0000000000638294

AUTHOR

Marco Alberghini

Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)

Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At mul…

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Abstract PR10: Inhibition of deacetylase SIRT1 offers a novel treatment option in metastatic Ewing sarcoma

Abstract Metastasis is the major cause of disease-related death in Ewing sarcoma. Patients, who present with clinically overt disseminated disease at diagnosis and those who relapse early with distant metastases have a poor outcome despite multi-modal high-dose chemotherapy. Therefore, new treatment options are highly warranted. Ewing sarcoma pathogenesis is driven by the chimeric ETS oncogene EWS-FLI1. We here describe regulation of sirtuin SIRT1 by EWS-FLI1 and its role in metastasis. SIRT1 belongs to a family of NAD+-dependent group III deacetylases that target histone and non-histone proteins in response to metabolic stress resulting in widespread gene expression changes through epigene…

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1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma

12 páginas, 6 figuras, 1 tabla.-- et al.

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Expression of insulin-like growth factor system components in Ewing's sarcoma and their association with survival.

Abstract Aims The role of IGF system in the pathogenesis of Ewing’s sarcoma (EWS) is well-documented. However, still little information is available about the value of IGF system components as indicators of prognosis. Understanding the clinical role for IGF system in EWS patients may be important because different subtypes of patients have distinct outcome and may require different treatment protocol. We evaluated the expression of insulin-like growth factor (IGF)-receptor (IGF-IR), insulin receptor (IR), IGF-I and some major intracellular mediators (IRS1, p-ERK) in specimens from EWS patients with primary localised untreated tumours. Patients and methods 290 samples were used for immunohis…

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