1,721,227 research outputs found
The therapeutic potential of the novel ribonuclease ranpirnase (Onconase®) in the treatment of malignant mesothelioma
No full textRibonucleases are a superfamily of RNA-cleaving enzymes that can be cytotoxic since the cleavage of RNA makes its information indecipherable. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to an inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models, including malignant mesothelioma. A large phase II trial showed that ranpirnase has diseasemodifying activity against mesothelioma. A first phase III study demonstrated that rampirnase may be combined with doxorubicin and that such an association is more active than Ranpirnase alone against mesothelioma. At present, another large, phase III trial in combination with doxorubicin has completed enrollment and its results are awaited. In all the above studies, ranpirnase died not demonstrate conventional anticancer activity, stabilizing progressive disease and potentially prolonging patients' survival. Finally, a better understanding of its mechanism of action, coupled with its favorable toxicity profile, especially characterized by the lack of major hematologic toxicities, makes ranpirnase an attractive drug to test in combination with other anticancer agents, in MMe as well as in other tumor types. © Springer-Verlag 2008
THE CONSTITUTIVE ACTIVATION OF MET, RON, SEA GENES INDUCES DIFFERENT BIOLOGICAL RESPONSES
Full text linkReceptor tyrosine kinases and integrins are activated by growth factors and extracellular matrix, respectively. Their activation leads to signal transduction cascades that control gene expression and cytoskeletal rearrangements. The “cross-talk” signaling between growth factor receptors and integrins controls many biological processes, including cell growth, differentiation, survival and migration. Up to now new mechanisms regulating their interplay are emerging. Here we describe some recent findings on the cooperation between ECM and growth factors receptors in cell behavior
Protein phosphatase 1 binds to phospho-Ser-1394 of the macrophage-stimulating protein receptor
No full textMalignant pleural mesothelioma: current treatments and emerging drugs
No full textBackground: Malignant pleural mesothelioma (MPM) is an uncommon disease whose incidence is increasing worldwide over the past 30 years. Surgical resection and radiotherapy represent the standard treatment in patient with resectable MPM. Chemotherapy is also necessary to reduce incidence of distant metastases, but the optimal setting of treatment (neoadjuvant, adjuvant and intrapleural) is not clarified. For the patients with unresectable MPM, the combination cisplatin and pemetrexed or ralitrexed is the standard treatment as supported by a Phase III study. Better understanding of molecular pathways involved in MPM has enabled inclusion of new drugs targeted against pathways responsible for proliferation, cell survival and angiogenesis. Objective: This review discusses the current treatment option, the specific signal pathways activated in MPM and the novel agents under evaluation in clinical trials. Methods: We use for this article abstracts, papers, oral presentations from ASCO and the website http://www.clinical-trials.gov. Results/conclusion: This review summarizes the activity of chemotherapy and of new agents under evaluation in clinical trials. The better understanding of molecular pathways activated in MPM will hopefully provide new therapeutic options for these patients in the future
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
Receptor for bombesin with associated tyrosine kinase activity.
No full textThe neuropeptide bombesin is known for its potent mitogenic activity on murine 3T3 fibroblasts and other cells. Recently it has been implicated in the pathogenesis of small cell lung carcinoma, in which it acts through an autocrine loop of growth stimulation. Phosphotyrosine (P-Tyr) antibodies have been successfully used to recognize the autophosphorylated receptors for known growth factors. In Swiss 3T3 fibroblasts, phosphotyrosine antibodies identified a 115,000-Mr cell surface protein (p115) that became phosphorylated on tyrosine as a specific response to bombesin stimulation of quiescent cells. The extent of phosphorylation was dose dependent and correlated with the mitogenic effect induced by bombesin, measured by [3H]thymidine incorporation. Tyrosine phosphorylation of p115 was detectable minutes after the addition of bombesin, and its time course paralleled that described for the binding of bombesin to its receptor. Immunocomplexes of phosphorylated p115 and phosphotyrosine antibodies bound 125I-labeled [Tyr4]bombesin in a specific and saturable manner and displayed an associated tyrosine kinase activity enhanced by bombesin. Furthermore, the 125I-labeled bombesin analog gastrin-releasing peptide, bound to intact live cells, was coprecipitated with p115. These data strongly suggest that p115 participates in the structure and function of the surface receptor for bombesin, a new member of the family of growth factor receptors with associated tyrosine kinase activity
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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