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Piccoli M.,University of Milan | Piccoli M.,Laboratory of Stem Cell for Tissue Engineering | Palazzolo G.,University of Milan | Palazzolo G.,Laboratory of Stem Cell for Tissue Engineering | And 24 more authors.
Journal of Cellular Biochemistry | Year: 2012

The synthetic purine reversine has been shown to possess a dual activity as it promotes the de-differentiation of adult cells, including fibroblasts, into stem-cell-like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti-cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. © 2012 Wiley Periodicals, Inc.

Fanzani A.,University of Brescia | Zanola A.,University of Brescia | Faggi F.,University of Brescia | Papini N.,University of Milan | And 5 more authors.
Skeletal Muscle | Year: 2012

The family of mammalian sialidases is composed of four distinct versatile enzymes that remove negatively charged terminal sialic acid residues from gangliosides and glycoproteins in different subcellular areas and organelles, including lysosomes, cytosol, plasma membrane and mitochondria. In this review we summarize the growing body of data describing the important role of sialidases in skeletal muscle, a complex apparatus involved in numerous key functions and whose functional integrity can be affected by various conditions, such as aging, chronic diseases, cancer and neuromuscular disorders. In addition to supporting the proper catabolism of glycoconjugates, sialidases can affect different signaling pathways by desialylation of many receptors and modulation of ganglioside content in cell membranes, thus actively participating in myoblast proliferation, differentiation and hypertrophy, insulin responsiveness and skeletal muscle architecture. © 2012 Fanzani et al.; licensee BioMed Central Ltd.

Anastasia L.,University of Milan | Anastasia L.,Laboratory of Stem Cell for Tissue Engineering | Piccoli M.,University of Milan | Piccoli M.,Laboratory of Stem Cell for Tissue Engineering | And 11 more authors.
Current Pharmaceutical Biotechnology | Year: 2011

Generation of pluripotent stem cells (iPSCs) from adult fibroblasts starts a "new era" in stem cell biology, as it overcomes several key issues associated with previous approaches, including the ethical concerns associated with human embryonic stem cells. However, as the genetic approach for cell reprogramming has already shown potential safety issues, a chemical approach may be a safer and easier alternative. Moreover, a chemical approach could be advantageous not only for the de-differentiation phase, but also for inducing reprogrammed cells into the desired cell type with higher efficiency than current methodologies. Finally, a chemical approach may be envisioned to activate resident adult stem cells to proliferate and regenerate damaged tissues in situ, without the need for exogenous cell injections. © 2011 Bentham Science Publishers Ltd.

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