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Physiological models for in vivo imaging and targeting the lymphatic system: Nanoparticles and extracellular vesicles. 

Imaging of the lymphatic vasculature has gained great attention in various fields, not only because lymphatic vessels act as a key draining system in the body, but also for their implication in autoimmune diseases, organ transplant, inflammation and cancer. Thus, neolymphangiogenesis, or the genera...

Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia. 

The Notch pathway is highly active in almost all patients with T-cell acute lymphoblastic leukemia (T-ALL), but the implication of Notch ligands in T-ALL remains underexplored. Methods: We used a genetic mouse model of Notch ligand delta like 4 (DLL4)-driven T-ALL and performed thymectomies and spl...

CSVS, a crowdsourcing database of the Spanish population genetic variability. 

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more...

Patient-reported outcomes from STARTRK-2: a global phase II basket study of entrectinib for ROS1 fusion-positive non-small-cell lung cancer and NTRK fusion-positive solid tumours. 

Patient-reported outcomes (PROs) are increasingly relevant endpoints in clinical trials, contributing to our understanding of risk-benefit profiles, in addition to efficacy and safety data. We investigated the impact of entrectinib on patient-reported symptoms, functioning, and health-related quali...

Gαq activation modulates autophagy by promoting mTORC1 signaling. 

The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous Gαq subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking Gαq/11 display higher basal autophagy, enhanced autopha...

PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. 

Cohesin is a chromatin-bound complex that mediates sister chromatid cohesion and facilitates long-range interactions through DNA looping. How the transcription and replication machineries deal with the presence of cohesin on chromatin remains unclear. The dynamic association of cohesin with chromat...

Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome. 

Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not u...

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers. 

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility varian...

RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment. 

The phagocytic integrins and complement receptors αMβ2/CR3 and αXβ2/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-...

Incidence and Survival Trends of Pancreatic Cancer in Girona: Impact of the Change in Patient Care in the Last 25 Years. 

(1) Background: We investigated the incidence and survival trends for pancreatic cancer (PC) over the last 25 years in the Girona region, Catalonia, Spain; (2) Methods: Data were extracted from the population-based Girona Cancer Registry. Incident PC cases during 1994-2015 were classified using the...

High-mobility group box (TOX) antibody a useful tool for the identification of B and T cell subpopulations. 

Thymocyte selection-associated high-mobility group box (TOX) is a DNA-binding factor that is able to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. TOX has multiple roles in the development of the adaptive immune system includi...

MicroRNA expression profiles in molecular subtypes of clear-cell renal cell carcinoma are associated with clinical outcome and repression of specific mRNA targets. 

Clear-cell renal cell carcinomas (ccRCC) can be divided into four transcriptomic subtypes, two of which have a favorable and two an unfavorable prognosis. To assess mechanisms driving these subtypes, we investigated their miRNA expression patterns. miRNAs are master regulators of mRNAs, that are wi...

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. 

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation c...

Brain metastasis models: What should we aim to achieve better treatments? 

Brain metastasis is emerging as a unique entity in oncology based on its particular biology and, consequently, the pharmacological approaches that should be considered. We discuss the current state of modelling this specific progression of cancer and how these experimental models have been used to ...

Brain metastasis. 

Brain metastasis, which commonly arises in patients with lung cancer, breast cancer and melanoma, is associated with poor survival outcomes and poses distinct clinical challenges. The brain microenvironment, with its unique cell types, anatomical structures, metabolic constraints and immune environ...

Universal scaling laws rule explosive growth in human cancers. 

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discover...

Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial. 

Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangioge...

A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants. 

The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two a...

The Roles of Imprinted SLC22A18 and SLC22A18AS Gene Overexpression Caused by Promoter CpG Island Hypomethylation as Diagnostic and Prognostic Biomarkers for Non-Small Cell Lung Cancer Patients. 

Genomic imprinting is a process that involves one gene copy turned-off in a parent-of-origin-dependent manner. The regulation of imprinted genes is broadly dependent on promoter methylation marks, which are frequently associated with both oncogenes and tumor suppressors. The purpose of this study w...

Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. 

Colon and rectal tumors, often referred to as colorectal cancer, show different gene expression patterns in studies that analyze whole tissue biopsies containing a mix of tumor and non-tumor cells. To better characterize colon and rectal tumors, we investigated the gene expression profile of organo...