1,721,290 research outputs found
Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson’s and Alzheimer’s Diseases
Full text linkGlioblastoma (GBM) is the deadliest brain tumor. Its poor prognosis is due to cell heterogeneity, invasiveness, and high vascularization that impede an efficient therapeutic approach. In the past few years, several molecular links connecting GBM to neurodegenerative diseases (NDDs) were identified at preclinical and clinical level. In particular, giving the increasing critical role that epigenetic alterations play in both GBM and NDDs, we deeply analyzed the role of miRNAs, small non-coding RNAs acting epigenetic modulators in several key biological processes. Specific miRNAs, transported by extracellular vesicles (EVs), act as intercellular communication signals in both diseases. In this way, miRNA-loaded EVs modulate GBM tumorigenesis, as they spread oncogenic signaling within brain parenchyma, and control the aggregation of neurotoxic protein (Tau, Aβ-amyloid peptide, and α-synuclein) in NDDs. In this review, we highlight the most promising miRNAs linking GBM and NDDs playing a significant pathogenic role in both diseases.Fil: Thomas, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Florio, Tullio. Università degli Studi di Genova; ItaliaFil: Perez Castro, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentin
Somatostatin/somatostatin receptor signalling: Phosphotyrosine phosphatases
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FGFR4 polymorphism as molecular determinant of the efficacy of mTOR inhibitors in GH-secreting pituitary adenomas
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Expression and function of SDF1 and CXCR4 in human normal pituitary gland and pituitary adenomas
No full textMolecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors
No full textThe current treatment of neuroendocrine tumors include the use of somatostatin (SST) agonists. These compounds are able to control most of the symptoms caused by the hypersecretory activity of the tumor cells, and for this reason, they provide a significant improvement in the well-being of the patients. Although, several reports also showed a possible direct antiproliferative activity of SST agonists in different neuroendocrine tumors, the therapeutic potential of an in vivo antiproliferative activity mediated by SST receptors is still debated. In recent years, there has been great insights on understaning the molecular basis of the antitumoral activity of SST that appears to be exerted via both direct and indirect mechanisms. Direct mechanisms require the activation of SST receptors in tumor cells and the induction of cell cycle arrest or apoptosis, mainly through the regulation of phosphotyrosine phosphatase (PTP) and MAP kinase activities. The indirect mechanisms involve the inhibition of tumor angiogenesis and the inhibition of the secretion of factors which are required for tumor growth. Here, we will review the molecular mechanisms which are implicated in the antiproliferaitve activity of SST. Such an understanding is necessary for improving the antitumoral efficacy of SSTR agonists as well as for the development of novel therapeutic strategies
Meccanismi molecolari dell’azione antiproliferativa della somatostatina
No full textSomatostatin (SST), an peptide expressed in most organs and tissues, and controlling a wide range of physiological activities, is also one of the main endogenous regulators of cell proliferation. Thus, it has been proposed its clinical use in the cancer pharmacological therapy, but the outcome of the trials performed has been largely unsatisfactory. However, in the past few years, a great bulk of novel information about the molecular mechanisms involved in the SST antiproliferative activity have raised again the possibility of its use in the oncological field. Here we described, in the context of the recent literature observations on the transduction mechanisms regulated by SST, the effects of SST on two phosphotyrosine phosphatases (PTP) that in different cellular systems may mediate the growth inhibition of the peptide. First, in a thyroid cell line we identified a receptor-like PTP, named PTP, whose expression is absolutely required for the antiproliferative effects of the peptide. Indeed, in an in vitro model transformed thyroid cells SST is not able to inhibit cell proliferation unless this PTP is expressed. The second PTP involved is SHP-2, a SH2 containing, cytosolic, membrane-bound PTP. In CHO cells expressing SSTR1 the antiproliferative activity of SST is mediated by the activation of MAP kinase through SHP-2 and the induction of the cyclin-dependent kinase inhibitor p21cip1/waf1. Thus, the identification of more precise molecular mechanisms of the SST antiproliferative activity may allow a reconsideration for the clinical use of SST analogues with more selective growth inhibitory activity
Adult Pituitary Stem Cells: From Pituitary Plasticity to Adenoma Development
No full textThe pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed.</jats:p
Characterization of the differential efficacy of somatostatin receptor agonists in the inhibition of the growth of experimental gliomas and identification of the intracellular mechanisms involved
No full textSomatostatin (SST) exerts antiproliferative effects in normal and tumor epithelial and endocrine cells through the activation of five G protein-coupled receptors (SSTR15). Somatostatin receptors are expressed in several human tumors, including brain cancer. Multiple intracellular pathways are involved in the antiproliferative effects of SST, both direct (cytostatic, pro-apoptotic) and indirect (antiangiogenic, antiendocrine). In particular, modulation of phosphotyrosine phosphatase (PTP) h activity is considered as a major mechanism in SST regulation of cell growth. Among brain cancers, malignant gliomas are aggressive, infiltrating, and highly vascularized lesions characterized by poor prognosis. The highly tumorigenic rat glioma C6 cell line natively expressing SSTR1, 2, 3, and 5, is a reliable experimental model for the study of glioma growth and neoangiogenesis.
As tumor cells express multiple SSTRs, it is essential to deepen the individual role of the different subtypes in the regulation of cell proliferation and intracellular pathways. In C6 cells, in vitro and in vivo, SST and SSTR1, 2, and 5 selective agonists act as cytostatic agents via PTPh-dependent inhibition of ERK1/2 activity and upregulation of p27kip1. SSTR1, 2, and 5 activation leads to tumor growth inhibition acting on both cell proliferation and neoangiogenesis. Somatostatin receptor 5 activation showed the highest efficacy, although the combined activity of different SSTR subtypes resulted in additive effects. The present review summarizes the cytostatic activity of SST and presents novel insights into the individual role of SSTR, bringing this knowledge into perspective for the future use of SSTRs as molecular targets for antiproliferative strategies
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