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زیست شناسی::
فاکتور رشد اندوتلیال عروقی
Several biomarkers, including absolute lymphocyte count (ALC) [62, 63], sustained inducible T-cell co-stimulator (ICOS) [64], T-cell responses to tumor antigen NY-ESO-1 [65], myeloid-derived suppressor cells (MDSC) [66], and vascular endothelial growth factor (VEGF) [67], have been reported to be associated with clinical benefit from ipilimumab.
Generally, Tregs are divided into two principal subsets, naturally occurring Tregs (nTregs) which have differentiated in the thymus and inducible Tregs (iTregs) which differentiate in the periphery from naive CD4 T cells by VEGF,
21.5.2 Vascular Endothelial Growth Factor Receptor-2 (VEGFR2)
Recently, others have shown that VEGF provides Tregs with a direct VEGFR2-dependent co-stimulatory prolifera- tion signal [65, 80, 81] and that intratumoral Tregs produce elevated levels of VEGF.
Thus, autocrine VEGF/VEGFR2 signaling might be important for Treg maintenance.
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2
عمومی::
فاکتور رشد اندوتلیال عروقی، فاکتور رشد اندوتلیال عروقی
, interleukins; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MCP-1/5, monocyte chemoattractant protein-1/5 (CCL2/CCL12); MHCII, major histocompatibility complex class II; MIP- 1α/β, macrophage inflammatory protein-1 alpha/beta (CCL3/CCL4); MNCs, mononuclear cells; MMPs, matrix metalloproteinases; MSCs, mesenchymal stromal cells; NF-κβ, nuclear factor kappa beta; PAMPs, pathogen-associated molecular patterns; PDGF, platelet-derived growth factor; PGE-2, prostaglandin E-2; ROS, reactive oxygen species; TAMs, tumor-associated macrophages; TGF- β1, transforming growth factor beta 1; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor.
Pro-wound healing macrophages produce elevated levels of growth factors such as PDGF, insulin-like growth factor 1 (IGF-1), VEGF and TGF-β1 (Murray and Wynn, 2011; Vannella and Wynn, 2017), which aid in cellular proliferation, granulation tissue formation, and angiogenesis.
Secreted: IL-10, CD206, TGF-β, MMP-9 involved in vascular and matrix remodeling; some shared characteristics with Mhem M2d - - Secreted: VEGF, IL-10, IL-12, TNF-α, pro-angiogenic; activated in vitro by TGF-β stimulating adenosine and toll-like receptors Mhem HA-Mac; Heme-directed macrophage M(Hb) Surface: CD163, CD206
Secreted: IL-10, MIF, CXCL12, VEGF, IL-6, located nearby tumors; promote angiogenesis and cell proliferation; M2-like IL-23, TGF-β
They produce high levels of vascular endothelial growth factor (VEGF) as well as IL-10 and TGF-β.،Hyperoxia leads to suppression of oxygen-regulated angiogenic growth factors, particularly erythropoietin39,40 and vascular endothelial growth factor (VEGF),41 which in turn causes both cessation of retinal vessel growth and loss of some existing retinal vessels42 (a process that has been partly reversed in mice with the replacement of VEGF and erythropoietin).39-42 Some investigators43 speculate that in more mature infants, exposure to high oxygen concentrations causes loss of existing vessels not seen with controlled oxygen delivery, which mainly causes cessation of vessel growth.
Phase 2 is characterised by proliferation of blood vessels largely in response to hypoxia- driven increases in VEGF and erythropoietin.48,49 The new vessels poorly perfuse the retina and are leaky, which leads to fibrous scar formation and retinal detachment.
Theoretically, oxygen in phase 2 of retinopathy of prematurity could suppress high concentrations of oxygen-regulated growth factors such as VEGF that cause proliferative disease.
Bevacizumab injected into the eye leaks into systemic circulation and reduces systemic VEGF concentrations,162 and might suppress systemic vascular growth or have other as-yet-unknown negative effects.163 Additional studies to assess the best choice of anti-VEGF drug, the optimum dose, the pharmacokinetics, and short-term and long-term safety are warranted.164,165
(C) Phase 2: the hypoxic retina stimulates expression of the oxygen-regulated factors such as erythropoietin (EPO) and vascular endothelial growth factor (VEGF), which stimulate retinal neovascularisation.
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