Angiogenesis Inhibitor Therapies: Focus on Kidney Toxicity and Hypertension

Izzedine, Hassane; Rixe, Olivier; Billemont, Bertrand; Baumelou, A; Deray, Gilbert

doi:10.1053/j.ajkd.2007.04.025

Cited by 176 publications

(143 citation statements)

References 75 publications

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“…Monoclonal antibodies that interfere with VEGFR signaling-including bevacizumab, sunitinib, and sorafenib-also interrupt angiogenesis by disrupting VEGF-mediated NO signaling. Effects on NO could explain some of the known side effects of these medications, including hypertension (Izzedine et al 2007) and thrombosis, the latter of which has been observed up to 33% more often among patients taking bevacizumab compared with placebo (Nalluri et al 2008). Thrombospondins or their derivatives show significant promise as effective angiogenesis inhibitors and anticancer agents in animal models (Miao et al 2001), and clinical trials are currently under way evaluating the efficacy of ABT-510 in several solid tumors.…”

Section: Suppression Of Nitric Oxide Signaling Through Cd36 and Cd47mentioning

confidence: 99%

Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2

Lawler

2012

Cold Spring Harbor Perspectives in Medicine

412

335

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Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF. Several of the membrane receptor systems and signal transduction molecules that mediate the effects of TSP-1 and TSP-2 have been elucidated. TSP-1 and TSP-2 exert their direct effects through CD36, CD47, and integrins. Recent data indicate that CD36 and b1 integrins collaborate to transmit the signals that are initiated by TSP-1 and TSP-2. Furthermore, these receptors appear to associate with VEGFR2 to form a platform for the integration of positive and negative signals for angiogenesis. Cross talk between pro-and antiangiogenic signal transduction pathways may enable TSP-1 and TSP-2 to inhibit angiogenesis by antagonizing survival pathways while also activating apoptotic pathways. CD36 and CD47 are both involved in the suppression of nitric oxide (NO). Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.

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Section: Suppression Of Nitric Oxide Signaling Through Cd36 and Cd47mentioning

confidence: 99%

Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2

Lawler

2012

Cold Spring Harbor Perspectives in Medicine

412

335

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“…In common medical language, the names typical or post-diarrheal (D+) HUS describe the most frequent form of HUS in children, due to Shigatoxin (Stx) producing Escherichia coli (STEC), mostly E coli 0157:H7. By opposition, the name atypical HUS (aHUS) has been historically used to describe any HUS not due to STEC, thus including: i) "Secondary" aHUS, due to a variety of causes, including infectious agents different from STEC, mostly Streptococcus pneumoniae (S pneumoniae) (via neuraminidase of S pneumoniae and T antigen exposure), human immunodeficiency virus and H1N1 influenza A, malignancy, cancer chemotherapy and ionizing radiation, bone marrow or solid organ transplantation, calcineurin inhibitors, sirolimus or anti vascular endothelial growth factor (VEGF) agents, pregnancy, HELLP (Hemolytic anemia, elevated Liver enzymes, and Low Platelets) syndrome, malignant hypertension, glomerulopathies, systemic diseases (systemic lupus erythematous and antiphospholipid antibody syndrome, sclerodermia) or, in children, methyl malonic aciduria with homocystinuria, cblC type, a rare hereditary defect of cobalamine metabolism [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Of note, it is now acknowledged that using the aHUS terminology rather than an etiological-based denomination (e.g.…”

Section: Disease Name and Synonymsmentioning

confidence: 99%

Atypical Hemolytic Uremic Syndrome

Loirat¹,

Frémeaux‐Bacchi²

2016

Pediatric Kidney Disease

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Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early.

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“…Loss of fenestration of renal glomerular capillaries also occurs, which might contribute to hypertension and proteinuria (Izzedine et al, 2007). Vascular endothelial growth factor also promotes endothelial nitric oxide production, and the removal of this stimulus may lead to vasoconstriction and hypertension (Baffert et al, 2006;Kamba et al, 2006).…”

Section: Toxicity With Vegf Inhibitorsmentioning

confidence: 99%