Redox Regulation of the AMP-Activated Protein Kinase

Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas.

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies

The positive effects of exercise in chemotherapy-related cardiomyopathy

Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms including breast adenocarcinoma, small cell lung cancer and acute leukemia. Early and late anthracycline-induced cardiotoxicity is a well-known phenomenon, and the incidence of heart failure in patients receiving doxorubicin is 2.2%, with a mortality rate over 60% at 2 years. Prognosis can be improved by prevention, early detection and treatment. A specific treatment for anthracycline-induced cardiotoxicity is not yet available, but non-pharmacological measures such as exercise, lifestyle changes and control of risk factors have shown a cardioprotective effect. Exercise training represents a viable non-pharmacological treatment as it increases cardiovascular reserve and endothelial function, regulates proapoptotic signaling, protects against reactive oxygen species (ROS), and decreases autophagy/lysosomal signaling. However, no current guidelines are available for prevention management in cancer patients. Pharmacological measures both for prevention and treatment are those used for heart failure (β-blockers, angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, statins, dexrazoxane and aldosteron antagonists). In this chapter, we will discuss how the evaluation, monitoring and prevention of chemotherapy-related cardiomyopathy is correlated with physical exercise