Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics.

Day by day, the health and economical burden of cancer increases globally. Indeed it can be considered that there is ''cancer pandemic''. Blocking the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors (ACEI) or angiotensin-receptor blockers (ARB) are widely used measures to treat hypertension and heart failure. It has been recently suggested the activation and blocking of RAS has been associated with various types of cancer in epidemiological and experimental studies. Various studies have shown that RAS blockage is protective in some cancers. However, although fewer, contradictory data also showed that RAS blockage is either not related or adversely related to cancer. Although the reasons for these findings are not exactly known, different types of receptors and effectors in RAS may account for these findings. In the current review, we summarize the different RAS receptors and cancer development with regard to epidemiology, and pathogenesis including cell signaling pathways, apoptosis, genetic and epigenetic factors.

Successful everolimus therapy for SEGA in pediatric patients with tuberous sclerosis complex.

PURPOSE: Tuberous sclerosis complex (TSC) is associated with hamartomatous growths including subependymal giant cell astrocytomas (SEGAs). Although, SEGAs are slow-growing glioneuronal tumors, they represent a significant cause of morbidity and mortality due to the risk of sudden death from acute hydrocephalus. Neurosurgical resection has been the mainstay of therapy, since radiotherapy and chemotherapy were proved inefficient in those tumors. Recent studies support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis and suggest it might represent a disease-modifying treatment for other aspects of tuberous sclerosis. METHODS: We describe the clinical and radiological progression of three pediatric patients with definitive diagnosis of TSC and SEGA, which have been treated with everolimus. RESULTS: Up to 34 % sustained SEGA decrease was observed in the three cases. All three patients have experienced seizure control and two of them have showed cognitive and behavioral improvement. Everolimus has been well tolerated by all. No severe adverse events have been observed to date. CONCLUSION: Everolimus offers significant promise in treating SEGAs. Studies are required to explore optimal therapy duration and management upon discontinuing therapy.