1,721,120 research outputs found
ACQUIRED ALTERATIONS OF SPHINGOSINE-1-PHOSPHATE METABOLISM CONFER STEMNESS AND DRUG RESISTANCE PROPERTIES ON GLIOBLASTOMA MULTIFORME: A NEW POTENTIAL TARGET FOR A COMBINED APPROACH TO TREAT BRAIN CANCER
Full text linkThe eradication of glioblastoma multiforme (GBM) (WHO grade 4) remains a tremendous clinical challenge in human oncology. Indeed, this tumor accounts for the most common, aggressive and lethal primary brain cancer in adults, exhibiting a dismal prognosis, despite extensive surgical resection and adjuvant radio- and chemo-therapy. The finding that GBM contains functional subsets of cells with stem-like properties named glioblastoma stem cells (GSCs) has opened up novel opportunities and promises for the development of new therapies for this devastating cancer. GSCs are self-renewing, multipotent cells, with the capacity to establish and maintain glioma tumors at the clonal level, leading to the hypothesis that they are tumor-initiating cells. Moreover, these rare subpopulations of cells possess an elevated proliferative potential, and intrinsic resistance to therapy, being thus considered a key determinant driving tumor growth, and relapse after resection and therapy. In serum free culture conditions, GSCs form neurospheres. free-floating cell aggregates with a spheroid morphology. These neurospheres preserve many of the important characteristics of the parent tumor, as cell heterogeneity and the ability to drive the parent tumor’s cell invasiveness, when transplanted in murine brain. In addition, GSCs possess the capacities to give rise to a heterogeneous population of cells such as endothelial cells (glioblastoma endothelial cells, GECs) which may directly participate in the vascularization, a critical step in tumors, particularly in malignant GBM, one of the most vascularized/angiogenic tumor described. Moreover, it has been observed that microvasculature structures are the regions responsible for the localization and the maintenance of GSCs.
Different molecules, including lipid mediators appear to play a key role in the GBM microenvironment. Among lipid mediators involved in GSC properties, ceramide (Cer) and sphingosine-1-phosphate (S1P) has recently emerged as key signals, able to control growth, invasion, and therapy resistance in various human cancers, including GBMs. Of relevance, the presence of S1P in both glioma cell lines and human gliomas is critical for tumor cell proliferation and survival, a down-regulation of sphingosine kinase 1 (SK1) suppressed growth of human GBM cells and xenografts, and a higher expression of S1P receptor 1 (S1PR1) in GBM has been correlated with poor prognosis. However, little is known on the role of Cer and S1P in GSCs. Recent studies reported that S1P acts as an invasive signal in GSCs, and that the inhibition of SKs, or the administration of a S1PR antagonist, results in GSC death. Very recently it was reported that GSCs derived from U87GBM cells, and those isolated from a human GBM specimen can release S1P extracellularly, and that S1P acts as a first messenger to enhance GSC chemoresistance to Temozolomide.
In GSC invasiveness and chemoresistance very little is known about autocrine machinery controlling GSC proliferation and particularly on the significance of S1P in these events. In order to expand previous investigation on S1P and to better understand its role on GSC activity and chemoresistance in this project I focused on the pivotal role of S1P on GSC stemness properties
Erythropoietin increase neuronal differentiation of neural stem cells and death-resistant neural stem cells
No full textDeath-resistant neural progenitors yield mostly neurons : an erythropoietin-dependent process
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Realizing the Unexploited Potential of Games on Serious Challenges
No full textGames are very popular for their entertainment purpose that attracts people of every age and gender. They also represent a very successful industry; leveraging on the wide popularity of games among all the segments of the consumer market, game companies have been able to generate higher revenues than the movie industry.
However, considering games just as a matter of fun and money is definitely wrong. Games also represent a challenging topic for researchers all over the world. One of the reasons is the correlation between problems that emerge in developing innovative game experiences and those typical of other conventional research fields in computer science. We can hence state that games are factually contributing to knowledge advancement. In this paper we discuss this issue with details from relevant examples
From Fun Technology to Serious Applications: Lessons from a Few Exemplar Cases
No full textThis short contribution discusses a few exemplar cases that show how fun technology may evolve into useful tools that provide support to the development of more serious applications
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
DTN Content Sharing Among Commuters
No full textWhen discussing vehicular networking we have also to consider the multitude of commuters daily travelling to/from work through public transportation means such as buses, metros, and trains. Indeed, through their smartphones, commuters can generate traffic while moving, thus embodying a significant part of an urban communication scenario. In this context, we discuss a way to port the P2P paradigm into mobile disconnected networks composed by commuters' smartphones. Different from classical P2P file-sharing, users could exchange data in proximity with each other; they can also leverage on peer mobility and encounters in order to extend a requesting peer's reach-area to other local disconnected networks. This is achieved by implementing a DTN-like store-delegate-and-forward communication model over underlying social networks where a peer can delegate unaccomplished data downloads to frequently encountered peers. We show how involving frequently encountered peers/commuters improves the success ratio for the data search request while reducing useless communication overhead
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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