Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition.

Within the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering with the net charges of the nucleosomes, is a key player in this regulation. Here, we report that the oncoprotein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that a condition in which SET is accumulated, the severe Schinzel-Giedion Syndrome (SGS), is characterized by a failure in the usage of the distal regulatory regions typically employed during fate commitment. This is accompanied by the usage of alternative enhancers leading to a massive rewiring of the distal control of the gene transcription. This represents a (mal)adaptive mechanism that, on one side, allows to achieve a certain degree of differentiation, while on the other affects the fine and corrected maturation of the cells. Thus, we propose the differential in cis-regulation as a contributing factor to the pathological basis of SGS and possibly other the SET-related disorders in humans.

Factors contributing to satisfaction with care in cancer outpatients.

OBJECTIVES: To evaluate satisfaction with care (SC) in cancer patients treated at a Spanish day hospital, to identify determinants of SC, and to assess the association between SC and quality of life (QL). METHODS: Cross-sectional study in which 119 patients undergoing outpatient chemotherapy completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Cancer Outpatient Satisfaction with Care questionnaire for chemotherapy (OUT-PATSAT35 CT), and an item on loyalty. Bivariate correlations between each subscale of the OUT-PATSAT35 CT and overall satisfaction, and between the subscales of OUT-PATSAT35 CT and QLQ-C30, were calculated. Multiple linear regression models were used to analyze determinants of patients' SC. RESULTS: Mean age was 62.5 years (SD 11.7), and 54.6% of the sample were female. Mean scores for SC were > 75 out of 100 on all OUT-PATSAT35 CT subscales, except environment. Overall satisfaction was higher than satisfaction in any subscale, and all patients would choose the same day hospital again. Correlation with overall satisfaction was moderate but statistically significant for all subscales. Patients treated for tumor recurrence and those undergoing palliative treatment manifested significantly lower overall satisfaction. Correlation between the EORTC QLQ-C30 and the OUT-PATSAT35 CT was not statistically significant, although patients with better health status reported higher satisfaction in several subscales. CONCLUSION: Patient-reported SC and loyalty towards the day hospital were high. Disease evolution and aim of treatment were determinants of overall satisfaction. The correlation between SC and QL was unclear. Some areas for improving care were noted.

PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/ß-catenin pathway.

Pancreatic adenocarcinoma upregulated factor (PAUF), also known as ZG16B, was previously found in the secretome of metastatic colorectal cancer cells. Here, we demonstrated the presence of PAUF at the intracellular level and its multiple effects on cancer progression. An initial decline of PAUF expression was observed at early stages of colorectal cancer followed by an increase at the metastatic site. PAUF was located at different cellular compartments: membrane-associated vesicles, endosomes, microtubule-associated vesicles, cell growth cones and the cell nucleus. PAUF loss in two colorectal cancer cell lines caused severe alterations in the cell phenotype and cell cycle, including tetraploidy, extensive genomic alterations, micronuclei and increased apoptosis. An exhaustive analysis of the PAUF interactome using different proteomic approaches revealed the presence of multiple components of the cell cycle, mitotic checkpoint, Wnt pathway and intracellular transport. Among the interacting proteins we found ZW10, a moonlighting protein with a dual function in membrane trafficking and mitosis. In addition, PAUF silencing was associated to APC loss and increased ß-catenin nuclear expression. Altogether, our results suggest that PAUF depletion increases aneuploidy, promotes apoptosis and activates the Wnt/ß-catenin pathway in colorectal cancer cells facilitating cancer progression. In summary, PAUF behaves as a multifunctional protein, with different roles in cancer progression according to the extra- or intracellular expression, suggesting a therapeutic value for colorectal cancer.

Development of a dual-cure mineral trioxide aggregate-based cement: Biological, physical, and mechanical properties.

PURPOSE: The purpose of this study is to compare the physical, mechanical, and biocompatibility properties of a new dual-cure white mineral trioxide aggregate (D-W-MTA) and a commercial W-MTA. MATERIALS AND METHODS: Diametral tensile strength (DTS), water sorption (WSp), and water solubility (WSl) tests were performed. Cytotoxicity was observed in primary culture of human pulp fibroblasts (HPFs) and mouse 3T3/NIH fibroblast lineage. Specimens of both materials were embedded in 1 mL of Dulbecco's modified essential medium for 24 h. Cells were incubated for 24 h with the eluates. Cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and genotoxicity by micronucleus (MN) formation. Data were analyzed by ANOVA and Kruskal-Wallis tests considering P < 0.05. RESULTS: D-MTA and W-MTA not showed cytotoxic effect on the two cell lines. However, D-MTA stimulated HPF growth. The MN count was similar to that of the control group for D-MTA and W-MTA. D-MTA presented lower DTS and WSl. Nevertheless, WSp was similar in the two groups. CONCLUSION: The results suggest that D-MTA is a promising material for pulp capping. Thus, in vivo tests should be performed to evaluate the performance of this material.