Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos.

The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physical properties of the embryo to generate collective dynamics. Here, we show that synchronization of the cell cycle in Drosophila embryos requires accurate nuclear positioning, which is regulated by the cell-cycle oscillator through cortical contractility and cytoplasmic flows.

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine.

Intrahepatic cholangiocarcinoma (ICC) is one of the most lethal liver cancers. Late diagnosis and chemotherapy resistance contribute to the scarce outfit and poor survival. Resistance mechanisms are still poorly understood.

Arytenoid Fixation in Laryngeal Cancer: Radiological Pictures and Clinical Correlations with Respect to Conservative Treatments.

The aim of this retrospective study was to identify different radiological features in intermediate⁻advanced laryngeal cancer (LC) associated with arytenoid fixation, in order to differentiate cases still safely amenable to conservative treatment by partial laryngectomy or chemoradiotherapy. : 29 consecutive patients who underwent open partial horizontal laryngectomies (OPHLs), induction chemotherapy followed by radiotherapy in the case of >50% response (IC + RT) or total laryngectomy were classified as: pattern I (supraglottic LC fixing the arytenoid due to weight effect), pattern II (glottic LC involving the posterior paraglottic space and spreading toward the crico-arytenoid joint and infraglottic extension <10 mm), pattern III (glottic-infraglottic LC involving the crico-arytenoid joint and infraglottic extension >10 mm) and pattern IV (transglottic and infraglottic LC with massive crico-arytenoid unit involvement, reaching the hypopharyngeal submucosa). All glottic cancers treated with surgery were studied by a cross sectional approach.

Immunotherapy Associated Pulmonary Toxicity: Biology Behind Clinical and Radiological Features.

The broader use of immune checkpoint blockade in clinical routine challenges clinicians in the diagnosis and management of side effects which are caused by inflammation generated by the activation of the immune response. Nearly all organs can be affected by immune-related toxicities. However, the most frequently reported are: fatigue, rash, pruritus, diarrhea, nausea/vomiting, arthralgia, decreased appetite and abdominal pain.

Proton pump inhibitors promote the growth of androgen-sensitive prostate cancer cells through ErbB2, ERK1/2, PI3K/Akt, GSK-3β signaling and inhibition of cellular prostatic acid phosphatase.

Prostate cancer (PCa) is one of the most common cancer in men. Although hormone-sensitive PCa responds to androgen-deprivation, there are no effective therapies for castration-resistant PCa. It has been recently suggested that proton pump inhibitors (PPIs) may increase the risk of certain cancers; however, association with PCa remains elusive.

TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers.

Objective: Relapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities.

One tool to find them all: a case of data integration and querying in a distributed LIMS platform.

In the last years, Laboratory Information Management Systems (LIMS) have been growing from mere inventory systems into increasingly comprehensive software platforms, spanning functionalities as diverse as data search, annotation and analysis. Our institution started in 2011 a LIMS project named the Laboratory Assistant Suite with the purpose of assisting researchers throughout all of their laboratory activities, providing graphical tools to support decision-making tasks and building complex analyses on integrated data. The modular architecture of the system exploits multiple databases with different technologies.

TFEB controls vascular development by regulating the proliferation of endothelial cells.

Transcription factor TFEB is thought to control cellular functions-including in the vascular bed-primarily via regulation of lysosomal biogenesis and autophagic flux. Here, we report that TFEB also orchestrates a non-canonical program that controls the cell cycle/VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB depletion halts proliferation at the G1-S transition by inhibiting the CDK4/Rb pathway.

Functional fat injection under local anesthesia to treat severe postsurgical dysphagia, case report.

Background: In this study, we present the first application of functional fat injection performed under local anesthesia in the treatment of severe dysphagia secondary to head and neck cancer surgery.

Methods: Functional fat injection was performed using a transcervical approach. Control of injection depth and site was performed through a transnasal flexible endoscope.

Irreversible Activation of Rho-activated Kinases Resulted from Evolution of Proteolytic Sites within Disordered Regions in Coiled-coil Domain.

Activation of Rho-associated protein kinase 1 (ROCK1) and myotonic dystrophy kinase-related CDC42-binding kinase alpha (MRCKα) by caspases during apoptosis in vertebrates represents a prototypical example of co-option of kinases by proteases. How caspases acquired the ability to control these proteins during evolution of vertebrates is still unknown. Here, we report a phylogenetic and molecular study on the acquisition of caspase-cleavage sites in the family of Rho-activated kinases (RaKs).

RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples.

Single-molecule RNA fluorescence in situ hybridization (smFISH) represents a promising approach to quantify the expression of clinically useful biomarkers in tumor samples. However, routine application of smFISH to formalin-fixed, paraffin-embedded (FFPE) samples is challenging due to the low signal intensity and high background noise. Here we present RollFISH, a method combining the specificity of smFISH with the signal boosting of rolling circle amplification.

Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test.

Objective: Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme.

Methods: Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders).

Rationale for the use of metronomic chemotherapy in gastrointestinal cancer.

Introduction: Metronomic chemotherapy (mCT) is endowed with various properties, ranging from antiangiogenic to immunomodulation, and may revert tumor resistance to conventional drug administration. A variety of antineoplastic agents displayed activity when administered with metronomic schedules in preclinical models of gastrointestinal cancers. However, most of the field is still unexplored.

A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma.

Background: Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS.

Methods: Eligible patients had received ≥ one line of chemotherapy.

Survivin-peptide vaccination elicits immune response after allogeneic nonmyeloablative transplantation: a safe strategy to enhance the graft versus tumor effect.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an adoptive immunotherapy strategy whose effectiveness relies on graft-versus-tumor (GVT) effect. We explored the feasibility of enhancing GVT after allo-HCT by peptide vaccination. Two myeloma patients were transplanted with a fludarabine-total body irradiation conditioning regimen and vaccinated with an HLA-A*0201-restricted modified survivin nonapeptide, plus montanide as adjuvant.

The Dilemma of HER2 Double-equivocal Breast Carcinomas: Genomic Profiling and Implications for Treatment.

The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 guidelines for HER2 assessment have increased the number of HER2 equivocal breast carcinomas following in situ hybridization reflex testing, that is, HER2 "double equivocal" (equivocal protein expression and equivocal gene copy number). Forty-five double-equivocal carcinomas were subjected to Prosigna analysis. Twenty-seven cases were investigated for the expression of genes found to be differentially expressed between estrogen receptor (ER)-positive/HER2-positive (N=22) and ER-positive/HER2-negative (N=22) control cases.

Next generation immune-checkpoints for cancer therapy.

The discovery and clinical application of immune-checkpoint inhibitors has dramatically improved the treatments, outcomes and therapeutic concepts in multiple tumor settings. This breakthrough was mainly based on monoclonal antibodies blocking the inhibitory molecule CTLA-4 and or the PD-1/PD-L1 axis, with the aim of counteracting major tumor immune evasion mechanisms. Even acknowledging these important successes, not all the patients benefit from these treatments.

A predictive score for optimal cytoreduction at interval debulking surgery in epithelial ovarian cancer: a two- centers experience.

Background: Optimal cytoreduction (macroscopic Residual Tumor, RT = 0) is the best survival predictor factor in epithelial ovarian cancer (EOC). It doesn't exist a consolidated criteria to predict optimal surgical resection at interval debulking surgery (IDS). The aim of this study is to develop a predictive model of complete cytoreduction at IDS.

Computer-based self-training for CT colonography with and without CAD.

Objectives: To determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning.

Methods: Institutional review board approval and patients' informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres.

JOURNAL CLUB: Extracolonic Findings at CT Colonography: Systematic Review and Meta-Analysis.

Objective: The purpose of this study was to perform a systematic review and meta-analysis of published studies on CT colonography (CTC) in which extracolonic findings were assessed.

Materials And Methods: A systematic review of studies of screening CTC and of CTC to evaluate symptoms (1994-June 2017) was conducted to estimate the rate of extra-colonic findings and associated additional workup recommendations. The primary outcome was potentially important extracolonic findings, defined as CT Colonography Imaging Reporting and Data System (C-RADS) category E4 or as having high clinical importance (if C-RADS was not used).

Consensus guidelines for the use and interpretation of angiogenesis assays.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations.

Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study.

Background: Aflibercept combined with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) as second-line treatment of metastatic colorectal cancer (mCRC) significantly improved survival compared with FOLFIRI alone in the pivotal VELOUR (aflibercept vs. placebo in combination with irinotecan and 5-fluorouracil in the treatment of patients with metastatic colorectal cancer after failure of an oxaliplatin-based regimen) trial. No quality-of-life assessment was performed in VELOUR; therefore, the ASQoP (Aflibercept Safety and Quality-of-Life Program) trial was designed to capture the safety and health-related quality of life (HRQL).

PARP Inhibitors in Ovarian Cancer.

Background: Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients.

Objectives: The study aimed to highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis.