The landscape of cancer-rewired GPCR signaling axes.

We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns.

Mapping functional to morphological variation reveals the basis of regional extracellular matrix subversion and nerve invasion in pancreatic cancer.

Intratumor morphological heterogeneity of pancreatic ductal adenocarcinoma (PDAC) predicts clinical outcomes but is only partially understood at the molecular level. To elucidate the gene expression programs underpinning intratumor morphological variation in PDAC, we investigated and deconvoluted at single cell level the molecular profiles of histologically distinct clusters of PDAC cells. We identified three major morphological and functional variants that co-exist in varying proportions in all PDACs, display limited genetic diversity, and are associated with a distinct organization of the extracellular matrix: a glandular variant with classical ductal features; a transitional variant displaying abortive ductal structures and mixed endodermal and myofibroblast-like gene expression; and a poorly differentiated variant lacking ductal features and basement membrane, and showing neuronal lineage priming.

Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide.

Histone-modifying enzymes depend on the availability of cofactors, with acetyl-coenzyme A (CoA) being required for histone acetyltransferase (HAT) activity. The discovery that mitochondrial acyl-CoA-producing enzymes translocate to the nucleus suggests that high concentrations of locally synthesized metabolites may impact acylation of histones and other nuclear substrates, thereby controlling gene expression. Here, we show that 2-ketoacid dehydrogenases are stably associated with the Mediator complex, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails.

Native extracellular matrix probes to target patient- and tissue-specific cell-microenvironment interactions by force spectroscopy.

Atomic Force Microscopy (AFM) is successfully used for the quantitative investigation of the cellular mechanosensing of the microenvironment. To this purpose, several force spectroscopy approaches aim at measuring the adhesive forces between two living cells and also between a cell and an appropriate reproduction of the extracellular matrix (ECM), typically exploiting tips suitably functionalised with single components ( collagen, fibronectin) of the ECM. However, these probes only poorly reproduce the complexity of the native cellular microenvironment and consequently of the biological interactions.

Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells.

Objective: Pancreatic ductal adenocarcinomas (PDACs) include heterogeneous mixtures of low-grade cells forming pseudoglandular structures and compact nests of high-grade cells organised in non-glandular patterns. We previously reported that low-grade PDAC cells display high expression of interferon regulatory factor 1 (IRF1), a pivotal transcription factor of the interferon (IFN) system, suggesting grade-specific, cell-intrinsic activation of IFN responses. Here, we set out to determine the molecular bases and the functional impact of the activation of IFN-regulated responses in human PDACs.

The REAL (REctal Anastomotic Leak) score for prediction of anastomotic leak after rectal cancer surgery.

Background: Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic leak is a key component of surgical planning, including the opportunity to create a defunctioning stoma.

Objective: The purpose of this study was to identify and quantify the risk factors for anastomotic leak to minimize risk by either not restoring bowel continuity or protecting the anastomosis with a temporary diverting stoma.

Transhiatal distal esophagectomy for Siewert type II cardia cancer can be a treatment option in selected patients.

Background: While surgical treatment of Siewert I and III (S1,S3) Esophagogastric Junction (EGJ) cancer is codified, the efficay of transhiatal procedure with anastomosis in the lower mediastinum for Siewert II (S2) still remains a dibated topic.

Methods: This is a large multicenter retrospective study. The results of 598 consecutive patients submitted to resection with curative intent from January 2000 to January 2017 were reported.

Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

Aim: To investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.

Methods: We proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate.

Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a.

EVOLUTION OF THE IEC AND EN STANDARDS FOR INDIVIDUAL MONITORING OF IONISING RADIATION.

This article presents the evolution of the International Electrotechnical Commission (IEC) and the European standards for individual monitoring of ionising radiation issued, respectively, from the committees IEC/Sub Committee 45B and European Committee for Electro-technical Standardization/Technical Committee 45B 'Radiation protection instrumentation'. Standards for passive individual photon and beta dosimetry systems as well as those for active individual monitors are discussed. A neutron ambient dose equivalent (rate) meter standard and a technical report concerning the determination of uncertainty in measurement are also covered.

Bariatric surgery improves urinary incontinence but not anorectal function in obese women.

Background: While the association between obesity and urinary incontinence (UI) in women has been clearly documented, the relationship with anal incontinence (AI) is less well defined; moreover, while bariatric surgery has been shown to improve UI, its effect on AI is still unclear.

Methods: A total of 32 obese women were studied by means of PFDI-20 and PFIQ-7 questionnaires and anorectal manometry before and after bariatric surgery and compared with 71 non-obese women.

Results: Obese women showed worse overall questionnaire results (OR 5.

IEC standards for individual monitoring of ionising radiation.

This paper presents IEC/SC 45B 'Radiation protection instrumentation' and its standards for individual monitoring of ionising radiation: IEC 61526 Ed. 3 for active personal dosemeters and IEC 62387-1 for passive integrating dosimetry systems. The transposition of these standards as CENELEC (European) standards is also discussed together with the collaboration between IEC/SC 45B and ISO/TC 85/SC 2.