189,802 research outputs found
Medicina interna sistematica. Con CD-ROM - Cinque P; Castagna A; Novati R; Capitolo 94 Infezioni del Sistema Nervoso Centrale
No full text
Seminario di Linguistica e Didattica delle Lingue. Scritti in onore degli ottant’anni di Giovanni Freddi
No full textInclude, di Balboni: “La glottodidattica veneziana: una ‘scuola’?”, pp. 19-54
A semantic-based system for querying personal digital libraries
No full textThis is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-540-28640-0_4. Copyright @ Springer 2004.The decreasing cost and the increasing availability of new technologies is enabling people to create their own digital libraries. One of the main topic in personal digital libraries is allowing people to select interesting information among all the different digital formats available today (pdf, html, tiff, etc.). Moreover the increasing availability of these on-line libraries, as well as the advent of the so called Semantic Web [1], is raising the demand for converting paper documents into digital, possibly semantically annotated, documents. These motivations drove us to design a new system which could enable the user to interact and query documents independently from the digital formats in which they are represented. In order to achieve this independence from the format we consider all the digital documents contained in a digital library as images. Our system tries to automatically detect the layout of the digital documents and recognize the geometric regions of interest. All the extracted information is then encoded with respect to a reference ontology, so that the user can query his digital library by typing free text or browsing the ontology
CYTOTOXIC EFFECTS OF PERIFOSINE IN HUMAN GLIOBLASTOMA CELLSARE ASSOCIATED TO AN ALTERED CERAMIDE METABOLISM
No full textBackground: Glioblastoma multiforme (GBM) is the most malignant brain tumor and, despite aggressive therapy, prognosis for patients is poor. Temozolomide (TMZ), the chosen drug in GBM therapy, exerts cytotoxic effects also through an increase of ceramide levels. Perifosine (PF) is currently being tested for treatment of major human cancers, but little is known about its efficacy in gliomas. The aim of this work is to evaluate in GBM cell lines if PF is able to regulate sphingolipid metabolism and to enhance the cytotoxic effect of TMZ.
Results: The results obtained demonstrated that in different GBM cell lines, the treatment with PF led to a dose-dependent decrease in cell viability. In all GBM cells lines, PF promoted a time-dependent decrease of p-Akt levels, with an about 50% decrease after 4 hour treatment. In these conditions, metabolic studies showed that treatment with PF significantly modified sphingolipid (SL) metabolism by inhibiting sphingomyelin (SM) and, in a lesser extent, glycosphingolipid (GSL) biosynthesis with a consequent accumulation of ceramide (Cer). In addition, PF weakly reduced sphingosine-1-phosphate (S1P) biosynthesis. The treatment with LY294002, in conditions giving an almost complete inhibition of the PI3K/Akt pathway, only partly mimicked the effects of PF on SL metabolism, suggesting that PF could regulate SL metabolism also through a mechanism other than Akt inhibition. In the same GBM cell lines, the treatment of PF in combination with TMZ had an additive, but not synergistic cytotoxic effect. More of interest, a TMZ resistant cell line, that is characterized by an altered SL profile, a high capacity to release S1P and in which TMZ is unable to accumulate Cer, was still sensitive to PF.
Conclusions: These data suggest that PF can exert its anticancer activity through a marked modulation of sphingolipid metabolism with increased Cer/S1P ratio, where Cer acts as a pro-death and S1P as a survival factor. PF in combination with TMZ could thus improve the treatment efficacy in GBM
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