The role of interleuchin 6 (IL-6) in the promotion of an aggressive and stem cell-like phenotype in human breast cancer cells and in stem/progenitor cells expanded in vitro as mammospheres

High serum levels of Interleukin-6 (IL-6) correlate with poor outcome in breast cancer patients. However no data are available on the relationship between IL-6 and stem/progenitor cells which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in mammospheres (MS), multi-cellular structures enriched in stem/progenitor cells of the mammary gland, and also in MCF-7 breast cancer cells. We show that MS from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. We find that IL-6 mRNA is detectable only in basal-like breast carcinoma tissues, an aggressive variant showing stem cell features. Our results reveal that IL-6 triggers a Notch-3-dependent up-regulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and MCF-7 derived spheroids. Moreover, IL-6 induces a Notch-3-dependent up-regulation of the carbonic anhydrase IX gene, which promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, an autocrine IL-6 loop relies upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3 expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.

Neocostituzionalismo e positivizzazione dei valori

This doctoral thesis seeks to make a comprehensive analysis of neoconstitutionalism, studying their manifestations in constitutional law and doctrine. Neoconstitutionalism, as a new manifestation of constitutional phenomenon that emerged after World War II, is characterized by the need to take any legal possession of certain premises, materials of an immovable, coinciding with the fundamental human rights, which will fall outside the potential political majorities, and become its cornerstone. These assumptions are intended as safeguards needed to protect human dignity and the democratic system itself against anyone, even taking advantage of a power obtained democratically which intends to demolish the pillars of democracy and to establish tyranny. The Constitution is enshrined as a basic rule of real system, a repository of these fundamental rights, the observance by public authorities becomes inexcusable. This will involve a role for judicial review in its protection. Thus, supremacy of the constitution, deepening respect for and promotion of fundamental rights and role of constitutional judge as the guarantor of its validity are the bases of neoconstitutionalism, a legal phenomenon not only current, but evolving.

Diversity and local democracy. The case of Republic of Macedonia - implications of ethnic diversity on municipal decision making and organizational performance

This research seeks to review the level of knowledge achieved in interpreting the relationship between the ethnic diversity at the workplace in the public sector and the organizational performance; as well as seeks to contribute in understanding the implications of this relationship. The study commenced with investigating the academic research in the relevant area addressing the following research questions: (a) How are diversity management and organizational performance conceptualized? (b) What are the existing findings of research concerning diversity at the workplace in the public organizations and organizational performance? (c) What factors intervene the relationship between the diversity and organizational performance? Based on the findings from the review of the academic research, this study seeks to contribute in understanding the ethnic diversity – performance relationship and its mplications at the local level in the Macedonian context. The reform process in Macedonia as a multicultural society, where for many years, inter-ethnic relations have been one of the most sensitive political issues, affecting both the stability of the country and the progress, focused mainly on the implementation of the decentralization and inclusion of ethnic minorities in the decision making process. With the implementation of the Ohrid Framework Agreement workforce at the units of local self-government in Republic of Macedonia is becoming more balanced with respect to ethnic minorities, with more workforce participation than ever by Albanians, Turks, Roma and other minorities. As public organizations at local level become more diverse along ethnic lines, it makes sense to pay more attention to how different ethnic groups interact with one another at work. Thus it gives additional importance on the research question addressed in the study and gives significance of the research in a broader scope.

The Influence of Direct Democracy on Agency Costs: Lessons from Corporate Governance

This dissertation seeks to improve the usage of direct democracy in order to minimize agency cost. It first explains why insights from corporate governance can help to improve constitutional law and then identifies relevant insights from corporate governance that can make direct democracy more efficient. To accomplish this, the dissertation examines a number of questions. What are the key similarities in corporate and constitutional law? Do these similarities create agency problems that are similar enough for a comparative analysis to yield valuable insights? Once the utility of corporate governance insights is established, the dissertation answers two questions. Are initiatives necessary to minimize agency cost if referendums are already provided for? And, must the results of direct democracy be binding in order for agency cost to be minimized?

La Città Inclusiva. Educazione, democrazia e giustizia sociale: la ricerca di una prospettiva e di strategie che promuovano umanizzazione e inclusione

L'interrogativo da cui nasce la ricerca riguarda la possibilità di individuare, in controtendenza con la logica neoliberista, strategie per l'affermarsi di una cultura dello sviluppo che sia sostenibile per l'ambiente e rispettosa della dignità delle persone, in grado di valorizzarne le differenze e di farsi carico delle difficoltà che ognuno può incontrare nel corso della propria esistenza. Centrale è il tema del lavoro, aspetto decisivo delle condizioni di appartenenza sociale e di valorizzazione delle risorse umane. Vengono richiamati studi sulla realtà in cui siamo immersi, caratterizzata dal pensiero liberista diventato negli ultimi decenni dominante su scala globale e che ha comportato una concezione delle relazioni sociali basata su di una competitività esasperata e sull’esclusione di chi non sta al passo con le leggi di mercato: le conseguenze drammatiche dell'imbroglio liberista; la riduzione delle persone a consumatori; la fuga dalla comunità ed il rifugio in identità separate; il tempo del rischio, della paura e della separazione fra etica e affari. E gli studi che, in controtendenza, introducono a prospettive di ricerca di uno sviluppo inclusivo e umanizzante: le prospettive della decrescita, del business sociale, di una via cristiana verso un'economia giusta, della valorizzazione delle capacità delle risorse umane. Vengono poi indagati i collegamenti con le esperienze attive nel territorio della città di Bologna che promuovono, attraverso la collaborazione fra istituzioni, organizzazioni intermedie e cittadini, occasioni di un welfare comunitario che sviluppa competenze e diritti insieme a responsabilità: l'introduzione delle clausole sociali negli appalti pubblici per la realizzazione professionale delle persone svantaggiate; la promozione della responsabilità sociale d'impresa per l'inclusione socio-lavorativa; la valorizzazione delle risorse delle persone che vivono un’esperienza carceraria. Si tratta di esperienze ancora limitate, ma possono costituire un riferimento culturale e operativo di un modello di sviluppo possibile, che convenga a tutti, compatibile con i limiti ambientali e umanizzante.