Emilio Chiosi

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Leptin has been hypothesized to be a pathophysiologic link between obesity and cardiovascular diseases. Because the adenylate cyclase (AC) system is a main effector of beta-adrenergic receptors and leptin has been shown to modulate AC activity in other cell lines, a leptin impact on cardiac AC activity was hypothesized. Therefore, acute and chronic effects(More)
Cancer is a major public health problem and the second leading cause of mortality around the world. Although continuous advances in the science of oncology and cancer research are now leading to improved outcomes for many cancer patients, novel cancer treatment options are strongly demanded. Naturally occurring compounds from a variety of vegetables,(More)
Elevation of cAMP inhibits the proliferation and expression of transformed phenotype in several cell types, including breast cancer cells. Leptin has been shown to act as a mitogen/survival factor in many types of cancer cells. In the present work, we have studied the impact of cAMP elevation on leptin-induced proliferation of breast cancer cells. Here we(More)
Doxorubicin (Doxo) is a widely used anticancer drug given for the treatment of leukemias, lymphomas, and solid tumors. Despite its potent antitumor effects, the cardiotoxicity of this drug limits its clinical use. The biochemical mechanisms of Doxo-induced cardiotoxicity remain unclear. Doxo has been shown to induce apoptosis in cardiomyocytes that seems to(More)
BACKGROUND cAMP is a second messenger that plays a role in intracellular signal transduction of various stimuli. a major function of cAMP in eukaryotes is activation of cAMP-dependent protein kinase (PKA). PKA is the best understood member of the serine-threonine protein kinase superfamily, and is involved in the control of a variety of cellular processes.(More)
In order to elucidate how phosphate regulates cellular functions, we investigated the effects of inorganic phosphate (Pi) on adenylate cyclase (AC)/cyclic AMP (cAMP) axis. Here we describe that Pi treatment of human osteosarcoma U2OS cells results in a decrease of both intracellular cAMP levels and AC activity, and in a cell growth inhibition. The(More)
Previously, we have shown that leptin potentiates the antiproliferative action of cAMP elevating agents in breast cancer cells and that the protein kinase A (PKA) inhibitor KT-5720 prevented the antiproliferative effects induced by the leptin plus cAMP elevation. The present experiments were designed to gain a better understanding about the PKA role in the(More)
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. The clinical outcome for osteosarcoma remains discouraging despite aggressive surgery and intensive radiotherapy and chemotherapy regimens. Thus, novel therapeutic approaches are needed. Previously, we have shown that inorganic phosphate (Pi) inhibits proliferation and(More)
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents and is characterized by a high metastatic potential. Its clinical outcome remains discouraging despite aggressive treatments. Thus, novel therapeutic approaches are needed. Recent results indicate that inorganic phosphate (Pi) is capable of affecting specific signal(More)
The adenylate cyclase (AC)/cyclic AMP (cAMP)/cAMP-dependent protein kinase pathway controls many biological phenomena. The ubiquitin/proteasome system, controlling the levels of many proteins, modulates important cellular processes such as cell cycle and cell growth. Here we describe a novel mechanism for AC regulation by proteasome pathway. Pharmacological(More)