TCTN2:a novel tumor marker with oncogenic properties

Tectonic family member 2 (TCTN2) encodes a transmembrane protein that belongs to the tectonic family, which is involved in ciliary functions. Previous studies have demonstrated the role of tectonics in regulating a variety of signaling pathways at the transition zone of cilia. However, the role of tectonics in cancer is still unclear. Here we identify that TCTN2 is overexpressed in colorectal, lung and ovary cancers. We show that different cancer cell lines express the protein that localizes at the plasma membrane, facing the intracellular milieu. TCTN2 over-expression in cancer cells resulted in an increased ability to form colonies in an anchorage independent way. On the other hand, downregulation of TCTN2 using targeted epigenetic editing in cancer cells significantly reduced colony formation, cell invasiveness, increased apoptosis and impaired assembly of primary cilia. Taken together, our results indicate that TCTN2 acts as an oncogene, making it an interesting cancer-associated protein and a potential candidate for therapeutic applications.</p

Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

<p>Abstract</p> <p>Background</p> <p>Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma.</p> <p>Methods</p> <p>Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m²daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival.</p> <p>Results</p> <p>Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable.</p> <p>Conclusion</p> <p>Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future.</p> <p>Trial registration</p> <p>NCT00953394</p

Science case study and scientific simulations for the enhanced X-ray Timing Polarimetry mission, eXTP

The X-ray astronomy mission eXTP (enhanced X-ray Timing Polarimetry) is designed to study matter under extreme conditions of density, gravity and magnetism. Primary goals are the determination of the equation of state (EoS) of matter at supranuclear density, the physics in extremely strong magnetic fields, the study of accretion in strong-field gravity (SFG) regime. Primary targets include isolated and binary neutron stars, strong magneticfield systems like magnetars, and stellar-mass and supermassive black holes. In this paper we report about key observations and simulations with eXTP on the primary objectives involving accretion under SFG regimes and determination of NS-Eo

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

AIH sera recognize UNQ9419 and CHAD.

<p>(A), SDS-PAGE (left panel) and western blot against anti-His antibody analysis (right panel) of the purified UNQ9419 and CHAD recombinant proteins. (B), western blot analysis of the purified UNQ9419 and CHAD recombinant proteins against sera from AIH patients (left panel) and no AIH subjects (right panel), respectively.</p

Evaluation of AIH-associated autoantigens.

<p>(A) The heatmap summarizes the recognition frequencies among different sample groups (AIH, HD and the VH) for the new four autoantigens out of the 31 candidates selected with the proposed bioinformatic strategy after DELFIA screening. Colour intensity denotes the degree of recognition frequency within the sample group. (B) Recognition frequency for two of the four autoantigens, that were statistical significant. (C) Signals distribution detected for each of the new two proteins are displayed. Statistical differences in recognition frequency (ChiSquare test) and in signal intensity (t test) are denoted as single (p<0,05), double (p<0,001) or triple stars (p <0,0001). (D), ROC curve of the biomarker candidates exhibited AUCs of 0.899 (SE = 87.5% and SP = 77.7%), 0.782 (SE = 65.0% and SP = 81.5%) for UNQ9419 and CHAD, respectively. The arrows denote best cut-off points. Combo curve represents the combination, UNQ9419+CHAD, which exhibited AUC of 0.915 (SE = 95.0% and SP = 76.2%).</p