Successful treatment of Neuroblastoma in an adolescent with intra-arterial embolization before surgery

Abstract Introduction Neuroblastoma in the adolescent is characterized by indolent growth and poor outcome. Surgical resection of the tumor is an essential part of the multimodality treatment. Surgical complications depend on the presence of Image Defined Risk Factors (IDRFs). Methods We present an adolescent with pelvic neuroblastoma and epidural compression. To facilitate tumor resection, the patient underwent preoperative selective embolization. Results After selective embolization a subsequent complete resection etraspinal localisation was performed without complication with complete remission after 2 years. Conclusions Preoperative embolization is a safe and feasible technique that can help pediatric surgical oncologist to reduce complications IDRFs-related

Exosomes from Plasma of Neuroblastoma Patients Contain Doublestranded DNA Reflecting the Mutational Status of Parental Tumor Cells

Neuroblastoma (NB) is an aggressive infancy tumor, leading cause of death among preschool age diseases. Here we focused on characterization of exosomal DNA (exo-DNA) isolated from plasma cell-derived exosomes of neuroblastoma patients, and its potential use for detection of somatic mutations present in the parental tumor cells. Exosomes are small extracellular membrane vesicles secreted by most cells, playing an important role in intercellular communications. Using an enzymatic method, we provided evidence for the presence of double-stranded DNA in the NB exosomes. Moreover, by whole exome sequencing, we demonstrated that NB exo-DNA represents the entire exome and that it carries tumor-specific genetic mutations, including those occurring on known oncogenes and tumor suppressor genes in neuroblastoma (ALK, CHD5, SHANK2, PHOX2B, TERT, FGFR1, and BRAF). NB exo-DNA can be useful to identify variants responsible for acquired resistance, such as mutations of ALK, TP53, and RAS/MAPK genes that appear in relapsed patients. The possibility to isolate and to enrich NB derived exosomes from plasma using surface markers, and the quick and easy extraction of exo-DNA, gives this methodology a translational potential in the clinic. Exo-DNA can be an attractive non-invasive biomarker for NB molecular diagnostic, especially when tissue biopsy cannot be easily available

SOS - Piattaforme e Impatti Offshore Report tecnico. I Campagna oceanografica 13-19 maggio 2018

Nell’ambito della convenzione stipulata tra il Ministero dell’Ambiente e della Tutela del Territorio e del Mare (MATTM) e il Dipartimento Scienze del Sistema Terra e Tecnologie per l’Ambiente del CNR (DTA), “SOS-Piattaforme & Impatti Off-Shore” è stata prevista un’indagine ambientale nell’area di interesse di 10 piattaforme off-shore ENI presenti nella zona costiera compresa tra Ravenna e Pescara. In particolare, le attività previste fanno riferimento alla sezione Macro-Attività D della convenzione. Obiettivo principale delle attività di indagine è lo studio della modalità di dispersione in mare delle acque di produzione e una caratterizzazione chimico-fisica ed ecotossicologica delle stesse e delle matrici ambientali (acqua, sedimenti, biota) che ricevono lo scarico. L’attività di ricerca prevede un approccio di analisi ‘integrato’ di tipo chimico, e fisico per lo studio degli effetti della dispersione in mare delle acque di produzione ed ecotossicologico per la valutazione di eventuali danni a organismi selezionati dopo la loro esposizione all’acqua di produzione e all’acqua di mare prelevata a diverse distanze dal punto di scarico. Inoltre, l’azione di ricerca è volta alla definizione di un approccio metodologico innovativo per le future attività di monitoraggio da effettuare attorno alle piattaforme off-shore per la verifica di processi e meccanismi di impatto sull’ambiente e l’ecosistema principalmente da parte dello scarico di acque di produzione. Questa relazione descrive le attività di campionamento e acquisizione dati effettuate durante la I Campagna Oceanografica nell’ambito della convenzione “SOS-Piattaforme & Impatti Off-Shore”. La campagna di campionamento si è svolta nel periodo 13-19 maggio 2018 a bordo del mezzo navale ROCCO UNO della Marine Consulting International e dei mezzi navali ENI KING DAVID e MARE GRIGIO

Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees

<p>Abstract</p> <p>Background</p> <p>Esthesioneuroblastoma (ENB) is a rare, aggressive tumor with no established treatment in children. We analyzed a series of pediatric ENB patients with the aim of improving our knowledge of this disease.</p> <p>Methods</p> <p>9 patients (6 males; age 0.9-18 years, median 9.9) were identified by searching the AIEOP (<it>Italian Association of Pediatric Hematology and Oncology</it>) registry and the national databases of rare tumors, soft tissue sarcomas (STS) and neuroblastomas. The data on the cases included in STS treatment protocols were collected prospectively and histology was centrally reviewed; the data and histology concerning the other children were reviewed for the purpose of this analysis.</p> <p>Results</p> <p>All tumors occurred in the sinonasal region with bone erosion (7 patients) and intracranial (4) or intraorbital (4) extension. Three patients were in Kadish stage B, and 6 in stage C. Complete tumor resection was very difficult to achieve, but adding chemotherapy and radiotherapy enabled tumor control in 8 patients. Response to chemotherapy was evident in 5/7 evaluable cases. Radiotherapy (48.5-60 Gy) was delivered in all children but one, due to early disease progression. With a median follow-up of 13.4 years (range 9.2-22.9), 7 patients are alive in 1^stand one in 2nd complete remission. All surviving patients developed treatment-related sequelae, the most frequent being endocrine dysfunctions (4 patients) and craniofacial growth impairments (4 patients).</p> <p>Conclusions</p> <p>Our findings confirm that ENB in children has an aggressive presentation, but multimodal therapy can cure most patients. Our results are encouraging but future strategies must optimize treatment in terms of survival and related morbidities.</p

Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma is the most common, pediatric, extra-cranial, malignant solid tumor. Despite multimodal therapeutic protocols, outcome for children with a high-risk clinical phenotype remains poor, with long-term survival still less than 40%. Hereby, we evaluated the potential of non-coding RNA expression to predict outcome in high-risk, stage 4 neuroblastoma.</p> <p>Methods</p> <p>We analyzed expression of 481 Ultra Conserved Regions (UCRs) by reverse transcription-quantitative real-time PCR and of 723 microRNAs by microarrays in 34 high-risk, stage 4 neuroblastoma patients.</p> <p>Results</p> <p>First, the comparison of 8 short- versus 12 long-term survivors showed that 54 UCRs were significantly (<it>P </it>< 0.0491) over-expressed in the former group. For 48 Ultra Conserved Region (UCRs) the expression levels above the cut-off values defined by ROC curves were strongly associated with good-outcome (OS: 0.0001 <<it>P </it>< 0.0185, EFS: 0.0001 <<it>P </it>< 0.0491). Then we tested the Transcribed-UCR (T-UCR) threshold risk-prediction model on an independent cohort of 14 patients. The expression profile of 28 T-UCRs was significantly associated to prognosis and at least 15 up-regulated T-UCRs are needed to discriminate (<it>P </it>< 0.0001) short- from long-survivors at the highest sensitivity and specificity (94.12%). We also identified a signature of 13 microRNAs differently expressed between long- and short-surviving patients. The comparative analysis of the two classes of non-coding RNAs disclosed that 9 T-UCRs display their expression level that are inversely correlated with expression of 5 complementary microRNAs of the signature, indicating a negative regulation of T-UCRs by direct interaction with microRNAs. Moreover, 4 microRNAs down-regulated in tumors of long-survivors target 3 genes implicated in neuronal differentiation, that are known to be over-expressed in low-risk tumors.</p> <p>Conclusions</p> <p>Our pilot study suggests that a deregulation of the microRNA/T-UCR network may play an important role in the pathogenesis of neuroblastoma. After further validation on a larger independent set of samples, such findings may be applied as the first T-UCR prognostic signature for high-risk neuroblastoma patients.</p

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM