1,720,979 research outputs found
Two distinct antitumor patwways activated by transfected poly(I:C) in androgen-independent prostate cancer cells
No full textIntroduction
Prostate cancer (PCa) represents the second leading cause of cancer death in men and develops as a result of the accumulation of genetic and epigenetic alterations. Data from literature suggest that new therapeutic targets are emerging and in particular, it is known that the activation of Toll-like Receptors 3 (TLR3), expressed by cancer cells has a pro-apoptotic and thus anti-tumoral effect in different tumors (Cheng & Xu, 2010). We previously demonstrated that the synthetic analogue of dsRNA, poly(I:C), (specific TLR3-ligand), induces apoptosis in the androgen-dependent prostate cancer cell line LNCaP in a TLR3-dependent fashion, whereas a weaker apoptotic effect is observed in more aggressive and androgen-independent prostate cancer cell lines PC3 (Paone et al, 2008) and DU-145 (Galli et al, 2013). In this regard, we have recently demonstrated that the encapsulation of poly(I:C) with three different formulations of cationic liposomes were up to 10 times more efficient than the free drug in eliminating both PC3 and DU145 cells (Palchetti et al, 2013). These data suggest that transfected poly(I:C) could raise apoptotic rate by stimulating cytosolic dsRNA receptors. In the present paper we analyzed the receptors and signalling pathways involved in apoptosis induced by poly(I:C) transfected by lipofectamine (the most common transfection agent) compared with free poly(I:C) in PC3 and DU145 cells.
Material and Method
We evaluated cell viability by MTT assay and apoptosis by cell cycle analysis by FACS and caspase activity. SiRNA approach and Western Blot analysis were performed to determine the receptors and signal transduction molecules involved in transfected poly(I:C)-induced effects.
Results and discussion
Poly(I:C) transfected by lipofectamine [in-poly(I:C)] inhibits cell viability in PC3 and DU145 cells in a dose dependent manner with the highest efficiency at 2μg/ml of poly(I:C) compared to twelve-fold higher poly(I:C) concentration (25μg/ml) and induces caspase-dependent intrinsic and extrinsic apoptosis.
By using genetic inhibition of different poly(I:C) receptors we demonstrated the crucial role of TLR3 and Src in in-poly(I:C) induced apoptosis. Moreover, we show that IRF3-mediated signaling causes the upregulation of TLR3, cytosolic receptors (RLH) and interferon-beta expression. Our data highlight the multiple signaling triggered by in-poly(I:C) leading to antitumor responses.
Conclusion
We can conclude that the treatment of PC3 and DU145 cells with in-poly(I:C) activates two distinct anti-tumor pathways: one mediated by TLR3, dependent on Src leading to a remarkable apoptosis and the other one mediated by cytosolic receptors, dependent on IRF-3 leading to themselves up-regulation and interferon-beta expression
Molecular analysis of poly(I:C)-induced antitumor effects in androgen-independent prostate cancer cells
No full textTransfected poly(I:C) activates different dsRNA receptors leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells
Full text linkBackground: Castration-resistant prostate cancer (CRPC) is refractory to chemo-radiotherapy.
Results: Transfection of the synthetic analog of dsRNA poly(I:C) simultaneously stimulates apoptosis and IFN- expression
through different pathways in androgen-independent prostate cancer (PCa) cells.
Conclusion: Dual parallel pathways triggered by distinct receptors activate direct and immunologically mediated antitumor
effects in advanced PCa.
Significance: The proapoptotic/immunoadjuvant poly(I:C)-Lipofectamine complex may offer new therapeutic insights into CRPC
Structural characterization of cationic liposome/poly(I:C) complexes showing high ability in eliminating prostate cancer cells
No full textPolyriboinosinic acid-polyribocytidylic acid (poly(I:C)) is a mimic of viral double-strand (ds) RNA that induces apoptosis in many cancer cells. However, toxicity and stability issues so far prevented its application as it undergoes enzymatic degradation and bear the potential to trigger undue immune stimulation as well as autoimmune disorders. Encapsulation of antitumor drugs is frequently used to improve their effectiveness by lowering the necessary dosage. In this study we examined the ability of cationic liposomes to deliver poly(I:C) into PC3 and DU145 cell lines, derived from human bone and brain prostate cancer metastasis, respectively. The first formulation was made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC). The second one was the binary lipid system made of the cationic 3 beta-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE), while the third formulation was the multicomponent (MC) lipid system encapsulating the four lipid species simultaneously. Synchrotron small angle X-ray scattering revealed that cationic liposome/poly(I:C) complexes exhibit lamellar phases structurally similar to cationic liposome/DNA complexes. We further found that cationic liposomes/poly(I:C) complexes were up to 10 times more efficient in eliminating metastatic prostate cancer cells than the free drug. Finally, the ability of distinct lipid formulations to induce apoptosis could inversely correlate with their endosomal escape ability. This property of cationic liposome/poly(I:C) complexes contrasts to cationic liposome/DNA complexes, where the endosomal escape ability is the rate-limiting step for the transfection efficiency
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
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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