1,220 research outputs found

    Introduction by Manuela Gieri

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    In the introduction to the volume, the author outlines the development of Italian cinema from its early days to the present

    Natural compounds, antioxidant, and antiandrogens in the prevention of prostate cancer: in vivo evidences from murine models and human clinical studies.

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    Prostate cancer (PCa)is the most frequent malignant neoplasia in men. The number of cases has continuously increased over the past decades, partly due to the higher life expectancy. Additional factors are the high caloric diet and lack of physical exercise, typically seen in the Western countries. Notably, up to 40% of cancer incidents are preventable by consuming a healthy diet, regular physical activity, and maintenance of optimum body weight, and more than 20% by consuming vegetables and fruits. PCa represents an ideal candidate disease for chemoprevention. It is typically diagnosed in elderly men and even a modest delay in the neoplastic development could result in substantial reduction in the incidence of the clinically detectable disease.In this chapter we will review the history, the development, and the applications of some of the most common animal models of PCa,and we will discuss of the role of animal models in translational research

    IN VITRO AND IN VIVO STUDIES FOR THE TREATMENT OF BASAL LIKE BREAST CANCER (BLBC) WITH AZOLATE/PHOSPHANE GOLD(I) COMPOUNDS

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    IN 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

    Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

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    Correction to: Nature Genetics, 50, 928–936 (2018), https://doi.org/10.1038/s41588-018-0142-8, published online 11 June 2018. In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.No Full Tex

    Discrimination of Different Human Cell Lines by Using FT-IR Spectra Spectroscopy

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    Fourier transform infrared (FT-IR) spectroscopy is a powerful analytical technique used to obtain molecular fingerprints of various biological samples. This study aims to compare the FT-IR spectra of three distinct cell lines, SH-SY5Y (neuroblastoma), HepG2 (hepatocellular carcinoma), and MCF-10A (epithelial mammary), to identify characteristic features in their spectra that can be used for this purpose. The FT-IR spectra revealed significant protein, lipid, and nucleic acid content variations among the cell lines. The differences mentioned above reflect each cell type’s unique biochemical environment and metabolic states. This distinction can help identify different cell lines. Understanding these spectral differences can provide insights into the molecular basis of cellular functions and aid in the development of cell-specific therapeutic strategies

    Pathological changes of the anatomical structure and markers of the limbal stem cell niche due to inflammation.

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    PURPOSE: The corneoscleral limbus is the site of corneal epithelial stem cells (SC). The aim of this study is to evaluate the expression of different SC markers in the normal human limbus and to determine how this is affected by inflammation. METHODS: Corneoscleral specimens from healthy and inflamed donor eyes were examined by immunohistochemistry/immunofluorescence for p63, vimentin, laminin 5, integrin α6, β1, β4, ABCG2, desmoglein 3, connexin 43, N-cadherin, and cytokeratins 12 and 15. The distribution and anatomic structure of the limbal crypts and the percentage of SC marker antigens in healthy donors were analyzed. In inflamed tissues, we evaluated the anatomic structure of the limbal epithelial crypt (LEC) and the positivity for SC markers. RESULTS: In normal limbus, the niche structures were distributed differently. The variability of their number correlated with the percentage of p63 positivity. Integrin β1 staining directly correlated with p63 positivity while the remaining proteins were variably and widely distributed. Double staining for p63 and vimentin did not reveal any co-localization. In inflamed eyes, the basal cells in the crypts were "stretched" and surrounded by inflammatory cells, and only a few SC markers were still present. CONCLUSIONS: Diseases involving the limbus may result in marked changes of expression of SC markers within the LEC and also alter the crypt structure

    La biografía de Manuela Cambronero

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    Manuela Cambronero’s biography has been a pending issue until now, given that her figure has not aroused interest and no studies which focus on clarifying her origins and chronology have been published. This information is essential as a starting point for any work on the author, which is why elucidating these unknowns through direct archive research is a sine qua non. Consequently, locating Manuela Cambronero’s baptismal, marriage and death certificates is the only reliable way to dispel any doubt about her provenance and to determine the exact places and dates of the trans-cendental events of her life.La biografía de Manuela Cambronero ha sido una cuestión pendiente hasta ahora, pues, como su figura no ha suscitado interés, no se han publicado estudios centrados en esclarecer su origen y su cronología. Esta información es esencial como punto de partida para cualquier trabajo sobre la autora, por lo que dilucidar estas incógnitas a través de la búsqueda directa en archivos se convierte en una condición sine qua non. En consecuencia, la localización de los certificados de bautismo, de matrimonio y de defunción de Manuela Cambronero es la única vía fiable para disipar las dudas sobre su procedencia y para concretar los lugares y fechas exactas de los eventos trascendentales de su vida

    Manuela Sáenz en varios textos

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    This report is an attempt to analyze the narrative discourse order in the novel “La esposa del Dr. Thorne” (Dr. Thorne’s Wife) of the Venezuelan writer Denzil Romero, in the light of ¨Las cuatro estaciones de Manuela” (“The Four Seasons of Manuela”) of the American author Víctor W. von Hagen, and of “Manuela. Sus diarios perdidos y otros papeles”, (Manuela. Lost Diaries and Other Papers) of the Ecuadorian Carlos Álvarez Saá. This paper is a risky comparison between a book of fiction, presumably based on real facts, where Manuela’s eroticism is the central theme in Romero, the large literary chronicles issued by von Hagen and the compilation and discovery of alleged original and historic texts (letters and diaries) produced by Álvarez Saá. It is also a research exercise where, whimsically, what the official discourse says, as it may be viewed by the school of Venezuela or that of Quito, is mixed with the fictionalization of that discourse. It is, too, a possible vindication of Manuela Sáenz as a person and/or predominant character in the fights for the independence of America beyond her ¨circumstantial¨ relationship with Simón Bolívar. It is, to a certain extent, a look into how literary texts and the perceptions of history about a character (Manuela) tend to a “rearrangement” in present times and how there has been an attempt to consolidate the figure of Manuela Sáenz as a heroine, awarding a victory to what von Hagen calls “the school of Quito”.Si prese l’analisi dell’ordine discorsivo narrativo del romanzo dell’autore venezuelano Denzil Romero, La sposa del Dott.re Thorne, attraverso le comparazioni delle opere dell’autore statunitense Víctor W. Von Hagen, Le quattro stagioni di Manuela e dell’ autore ecuadoregno Carlos Álvarez Saá, Manuela, i suoi diari persi ed altre carte. È una comparazione azzardadata tra un libro di finzione, forse basato in fatti reali, dove l’erotismo della donna (Manuela) costituisce la tematica centrale, nell’opera di Romero, con la lunga cronaca letteraria che fa von Hagen e la compilazione e la scoperta di supposti testi originali e storici (lettere, diari) che fa Álvarez Saá. È un esercizio di ricerca dove si mescolano, in modo capriccioso, il campo d’attività del Venezuela o quello del Quito, e la finzione di quello ufficiale. È anche la rivendicazione possibile di Manuela Sáenz come persona e/o personaggio preponderante nelle lotte indipendentistiche dell’America che era aldilà della relazione congiunturale con Simón Bolívar. Si vuole vedere, fino a un certo punto, come i testi letterari e le percezioni della storia su un personaggio (Manuela) tendono a sistemarsi con i tempi attuali e come si ha voluto affiancare la figura eroica di Manuela Sáenz, concedendole il trionfo, forse secondo la tesi di von Hagen: quella che lui definisce la scuola di Quito.Se pretendeu analisar a ordem discursivo-narrativa do romance do venezuelano Denzil Romero, “La esposa del Dr. Thorne”, à luz das obras do americano Víctor W. von Hagen, ¨Las cuatro estaciones de Manuela” e do equatoriano Carlos Álvarez Saá, “Los diários perdidos de Manuela Sáenz y otros papeles”. Este trabalho é a comparação arriscada entre um livro de ficção, baseado aparentemente em fatos reais, no qual o erotismo da mulher (Manuela) é o tema central, em Romero, com a extensa crônica literária que lhe faz von Hagen e a recopilação e a descoberta de aparentes textos originais e históricos (cartas, diários) que faz Álvarez Saá. Também é um exercício de pesquisa em que, de maneira especial, se mistura o que diz o discurso histórico oficial, segundo seja visto pela escola da Venezuela ou a de Quito, com a visão dada pela ficção a esse discurso. É, ao mesmo tempo, um pouco a possível reivindicação de Manuela Sáenz como pessoa e/ou personagem preponderante nas lutas de independência da América que chegavam além do seu ¨controvertido¨ relacionamento com Simón Bolívar. É ver, de certa forma, como os textos literários a as percepções da história sobre uma personagem (Manuela) têm tendência a ¨se readaptar” nos tempos atuais e como se quis dar força à figura de heroína de Manuela Sáenz, dando uma vitória a ela na que, tal vez, von Hagen denomina “a escola de Quito”.Se pretendió el análisis del orden discursivo narrativo de la novela del venezolano Denzil Romero, “La esposa del Dr. Thorne”, a luz de las obras del estadounidense Víctor W. von Hagen, ¨Las cuatro estaciones de Manuela” y del ecuatoriano Carlos Álvarez Saá, “Manuela. Sus diarios perdidos y otros papeles”. Este trabajo es la comparación riesgosa entre un libro de ficción, basado presumiblemente en hechos reales, donde el erotismo de la mujer (Manuela) es el tema central, en Romero, con la larga crónica literaria que hace von Hagen y la recopilación y descubrimiento de presuntos textos originales e históricos (cartas, diarios) que hace Álvarez Saá. Es también un ejercicio de investigación donde de manera caprichosa se mezcla lo que dice el discurso histórico oficial, según sea visto por la escuela de Venezuela o de Quito, y la ficcionalización de ese discurso. Es también un poco la posible reivindicación de Manuela Sáenz como persona y/o personaje preponderante en las luchas independentistas de América que iban más allá de la ¨coyuntural¨ relación con Simón Bolívar. Es ver, hasta cierto punto, cómo los textos literarios y las percepciones de la historia sobre un personaje (Manuela) tienden a ¨reacomodarse” en los tiempos actuales y cómo se ha querido afianzar la figura de heroína de Manuela Sáenz, dándole el triunfo, tal vez, a lo que llama von Hagen “la escuela de Quito”

    Synovium-derived stromal cell-induced osteoclastogenesis: a potential osteoarthritis trigger

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    Purpose: To shed light on the idea that mesenchymal stem/stromal cells (MSCs) recruited in synovium (SM) (i.e. Synovium-Derived Stromal Cells, SDSCs) could be involved in Osteoarthritis (OA) pathophysiology. Attention was also paid to a further stromal cell type with a peculiar ultrastructure called telocytes (TCs), whose role is far from clarified. Methods: In the present in vitro study, we compared SDSCs isolated from healthy and OA subjects in terms of phenotype, morphology and differentiation potential as well as in their capability to activate normal Peripheral Blood Mononuclear Cells (PBMCs). Histological, immunohistochemical and ultrastructural analyses were integrated by qRT-PCR and functional resorbing assays. Results: Our data demonstrated that both SDSC populations stimulated the formation of osteoclasts from PBMCs: the osteoclast-like cells generated by healthy-SDSCs via transwell co-cultures were inactive, while OA-derived SDSCs have a much greater effectiveness. Moreover, the presence of TCs was more evident in cultures obtained from OA subjects and suggests a possible involvement of these cells in OA. Conclusions: Osteoclastogenic differentiation capability of PBMCs from OA subjects, also induced by B synoviocytes has been already documented. Here we hypothesized that SDSCs, generally considered for their regenerative potential in cartilage lesions, have also a role in the onset/maintenance of OA. Clinical relevance: Our observations may represent an interesting opportunity for the development of a holistic approach for OA treatment, that considers the multifaceted capability of MSCs in relation to the environment
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