200 research outputs found
La diplomazia pastorale di Mons. Roncalli tra Sofia e Istanbul
No full textThe episcopal ministry of Monsignor Angelo Giuseppe Roncalli makes it clear the link between “faith” and “diplomacy”. His “pastoral diplomacy” was particularly effective between 1925 and 1953, his years as Papal Representative. In Bulgaria the future John XXIII, Visitor and Delegate Apostolic between 1925 and 1934, had to cope with thorny affairs, such as the Royal Wedding and the Royal Baptism. He was nevertheless able to maintain good relations with the Royal House without altering Catholic doctrine. Appointed Apostolic Delegate to Turkey (and Greece), Roncalli was ignored by the new Republic of Mustafa Kemal, which pursued a policy of marked secularization. He therefore inspired his mission to the principle “flectar, non frangar”, agreed not to wear the cassock without protesting exceedingly, and succeeded in reducing the area of litigation with the Government. Towards the end of 1944 Archbishop Roncalli became Apostolic Nuncio to France: it can be assumed that his soft diplomacy, full of pastoral spirit, had been particularly appreciated by Pope Pius XII, who sent him to normalize the important but strained relations with the “Eldest Daughter” of the Church
Il futuro Papa Giovanni XXIII a bordo di una nave della Regia Marina
No full textIl saggio ricostruisce la vicenda di Angelo Roncalli a bordo di una nave della Regia Marin
Histopathological classification of hepatocellular carcinoma
No full textRecent advances in the understanding of HCC heterogeneity have shown not only distinct molecular classes with potential therapeutical implications but also have suggested that subclasses might be mirrored by tumour morphology and phenotype. The classification of HCC is therefore shifting from a more traditional, morphology-based approach to a more functional approach with clinical implications. The classical histological patterns (trabecular, pseudoglandular, solid, etc.) are still taken into account but in combination with other parameters such as cell grading, clonal changes, type and extent of vascularisation, tumour immunophenotype etc. This array of morpho-phenotypical features is expected to ultimately provide information about cell of origin, tumour behaviour and, hopefully, treatment sensitivity. In this chapter we will give a brief overview on modern principles of hepatic carcinogenesis by outlining the events/lesions bridging the microscopic dysplasia to advanced HCC. In this context special emphasis will be given to novel concepts and diagnostics and differential diagnosis of small HCC (of early and progressed type), which is the main target of the surveillance in the cirrhotic population. Novel and emerging subpopulations of HCC will also be considered, for example HCC with stem/progenitor cell phenotype and mixed hepatobiliary forms which are filling the traditional separation between two entities (HCC and cholangiocarcinoma), likely more inter-related than previously thought
Hepatocellular carcinoma: a clinical and pathological overview
No full textHCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management
Contemporary Italian Women Philosophers: Stretching the Art of Thinking
No full textPublisher URL: https://www.sunypress.edu/p-7163-contemporary-italian-women-phil.aspxA unique portrayal of the theoretical positions of eleven Italian women thinkers who share the practice of philosophy and extend philosophical work and interests beyond the realm of the discipline strictly defined.
Gathering the contributions of eleven contemporary Italian women thinkers who share a philosophical practice, Contemporary Italian Women Philosophers embraces a general interrelationality, fluidity, and overlapping of concepts for a border-crossing that affects what it means to be subjects that are embodied and participants in the life of their communities, thereby shaping a sense of belonging. Common threads are revealed through the exploration of radically diverse themes (the body, subjectivity, power, freedom, equality, liberation, the emotions, symbolism and metaphors, maternity, reproduction, responsibility, the political, the economic) and approaches (autobiographical styles, personal narratives, rootedness in the everyday, advancement of relationality, empathic responsibility, passions, and commitment to the flourishing of the polis). In their differences, these previously unpublished essays give the reader a glimpse of the fecund and articulated philosophical work of women in the Italian context—a context which has not been and still is not always benign toward women’s distinctive originality and creativity.
Silvia Benso is Professor of Philosophy at the Rochester Institute of Technology. She is the author and editor of several books, including Viva Voce: Conversations with Italian Philosophers, also published by SUNY Press. Elvira Roncalli is Associate Professor of Philosophy at Carroll College
The mission of the Apostolic Visitor and Delegate Monseigneur Angelo Giuseppe Roncalli in Bulgaria (1925-1934). Historical and diplomatic study based on the newly unearthed archival documents.
No full textIl decennio bulgaro di Mons. Angelo Giuseppe Roncalli (1925-1934) è un capitolo importante nella vicenda biografica di un uomo che, eletto Papa nel 1958, avrebbe segnato una svolta importante nel cammino verso l’unità delle Chiese cristiane: lo sviluppo della sensibilità ecumenica.
In Bulgaria egli fu Visitatore apostolico con il compito soprattutto di provvedere ai gravi bisogni della piccola e disastrata comunità cattolica. L’incarico, inizialmente a termine, si trasformò in una permanenza decennale durante la quale il rappresentante della Santa Sede pose le basi per la fondazione di una Delegazione apostolica; egli stesso, infatti, ne fu nominato primo rappresentante.
Scopo di questa tesi di dottorato è offrire una ricostruzione della missione di Mons. Roncalli in Bulgaria nell’ottica storico-diplomatica, basata, grazie all’apertura degli Archivi Vaticani dei fondi del Pontificato di Pio XI (6 febbraio 1922 - 10 febbraio 1939), su un lungo e attento studio archivistico.Monseigneur Angelo Giuseppe Roncalli’s Bulgarian decade (1925-1934) is an important chapter of the men who, elected Pope in 1958, was able to lead the first steps of change in bringing together Christian churches: the transformation of ecumenical sensibility.
He was Apostolic Visitor in Bulgaria and his important mission was focused on looking after the problematic catholic community. At the beginning, Mons. Roncalli’s permanence was supposed to be temporary, but it easily was transformed in ten very important years of catholic mission. The Holy See’s representative indeed established the Apostolic Delegation in Bulgaria becoming himself the first representative on charge.
The hereby presented purpose is offering to wide audience a specific reconstruction of Monseigneur Angelo Roncalli’s operation in Bulgaria through a historical and diplomatic look. The accomplishment of this study is completely based on the newly unearthed documents of Pope Pius XI treasured in the Vatican Secret Archives
A large set of miRNAs is dysregulated since the earliest steps of human hepatocellular carcinoma development
No full textHepatocellular carcinoma (HCC) mostly results from a stepwise process characterized by the development of
premalignant lesions, such as low- (LGDN) or high-grade (HGDN) dysplastic nodules in a cirrhotic setting. MicroRNAs
(miRNAs) are small noncoding RNAs involved in post-transcriptional regulation of gene expression than can act as
oncogenes or tumor suppressors. Whether and which miRNAs are involved in the early stages of HCC development
remains elusive. Here, small RNA sequencing was applied to profile miRNA expression in 55 samples (cirrhotic
nodules, CNs), LGDNs, HGDNs, early HCCs (eHCCs) and small progressed HCCs (pHCCs), obtained from 17
patients bearing HCCs of different etiology. A miRNA expression signature of 62 miRNAs distinguishing pHCCs from
matched CNs was identified. Interestingly, 52 of these miRNAs discriminated CNs from LGDNs/HGDNs, regardless of
the etiology, and remained modified along the tumorigenic process. Functional analysis of the predicted mRNA targets
of deregulated miRNAs identified common modifications between early and late stages of HCC development likely
involved in the stepwise process of HCC development. Our results demonstrate that miRNAs deregulation takes place
very early in human liver carcinogenesis, implying their critical role in the tumorigenic process. The identification of
miRNAs discriminating cirrhotic from neoplastic nodules may have relevant translational implications for early
diagnosis
MESENCHYMAL FEATURES MEDIATED BY TWIST1 IN COLORECTAL CANCER CELLS AND MICROENVIRONMENT
No full textBackground. Colorectal cancer (CRC) is a major cause of death for cancer in western countries, ranking third in both sexes. Therapeutic developments in the past decades have extended life expectancy in patients with advanced disease (i.e., stage III), and even for those with distant metastasis (i.e., stage IV). Most treatments for advanced disease nowadays include a combination of chemotherapy with target therapy. Despite advances, the fact that metastatic colorectal cancer remains largely incurable, pushes to pursue a better understanding of the factors underlying cancer progression. Nowadays, a major field of investigation is the relationship between epithelial tumor cells and the surrounding compartment, namely tumor microenvironment, and in particular its contribution to cancer progression.
The tumor microenvironment essentially comprises tumor infiltrating cells, vasculature, extracellular matrix, plus other matrix associated molecules. Transformed cells can modulate the functions of stromal cells, likely to facilitate their own growth and survival. In this Darwinian perspective, outgrowth of cancer cells goes together with local changes. Such changes, like clonal ones, are likely progressive, from the stage of local invasion, up to regional lymph-node colonization and finally to the development of distant metastasis.
Infiltrating cells are a mix of populations having myeloid or mesenchymal origin, including tumor-associated macrophages, myeloid -derived suppressor cells, mast cells, monocytes, neutrophils, CD3+ T cells, natural killers, dendritic cells, endothelial cells, mesenchymal stem cells and cancer-associated fibroblasts. Taken together, all these players are involved in a double-faced game, in which an anti-tumor effect (such as that exerted by CD3+ cells in early CRC, [1]) is counteracted by a cancer promoting one (e.g., that exerted by macrophages [2]. Currently, this cancer-microenvironment match implies contradictory and controversial data, largely depending upon the investigated cell population and upon the experimental setting. This Ariadnes' thread seems unravelled, mainly because of the contemporaneous evolution of both tumor and microenvironment cells during multi-stage tumor progression. What is certainly perceived today, is that a switch from a genetic to a non-clonal prospective is required to understand tumor evolution. Clearly, the dynamic architecture of the stromal compartment and the interactions therein, need to be reconciled with the evidences concerning genetic irreversible changes in stromal cells. The latter include loss of heterozygosis, microsatellite instability (MSI) [3], trisomy of Chromosome 7 in connective tissues elements of CRC [4], and p53 mutations (in the stroma of breast carcinoma[5]). These surprising results rise the possibility that the stromal compartment contains not only an admixture of non-neoplastic cells, but also cancer cells with an aggressive and invasive phenotype which became able to invade the surrounding tissues by mimicking fibroblast morphology. This metamorphosis would be possible through the re-use of an embryonic program by cancer cells, that is the epithelial to mesenchymal transition (EMT). Originally, in a murine model of spontaneous metastatic breast cancer, Weinberg and Coll. demonstrated that the highest aggressive potential of cancer cell was reached after their transition from an epithelial to a mesenchymal morphology (i.e., EMT), driven by Twist1 gene [6]. Twist1 expression and EMT are strictly associated with the acquisition of a spindle-like fibroblast morphology, the down-regulation of the epithelial marker E-cadherin and the expression of mesenchymal ones (N-cadherin and vimentin), with metastases development, and with the inhibition of the key pathway of senescence p16 driven [7]. Currently, many studies demonstrate that this embryonic program is activated by a set of transcription factors which act pleiotropically. These include Snail, Slug, Zeb1/2, and obviously Twist1. These regulators are expressed in various combination in a number of malignant tumor types and have been shown in experimental models of carcinoma formation to be casually important for programming invasion [8], [9], [10], [11].
The issues. The multi-step process of metastasis development, recapitulated by local invasion, intravasation, extravasation, colonization and growth in distant organs, postulates that cells undergoing EMT should be able to complete each individual step. However, no experimental evidence of the EMT process has been provided for the first step of local invasion (nor for the following ones) in tissues specimens of human malignancies. Similarly, proof of EMT in human epithelial cancer cells remains partial, largely derived from murine models, and based on ectopic expression of EMT regulators, or on stimulation to achieve transient mesenchymal features. Although several studies demonstrate the expression of EMT transcription factors in both the tumoral and stromal compartments of different cancers [12], [13], [14], they do not directly link this expression to the presence of cancer infiltrating cells.
The experimental work. We moved from the unexplained evidence of genetic and chromosomal abnormalities in the stromal compartment of solid tumors, and from the role of Twist1 as EMT regulator in cancer cells.
Moving by microarray data of a pool of CRC cells, we first show that tumor cells with a permanent mesenchymal signature, in a stable EMT state, can arise from epithelial CRC cells, both in humans and mice. Then we clarify that, within the mesenchymal signature, Twist1 plays a crucial role in the migration and invasion of CRC tumor cells.
By a combination of immuno-based and cytogenetic methods we detected in human CRC a Twist1+subpopulation of stromal cells, with a mesenchymal phenotype. This subpopuation was more represented in MS-stable CRC than in less metastatic MS-unstable CRC, and was associated with advanced CRC stage and with worse survival. Additionally, we showed that Twist1 transcript is degraded in MSI CRC, due to a frameshifted 3’-UTR, and propose that this mechanism contributes to the low capability of MSI CRC to exploit EMT to undergo metastasis. Finally, we identified Twist1+, stromal cells which share genetic changes with epithelial cancer cells, establishing a genetic link between epithelial and mesenchymal components of CRC.
In summary, we provide data from an original cellular model to tissue studies to prove the occurrence of EMT in human CRC. We demonstrated the presence of tumor cells in the stroma of CRC tumors and we give a method to identify those cells undergone to EMT and able to invade the surrounding tissues. Thus, our results readdress the study approach to the stromal compartment from that of a recipient of non-neoplastic cells to an incubator of cancer EMT cells able to disrupt tissues by mimicking activated fibroblast.
The experimental demonstration of human CRC in stable EMT, coupled to the identification of previously postulated tumor cells with mesenchymal morphology in the stromal compartment, add substantial evidence to EMT, translating a model it into a real phenomenon contributing to the metastatic process of human CRC. In a clinical perspective, our study highlights the importance to re-evaluate the target therapy of solid tumors from the epithelial compartment to include the mesenchymal one
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