1,721,015 research outputs found
Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells
Get PDFThe role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H1 and H2 and that the selective H1 antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H2 antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of β-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and β-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth
Lipid nanocarrier for the treatment of hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Unlike most solid tumors the incidence and mortality of HCC have increased in the United States and Europe in the past decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies [1,2].
To improve the delivery of therapeutic agents to tumor cells in vivo it’s necessary to overcome several problems, such as drug resistance at the tumor level due to physiological barriers (non cellular based mechanism), drug resistance at the cellular level (cellular mechanism), drug distribution, biotransformation and clearance of anticancer drugs in the body. At the purpose to increase selectivity of drugs towards cancer cells while reducing their toxicity towards normal tissues, a promising strategy could be to entrap antitumor drugs into colloidal nanoparticles. Nanosystems may act as drug vehicles able to target tumor tissues or cells, protecting it from premature inactivation during its transport. At the tumor level the accumulation mechanism of intravenously injected nanoparticles relies on a passive diffusion or convection across the leaky hyperpermeable tumor vasculature [3-5].
For the treatment of HCC several drugs are under development, but the only one with proven survival benefit is sorafenib. This agent is a multikinase inhibitor that blocks Raf signaling and VEGF, PDGF and c-Kit. It has antiproliferative and antiangiogenic activity and delays tumor progression [1,2].
In order to produce a new colloidal system able to deliver this drug in the tumor tissue and decrease its side effects, nanostructured lipid carriers (NLCs) were developed using tripalmitin, Miglyol 812 and sorafenib. The obtained nanosystems were characterized in terms of size, polidispersity index, zeta potential and morphology using Scanning Electron Microscopy. Moreover, technological-pharmaceutical characterization of NLC was made. Stability studies showed that the systems were stable up to 60 days, while particle aggregation occurred after a period of storage of 90 days. Afterwards, for this reason, the same systems were prepared with the addition of two cryoprotectors (threalose and glycerol) before freezing and lyophilization. Finally, in vitro biological studies were carried out by MTS assays using human hepatocellular carcinoma HepG2, Hep3B, Huh7 and PLC/PRF/5 cells. Results obtained demonstrate an improved efficacy of sorafenib-loaded NLC compared to the free drug in Huh7 cells, whereas in HepG2 and PLC/PRF/5 cells sorafenib-loaded NLCs maintain an antitumor activity comparable to free drug.
Considering that solid tumours present much more favourable conditions for preferential accumulation of colloidal sized drug delivery systems, sorafenib-loaded NLC can be useful for application in liver cancer therapy.
[1] A. Forner, J.M. Llovet and J. Bruix, Lancet, 379, 1245 (2012).
[2] M. Cervello, J.A. McCubrey, A. Cusimano, N. Lampiasi, A. Azzolina and G. Montalto, Oncotarget, 3, 236 (2012).
[3] I. Brigger, C. Dubernet and P. Couvreur, Adv. Drug Del. Rev., 54, 631 (2002).
[4] M.L. Bondì, A. Azzolina, E.F. Craparo, G. Capuano, N. Lampiasi , G. Giammona and M. Cervello, Curr. Nanoscience, 5, 39 (2009).
[5] M.L. Bondì, E.F. Craparo, G. Giammona, M. Cervello, A. Azzolina, P. Diana, A. Martorana and G. Cirrincione, Drug Deliv., 14, 61 (2007)
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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