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A combined approach with rituximab plus anti-TRAIL-R agonistic antibodies for the treatment of haematological malignancies.
No full textMolecular targeted therapies have changed the landscape of cancer research. Agonistic monoclonal antibodies (MoAbs) targeting TRAIL-death receptors (TRAIL-Rs) have been developed and currently used in clinical trials. Binding of such antibodies to TRAIL-R1 and TRAIL-R2 results in death inducing signalling complex (DISC) formation and induction of apoptosis, which represents a natural mechanism of cell growth control and an ideal target for drug development. These novel fully humanized compounds have been associated with conventional chemotherapy in the treatment of advanced solid malignancies, including different types of lymphoma. Here we outline the rationale and potential of a new molecular-based strategy combining agonistic anti-TRAIL-death receptor monoclonal antibodies plus the pioneer of the new biological frontiers of cancer therapy: rituximab
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
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
Curcuma longa Hepatotoxicity: A Baseless Accusation. Cases Assessed for Causality Using RUCAM Method
Full text linkCurcuma longa is a perennial herb that belongs to the Zingiberaceae family. To date, literature includes more than 11.000 scientific articles describing all its beneficial properties. In the last 3 decades various surveys by the U.S. Food and Drug Administration (FDA) concluded that curcumin, the most active ingredient of the drug, is a “generally safe” compound with strong anti-oxidant effects. Curcuma longa was introduced in the daily diet by ayurvedic teachers due to its beneficial effects on health. Nonetheless, recently several reports, from the various global surveillance systems on the safety of plant products, pointed out cases of hepatotoxicity linked to consumption of food supplements containing powdered extract and preparations of Curcuma longa. The latest trend is the use of Curcuma longa as a weight-loss product in combination with piperine, which is used to increase its very low systemic bioavailability. Indeed, only 20 mg piperine, one of the alkaloids found in black pepper (Piper nigrum), assumed at the same time with 2 g curcumin increased 20-fold serum curcumin bioavailability. This combination of natural products is now present in several weight loss supplements containing Curcuma longa. The enhanced drug bioavailability caused by piperine is due to its potent inhibition of drug metabolism, being able to inhibit human P-glycoprotein and CYP3A4, while it interferes with UDP-glucose dehydrogenase and glucuronidation activities in liver. While only few cases of hepatotoxicity, assessed using Roussel Uclaf Causality Assessment Method (RUCAM) method, from prolonged intake of piperine and curcumin have been reported, it would be reasonable to speculate that the suspected toxicity of Curcuma longa could be due to the concomitant presence of piperine itself. Hence, not only there is the need of more basic research to understand the etiopathology of curcumin-related hepatotoxicity and of the combination curcumin-piperine, but human trials will be necessary to settle this dispute
PI-3K/Akt and NF-κB/IκBα pathways are activated in Jurkat T cells in response to TRAIL treatment
No full textThe aim of this work was to evaluate the involvement of survival pathways in the response of Jurkat T leukaemic cells sensitive to the cytotoxic action of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2L. Jurkat T cells express TRAIL-R2/DR5 and TRAIL-R4/DcR2 receptors and start to die by apoptosis early (3 h) upon TRAIL administration reaching a dose-dependent increase in the percentage of dead cells within 48 h (up to 85-90%). This increase in cell death is accompanied by a dose-dependent significant (P < 0.05) increase in the G0/G1 phase of the cell cycle and reverted by the treatment with a broad inhibitor of caspases, z-VAD-fmk. Co-treatment of the cells with inhibitors of PI-3 kinase (LY294002) and nuclear factor kappa B (NF-kappaB) (SN50) pathways leads to an earlier significantly increased cytotoxicity, respectively in the form of apoptosis and necrosis. Consistently with the data obtained with the pharmacological inhibitors, the activation and nuclear translocation of both PI-3K and NF-kappaB were observed. In summary, our results provide evidence that even in sensitive neoplastic cells TRAIL paradoxically activates pro-survival pathways, which protect against TRAIL-mediated death since their inhibition leads to an earlier and increased cytotoxicity
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma
Full text linkPancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression
Redox control of IL-6-mediated dental pulp stem-cell differentiation on alginate/hydroxyapatite biocomposites for bone ingrowth
Full text linkComposites and porous scaffolds produced with biodegradable natural polymers are very promising constructs which show high biocompatibility and suitable mechanical properties, with the possibility to be functionalized with growth factors involved in bone formation. For this purpose, alginate/hydroxyapatite (Alg/HAp) composite scaffolds using a novel production design were successfully developed and tested for their biocompatibility and osteoconductive properties in vitro. Redox homeostasis is crucial for dental pulp stem cell (DPSC) differentiation and mineralized matrix deposition, and interleukin-6 (IL-6) was found to be involved not only in immunomodulation but also in cell proliferation and differentiation. In the present study, we evaluated molecular pathways underlying the intracellular balance between redox homeostasis and extracellular matrix mineralization of DPSCs in the presence of composite scaffolds made of alginate and nano-hydroxyapatite (Alg/HAp). Prostaglandin-2 (PGE2) and IL-6 secretion was monitored by ELISA assays, and protein expression levels were quantified by Western blotting. This work aims to demonstrate a relationship between DPSC capacity to secrete a mineralized matrix in the presence of Alg/HAp scaffolds and their immunomodulatory properties. The variation of the molecular axis Nrf2 (nuclear factor erythroid 2-related factor 2)/PGE2/IL-6 suggests a tight intracellular balance between oxidative stress responses and DPSC differentiation in the presence of Alg/HAp scaffolds
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