BRBNS) with gastrointestinal (GI) manifestations requiring previous endoscopy and bowel resection (Figure 1a,b) presented with frontal headaches and intermittent pain with eye movement. Examination was unremarkable with normal visual acuity, motility, and symmetric globe position without proptosis. An MRI was ordered due to the patient’s headaches which showed large right lobulated extraconal superomedial (Figure 2a) and inferolateral (Figure 2b) orbital masses with precontrast hypointensity and postcontrast hyperintensity (Figure 2c) consistent with a venous malformation. Due to her unremarkable examination and lack of orbital signs, the decision was made to observe with serial follow-up. BRBNS is a disease that presents with an initial dominant lesion followed by multiple skin, soft tissue, central nervous system, and GI tract venous malformations. Orbital involvement (as a venous malformation) is uncommon in patients with BRBNS, occurring in approximately 5% of reported cases. Activating mutations in the angiopoietin receptor TIE2/TEK on chromosome 9p have been implicated as a potential cause of BRBNS. Morbidity is usually related to GI lesions, which can cause bleeding and chronic anemia. Current medical treatment for BRBNS is pharmacologic: anticholinergic agents, beta-blockers, sirolimus, interferon-alpha, and corticosteroids or surgical: polypectomy, band ligation, clipping, argon plasma coagulation, and Nd:YAG photocoagulation. Orbital treatment is accomplished via a combination of endovascular embolization and surgical excision.