Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.

The Hippo pathway is an evolutionarily conserved modulator of developmental biology with a key role in tissue and organ size regulation under homeostatic conditions. Like other signaling pathways with a significant role in embryonic development, the deregulation of Hippo signaling contributes to oncogenesis. Central to the Hippo pathway is a conserved cascade of adaptor proteins and inhibitory kinases that converge and regulate the activity of the oncoproteins YAP and TAZ, the final transducers of the pathway.

Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness.

The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis.

Small round cell sarcomas.

Undifferentiated small round cell sarcomas (SRCSs) of bone and soft tissue comprise a heterogeneous group of highly aggressive tumours associated with a poor prognosis, especially in metastatic disease. SRCS entities mainly occur in the third decade of life and can exhibit striking disparities regarding preferentially affected sex and tumour localization. SRCSs comprise new entities defined by specific genetic abnormalities, namely EWSR1-non-ETS fusions, CIC-rearrangements or BCOR genetic alterations, as well as EWSR1-ETS fusions in the prototypic SRCS Ewing sarcoma.

An international working group consensus report for the prioritization of molecular biomarkers for Ewing sarcoma.

The advent of dose intensified interval compressed therapy has improved event-free survival for patients with localized Ewing sarcoma (EwS) to 78% at 5 years. However, nearly a quarter of patients with localized tumors and 60-80% of patients with metastatic tumors suffer relapse and die of disease. In addition, those who survive are often left with debilitating late effects.

Isolation, Molecular Identification and Antibacterial Potential of Marine Bacteria from Deep Atlantic Ocean of Morocco.

Background: Antibiotic resistance is an important concern for the public health authorities at global level. It is detrimental to human and environmental ecosystems, thus, there is a big need for natural bioactive compounds. In this work, we aimed to find out biomolecules derived from marine bacteria that may constitute an alternative to antibiotics.

Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions.

Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin.

Cytotoxicity and Effects on the Synapsis Induced by Pure Cylindrospermopsin in an E17 Embryonic Murine Primary Neuronal Culture in a Concentration- and Time-Dependent Manner.

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo.

The role of PemIK (PemK/PemI) type II TA system from Klebsiella pneumoniae clinical strains in lytic phage infection.

Since their discovery, toxin-antitoxin (TA) systems have captivated the attention of many scientists. Recent studies have demonstrated that TA systems play a key role in phage inhibition. The aim of the present study was to investigate the role of the PemIK (PemK/PemI) type II TA system in phage inhibition by its intrinsic expression in clinical strains of Klebsiella pneumoniae carrying the lncL plasmid, which harbours the carbapenemase OXA-48 and the PemK/PemI TA system.

Adaptation of clinical isolates of Klebsiella pneumoniae to the combination of niclosamide with the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PaβN): co-resistance to antimicrobials.

Objectives: To search for new means of combatting carbapenemase-producing strains of Klebsiella pneumoniae by repurposing the anti-helminth drug niclosamide as an antimicrobial agent and combining it with the efflux pump inhibitor (EPI) phenyl-arginine-β-naphthylamide (PaβN).

Methods: Niclosamide and PaβN MICs were determined for six clinical K. pneumoniae isolates harbouring different carbapenemases by broth microdilution and chequerboard assays.

Sleep-related hypermotor epilepsy with genetic diagnosis: description of a case series in a tertiary referral hospital.

Introduction: Sleep-related hypermotor epilepsy (SHE) is characterized by asymmetric tonic/dystonic posturing and/or complex hyperkinetic seizures occurring mostly during sleep. Experts agree that SHE should be considered a unique syndrome.

Purpose: We present 8 cases of SHE for which a genetic diagnosis was carried out using a multigene epilepsy panel.

Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed.

Study of a Waste Kaolin as Raw Material for Mullite Ceramics and Mullite Refractories by Reaction Sintering.

A deposit of raw kaolin, located in West Andalusia (Spain), was studied in this work using a representative sample. The methods of characterization were X-ray diffraction (XRD), X-ray fluorescence (XRF), particle size analysis by sieving and sedimentation, and thermal analysis. The ceramic properties were determined.

E3 ubiquitin ligase Atrogin-1 mediates adaptive resistance to KIT-targeted inhibition in gastrointestinal stromal tumor.

KIT/PDGFRA oncogenic tyrosine kinase signaling is the central oncogenic event in most gastrointestinal stromal tumors (GIST), which are human malignant mesenchymal neoplasms that often feature myogenic differentiation. Although targeted inhibition of KIT/PDGFRA provides substantial clinical benefit, GIST cells adapt to KIT/PDGFRA driver suppression and eventually develop resistance. The specific molecular events leading to adaptive resistance in GIST remain unclear.

Biomaterials in periapical regeneration after microsurgical endodontics: A narrative review.

Background: The objective of this narrative review was to analyze the available scientific evidence regarding the application of biomaterials in endodontic microsurgery and its influence in post-surgical tissue repair.

Material And Methods: The review question was Do biomaterials used in endodontic microsurgery influence post-surgical tissue repair and regeneration? Systematic MEDLINE/PubMed review was used to evaluate and present the results.

Results: The search yielded 131 references, 82 of which were selected for full text review after reading the abstracts.

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma.

The invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients).

Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas.

Use of contemporary technologies and new materials in undergraduate Endodontics teaching.

Background: This study aims to analyze the use of contemporary technologies and materials in undergraduate endodontic teaching in Spain.

Material And Methods: The survey was sent to the undergraduate endodontic programme leads in the 23 Spanish dental schools. The survey asked about the use of magnification, ultrasonic devices, electronic apex locator, rotary instruments, root-filling techniques, and bioceramic cements in the teaching of endodontics.

Polycationic cyclodextrin nanoparticles induce apoptosis and affect antitumoral activity in HepG2 cell line: An evaluation at the molecular level.

Hepatocellular carcinoma (HCC) is a highly metastatic primary liver cancer generating molecular alterations that end up escaping the apoptotic machinery and conferring multidrug resistance. Targeted medicines with increased and selective cytotoxicity and minimal drug resistance are essential for the treatment of HCC. In this study, a self-assembled polycationic (PC) amphiphilic β-cyclodextrin (βCDC6) nanoparticle formulation was characterized and its efficacy over HCC cell line HepG2 was evaluated in terms of cytotoxicity, apoptotic potential, chemosensitivity and mitochondrial balance utilizing biochemical, gene expression and proteomic approaches without encapsulating an anti-neoplastic agent.

Selective modulation by PARP-1 of HIF-1α-recruitment to chromatin during hypoxia is required for tumor adaptation to hypoxic conditions.

Background: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded.

Sarcoma classification by DNA methylation profiling.

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate.

(Immuno)histological Analysis of Ewing Sarcoma.

The diagnosis of Ewing sarcoma requires the integration of the information generated from numerous techniques, some of them being very sophisticated. However, the first steps of the diagnostic process are crucial to achieve the maximum possible diagnostic performance. In this chapter we will review how to handle the diagnostic specimen from its collection, how to prepare it for diagnosis, how to make a complete pathology report, and provide guidance for the reasonable use of immunohistochemical techniques in this malignancy.

Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors.

The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children's malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region.

Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver.

Erlotinib (ERL), a tyrosine kinase inhibitor approved for therapeutic use in non-small cell lung cancer is further researched for eventual liver cancer treatment. However, conventional ERL has important bioavailability problems resulting from oral administration, poor solubility and gastrointestinal degradation into inactive metabolites. Alternative administration routes and nanoparticulate drug delivery systems are studied to prevent or reduce these drawbacks.