Oncogenic Functions of Alternatively Spliced Isoform in Retroperitoneal Liposarcoma.

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment, while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark.

Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research.

Liposarcoma is one of the most common soft tissue sarcomas, however, its occurrence rate is still rare compared to other cancers. Due to its rarity, experiments are an essential approach to elucidate liposarcoma pathobiology. Conventional cell culture-based research (2D cell culture) is still playing a pivotal role, while several shortcomings have been recently under discussion.

Extracellular Vesicle - MDM2-DNA as a Potential Liquid Biopsy Biomarker for Disease Identification in Retroperitoneal Liposarcoma.

Objective: We aimed to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus post-operative surveillance visits. To determine whether EV-MDM2 may serve as a possible first-ever biomarker of liposarcoma recurrence.

Background: A hallmark of well-differentiated and de-differentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification, with recurrence rates of >50% even after complete resection.

Comparison of three-dimensional cell culture techniques of dedifferentiated liposarcoma and their integration with future research.

Dedifferentiated liposarcoma is a formidable sarcoma subtype due to its high local recurrence rate and resistance to medical treatment. While 2D cell cultures are still commonly used, 3D cell culture systems have emerged as a promising alternative, particularly scaffold-based techniques that enable the creation of 3D models with more accurate cell-stroma interactions. To investigate how 3D structures with or without the scaffold existence would affect liposarcoma cell lines growth morphologically and biologically.

Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient supplies. PDAC aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor microenvironment. Dysregulation of the onco-suppressor miR-15a has been extensively documented in PDAC.

A plasma miRNA-based classifier for small cell lung cancer diagnosis.

Introduction: Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges.

Three dimensional models of dedifferentiated liposarcoma cell lines: scaffold-based and scaffold-free approaches.

Sarcomas are rare malignancies, the number of reports is limited, and this rarity makes further research difficult even though liposarcoma is one of major sarcomas. 2D cell culture remains an important role in establishing basic tumor biology research, but its various shortcomings and limitations are still of concern, and it is now well-accepted that the behavior of 3D-cultured cells is more reflective of in vivo cellular responses compared to 2D models. This study aimed to establish 3D cell culture of liposarcomas using two different methods: scaffold-based (Matrigel extracellular matrix [ECM] scaffold method) and scaffold-free (Ultra-low attachment [ULA] plate).

Emissions of pharmaceuticals and plant protection products to the lagoon of Venice: development of a new emission inventory.

Estimating the emissions of chemical pollutants to water is a fundamental step for the development and application of effective and sustainable management strategies of water resources, but methods applied so far to build chemicals inventories at the European or national scale show several limitations when applied at the local scale. The issue is particularly relevant when considering contaminants of emerging concern (CECs), whose environmental releases and occurrence are still poorly studied and understood. In this work, an approach to estimate water emissions of nine active pharmaceutical ingredients (APIs) and ten most applied plant protection products (PPPs) is presented, considering proxy indicators (e.

Extracellular Vesicle MicroRNA in Malignant Pleural Effusion.

Lung and breast cancer are the two most common causes of malignant pleural effusion (MPE). MPE diagnosis plays a crucial role in determining staging and therapeutic interventions in these cancers. However, our understanding of the pathogenesis and progression of MPE at the molecular level is limited.

In situ hybridization to detect DNA amplification in extracellular vesicles.

EVs have emerged as an important component in tumour initiation, progression and metastasis. Although notable progresses have been made, the detection of EV cargoes remain significantly challenging for researchers to practically use; faster and more convenient methods are required to validate the EV cargoes, especially as biomarkers. Here we show, the possibility of examining embedded EVs as substrates to be used for detecting DNA amplification through ultrasensitive in situ hybridization (ISH).

Dissecting the Inner Galaxy with γ-Ray Pixel Count Statistics.

We combine adaptive template fitting and pixel count statistics in order to assess the nature of the Galactic Center excess in Fermi-LAT data. We reconstruct the flux distribution of point sources well below the Fermi-LAT detection threshold, and measure their radial and longitudinal profiles in the inner Galaxy. We find that all point sources and the bulge-correlated diffuse emission each contributes O(10%) of the total inner Galaxy emission, and disclose a potential subthreshold point-source contribution to the Galactic Center excess.

MiREDiBase, a manually curated database of validated and putative editing events in microRNAs.

MicroRNAs (miRNAs) are regulatory small non-coding RNAs that function as translational repressors. MiRNAs are involved in most cellular processes, and their expression and function are presided by several factors. Amongst, miRNA editing is an epitranscriptional modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their biogenesis and target-binding ability.

A novel Ventricular map of Electrograms DUration as a Method to identify areas of slow conduction for ventricular tachycardia ablation: The VEDUM pilot study.

Background: Bipolar electrogram (EGM) duration is indicative of local activation property and, if prolonged, is useful to discover areas of slow conduction favoring arrhythmias.

Objective: The present study aimed to create a map of EGM duration during the ventricular tachycardia (VT) (Ventricular Electrograms DUration as a Method map [VEDUM map]) to verify if the slowest activation area is crucial for reentry and could represent a suitable target for rapid VT interruption during ablation.

Methods: Prospectively 30 patients were enrolled for this study.

MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia.

Cancer-associated cachexia is a heterogeneous, multifactorial syndrome characterized by systemic inflammation, unintentional weight loss, and profound alteration in body composition. The main feature of cancer cachexia is represented by the loss of skeletal muscle tissue, which may or may not be accompanied by significant adipose tissue wasting. Such phenotypic alteration occurs as the result of concomitant increased myofibril breakdown and reduced muscle protein synthesis, actively contributing to fatigue, worsening of quality of life, and refractoriness to chemotherapy.

Groundwater contamination by fluorinated aromatics: Benzotrifluoride and its derivatives.

Benzotrifluoride (BTF) and its derivatives (BTFs) were found in the groundwater of the Veneto region (Italy) as a result of industrial contamination dating back to the 1970s. In the first survey, BTF and 6 BTFs were identified, out of which 4-chloro-3nitrobenzotrifluoride (3N4CBTF) was the only quantified analyte (concentration up to 1 mg L) and was used to trace the contamination plume. A survey carried out in 2008-2009 after the development of more suitable analytical procedures based on GC-MS, allowed to determine 4 new derivatives in addition to BTF and BTFs previously identified, with the most abundant compounds found at concentrations up to 11.

MiR-124a Regulates Extracellular Vesicle Release by Targeting GTPase Rabs in Lung Cancer.

Lung cancer is the leading cause of cancer mortality worldwide. Increased understanding of the molecular mechanisms of the disease has led to the development of novel therapies and improving outcomes. Recently, extracellular vesicles (EVs) have emerged as vehicles for the transfer of genetic information between tumors and their microenvironment and have been implicated in lung cancer initiation, progression, and response to therapy.

Complete Electroanatomic Imaging of the Diastolic Pathway Is Associated With Improved Freedom From Ventricular Tachycardia Recurrence.

Background: The development of multielectrode mapping catheters has expanded the spectrum of mappable ventricular tachycardias (VTs). Full diastolic pathway recording has been associated with a high rate of VT termination during radiofrequency ablation as well as noninducibility at study end. However, the role of diastolic pathway mapping on VT recurrence has yet to be clearly elucidated.

Simultaneous endo-epicardial-high density mapping of ventricular tachycardia with the use of multi-electrode mapping catheters.

We herein describe a case of VT in an ischemic cardiomyopathy patient utilizing a novel technique of simultaneous endo-epicardial high-density mapping. Epicardial access, in addition to retrograde aortic endocardial access, was performed. Following the creation of the respective endocardial and epicardial electrical substrate maps, activation mapping of the VT was then performed simultaneously with two overlapping HD Grid catheters.

Exosomal miRNA signatures of pancreatic lesions.

Background: Pancreatic and peri-pancreatic neoplasms encompass a variety of histotypes characterized by a heterogeneous prognostic impact. miRNAs are considered efficient candidate biomarkers due to their high stability in tissues and body fluids. We applied Nanostring profiling of circulating exosomal miRNAs to distinct pancreatic lesions in order to establish a source for biomarker development.

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options.

Cancer cachexia (CC) is a multifactorial syndrome characterized by systemic inflammation, uncontrolled weight loss and dramatic metabolic alterations. This includes myofibrillar protein breakdown, increased lipolysis, insulin resistance, elevated energy expediture, and reduced food intake, hence impairing the patient's response to anti-cancer therapies and quality of life. While a decade ago the syndrome was considered incurable, over the most recent years much efforts have been put into the study of such disease, leading to the development of potential therapeutic strategies.

Grid Mapping Catheter for Ventricular Tachycardia Ablation.

Background: A new grid mapping catheter (GMC)-allowing for bipolar recordings of the electrograms in each orthogonal direction-became available. The aim of the current study is to evaluate the utility of the GMC in creating substrate and ventricular tachycardia (VT) activation maps during VT ablation procedures.

Methods: From December 2017 to July 2018, 41 consecutive patients undergoing a VT ablation procedure using a GMC were studied.

Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes.

Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects.