Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

BACKGROUND: Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. METHODS: A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. RESULTS: In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. CONCLUSION: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients

"Heimat Südtirol" : the coexistence of German- and Italian-speaking inhabitants of the province of Bolzano (Italy)

Cette étude aspire à expliquer les raisons de la cohabitation - basée sur une différentiation linguistique - entre les germanophones et les italophones qui constituent la population du département du Haut-Adige/Tyrol du Sud (situé dans l'extrémité nord-orientale de l'Italie). Ce territoire, qui appartenait, historiquement, au Tyrol autrichien, a été annexé à l'Italie en 1918, raison pour laquelle il est constitué de deux tiers de germanophones qui ont toutefois réussi à maintenir leurs spécificités (notamment linguistique et culturelle) grâce à une large autonomie administrative et juridique, obtenue en 1972 après bien des vicissitudes faites de vexations et de luttes revendicatives. Cette autonomie a instauré un système social basé sur la séparation, institutionnellement orchestrée et idéologiquement alimentée par le monde politique et médiatique, des deux groupes linguistiques. Cela a engendré, chez les habitants italophones, un fort « malaise » identitaire. En partant du présupposé que le « modèle sud-tyrolien » - dont la genèse et la mise en pratique font l'objet d'explicitations - n´est pas remis en question dans la mesure ou il est désormais devenu une « seconde nature ». La question qui est au centre de cette recherche consiste à se demander pourquoi cette réalité binaire, fondée sur une distinction « ethnique », se maintient dans le temps malgré une ambition déclarée d'interculturalité et de bilinguisme. Cette étude, axée sur l'immersion dans la quotidienneté de la population, nous porte à interroger la quotidienneté et la subjectivité des individus : il s´agit d´accéder à leurs visions du monde grâce à l'analyse de leur imaginaire social, de leurs mémoires collectives, de leur définition de l´autre et des identités sud-tyroliennes. Ainsi, si la langue et les institutions freinent le contact entre les deux groupes, la dynamique de reproduction de la séparation est intériorisée et par conséquent pratiquée par les individus. De fait, la Heimat - concept propre au monde germanophone qui a fini par s'imposer largement au sein de ce travail - participe en tant que « monde-de-la-vie » à cette séparation vécue dont la remise en question saperait les fondements mêmes de ce vivre ensemble spécifique qui va désormais de soi. Malgré la « dimension utopique » qu'elle renferme (Bloch), il semble difficile, au vu du fatalisme de la population qui s'en remet aux générations à venir, de se soustraire à cette « Heimat Südtirol » qui ne laisse que peu de place à l'idée d'un avenir autre capable de dépasser la séparation.This study analyses the coexistence between the German- and Italian-speaking population of the province of Bolzano - South Tyrol. The focus is on approaches that can explain the separated realities of these two linguistic groups. Before the annexation to Italy in 1918, South Tyrol was part of the Austro-Hungarian Empire. Two thirds of the population speaks German and preserve its linguistic and cultural features due to its administrative and legislative autonomy, which has been obtained after long struggles for recognition. This has produced a social system, which is based on the separation of the two linguistic groups supported by institutions, for instance schools, reinforced by politics and media. These developments led to a widespread identitary uneasiness of the Italian-speaking population. The central question is on how this "ethnic" separation is based on and could be preserved. It was supposed that this "South Tyrol model" is not questioned as it is perceived as a "second nature". By studying the everyday life, the perceptions and visions of the German- and Italian-speaking population, this study intends to provide explanations to the largely separated coexistence. This study uses a qualitative research approach. Group interviews were conducted with members of the Geman- and Italian-speaking population in different municipalities. In addition, expert interviews were carried out with political representatives. Results of this study suggest that different factors explain the separated coexistence by linguistic belonging: the collective memories and their transmission to younger generations; the relationships of power and domination; the definitions of "we" and the other; as well as the different South Tyrolean identities of the German- and Italian-speaking population. Encounters between the two linguistic groups are additionally hampered by the different languages and the institutional separation. The division is internalised by the two linguistic groups and practiced in accordance. This results in a dynamic of reproduction that perpetuates this model of coexistence. The Heimat as "lifeworld", which manifests itself in this separation, plays an important role for the coexistence. The "utopian dimension" of the Heimat (Bloch) does not allow to escape and to imagine a possible future which would overcome this specific type of lifeworld "Heimat Südtirol". On the contrary, this is left to the fatalism and future generations

Entrepreneurial ecosystems in tourism : an analysis of characteristics from a systems perspective

This paper transfers the concept of entrepreneurial ecosystems (EEs) to tourism. First it investigates the characteristic of an EE in tourism by comparing it to an existing model. Second, the sector-specificity of the EE in tourism is discussed by referring to the system’s boundaries, operations and purposes, thus linking research on EEs in tourism more strongly to key concepts of systems theory. This is done by evaluating 19 interviews from South Tyrol in a qualitative approach using GABEK (Holistic Processing of Linguistic Complexity), which includes rule-based coding of interviews and visualisation of results in a network graph. Results show that the evaluated EE in tourism shares features familiar to EEs in other business sectors. This is an elevated role of long-standing entrepreneurs, social networks, governance, shared knowledge and learning. However, there are also tourism-specific features, such as culture and landscape, which directly provide resources for entrepreneurship. Governance does not emerge from the interaction of entrepreneurs, but from public bodies. The system’s output is not ambitious entrepreneurship, but innovative, sustainable and collective entrepreneurship. However, there is the need for further research to clearly determine the system’s sector specificity

Social and Labor Integration of Asylum Seekers in Rural Mountain Areas—A Qualitative Study

Migration into Europe affects the Alps in various ways. The recent influx of refugees and a higher number of asylum requests has presented governance challenges for mountain communities. In Italy, the responsibility of regions to host asylum seekers increased when a national system was implemented to distribute asylum seekers throughout the country. This study explored the impact of current distributions through the analysis of 2 rural mountain municipalities in the northeast Italian Alps in the Autonomous Province of Bolzano (also known as South Tyrol) in which reception facilities for asylum seekers have been established. A qualitative research approach offered empirical insights into the functioning of the reception system and governance in these communities. Our social network analysis of the research data, focusing on the labor integration of asylum seekers, indicated that stronger relational linkages among actors in rural mountain communities may facilitate access to the labor market for asylum applicants