Nitric Oxide in Health and Disease

Dr. Morbidelli’s experience is within the molecular and biochemical pharmacology of angiogenesis and microcirculation and its biological application in diseases and cancer. Through of a plethora of in vitro and in vivo models, she has contributed to the characterization of the pro- and antiangiogenic activities of designed synthetic molecules and natural products and their potential applications in angiogenesis-dependent diseases of the cardiovascular system, ocular disorders, neurovascular diseases and cancer. She co-organized with Professor Bonavida the Fourth International Workshop on “Nitric Oxide in Cancer” held in Sevilla in March 13-14, 2015. The meeting addressed different topics such as NO, mutagenesis, carcinogenesis, tumor promotion and tumor growth; NO regulation of cell death pathways; NO and proliferation and epithelial-mesenchymal transition; Regulation of immune response by NO; Antitumoral activity of NO-based releasing strategies: pre-clinical studies; Antitumoral activity of NO-based releasing strategies: clinical trials. Dr. Bonavida has vast expertise and various reported publications in the field of tumor cell sensitization to chemotherapy (a total of greater than 500 publications) and in particular the novel role of Nitric Oxide (NO) donors in chemo-sensitization and reversal of drug resistance. In addition, he was the first scientist to co-organize an international meeting on the topic (First International Workshop on NO and Cancer, 2005). Dr. Muntané’s scientific career has been all devoted to the study of the relevance of oxidative and nitrosative stress in cell proliferation and death in different experimental models and clinical settings such as acute hepatocellular injury and hepatocarcinoma. The relevance of the temporal, dose and compartmentalization of nitric oxide (NO) release has been related to cytotoxicity, as well as the cytoprotective properties of classical antioxidants, prostanoids and alpha-tocopherol in different experimental models of liver injury. The anti-tumoral properties of NO has also been demonstrated using NO-donors and nitric oxide synthase type III (NOS3) overexpression in in vivo and in vitro models. The involvement of NO in the antitumoral properties of the molecular recommended therapies for patients with advanced hepatocarcinoma, such as the tyrosine kinase inhibitor Sorafenib, has also been studied comprehensively by Dr. Muntané’s lab.

Section 1: General properties of NO/metabolites in human diseasesSection 2: Development of novel NO donors/inhibitors and NO complexes: properties, cell signaling, synergy Section 3: Pharmacokinetics of NO donors/inhibitors in animal models and toxicities Section 4: Red-Ox signaling and modification of proteins. Characterization of their modified functions Section 5: Therapeutic applications of NO donors/inhibitors in non-cancer related human diseases Section 6: Therapeutic applications of NO donors/inhibitors in various cancersConcluding remarks and future perspectives