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Coni S.,Institute Of Biologie Valrose | Infante P.,Italian Institute of Technology | Gulino A.,Italian Institute of Technology | Gulino A.,University of Rome La Sapienza | Gulino A.,Neuromed Institute
Biochemical Pharmacology | Year: 2013

Hedgehog is a key morphogen regulating embryonic development and tissue repair. Remarkably, when misregulated, it leads to tumorigenesis. Hedgehog signaling is triggered by binding of ligands with transmembrane receptor Ptch and is subsequently mediated by transcriptional effectors belonging to the Gli family, whose functions is tuned by a number of molecular interactions and post-synthetic modifications. The complex of these regulatory circuitries provides a tight control of developmental processes, mainly involving the modulation of genes determining the fate of stem cells. Similarly, Hedgehog regulates cancer stem cells fostering tumorigenesis. To this regard, these processes represent promising targets for novel therapeutic strategies aiming at the control of stemness reactivation and maintenance in cancer. © 2012 Elsevier Inc.

De Smaele E.,University of Rome La Sapienza | Ferretti E.,University of Rome La Sapienza | Gulino A.,University of Rome La Sapienza | Gulino A.,Neuromed Institute
Brain Research | Year: 2010

The use of miRNAs as biomarkers has gained growing interest in the last few years. Their role in regulating a great variety of targets and, as a consequence, multiple pathways, makes their use in diagnostics a powerful tool to be exploited for early detection of disease, risk assessment and prognosis and for the design of innovative therapeutic strategies. While still not fully validated, profiling of blood cells, exosomes or body fluid miRNAs would represent a tremendous and promising advance in non-invasive diagnostics of CNS disorders. A major challenge is represented by technological aspects of miRNA detection and discovery aiming to genome-wide high throughput, sensitive and accurate analysis. Although there is much to be learned in the field, this review will highlight the potential role of miRNA as a new class of biomarkers in several CNS disorders, including neurodegenerative diseases such as Alzheimer, Huntington and Parkinson diseases, schizophrenia and autism as well as different types of cancer (e.g. gliomas and medulloblastomas). © 2010 Elsevier B.V. All rights reserved.

Gulino A.,University of Rome La Sapienza | Gulino A.,Neuromed Institute | Di Marcotullio L.,University of Rome La Sapienza | Screpanti I.,University of Rome La Sapienza
Experimental Cell Research | Year: 2010

Numb is an evolutionary conserved protein that plays critical roles in cell fate determination. Mammalian Numb displays a higher degree of structural complexity compared to the Drosophila homolog based on the number of encoding genes (Numb and Numb-like) and of alternative spliced isoforms. Accordingly, Numb proteins display a complex pattern of functions such as the control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion, cell migration, ubiquitination of specific substrates and a number of signaling pathways (i.e. Notch, Hedgehog, p53). Recent findings indicate that, besides controlling such physiologic developmental processes, subversion of the above Numb-dependent events plays a critical role in disease (e.g. cancer). We will review here the multiple functions of mNumb and their underlying molecular mechanisms in development and disease. © 2009 Elsevier Inc. All rights reserved.

Scaringi C.,University of Rome La Sapienza | Minniti G.,University of Rome La Sapienza | Caporello P.,Neuromed Institute | Enrici R.M.,University of Rome La Sapienza
Anticancer Research | Year: 2012

Glioblastoma is the most frequent primary malignant brain tumor in adults. Postoperative radiotherapy (RT) with concomitant and adjuvant chemotherapy with temozolomide is the standard treatment, however the prognosis remains poor with a median survival in the range of 12-15 months. In recent years, several targeted agents have been developed as potential inhibitors of molecular genetic and signal transduction pathways involved in gliomatogenesis, including those of vascular endothelial growth factor and its receptor, epidermal growth factor receptor, integrin, and mammalian target of rapamycin. The integrins are a family of transmembrane glycoprotein receptors that mediate cell matrix and cell-cell interactions, and are widely expressed in glioma cells and tumor vasculature. The critical role of integrins in angiogenesis, cell invasion and migration make them an attractive target for anticancer therapy. Inhibitory peptides and monoclonal antibodies to integrins are currently being investigated in clinical trials in patients with solid tumors, such as colorectal cancer, renal cell carcinoma, and melanoma. Cilengitide, a cyclized Arg-Gly-Glu(RGD)- containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide. In this review, we provide a brief overview of the preclinical experience and current clinical results of cilengitide therapy in patients with recurrent or newly diagnosed glioblastoma.

Minniti G.,Neuromed Institute | Minniti G.,University of Rome La Sapienza | Scaringi C.,University of Rome La Sapienza | Enrici R.M.,University of Rome La Sapienza
Radiation Oncology | Year: 2011

Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques. © 2011 Minniti et al; licensee BioMed Central Ltd.

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