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Azolate/phosphane Gold(I) compounds in antiproliferative therapy: a new frontier for the azolate gold(I) chemistry
No full textAzolate/phosphane Gold(I) compounds in antiproliferative therapy: a new frontier for the azolate gold(I) chemistry
Azolate gold(I) phosphane compounds have become good candidate for anticancer applications.[1] It was highlighted that azolate gold(I) phosphane compounds were mostly very active in the regards of many panel of cancer cells, in addition to cis-platin resistant cells. Moreover, inhibition studies of pivotal enzymes, such as the seleno dependent ThioredoxinaReductase (TrxR), and an enzyme involved in DNA synthesis such as DeHydroFolateReductase, were carried out highlighting in both cases IC50 ranging from nano- to micromolar scale, respectively.[1][2] In order to study the effectiveness of these new azolate gold(I) phosphane compounds as potential anticancer agents, and to understand in depth the Structure Activity Relationship (SAR) relationship, different cell viability assays (MTT assays) were performed on a human in vitro model of HER2-overexpressing breast cancer: SKBR-3 cells.[3] After this preliminary screening, the most promising and effective compounds were selected to extend the study on A17 cell line, a murine preclinical model of Basal Like Breast Cancer (BLBC).[4] Hence, their efficacy in suppressing BLBC growth in vivo was tested and IHC analysis on explanted tumors were carried on. Overall, in vitro assays demonstrated a remarkable activity for those compounds having the Ph3PAu+ moiety and substituted imidazolate as co-ligands. Concerning the in vivo study the compounds act significantly delaying tumor growth. Accordingly, IHC analysis revealed a remarkable anti-angiogenic activity associated with a lower expression of proliferative markers and a higher level of apoptotic markers in treated tumours in comparison with controls. Moreover, respect to cisplatin these compounds displayed a lower nephrotoxicity, although their liver toxicity was higher. These promising results open the way to further investigations in order to understand the mechanism of action of these new azolate gold (I) posphane complexes.
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[1] R. Galassi et al., Dalton Trans., 2012, (41), pp 5307-5318.
[2] R. Galassi et al., Dalton Trans., 2015, (44), pp 3043-3056.
[3] Fogh, J., Fogh J. M., Orfeo T, J Natl Cancer Inst. , 1977, (59), pp 221-6;
[4] M. Galiè et al., Carcinogenesis , 2005, (11), pp 1868-187
Azolate gold(I) phosphane complexes as innovative therapies for the treatment of HER2-driven breast cancer
No full textGold(I) compounds have been known as cytotoxic agents since 30 years ago1. Lastly, the inhibition activity studies on compounds (such as LAuL’, where L is a phosphane and L’ a co-ligand) led to the individuation of a likely molecular target2, renewing the interest on the field of these metallodrugs. In the design of active gold compounds, the proper hydro / lipophilic balancing provides the lowering of the overall toxicity, maintaining both a good cellular uptake and anticancer properties. Imidazoles and pyrazoles as co-ligands afford to gold(I) phosphane compounds having cytotoxic activity, but enough polarity to be soluble in physiological media. Different azolate gold(I)phosphane complexes have been synthesized. They contain substituents on imidazole or pyrazole ligands such as R = NO2, CF3, CN, Cl, CH2OH) or substituents such as COOH or COONHEt3 in the phosphane moiety. Some of them have been already tested as antitumoral in some panels of cancer cells, resulting active3. In this work we present the study of the cytotoxic effects of several gold(I) compounds and a natural compound on an in vitro model of HER2-overexpressing breast cancer. We tested the effectiveness of these compounds as potential anticancer agents on SKBR-3 cell line, a human breast cancer cell line that overexpresses the HER2 (Neu/ErbB-2) gene product4. These cells display an epithelial morphology in tissue culture and are a useful preclinical model to screen for new therapeutic agents which could overcome the drawback of resistance to HER2-targeted therapies5. In order to screen the cytotoxic activity of these new compounds on SKBR-3 cells we performed different cell viability assays. As conclusion we observed a detrimental effect on the cytotoxicity for those compounds having an ionic structure or highly hydrophilic polar substituents on the azolate or phosphane ligands and a remarkable activity for those compounds having the Ph3PAu+ moiety and substituted imidazolate as co-ligands.
1) Benoît Bertrand, and Angela Casini. Dalton Trans., 2014, 43, 4209. DOI: 10.1039/c3dt52524d
2) a) Peter J. Barnard, Susan J. Berners-Price. Coord. Chem. Rev. 2007, 251, 1889–1902. DOI:10.1016/j.ccr.2007.04.006. b) A. Bindoli, M. P. Rigobello, G. Scutari, C. Gabbiani, A. Casini, L. Messori, Coord. Chem. Rev., 2009, 253, 1692–1707. DOI: 10.1016/j.ccr.2009.02.026.
3) a) R. Galassi, A. Burini, S. Ricci, M. Pellei, M. P. Rigobello, A. Citta, A. Dolmella, V. Gandin, C Marzano. Dalton Trans., 2012, 41, 5307. DOI: 10.1039/c2dt11781a b)
4) Fogh J, Fogh JM, Orfeo T, 1977, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. , 59(1):221-6. DOI: 10.1016/j.bmcl.2013.11.058.
5) Saturnino C, Sirignano E, Botta A, Sinicropi MS, Caruso A, Pisano A, Lappano R, Maggiolini M, Longo P, 2014, New titanocene derivatives with high antiproliferative activity against breast cancer cells. Bioorg Med Chem Lett., 1;24(1):136-40. DOI: 10.1016/j.bmcl.2013.11.058
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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