Impaired neutrophil-mediated cell death drives Ewing's Sarcoma in the background of Down syndrome.

Introduction: Ewing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made.

Methods: Here, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches.

FOXA1 regulates alternative splicing in prostate cancer.

Dysregulation of alternative splicing in prostate cancer is linked to transcriptional programs activated by AR, ERG, FOXA1, and MYC. Here, we show that FOXA1 functions as the primary orchestrator of alternative splicing dysregulation across 500 primary and metastatic prostate cancer transcriptomes. We demonstrate that FOXA1 binds to the regulatory regions of splicing-related genes, including HNRNPK and SRSF1.

Integrative genomic and transcriptomic analyses illuminate the ontology of HER2-low breast carcinomas.

Background: The "HER2-low" nomenclature identifies breast carcinomas (BCs) displaying a HER2 score of 1+/2+ in immunohistochemistry and lacking ERBB2 amplification. Whether HER2-low BCs (HLBCs) constitute a distinct entity is debated.

Methods: We performed DNA and RNA high-throughput analysis on 99 HLBC samples (n = 34 cases with HER2 score 1+/HLBC-1, n = 15 cases with HER2 score 2+ and ERBB2 not amplified/HLBC-2N, and n = 50 cases with score 2+ and ERBB2 copy number in the equivocal range/HLBC-2E).

HaTSPiL: A modular pipeline for high-throughput sequencing data analysis.

Background: Next generation sequencing methods are widely adopted for a large amount of scientific purposes, from pure research to health-related studies. The decreasing costs per analysis led to big amounts of generated data and to the subsequent improvement of software for the respective analyses. As a consequence, many approaches have been developed to chain different software in order to obtain reliable and reproducible workflows.

Intragenic DNA methylation prevents spurious transcription initiation.

In mammals, DNA methylation occurs mainly at CpG dinucleotides. Methylation of the promoter suppresses gene expression, but the functional role of gene-body DNA methylation in highly expressed genes has yet to be clarified. Here we show that, in mouse embryonic stem cells, Dnmt3b-dependent intragenic DNA methylation protects the gene body from spurious RNA polymerase II entry and cryptic transcription initiation.

High-throughput single-base resolution mapping of RNA 2΄-O-methylated residues.

Functional characterization of the transcriptome requires tools for the systematic investigation of RNA post-transcriptional modifications. 2΄-O-methylation (2΄-OMe) of the ribose moiety is one of the most abundant post-transcriptional modifications of RNA, although its systematic analysis is difficult due to the lack of reliable high-throughput mapping methods. We describe here a novel high-throughput approach, named 2OMe-seq, that enables fast and accurate mapping at single-base resolution, and relative quantitation, of 2΄-OMe modified residues.

The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression.

In mammals the cell-cycle progression through the G1 phase is a tightly regulated process mediated by the transcriptional activation of early genes in response to mitogenic stimuli, whose dysregulation often leads to tumorigenesis. We here report the discovery by RNA-seq of cell-cycle regulated (CCR) long intergenic non-coding RNAs (lincRNAs), potentially involved in the control of the cell-cycle progression. We identified 10 novel lincRNAs expressed in response to serum treatment in mouse embryonic fibroblasts (MEFs) and in BALB/c fibroblasts, comparably to early genes.

Methylation-assisted bisulfite sequencing to simultaneously map 5fC and 5caC on a genome-wide scale for DNA demethylation analysis.

Active DNA demethylation is mediated by ten-eleven translocation (TET) proteins that progressively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). We have developed a methylation-assisted bisulfite sequencing (MAB-seq) method that enables direct genome-scale mapping and quantification of 5fC and 5caC marks together at single-base resolution. In bisulfite sequencing (BS), unmethylated cytosine residues (Cs), 5fCs and 5caCs, are converted to uracil and cannot be discriminated from each other.

TET1 is controlled by pluripotency-associated factors in ESCs and downmodulated by PRC2 in differentiated cells and tissues.

Ten-eleven translocation (Tet) genes encode for a family of hydroxymethylase enzymes involved in regulating DNA methylation dynamics. Tet1 is highly expressed in mouse embryonic stem cells (ESCs) where it plays a critical role the pluripotency maintenance. Tet1 is also involved in cell reprogramming events and in cancer progression.

Single-Base Resolution Analysis of 5-Formyl and 5-Carboxyl Cytosine Reveals Promoter DNA Methylation Dynamics.

Ten eleven translocation (Tet) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC can be further excised by thymine-DNA glycosylase (Tdg). Here, we present a genome-wide approach, named methylation-assisted bisulfite sequencing (MAB-seq), that enables single-base resolution mapping of 5fC and 5caC and measures their abundance.

TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway.

Ten eleven translocation (TET) enzymes catalyse the oxidative reactions of 5-methylcytosine (5mC) to promote the demethylation process. The reaction intermediate 5-hydroxymethylcytosine (5hmC) has been shown to be abundant in embryonic stem cells and tissues but strongly depleted in human cancers. Genetic mutations of TET2 gene were associated with leukaemia, whereas TET1 downregulation has been shown to promote malignancy in breast cancer.

Molecular characterization of toxigenic Clostridium difficile in a northern Italian hospital.

Clostridium difficile is responsible for more than 90 % of cases of antibiotic-associated diarrhea and pseudomembranous colitis. The most important virulence factors are two toxins called enterotoxin A and cytotoxin B; some C. difficile strains contain the C.

Erlotinib: early clinical development in brain cancer.

Introduction: Glioblastoma (GBM) is the most common brain cancer in adults. It is also, unfortunately, the most aggressive type and the least responsive to therapy. Overexpression of EGFR and/or EGFRvIII is frequently found in GBM and is frequently associated with the more malignant phenotype of the disease and a poor clinical outcome.

ASCO 2013: bevacizumab and glioblastoma--a marriage dissolution?

The prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months.

Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.

The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESCs), but its function in these cells is unknown. Through genome-wide analysis of Dnmt3L knockdown in ESCs, we found that Dnmt3L is a positive regulator of methylation at the gene bodies of housekeeping genes and, more surprisingly, is also a negative regulator of methylation at promoters of bivalent genes.

Genome-wide analysis identifies a functional association of Tet1 and Polycomb repressive complex 2 in mouse embryonic stem cells.

Background: Ten-Eleven Translocation (TETs)proteins mediate the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 is expressed at high levels in mouse embryonic stem cells (ESCs), where it mediates the induction of 5hmC decoration on gene-regulatory elements. While the function of Tet1 is known, the mechanisms of its specificity remain unclear.

Outcome of lumbar intervertebral foraminal stenosis surgery and depression.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS).

Protracted low dose of oral vinorelbine and temozolomide with whole-brain radiotherapy in the treatment for breast cancer patients with brain metastases.

Purpose: The management of brain metastases (BM) from breast cancer (BC) needs to be improved, and new therapeutic strategies are urgently requested. In this view, we have evaluated the efficacy, tolerability, and safety of concurrent low protracted dose of temozolomide (TMZ), metronomic oral vinorelbine (VNB), and radiotherapy in BC women with previously untreated BM.

Methods: Thirty-six patients with newly diagnosed BM were treated with TMZ orally administered at a dose of 75 mg/m(2) during whole-brain radiotherapy, followed by 4 weeks off-therapy and a subsequent administration of oral 70 mg/m(2) VNB fractionated in days 1, 3, and 5, weekly for three consecutive weeks plus TMZ at 75 mg/m(2) on days 1-21, all every 4 weeks for up to 12 additional cycles.

Trigeminal neuralgia and persistent trigeminal artery.

We report a case of trigeminal neuralgia caused by persistent trigeminal artery (PTA) associated with asymptomatic left temporal cavernoma. Our patient presented unstable blood hypertension and the pain of typical trigeminal neuralgia over the second and third divisions of the nerve in the right side of the face. The attacks were often precipitated during physical exertion.

The effect of inappropriate therapy on bacteremia by ESBL-producing bacteria.

Objective: To describe the impact of empiric appropriate treatment and the risk factors associated with mortality in patients with bacteremia by E. coli, K. pneumoniae and P.

Anatomical variant of origin of ophthalmic artery: case report.

We report on one case of variant origin of right ophthalmic artery (OA) from C4 choroidal segment of the right supraclinoid internal carotid artery. A 41-year-old woman affected by bitemporal hemianopsia performed Magnetic Resonance Imaging with gadolinium showing tuberculum sellae meningioma. During angiography we observed this variant of origin of OA.

A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma.

In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.

Use of a collagen biomatrix (TissuDura) for dura repair: a long-term neuroradiological and neuropathological evaluation.

Purpose: The aim of this study was to evaluate the clinical, neuroradiological, and neuropathological outcomes of patients treated with equine collagen foil (TissuDura) as a dura mater substitute during cranial and spinal neurosurgical procedures.

Materials And Methods: All patients treated at the Department of Neurosurgery of the Second University of Naples with TissuDura between 2005 and 2009 were included. Dural reconstruction was performed using TissuDura, overlaid 1 cm over the dural defect with additional fixation using fibrin glue.