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Increased IL-17RA and IL-17RC in End-Stage COPD and the Contribution to Mast Cell Secretion of FGF-2 and VEGF.
Roos, AB, Mori, M, Gura, HK, Lorentz, A, Bjermer, L, Hoffmann, HJ, Erjefält, JS, Stampfli, MR
Respiratory research. 2017;(1):48
Abstract
Mast cells are accumulated in advanced chronic obstructive pulmonary disease (COPD), and interleukin (IL)-17 signaling plays a role in disease progression. The expression, localization and functional relevance of IL-17 receptor (R)A and IL-17RC was explored in COPD by immunodetection, and functional assays.IL-17RA and IL-17RC was increased in very severe COPD, and expressed by mast cells. Increased secretion of the pro-angiogenic basic fibroblast growth factor and vascular endothelial growth factor was observed in vitro-maintained mast cells stimulated with IL-17A. Expression of these mediators was confirmed in end-stage COPD. Thus, accumulation of mast cells in COPD may contribute to vascular remodeling.
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Histopathologic Characterization of the Expression of Vascular Endothelial Growth Factor in a Case of Retinopathy of Prematurity Treated With Ranibizumab.
Fernandez, MP, Berrocal, AM, Goff, TC, Ghassibi, MP, Harper, CA, Chou, E, Michael, SK, Hellman, J, Dubovy, SR
American journal of ophthalmology. 2017;:134-140
Abstract
PURPOSE To characterize the expression of vascular endothelial growth factor (VEGF) in a patient with retinopathy of prematurity (ROP) treated with ranibizumab (Case 1) and compare it with a case of ROP without treatment (Case 2), a case of a premature baby without ROP (Case 3), and a case of a baby without history of ROP or prematurity (Case 4). DESIGN Observational case series. METHODS The eyes of the deceased babies were removed postmortem and were sent to the Florida Lions Ocular Pathology Laboratory, where they were processed. The specimens were immunostained using an antibody against VEGF. RESULTS All eyes except for the eyes in Case 4 disclosed positive VEGF staining. Positive staining was present within the nerve fiber layer, inner plexiform layer, and inner and outer nuclear layers and within the spindle-shaped cell population in the vanguard in Case 1. In the posterior pole, positive staining was only observed at the level of the nerve fiber layer. This case also demonstrated less positive staining when compared with Case 2, where positive staining was found within all layers of the retina. CONCLUSION Less VEGF staining was observed within the retina of the eyes treated with ranibizumab when compared with the VEGF staining in Case 2. This supports the idea that anti-VEGF agents are effective in reducing the amount of VEGF present in the retina. Furthermore, the fact that some expression of VEGF remains in the immature retina after injection supports the idea that anti-VEGF agents can suppress uncontrolled neovascularization without completely blocking the vascular drive for the vascularization of the immature retina.
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Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature.
Usui, J, Glezerman, IG, Salvatore, SP, Chandran, CB, Flombaum, CD, Seshan, SV
Human pathology. 2014;(9):1918-27
Abstract
Recently, cancer therapies have been supplemented by vascular endothelial growth factor (VEGF) inhibitors as anti-angiogenic agents. However, kidney-related adverse reactions associated with these agents clinically manifest as hypertension and proteinuria, the most severe form being thrombotic microangiopathy (TMA). We present the spectrum of pathological features in VEGF inhibitor-associated kidney disease. Clinicopathological findings of kidney disease were retrospectively studied in 5 cancer patients treated with anti-VEGF agents. Although 4 cases received bevacizumab (anti-VEGF-A), one was given sorafenib (small molecule tyrosine kinase inhibitor affecting VEGF-R2). All patients presented with acute kidney injury, hypertension, and/or proteinuria. All kidney biopsies showed recent and chronic endothelial injury of varying severity and vascular sclerosis, including 2 with typical active features of TMA. Furthermore, acute tubular injury with focal necrosis was seen in all cases. While administration of VEGF inhibitor was discontinued in 4 cases, it was resumed for 5 more doses, following steroid therapy in 1 case. Cessation of VEGF inhibitor therapy was successful in reversing anemia and led to improvement of hypertension and proteinuria in 4 of the 5 cases. One case with TMA progressed to end-stage renal disease. A range of renal pathologic lesions secondary to endothelial injury are noted often accompanied by acute tubular damage following anti-VEGF therapy, the most severe being TMA. While most of the clinical manifestations are reversible with discontinuation of therapy, the role of other nephrotoxic chemotherapeutic agents in enhancing renal injury including severe TMA and other host factors with possible poor outcome should be considered.
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No nephropathy in Type 2 diabetic patient with POEMS syndrome with an elevated plasma VEGF.
Baba, T, Østerby, R, Neugebauer-Baba, S, Nozawa, Y, Watanabe, T, Sakurai, K, Katoh, T, Watanabe, T
Diabetic medicine : a journal of the British Diabetic Association. 2004;(3):292-4
Abstract
Vascular endothelial growth factor (VEGF) is considered to have a role in the pathogenesis of diabetic retinopathy. Recent experimental observations that anti-VEGF neutralizing antibody fully abolished the hyperfiltration and the increase in urinary albumin excretion suggested the contribution of VEGF to the development of diabetic nephropathy, as well. Here, we present a case of POEMS (Crow-Fukase) syndrome with Type 2 diabetes, which was associated with elevated plasma VEGF level, but no sign of diabetic nephropathy. The findings obtained from this case did not support the hypothesis that VEGF may enhance the development of diabetic nephropathy.