1,668 research outputs found
Synthesis and characterization of poly-phosphane coinage metals complexes and study on the protein ligation and catalysis
No full textA series of coinage metals centered poly-phosphane complexes has been synthesized and characterized under photophysical, chemical and biochemical aspects also in combination with a protein. Poly-phosphane metal complexes possess many properties in the field of luminescence,[1] catalysis, [2] chemo sensing, [3] and of anticancer activity [4]. In this study phosphane ligands containing the carboxylic functional group in ortho or para position of PPh3 have been used. The introduction of this polar group has the double aim either to make more hydrophilic the complexes and to tune the binding ability of the phosphane. In the case of gold(I) complexes, the poly-phosphine compound have been studied in comparison with the corresponding [bis-triphenylphosphine-gold(I)chloride], where the carboxylic group is absent, to evaluate the influence of its presence in the photopysical properties as well as on the interaction with dihydrofolate reductase, a protein involved in cell proliferation, DNA duplication and many other biological functions [5]. Affinity constants have been estimated through quenching of fluorescence studies and inhibition constants have been evaluated through rate constant determination of the reduction of dihydrofolate (H2F) to tetrahydrofolate (H4F) with reduced nicotinamide adenide dinucleotide phosphate (NADPH) as hydride donor. The tests highlighted a catalytic activity of the gold(I) compounds versus the H2F, which is the substrate of the enzyme. A strong effect of the enzyme on the luminescence properties of the gold(I) complexes have been observed. A coinage metals homolog series have been also evaluated as antiproliferative agent by in vitro MTT tests.
Scheme. Schematic view of a homolog series of coinage metals complexes under study.
References
1. R. Edward, T. Tiekink, J. G. Kang, Coord. Chem. Rev. 2009, 253, 1627-1648
2. David J. Gorin, Benjamin D. Sherry, and F. Dean Toste, Chem. Rev. 2008, 108, 3351–3378
3. X. He, V. W. Yam, Coord. Chem. Rev. 2011, 2111-2123
4. R. Galassi, A.Burini, O. Camille Simon, A. Dolmella, D. Micozzi, S. Vincenzetti, S. Pucciarelli Dalton Trans., 2015, 44, 3043-3056 DOI: 10.1039/C4DT01542H
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STEREOPHOTOGRAMMETRIC ANALYSIS OF THE HUMAN FACE: A TOOL FOR MODERN MORPHOLOGISTS
No full textThe introduction of new technologies has provided, in the last years, a significant contribution to anthropometry. In this context, facial anthropometry has greatly benefited from optical instruments such as laser scanners and stereophotogrammetry.
The latter technique has proven to be accurate, repeatable and fast; therefore, taking into consideration its non-invasive nature, it has been increasingly applied to medicine, due to the relevant support that anthropometry can provide to this field.
A facial anthropometric assessment can provide reliable morphometric details about the presence of deformities and peculiar features connected to underlying pathological conditions, not always easily recognizable. In the case of certain neurologic diseases, it can also provide new insights about the genotype/phenotype correlation taking the close relationship between facial and cerebral development into consideration.
Furthermore, the three-dimensional morphometric evaluation of the face can reveal objective parameters useful for the planning and assessment of maxillo-facial and dental treatments, thus facilitating the clinical decisions and increasing the patients’ compliance.
The facial morphometric evaluations presented in the current thesis were performed through the VECTRA M3 3D stereophotogrammetric system (Canfield Scientific, Fairfield, NJ, USA). All the patients and control subjects involved were marked with a set of facial landmarks (adapted according to the different study purposes), before the acquisitions. Once the three-dimensional models were obtained, they were elaborated through the software of the stereophotogrammetric system. Data were analysed through different statistical techniques, according to the type of study executed. The morphometric evaluations were divided in two groups: facial morphometric analyses performed through a landmark-based approach and through a surface- based approach.
The first group included the studies: 1) “The face of adult patients affected by Dravet Syndrome: a 3D stereophotogrammetric preliminary assessment”, 2) “3D Craniofacial morphometric analysis of GLUT-1 DS patients” and 3) “Stereophotogrammetric analysis of a case of holoprosencephaly”.
The second group included the studies: 4) “3D stereophotogrammetric assessment of labial symmetry in a girl treated for a lymphatic malformation” and 5) “Facial reanimation assessment performed through 3D-3D superimposition: a new method”.
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For both assessed syndromes, study 1 and 2 allowed the individuation of facial features common among the patients, whose recognition can have a role in the diagnosis of the disease, both in children (study 2) and in adult cases (study 1). Study 3 allowed the identification of the presence of dysmorphic facial features in a girl affected by holoprosencephaly with an apparently normal aspect, thus sustaining the potential of the 3D stereophotogrammetric facial analysis in the morphometric characterisation of the face. Study 4 and 5 showed the usefulness of this technique for performing an objective surgical follow-up and final evaluation of maxillo-facial treatments, helping clinicians in their decisions and motivating the patients.
In conclusion, all the studies sustained the usefulness, for medical purposes, of an anthropometric assessment of the human face, performed through a three-dimensional stereophotogrammetric analysis. Moreover, they highlighted its applicability to different categories of patients, including children and people with intellectual disability; thus again justifying the increasing diffusion of stereophotogrammetry in clinical and research centres
Schermi. Immagini, corpi, condivisioni
No full textIn this book the author investigates the digital image proliferation of our times from an interdisciplinary point of view. Starting from the Visual Culture theoretical frame, Valentina Mignano explores the ways in which we interact with the screen, dealing with the "screen experience" in the first years of the network societ
ENTREPRENEURSHIP AND FEMALE ENTREPRENEURSHIP IN MARAMURES COUNTY
No full textInitiating and developing a business involves a considerable risk and a sustained effort in order to defeat the inertia against what is new. The person initiating a business, assuming the responsibility and risk of its development and benefiting from theentrepreneurship, female entrepreneurship, profit, businesses
Molecular determinants of peritoneal dissemination in gastric adenocarcinoma
No full textPeritoneal dissemination represents a poor prognostic indicator in gastric cancer. Despite a comprehensive molecular characterization of this disease, no peritoneal dissemination-specific signature has been identified, limiting the tailoring of the surgical and oncological treatments. In this review, we outline the available literature focusing on the role of the different molecular pathways involved in the acquisition of peritoneal metastatic dissemination. According to our results, several molecular determinants are associated with peritoneal carcinomatosis and are involved in several cellular and molecular carcinogenetic processes. However, a comprehensive understanding of the complex molecular landscape of gastric carcinosis is still lacking. More efforts should be made towards the integration of molecular and histologic data to perform a risk prediction assessment of peritoneal dissemination based on molecular profiling and histological evaluation
IN VITRO AND IN VIVO STUDIES FOR THE TREATMENT OF BASAL LIKE BREAST CANCER (BLBC) WITH AZOLATE/PHOSPHANE GOLD(I) COMPOUNDS
No full textIN VITRO AND IN VIVO STUDIES FOR THE TREATMENT OF BASAL LIKE BREAST CANCER (BLBC) WITH AZOLATE/PHOSPHANE GOLD(I) COMPOUNDS
Rossana Galassia, Alfredo Burinia, Oumarou Camille Simona, Anna Teresa Ramadoria, Stefania Pucciarelli,b Albana Hisy,c Manuela Iezzi,c Valentina Gambini b, Martina Tiliob, Cristina Marchini b, Augusto Amicib
a School of Science and Technology, Chemistry Division, Camerino University, Via Sant’ Agostino, I-62032 Italy.
b Department of Biosciences and Veterinary, University of Camerino, Via Gentile III da Varano, I-62032, Italy
c Aging Research Centre, G. d’Annunzio University, Chieti, 66100, Italy
e-mail: [email protected]
Breast cancer is a heterogeneous disease classified into molecular subtypes with distinctive gene expression signatures. Of all the molecular subtypes, BLBC has the worst negative outcome and prognosis. BLBCs are generally estrogen receptor (ER-) and progesterone receptor (PR)-negative and also lack high expression/amplification of HER2, limiting targeted therapeutic options. Thus, to date, Cisplatin remains the only possible therapeutic choice in the adjuvant or metastatic setting in the BLBC. Considering also several and serious side effects, new therapies are therefore an urgent unmet medical need for this patient population. 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. They show a mechanism of action involving the inhibition of seleno dependent ThioredoxinaReductase (TrxR), but they inhibit with IC50 in the micromolar scale also many other enzymes such as DeHydroFolateReductase.[1][2] In order to study the effectiveness of these new azolate gold(I) phosphane compounds as potential anticancer agents, 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.
References
[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
The use of initial tocolysis and maintenance tocolysis in preterm birth : guideline-based approach or off-label use - a survey on the current application in Switzerland
No full textAuthor Valentina Schedl, BscMasterarbeit Universität Linz 202
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
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
Guido Crepax – Valentina – The Shape of Her Time
No full textThe paper will focus on the analysis of Guido Crepax revolutionary comic book character Valentina that belongs to the golden age of the Italian comic-book genre fumetto. The aim is to explore whether Guido Crepax Valentina character was a "living doll" filling male fantasies of her creator or she was a woman empowered by her author struggling for many of the values of the women's culture that feminists today are trying to introduce into the mainstream. It also addresses research questions that focus on comic books and gender and empowerment at the decade of sexual liberation.Through Valentina case study the present paper is going to study an approach on the concept of woman in comics, and touch the border of female empowerment issue in contemporary world taking in consideration that her revolutionary strong and independent figure was born in a society where women have been frequently viewed as passive and represented as inferior to men and where questions of sexuality were considered taboo. Despite the fact that she angered some feminists by the way she was portrayed as an object of male gaze or a damsel in distress, there is nothing anti-feminist about Valentina. The aim here is to uncover feminist themes in the stories of Valentina and to explore what empowered her and made her a contemporary icon of style and symbol of liberated women
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