Reappraisal of treatment-induced renal dysfunction in patients receiving antiangiogenic agents in phase I trials

Lévy, Antonin; Albiges-Sauvin, Laurence; Massard, Christophe; Izzedine, Hassan; Éderhy, Stéphane; Bahleda, Ratio; Gomez‐Roca, Carlos; Chargari, Cyrus; Brocheriou-Spelle, I; Soria, Jean‐Charles

doi:10.1007/s10637-011-9671-z

Cited by 6 publications

(2 citation statements)

References 25 publications

(28 reference statements)

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“…In addition, we observed a median reduction in creatinine clearance of 9 mL/mn during maintenance bevacizumab. An equivalent reduction in creatinine clearance (9.8 to 11.6 mL/min/1.73 m2) was also observed by Levy et al, in a series of 72 patients with solid tumors who had been included in four Phase-I trials testing antiangiogenics [23].…”

Section: Discussionsupporting

confidence: 69%

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer

Gouy

Ferron

Gléhen

et al. 2016

Gynecologic Oncology

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Section: Discussionsupporting

confidence: 69%

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer

Gouy

Ferron

Gléhen

et al. 2016

Gynecologic Oncology

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“…At these doses, a renal thrombotic microangiopathy develops, leading to hypertension. 6,7 The absence of hypertension in CATT and IVAN suggests that systemic tissue VEGF suppression with bevacizumab is minimal at ocular doses.…”

mentioning

confidence: 99%

Bevacizumab vs ranibizumab—an appraisal of the evidence from CATT and IVAN

Ah-Fat

Zaidi

2013

Eye

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Slit2/Robo1 signaling is involved in angiogenesis of glomerular endothelial cells exposed to a diabetic-like environment

et al. 2018

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Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N. To remove the effect of Slit2 derived from mesangial cells, human renal mesangial cells (HRMCs) grown in high glucose (HG) medium (33 mM) were transfected with Slit2 siRNA and then the HG-HRMCs-CM with Slit2 depletion was collected after 48 h. HRGECs were cultured in the HG-HRMCs-CM or recombinant Slit2-N for 0, 6, 12, 24, or 48 h. The mRNA and protein expressions of Slit2/Robo1, PI3K/Akt and HIF-1α/VEGF signaling pathways were detected by quantitative real-time PCR, western blotting, and ELISA, respectively. The CCK-8 cell proliferation assay, flow cytometry and the scratch wound-healing assay were used to assess cell proliferation, cycles, and migration, respectively. Matrigel was used to perform a tubule formation assay. Our results showed that the HG-HRMCs-CM with Slit2 depletion enhanced the activation of Slit2/Robo1, PI3K/Akt, and HIF-1α/VEGF signaling in HRGECs in time-dependent manner (0-24 h post-treatment). In addition, the HG-HRMCs-CM with Slit2 depletion significantly promoted HRGECs proliferation, migration, and tube formation. Pretreatment of HRGECs with Robo1 siRNA suppressed the activation of PI3K/Akt and HIF-1α/VEGF signaling and inhibited angiogenesis, whereas PI3K inhibitor suppressed HIF-1α/VEGF signaling, without influencing Robo1 expression. In the HRGECs treated with Slit2-N, Slit2-N time-dependently enhanced the activation of Robo1/PI3K/Akt/VEGF pathway but not HIF-1α activity, and promoted HRGECs proliferation, migration, and tube formation. The effects induced by Slit2 were also abolished by Robo1 siRNA and PI3K inhibitor. Taken together, our findings indicate that in a diabetic-like environment, in addition to mesangial cells, autocrine activation of Slit2/Robo1 signaling of HRGECs may contribute to angiogenesis of HRGECs through PI3K/Akt/VEGF pathway; therefore, Slit2/Robo1 signaling may be a potent therapeutic target for the treatment of abnormal angiogenesis in early DN and may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis.

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Reappraisal of treatment-induced renal dysfunction in patients receiving antiangiogenic agents in phase I trials

Cited by 6 publications

References 25 publications

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer

Bevacizumab vs ranibizumab—an appraisal of the evidence from CATT and IVAN

Slit2/Robo1 signaling is involved in angiogenesis of glomerular endothelial cells exposed to a diabetic-like environment

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