Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Program verification and testing technologies

Program verification and testing techniques are crucial in fruitfully analyzing and validating complex software systems. This is an active research area and has produced various promising techniques in the last decade. However, many challenges lie ahead. We review the research area and summarize six papers selected from the Sixth International Symposium on Theoretical Aspects of Software Engineering (TASE 2012).     

Tool-supported enhancement of diagnosis in model-driven verification

We show on a case study from an autonomous aerospace context how to apply a game-based model-checking approach as a powerful technique for the verification, diagnosis, and adaptation of system behaviors based on temporal properties. This work is part of our contribution within the SHADOWS project, where we provide a number of enabling technologies for model-driven self-healing. We propose here to use GEAR, a game-based model checker, as a user-friendly tool that can offer automatic proofs of critical properties of such systems. Although it is a model checker for the full modal μ-calculus, it also supports derived, more user-oriented logics. With GEAR, designers and engineers can interactively investigate automatically generated winning strategies for the games, by this way exploring the connection between the property, the system, and the proof. This work has been partially supported by the European Union Specific Targeted Research Project SHADOWS (IST-2006-35157), exploring a Self-Healing Approach to Designing cOmplex softWare Systems. The project’s web page is at . This article is an extended version of Renner et al. [18] presented at ISoLA 2007, Poitiers, December 2007.     

Preface by the section editor

This special section is devoted to some of the novel approaches to hardware-like system verification that are currently being used in industry or the object of fielded research. The topics presented in this special section are based on a selection of the papers which appeared originally in the Proceedings of CHARME 2001, the Eleventh Advanced Research Working Conference on Correct Hardware Design and Verification Methods which took place in Livingston, Scotland, UK in September 2001. They are by no means a complete account of the numerous ways in which hardware and hardware-like systems are being subject to rigorous investigation, but they represent an interesting sample of today’s problems and of the techniques oriented around new uses of verification techniques. Published online: 10 April 2003     

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

Downexpression of miR-200c-3p Contributes to Achalasia Disease by Targeting the PRKG1 Gene

Achalasia is an esophageal smooth muscle motility disorder with unknown pathogenesis. Taking into account our previous results on the downexpression of miR-200c-3p in tissues of patients with achalasia correlated with an increased expression of PRKG1, SULF1, and SYDE1 genes, our aim was to explore the unknown biological interaction between these genes and human miR-200c-3p and if this relation could unravel their functional role in the etiology of achalasia. To search for putative miR-200c-3p binding sites in the 3′-UTR of PRKG1, SULF1 and SYDE1, a bioinformatics tool was used. To test whether PRKG1, SULF1, and SYDE1 are targeted by miR-200c-3p, a dual-luciferase reporter assay and quantitative PCR on HEK293 and fibroblast cell lines were performed. To explore the biological correlation between PRKG1 and miR-200c-3p, an immunoblot analysis was carried out. The overexpression of miR-200c-3p reduced the luciferase activity in cells transfected with a luciferase reporter containing a fragment of the 3′-UTR regions of PRKG1, SULF1, and SYDE1 which included the miR-200c-3p seed sequence. The deletion of the miR-200c-3p seed sequence from the 3′-UTR fragments abrogated this reduction. A negative correlation between miR-200c-3p and PRKG1, SULF1, and SYDE1 expression levels was observed. Finally, a reduction of the endogenous level of PRKG1 in cells overexpressing miR-200c-3p was detected. Our study provides, for the first time, functional evidence about the PRKG1 gene as a direct target and SULF1 and SYDE1 as potential indirect substrates of miR-200c-3p and suggests the involvement of NO/cGMP/PKG signaling in the pathogenesis of achalasia.     

Fining white wine with plant proteins: effects of fining on proanthocyanidins and aroma components

Plant-derived insoluble proteins (wheat gluten, and isolates from pea, lentil, and soybean) were used as fining agents in model white wine (made from Catalanesca grapes) after cold stabilization. Plant proteins were effective in giving a fast and remarkable decrease in turbidity. GC/MS and HPLC/MS approaches indicated that individual proteins had a different impact on the levels of compounds relevant to wine stability. Protein stability of wine was not affected by fining with plant proteins. Lentil proteins and gluten gave the best removal of monomeric and dimeric flavonol. Both caused a decrease in the total content of fermentative aroma compounds, such as ethyl esters, acetate esters, and alcohols. Lentil proteins had the highest impact on the aroma components, giving a marked decrease in aroma components. Gluten may thus be regarded as giving the best balance between fining efficacy and retention of aroma compounds. Also, gluten in the treated wines remained well below the suggested threshold for gluten-free foods. This study provides a methodological frame for thorough characterization of the impact of specific interventions on key wine components.     

The value of quality clues in the wine market: evidences from Lazio,Italy

The purpose of the paper is to contribute to understanding the role and effectiveness of different quality clues in the creation of value for the main wines of the Lazio region. The study presents a hedonic price model. An ordinary least squares and a quantile regression models were estimated. The latter is able to detect additional patterns related to the effects of the covariates. Prices are regressed on wine color, sub-regional area of origin, the type of certification of origin, and on experts' evaluation. The analysis is based on data released by three major Italian wine guides: Gambero Rosso, l'Espresso, and AIS (Italian Sommelier Association). Results show that: (i) white and red wines follow two different price patterns; (ii) prices are correlated with experts' evaluation; (iii) the impact of the latter is higher when other quality clues, such as geographical indications, are less effective; (iv) the role of different quality clues varies at different price levels and it is different for red and white wines; overall, wines from the Lazio region are associated with poor to mediocre quality levels. This may explain the decline in reputation and in market share that these wines are experiencing after centuries of popularity.