Molecular Profiling of Lymphatic Endothelial Cell Activation In Vitro

The lymphatic vascular system plays a key role in cancer progression. Indeed, the activation of lymphatic endothelial cells (LECs) through the lymphangiogenic process allows for the formation of new lymphatic vessels (LVs) that represent the major route for the dissemination of solid tumors. This process is governed by a plethora of cancer-derived and microevironmental mediators that strictly activate and control specific molecular pathways in LECs. In this work we used an in vitro model of LEC activation to trigger lymphangiogenesis using a mix of recombinant pro-lymphangiogenic factors (VFS) and a co-culture system with human melanoma cells. Both systems efficiently activated LECs, and under these experimental conditions, RNA sequencing was exploited to unveil the transcriptional profile of activated LECs. Our data demonstrate that both recombinant and tumor cell-mediated activation trigger significant molecular pathways associated with endothelial activation, morphogenesis, and cytokine-mediated signaling. In addition, this system provides information on new genes to be further investigated in the lymphangiogenesis process and open the possibility for further exploitation in other tumor contexts where lymphatic dissemination plays a relevant role

Diabetes risk reduction diet and endometrial cancer risk

Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case–control study (1992–2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium–low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55–0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56–1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60–1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28–0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention

Analyzing user actions within a Web 2.0 portal to improve a collaborative filtering recommendation system

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PTX3 shapes profibrotic immune cells and epithelial/fibroblast repair and regeneration in a murine model of pulmonary fibrosis

The long pentraxin 3 (PTX3) is protective in different pathologies but was not analyzed in-depth in Idiopathic Pulmonary Fibrosis (IPF). Here, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of IPF by looking at immune cells (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibro-blasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which pulmonary fibrosis was induced. Our data have shown that PTX3 overexpression in Tie2-PTX3 compared to WT or PTX3-KO: reduced CD68+ and CD163+ macrophages and the Tryptase+ mast cells during the whole experimental time; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21; SOX2 is reduced on days 14 and 21; CD44 is reduced on day 21. Therefore, PTX3 could act on the proimmune and fibrogenic microenvironment to prevent fibrosis in BLM-treated mice

The Butterfly Fauna Of The Italian Maritime Alps:Results Of The «Edit» Project

Bonelli, Simona, Barbero, Francesca, Casacci, Luca Pietro, Cerrato, Cristiana, Balletto, Emilio (2015): The butterfly fauna of the Italian Maritime Alps: results of the EDIT project. Zoosystema 37 (1): 139-167, DOI: 10.5252/z2015n1a6, URL: http://dx.doi.org/10.5252/z2015n1a

Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer

Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa

Adherence to the Mediterranean diet and nasopharyngeal cancer risk in Italy

Purpose: Few studies investigated the role of diet on nasopharyngeal cancer (NPC) risk in non-endemic areas. The aim of this study was to assess the association between adherence to the traditional Mediterranean diet and NPC risk in a southern European low-risk population. Methods: We conducted a hospital-based case-control study in Italy, including 198 histologically confirmed NPC cases and 594 matched controls. Dietary habits were collected by means of a validated food-frequency questionnaire, including 83 foods, food groups, or beverages. Adherence to the traditional Mediterranean diet was assessed through a Mediterranean Diet Score (MDS), based on nine dietary components characterizing this dietary profile, i.e., high intake of vegetables, fruits and nuts, cereals, legumes, and fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated odds ratios (ORs) of NPC, and the corresponding 95% confidence intervals (CIs), for increasing MDS (i.e., increasing adherence) using multiple logistic regression models, adjusted for major confounding factors. Results: As compared to MDS 64 4, the ORs of NPC were 0.83 (95% CI: 0.54\u20131.25) for MDS of 5 and 0.66 (95% CI: 0.44\u20130.99) for MDS 65 6, with a significant trend of decreasing risk (p 0.043). The corresponding population attributable fraction was 22%, indicating that 22% of NPC cases in this population would be avoided by shifting all subjects to a score 656. Conclusions: Our study supports a favorable role of the Mediterranean diet on NPC risk

Family history of cancer and the risk of cancer: a network of case-control studies

Background The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. Patients and methods This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. Results All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. Conclusions Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer site

Longer fixation duration while viewing face images

The spatio-temporal properties of saccadic eye movements can be influenced by the cognitive demand and the characteristics of the observed scene. Probably due to its crucial role in social communication, it is argued that face perception may involve different cognitive processes compared with non-face object or scene perception. In this study, we investigated whether and how face and natural scene images can influence the patterns of visuomotor activity. We recorded monkeys’ saccadic eye movements as they freely viewed monkey face and natural scene images. The face and natural scene images attracted similar number of fixations, but viewing of faces was accompanied by longer fixations compared with natural scenes. These longer fixations were dependent on the context of facial features. The duration of fixations directed at facial contours decreased when the face images were scrambled, and increased at the later stage of normal face viewing. The results suggest that face and natural scene images can generate different patterns of visuomotor activity. The extra fixation duration on faces may be correlated with the detailed analysis of facial features