Search

Prostate cancer at the castration-resistant stage (CRPC) is a leading cause of death among men due to resistance to anticancer treatments, including chemotherapy. We set up an in vitro model of therapy-induced cancer repopulation and acquired cell resistance (CRAC) on etoposide-treated CRPC PC3 cells, witnessing therapy-induced epithelial-to-mesenchymal-transition (EMT) and chemoresistance among repopulating cells. Here, we explore the metabolic changes leading to chemo-induced CRAC, measuring the exchange rates cell/culture medium of 36 metabolites via Nuclear Magnetic Resonance spectroscopy. We studied the evolution of PC3 metabolism throughout recovery from etoposide, encompassing the degenerative, quiescent, and repopulating phases. We found that glycolysis is immediately shut off by etoposide, gradually recovering together with induction of EMT and repopulation. Instead, OXPHOS, already high in untreated PC3, is boosted by etoposide to decline afterward, though stably maintaining values higher than control. Notably, high levels of EMT, crucial in the acquisition of chemoresistance, coincide with a strong acceleration of metabolism, especially in the exchange of principal nutrients and their end products. These results provide novel information on the energy metabolism of cancer cells repopulating from cytotoxic drug treatment, paving the way for uncovering metabolic vulnerabilities to be possibly pharmacologically targeted and providing novel clinical options for CRPC.

Apoptotic cells stimulate compensatory proliferation through the caspase-3-cPLA-2-COX-2-PGE-2-STAT3 Phoenix Rising pathway as a healing process in normal tissues. Phoenix Rising is however usurped in cancer, potentially nullifying pro-apoptotic therapies. Cytotoxic therapies also promote cancer cell plasticity through epigenetic reprogramming, leading to epithelial-to-mesenchymal-transition (EMT), chemo-resistance and tumor progression. We explored the relationship between such scenarios, setting-up an innovative, straightforward one-pot in vitro model of therapy-induced prostate cancer repopulation. Cancer (castration-resistant PC3 and androgen-sensitive LNCaP), or normal (RWPE-1) prostate cells, are treated with etoposide and left recovering for 18 days. After a robust apoptotic phase, PC3 setup a coordinate tissue-like response, repopulating and acquiring EMT and chemo-resistance; repopulation occurs via Phoenix Rising, being dependent on high PGE-2 levels achieved through caspase-3-promoted signaling; epigenetic inhibitors interrupt Phoenix Rising after PGE-2, preventing repopulation. Instead, RWPE-1 repopulate via Phoenix Rising without reprogramming, EMT or chemo-resistance, indicating that only cancer cells require reprogramming to complete Phoenix Rising. Intriguingly, LNCaP stop Phoenix-Rising after PGE-2, failing repopulating, suggesting that the propensity to engage/complete Phoenix Rising may influence the outcome of pro-apoptotic therapies. Concluding, we established a reliable system where to study prostate cancer repopulation, showing that epigenetic reprogramming assists Phoenix Rising to promote post-therapy cancer repopulation and acquired cell-resistance (CRAC).

Androgen deprivation therapy (ADT) is a powerful treatment for metastatic hormone-sensitive prostate cancer (mHSPC) patients, but eventually and inevitably, cancer relapses, progressing to the fatal castration-resistant (CR)PC stage. Progression implies the emergence of cells proliferating in the absence of androgen through still elusive mechanisms. We show here for the first time that ADT induces LNCaP mHSPC cells to collectively enter a metastable quasi-apoptotic state (QUAPS) consisting of partial mitochondrial permeabilization, limited BAX and caspase activation, and moderate induction of caspase-dependent dsDNA breaks; despite this, cells maintain full viability. QUAPS is destabilized by poly(ADP)-polymerase inhibition (PARPi), breaking off toward overt intrinsic apoptosis and culture extinction. Instead, QUAPS is rapidly and efficiently reverted upon androgen restoration, with mitochondria rapidly recovering integrity and cells collectively resuming normal proliferation. Notably, replication restarts before DNA repair is completed, and implies an increased micronuclei frequency, indicating that ADT promotes genetic instability. The recovered cells re-acquire insensitivity to PARPi (as untreated LNCaP), pointing to specific, context-dependent vulnerability of mHSPC cells to PARPi during ADT. Summarizing, QUAPS is an unstable, pro-mutagenic state developing as a pro-survival pathway stabilized by PARP, and constitutes a novel viewpoint explaining how ADT-treated mHSPC may progress to CRPC, indicating possible preventive countermeasures.

This paper investigates migrant representation patterns according to media political orientation, analyzing the coverage of key-events by liberal/conservative online newspapers of France, Greece, Italy, UK. From our textual and visual analysis, it is possible to recognize slight specificities between liberals and conservatives, but not indicative of a deep change of narratives. In both, we registered a prevalence of the "acceptance frame", an infrequent use of negative tones in texts and aesthetic topic in images, among the "topics of suffering" by Boltanski. Moreover, a domesticity approach limiting the possibility of new narratives of Europe and the rest of the world emerges.

Negli ultimi cinquant'anni la popolazione italiana è stata attraversata da profondi e radicali cambiamenti strutturali connessi ad alcune grandi trasformazioni del contesto demografico nazionale: la caduta della natalità e della fecondità (arrivata a livelli tra i più bassi al mondo); l'emergere e il diffondersi di nuovi modelli familiari; l'invecchiamento della popolazione; l'evoluzione del ruolo della donna nella società; l'importanza rapidamente crescente dell'immigrazione straniera e il formarsi di una società culturalmente più eterogenea. In termini di fecondità, l'Italia con 1,32 figli per donna si attesta sotto la media dell'Unione europea di 1,59. A partire dalla seconda metà degli anni settanta il tasso di fecondità totale (Tft) è sceso al di sotto del livello di sostituzione (2,1 figli per donna) e da almeno trent'anni presenta valori tra i più bassi del Continente. Il minimo storico è stato toccato nel 1995 con 1,19 figli per donna e la ripresa successiva, interrottasi per altro con la crisi economica, deve molto alle nascite da genitori stranieri. Del resto è solo la straordinaria crescita dell'immigrazione straniera, registrata nel ventennio a cavallo del nuovo millennio, ad aver impedito che la popolazione iniziasse a diminuire, contrastando un saldo naturale negativo e rallentando il processo di invecchiamento e la diminuzione della popolazione in età lavorativa. Ciò nonostante siamo uno dei paesi più vecchi al mondo e il perdurare della crisi economica ha ridotto il contributo demografico dell'immigrazione, determinando in questi ultimi anni anche un calo della popolazione.

Partendo dal concetto di progettualità, il contributo intende esplorare le dimensioni socio-culturali sottese alla bassa fecondità in Italia attraverso la lente interpretativa di due modelli culturali: la cultura della scelta e la cultura della responsabilità. In particolare, all'interno di questa prospettiva, la scelta riproduttiva e la progettualità del diventare genitori sono discussi focalizzando l'attenzione sulla rappresentazione sociale della maternità e il rapporto tra genitorialità e sfera extradomestica.

The principal originality of this article lies in the analysis on ethnicity and identity in an under-explored geographical/ethnic context, that is the Greek second generation in Italy. Through a field research, the article analyses second generation Greek migrants' process of identity construction, highlighting the emergence of a network of multiple and hybrid belongings as well as a combination of identities and dialectical positions. The field research findings show that hybrid belongings contradict the idea of cultural purity by revealing that all cultures are hybrid all along. In fact, self-representation and self-identification of the Greek second generation challenge traditional paradigms of ethnicity entailing a reworking of pre-existing hybridity rather than any simple combination of Italian and Greek identities. Another key argument that emerged from this fieldwork is the importance of the specific context, positions and conditions in which hybridity operates.

Summary Purpose In the Littoral Province of Cameroon, in the Sanaga River Valley, a door-to-door epidemiological study was carried out in order to evaluate the prevalence of epilepsy in a small village located in a geographically isolated area, hyper-endemic for onchocerciasis. It was followed by an electro-clinical evaluation of patients and a case–control study. Methods The study involved a three-phases design: in phase I, a screening questionnaire was administered, in phase II, the presence of epilepsy was confirmed with electro-clinical evaluation, and in phase III, risk factors for epilepsy, socio-economical factors and life habits were evaluated in patients and two matched controls for the age (±1 year) residents in the same village. Endemicity level of onchocerciasis was assessed in the village by measuring the prevalence of nodules in adult males aged ≥20 years (PNAM). Results One hundred eighty-one subjects (100 male and 81 female) were examined (91.9% of the overall population). The crude prevalence rate of active epilepsy was 105 per 1000 pop (CI 95% 60–150) while the age-adjusted prevalence rate was 134.5 cases per 1000 pop (CI 95% 90–178). Seizures were classified as generalized in 10 patients (52.6%) and partial in nine (47.4%). In 17 patients EEG was recorded. Afterward the electro-clinical classification this distribution was inverted: generalized seizures occurred in 35.3% of cases and partial seizures in 64.7% of cases. The PNAM was 62.5%. The surveyed village was classified as hyper-endemic for onchocerciasis. Among risk factors, only positive family history for epilepsy was found (p = 0.031). A sample pedigree of a family with 10 epileptic cases (4 included in the epidemiological study) was showed. Conclusions To our knowledge, this is the first door-to-door study that produce an adjusted prevalence rate on epilepsy in Cameroon. In according to studies done in Tanzania, Liberia, Uganda, and Ethiopia, our results (i.e., the high prevalence rate in a restricted area, the clinical characteristics of epileptic seizures, the positive family history for epilepsy and the type of pedigree of a family with epileptic patients) may be accounted for by the presence of an strong interaction between environmental and genetic factors in some circumscribed areas.

By using the findings of a field study concerning Greek student mobility in Italy, this paper makes a concrete contribution to the international and European debate on the study of transnational migration. It analyses the socio-cultural identity building process of Greek students in Italy, highlighting new forms of citizenship and cultural identities that often go beyond the perimeter of Nation-states and give rise to socialisation processes characterized by fluidity and syncretism. These new forms of citizenship and cultural identities, and the strategies through which identity is constructed in relation to others, involve the creation of transnational social spaces, the relations that Greek students maintain with their places of origin, the exchanges between the two sides of the Mediterranean and the way in which Greek students seek to reproduce social practices that recall the motherland.

(English) Brain drain is a phenomenon that Greece has experienced since late 1950, which has continued in subsequent decades and intensified over the 1990s. Although there was, in the first decade of the twenty-first century, a political and economic situation more stable than in the past, the unprecedented economic crisis that Greece is going through has caused, and will continue to cause, the increase in brain drain due to poor employment opportunities and strong austerity measures taken by past governments, which depress the level of living standards. If this massive human capital flight increases, which is very likely, it would surely worsen the situation as Greece would continue to suffer depression effects on its economy and to lose precisely the resources it needs for economic recovery. This article highlights some causes determining the brain drain in Greece, also in the light of some scientific surveys that analyse this phenomenon. Moreover, it tries to provide keys to ending the crisis and to economic recovery, starting from education and implementation of major reforms aimed at overcoming problems that have long plagued the Hellenic education system and that can enhance its quality, while maintaining commitments to equity and social justice. (Italiano) Quello del brain drain è un fenomeno che la Grecia ha vissuto fin dalla fine degli anni 1950 che ha continuato nei decenni successivi e che si è intensificato nel corso degli anni 1990. Nonostante vi sia stata, nel primo decennio del XXI secolo, una situazione politica ed economica piuttosto stabile rispetto al passato, l’attuale crisi economica senza precedenti che la Grecia sta attraversando ha provocato e continuerà a provocare l’aumento della fuga dei cervelli a causa delle scarse opportunità di lavoro e delle forti misure di austerità, prese dagli ultimi governi, che deprimono il livello standard di vita. Se la fuga massiccia di capitale umano dovesse assumere dimensione più grandi, cosa assai probabile, la situazione potrebbe sicuramente peggiorare perché così la Grecia continuerebbe a subire effetti depressivi per la propria economia e a perdere esattamente le risorse umane di cui ha bisogno per la ripresa economica. Questo articolo analizza alcune cause determinanti la fuga dei cervelli, alla luce anche di contributi scientifici che esaminano questo fenomeno. Individua inoltre alcune possibili chiavi di uscita dalla crisi e di ripresa economica, partendo dall’istruzione e dall’attuazione di importanti riforme finalizzate al superamento di problemi che hanno a lungo afflitto il sistema di istruzione ellenico e che possono migliorarne la qualità, pur mantenendo impegni di equità e giustizia sociale.

Without a doubt, the analysis of the Greek student mobility would be very useful in understanding aspects of Greek society and the reasons which prompted the students to leave their country, especially in this historical period characterised by an unprecedented economic crisis in Greece. This research aims at studying the characteristics of the Greek students in the Italian universities, providing suggestions for improving decision making and for ensuring equal opportunities for quality education. This survey analyses their migratory plans, training, expectations of study, evaluation of the universities and job prospects by taking as a hypothesis the "Ulysses metaphor", in that it is possible to return to Greece by means of their cultural capital. From a transnational perspective, this research tries to explain the dynamics of inclusion into the Roman social fabric and the process of creation of their cultural identity and the ties with Greek networks that are factors of social identification and enhancement of their cultural heritage from transnational contexts.

(English) (Italiano) Attraverso l’utilizzo dell’approccio biografico, sono state ricostruire le traiettorie di vita delle migranti polacche altamente qualificate presenti sul territorio della provincia romana. Si è indagato sulle modalità e sulle motivazioni dei progetti migratori all’interno di una prospettiva transnazionale, mettendo in risalto il ruolo attivo del social network polacco che giustifica l’elevata presenza polacca nella città di Roma da non ricondurre, in maniera riduttiva, a ragioni puramente economiche. Infine, largo spazio è stato dato all’analisi del percorso formativo e professionale per indagare su possibili problematiche legate al corretto utilizzo delle competenze professionali e al riconoscimento del titolo di studio alla luce del fenomeno del sottoinquadramento o del cosiddetto brain waste (spreco dei cervelli).

Attraverso l'utilizzo dell'approccio biografico, sono state ricostruire le traiettorie di vita delle migranti polacche altamente qualificate presenti sul territorio della provincia romana. Si è indagato sulle modalità e sulle motivazioni dei progetti migratori all'interno di una prospettiva transnazionale, mettendo in risalto il ruolo attivo del social network polacco che giustifica l'elevata presenza polacca nella città di Roma da non ricondurre, in maniera riduttiva, a ragioni puramente economiche. Infine, largo spazio è stato dato all'analisi del percorso formativo e professionale per indagare su possibili problematiche legate al corretto utilizzo delle competenze professionali e al riconoscimento del titolo di studio alla luce del fenomeno del sottoinquadramento o del cosiddetto brain waste (spreco dei cervelli).

Brain drain is a phenomenon that Greece has experienced since late 1950, which has continued in subsequent decades and intensified over the 1990s. Although there was, in the first decade of the twenty-first century, a political and economic situation more stable than in the past, the unprecedented economic crisis that Greece is going through has caused, and will continue to cause, the increase in brain drain due to poor employment opportunities and strong austerity measures taken by past governments, which depress the level of living standards. If this massive human capital flight increases, which is very likely, it would surely worsen the situation as Greece would continue to suffer depression effects on its economy and to lose precisely the resources it needs for economic recovery. This article highlights some causes determining the brain drain in Greece, also in the light of some scientific surveys that analyse this phenomenon. Moreover, it tries to provide keys to ending the crisis and to economic recovery, starting from education and implementation of major reforms aimed at overcoming problems that have long plagued the Hellenic education system and that can enhance its quality, while maintaining commitments to equity and social justice.

This article contributes to the literature on return migration of second-generation immigrants. Based on fieldwork on Greek migrants in Italy, it does so by examining the potential for and the actual performance of counter-diasporic migration. The research findings show that emotional attachment and a general desire to return to the homeland characterize the second-generation diaspora Greeks in Italy, although the possibility of an actual return may be imaginary. Regarding the reasons for counter-diasporic migration, there are numerous pull factors, including a prominent emotional and symbolic attraction. Greek origins, the bonds of kinship, and the presence of a transnational network play an important role in strengthening the relationship with the homeland and in shaping a life project founded on a strong desire to return to their ancestral homeland. In this sense, counter-diasporic migration represents another element in the cyclical movement that characterizes the Greek Diaspora with the phenomenon discussed in this article, as the final and long-awaited return home.

Some studies have recently attempted to go beyond the conception of migratory networks as static and immutable entities, inviting to consider their dynamic nature by broadening the perspective of networks that consider all the agents that contribute to the structuring of migrations. In line with this current debate, this paper provides interesting insights regarding the migration industry, including smuggling networks, and the use of technology by networks to build the migration project and gain awareness of risks and costs of migration, especially if irregular. This broadening of the network perspective is thus understood as a further step towards understanding migration as a social process, useful for analyzing the ability of networks to build migratory movements.