Oncoplastic conservative surgery for breast cancer: long-term outcomes of our first ten years experience

The main goal of oncoplastic breast surgery (OBS) is to optimize cosmetic outcomes and reduce patient morbidity, while still providing an oncologically-safe surgical outcome and extending the target population of conservative surgery. Although the growing number of reported experiences with oncoplastic surgery, few studies account for the long-term outcomes

Analysis of the gene expression profile of mouse male meiotic germ cells

Wide genome analysis of difference in gene expression between spermatogonial populations from 7-day-old mice and pachytene spermatocytes from 18-day-old mice was performed using Affymetrix gene chips representing approximately 12,500 mouse known genes or EST sequences, spanning approximately 1/3rd of the mouse genome. To delineate differences in the profile of gene expression between mitotic and meiotic stages of male germ cell differentiation, expressed genes were grouped in functional clusters. The analysis confirmed the previously described pre-meiotic or meiotic expression for several genes, in particular for those involved in the regulation of the mitotic and meiotic cell cycle, and for those whose transcripts are accumulated during the meiotic stages to be translated later in post-meiotic stages. Differential expression of several additional genes was discovered. In few cases (pro-apoptotic factors Bak, Bad and Bax), data were in conflict with the previously published stage-dependent expression of genes already known to be expressed in male germ cells. Northern blot analysis of selected genes confirmed the results obtained with the microarray chips. Six of these were novel genes specifically expressed in pachytene spermatocytes: a chromatin remodeling factor (chrac1/YCL1), a homeobox gene (hmx1), a novel G-coupled receptor for an unknown ligand (Gpr19), a glycoprotein of the intestinal epithelium (mucin 3), a novel RAS activator (Ranbp9), and the A630056B21Rik gene (predicted to encode a novel zinc finger protein). These studies will help to delineate the global patterns of gene expression characterizing male germ cell differentiation for a better understanding of regulation of spermatogenesis in mammals

The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Most patients present with advanced disease at diagnosis, which only permits palliative chemotherapeutic treatments. RNA dysregulation is a hallmark of most human cancers, including PDAC. To test the impact of RNA processing dysregulation on PDAC pathology, we performed a bioinformatics analysis to identify RNA-binding proteins (RBPs) associated with prognosis. Among the 12 RBPs associated with progression-free survival, we focused on MEX3A because it was recently shown to mark an intestinal stem cell population that is refractory to chemotherapeutic treatments, a typical feature of PDAC. Increased expression of MEX3A was correlated with higher disease stage in PDAC patients and with tumor development in a mouse model of PDAC. Depletion of MEX3A in PDAC cells enhanced sensitivity to chemotherapeutic treatment with gemcitabine, whereas its expression was increased in PDAC cells selected upon chronic exposure to the drug. RNA-sequencing analyses highlighted hundreds of genes whose expression is sensitive to MEX3A expression, with significant enrichment in cell cycle genes. MEX3A binds to its target mRNAs, like cyclin-dependent kinase 6 (CDK6), and promotes their stability. Accordingly, knockdown of MEX3A caused a significant reduction in PDAC cell proliferation and in progression to the S phase of the cell cycle. These findings uncover a novel role for MEX3A in the acquisition and maintenance of chemoresistance by PDAC cells, suggesting that it may represent a novel therapeutic target for PDAC

Scanning electron microscopy of cochlea in new-born rats exposed to hyperbaric oxygen: preliminary report

The aetiology of hearing loss in new-borns in neonatal intensive care is still debated. While the physiopathology of brain, lung and retina damage related to oxygen supplementation has been widely described, no studies have been carried out to define the relationship between hearing loss and supplementation of oxygen in new-borns. In the present investigation, the cochlear morphology of new-born rats was evaluated by means of scanning electron microscopy in order to assess morphological changes after supplemental oxygen administration. After treatment, electron microscopy revealed many changes in the morphology of outer hair cells, if compared to normal rats of the same age. The results suggest that cochlear changes are similar to those previously observed in other regions and may be related to a vascular mechanism of hypoxia-ischaemia and neovascularization and/or an oxidative stress

Scanning electron microscopy of cochlea in new-born rats exposed to hyperbaric oxygen: preliminary report

The aetiology of hearing loss in new-borns in neonatal intensive care is still debated. While the physiopathology of brain, lung and retina damage related to oxygen supplementation has been widely described, no studies have been carried out to define the relationship between hearing loss and supplementation of oxygen in new-borns. In the present investigation, the cochlear morphology of new-born rats was evaluated by means of scanning electron microscopy in order to assess morphological changes after supplemental oxygen administration. After treatment, electron microscopy revealed many changes in the morphology of outer hair cells, if compared to normal rats of the same age. The results suggest that cochlear changes are similar to those previously observed in other regions and may be related to a vascular mechanism of hypoxia-ischaemia and neovascularization and/or an oxidative stress

MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function

p53 mutations have profound effects on non-small-cell lung cancer (NSCLC) resistance to chemotherapeutic treatments. Mutant p53 proteins are usually expressed at high levels in tumors, where they exert oncogenic functions. Here we show that p53R175H, a hotspot p53 mutant, induces microRNA (miRNA)-128-2 expression. Mutant p53 binds to the putative promoter of miR128-2 host gene, ARPP21, determining a concomitant induction of ARPP21 mRNA and miR-128-2. miR-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-fluorouracyl treatments. At the molecular level, miR-128-2 post-transcriptionally targets E2F5 and leads to the abrogation of its repressive activity on p21 waf1 transcription. p21 waf1 protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance

The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1

The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin. This enables aberrant recruitment of MALAT1 on VEGFA pre-mRNA and modulation of VEGFA isoforms expression. Interestingly, VEGFA-dependent expression signatures associate with ID4 expression specifically in basal-like breast cancers carrying TP53 mutations. Our results highlight the key role for MALAT1 in control of VEGFA isoforms expression in breast cancer cells expressing gain-of-function mutant p53 and ID4 proteins

Spacetime Noncommutativity and Antisymmetric Tensor Dynamics in the Early Universe

This paper investigates the possible cosmological implications of the presence of an antisymmetric tensor field related to a lack of commutatitivity of spacetime coordinates at the Planck era. For this purpose, such a field is promoted to a dynamical variable, inspired by tensor formalism. By working to quadratic order in the antisymmetric tensor, we study the field equations in a Bianchi I universe in two models: an antisymmetric tensor plus scalar field coupled to gravity, or a cosmological constant and a free massless antisymmetric tensor. In the first scenario, numerical integration shows that, in the very early universe, the effects of the antisymmetric tensor can prevail on the scalar field, while at late times the former approaches zero and the latter drives the isotropization of the universe. In the second model, an approximate solution is obtained of a nonlinear ordinary differential equation which shows how the mean Hubble parameter and the difference between longitudinal and orthogonal Hubble parameter evolve in the early universe.Comment: 25 pages, Revtex file, 4 figures in attachmen