La Serenissima in scena. Da Goldoni a Paolini

Aspetti diversi, dall'Illuminismo ad oggi, della scena veneziana e veneta, nella centralità del rapporto tra interprete e autore, figure spesso coincidenti

Anaplastic astrocytoma (AA) and glioblastoma (GBM): a real-life experience in Padua Neuro-Oncology Center

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Citizen to Stay or Citizen to Go? Naturalization, Security, and Mobility of Migrants in Italy

https://doi.org/10.1080/15562948.2016.1208316We analyze the relation between naturalization, mobility, and security through 50 in-depth interviews with migrants of different origins living in two Italian regions. We show how migrants pursue naturalization both to protect themselves against bureaucracy and deportation and to move to a third country. The second migration is motivated by improving one's conditions, forced by the economic crisis, or completes the original migratory project once a strong passport is obtained. We argue that citizenship is not essentially linked to either stability or mobility and that mobility should be understood as neither exceptional nor always chosen

IL-6 Regulation on Skeletal Muscle Mitochondrial Remodeling During Cancer Cachexia in the \u3cem\u3eApc\u3csup\u3eMin/+\u3c/sup\u3e\u3c/em\u3e Mouse

BACKGROUND: Muscle protein turnover regulation during cancer cachexia is being rapidly defined, and skeletal muscle mitochondria function appears coupled to processes regulating muscle wasting. Skeletal muscle oxidative capacity and the expression of proteins regulating mitochondrial biogenesis and dynamics are disrupted in severely cachectic ApcMin/+ mice. It has not been determined if these changes occur at the onset of cachexia and are necessary for the progression of muscle wasting. Exercise and anti-cytokine therapies have proven effective in preventing cachexia development in tumor bearing mice, while their effect on mitochondrial content, biogenesis and dynamics is not well understood. The purposes of this study were to 1) determine IL-6 regulation on mitochondrial remodeling/dysfunction during the progression of cancer cachexia and 2) to determine if exercise training can attenuate mitochondrial dysfunction and the induction of proteolytic pathways during IL-6 induced cancer cachexia. METHODS: ApcMin/+ mice were examined during the progression of cachexia, after systemic interleukin (IL)-6r antibody treatment, or after IL-6 over-expression with or without exercise. Direct effects of IL-6 on mitochondrial remodeling were examined in cultured C2C12 myoblasts. RESULTS: Mitochondrial content was not reduced during the initial development of cachexia, while muscle PGC-1α and fusion (Mfn1, Mfn2) protein expression was repressed. With progressive weight loss mitochondrial content decreased, PGC-1α and fusion proteins were further suppressed, and fission protein (FIS1) was induced. IL-6 receptor antibody administration after the onset of cachexia improved mitochondrial content, PGC-1α, Mfn1/Mfn2 and FIS1 protein expression. IL-6 over-expression in pre-cachectic mice accelerated body weight loss and muscle wasting, without reducing mitochondrial content, while PGC-1α and Mfn1/Mfn2 protein expression was suppressed and FIS1 protein expression induced. Exercise normalized these IL-6 induced effects. C2C12 myotubes administered IL-6 had increased FIS1 protein expression, increased oxidative stress, and reduced PGC-1α gene expression without altered mitochondrial protein expression. CONCLUSIONS: Altered expression of proteins regulating mitochondrial biogenesis and fusion are early events in the initiation of cachexia regulated by IL-6, which precede the loss of muscle mitochondrial content. Furthermore, IL-6 induced mitochondrial remodeling and proteolysis can be rescued with moderate exercise training even in the presence of high circulating IL-6 levels

Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules

Background: Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results: The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions: We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.[Figure not available: see fulltext.

Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients.

Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. Conclusions: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use

Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: A retrospective study in a sample of Italian cancer genetics clinics

Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment

The effect of radiation dose on mouse skeletal muscle remodeling

BackgroundThe purpose of this study was to determine the effect of two clinically relevant radiation doses on the susceptibility of mouse skeletal muscle to remodeling.Materials and methods.Alterations in muscle morphology and regulatory signaling were examined in tibialis anterior and gastrocnemius muscles after radiation doses that differed in total biological effective dose (BED). Female C57BL/6 (8-wk) mice were randomly assigned to non-irradiated control, four fractionated doses of 4 Gy (4x4 Gy; BED 37 Gy), or a single 16 Gy dose (16 Gy; BED 100 Gy). Mice were sacrificed 2 weeks after the initial radiation exposure.ResultsThe 16 Gy, but not 4x4 Gy, decreased total muscle protein and RNA content. Related to muscle regeneration, both 16 Gy and 4x4 Gy increased the incidence of central nuclei containing myofibers, but only 16 Gy increased the extracellular matrix volume. However, only 4x4 Gy increased muscle 4-hydroxynonenal expression. While both 16 Gy and 4x4 Gy decreased IIB myofiber mean cross-sectional area (CSA), only 16 Gy decreased IIA myofiber CSA. 16 Gy increased the incidence of small diameter IIA and IIB myofibers, while 4x4 Gy only increased the incidence of small diameter IIB myofibers. Both treatments decreased the frequency and CSA of low succinate dehydrogenase activity (SDH) fibers. Only 16 Gy increased the incidence of small diameter myofibers having high SDH activity. Neither treatment altered muscle signaling related to protein turnover or oxidative metabolism.ConclusionsCollectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these effects appear to be related to fiber type and oxidative metabolism

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

Background: Fascin is overexpressed in many cancers, including colorectal, but its role in the malignant transformation of benign colorectal adenomas is unclear. Methods: Immunohistochemical analysis of fascin expression was carried out in resected human colorectal adenoma specimens. The effects of forced overexpression of fascin on adenoma cell motility were also analysed. Results: We show fascin overexpression in adenomas increasing with tumour size, histological type, and degree of dysplasia and increased cell motility in adenoma cell lines following fascin transfection. Conclusion: These data suggest an important role for fascin in the malignant progression of colorectal tumours