Nephrotoxicity of anti-angiogenesis drugs

Neoangiogenesis is a basic factor for most physiological as well as pathological processes i.e. tumor metastases. The most important is vascular endothelium growth factor (VEGF) and its receptors (VEGFR1/2) in angiogenesis processes. Nowadays antiangiogenic agents (which inhibit VEGF like bevacizumab neither VEGFR2 like ramucirumab) are widely used in very different chemotherapeutic regimens in clinical oncology. The signalling pathway VEGF-VEGFR plays a crucial role in supporting of adequate kidney function. Appearance of antiangiogenic drugs led to adverse nephrotoxic effects: arterial hypertension, proteinuria, rarely nephrotic syndrome, and kidney dysfunction. Various hystological variants of nephropathy are described, however, in most cases, signs of thrombotic microangiopathy of the renal vessels are noted. This literature review discusses mechanisms, clinical and morphological aspects of nephropathy associated with antiangiogenic drugs.

Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia

Background: Caffeine represents the most used psychoactive drug in the world acting through different mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme (GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors (HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium growth factor (VEGF), a key player in angiogenesis and cell migration. Methods: In this work, we have investigated whether caffeine counteracts GBM progression by modulating hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades. Results: Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and MAPK/ERK signaling pathways both implied in HIFs regulation. Conclusion: The present data give new insight into antitumor activity of caffeine during GBM progression.

Serum VEGF Level Is Different in Adolescents Smoking Waterpipe versus Cigarettes: The Irbid TRY

Waterpipe (Wp) use is associated with most devastating diseases and particularly popular among adolescents. Vascular endothelium growth factor (VEGF) is essential for generating new vessels. The effect of smoking tobacco on VEGF is controversial and unknown among adolescents. Therefore, the current study compared serum VEGF in adolescents smoking cigarettes (Cg) only (9.3%), Wp only (19.6%), and dual (Wp and Cg) (36.4%) versus nonsmokers (34.6%) in adolescents. A self-reported questionnaire and enzyme-linked immunosorbent assay (ELISA) were used to obtain smoking status and serum VEGF, respectively, in 475 (age: 14.6 ± 1.0 years) boys (n = 263) and girls (n = 212) from Irbid, Jordan. The analysis showed that smoking status (R2 = 0.021; p = 0.001) and gender (R2 = 0.035; p = 0.000) can predict VEGF. Furthermore, 2-way-ANCOVA revealed that VEGF was lower in the dual cohort versus the Cg (33.4%; p = 0.04) and nonsmoker (29.6%; p = 0.003) cohorts; VEGF in smokers, was lower (33.6%; p = 0.04) in the Wp versus nonsmokers in the boys but not the girls. These results are unique and suggest that smoking lowers VEGF, which might adversely affect vascular growth and function. This is alarming given that adolescents are still in the development stage and smoking, particularly Wp, is popular among them. Therefore, interventions targeting smoking among schoolchildren are urgently needed to avoid the negative effects of smoking, especially on vascular health.

Anti-VEGF agents in the treatment of diabetic macular edema

Diabetic macular edema (DME) is a common complication associated with the loss of visual acuity in diabetic patients. Intravitreal injections of vascular endothelium growth factor (VEGF) inhibitors (anti-VEGF therapy) have been proposed recently as a new treatment option for patients with DME. In this review we summarized results of randomized clinical trials of VEGF inhibitors in DME patients. The results indicate that all studied inhibitors (ranibizumab, bevacizumab, pegaptanib and aflibersept) reduce the retinal thickness and improve of visual acuity in DME when are used as a monotherapy or in combination with the laser treatment. Optimal course duration and effectiveness predictors of anti-VEGF therapy in DME should be elucidate in the future studies.