Search results for "Genes"

Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors

2021

Adenosine A2A receptor mediates the promotion of wound healing and revascularization of injured tissue, in healthy and animals with impaired wound healing, through a mechanism depending upon tissue plasminogen activator (tPA), a component of the fibrinolytic system. In order to evaluate the contribution of plasmin generation in the proangiogenic effect of adenosine A2A receptor activation, we determined the expression and secretion of t-PA, urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and annexin A2 by human dermal microvascular endothelial cells stimulated by the selective agonist CGS-21680. The plasmin generation was assayed through an enzymatic assay a…

CNS Macrophages Control Neurovascular Development via CD95L.

2017

The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific del…

FGFR a promising druggable target in cancer: Molecular biology and new drugs.

2017

Abstract: Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share …

Numerical Treatment of the Filament-Based Lamellipodium Model (FBLM)

2017

We describe in this work the numerical treatment of the Filament-Based Lamellipodium Model (FBLM). This model is a two-phase two-dimensional continuum model, describing the dynamics of two interacting families of locally parallel F-actin filaments. It includes, among others, the bending stiffness of the filaments, adhesion to the substrate, and the cross-links connecting the two families. The numerical method proposed is a Finite Element Method (FEM) developed specifically for the needs of this problem. It is comprised of composite Lagrange–Hermite two-dimensional elements defined over a two-dimensional space. We present some elements of the FEM and emphasize in the numerical treatment of t…

A useful procedure for detection of polyamines in biological samples as a potential diagnostic tool in cancer diagnosis

2017

Abstract Background Polyamines present in human body are frequently considered as markers of occurrence of cancer. Therefore, the availability of simple and efficient method for determination of their level in body liquids and tissues is of some interest. Methods Supported liquid membrane technology coupled with HPLC seems to be an appropriate technique to follow the level of polyamines in human blood and urine. Thus, the membranes of two different geometries: flat sheet and hollow fiber were studied as a mean for separation and enrichment of studied polyamines from urine and tissue samples in order to prepare samples to be analyzed by HPLC. Conclusions Developed extraction systems offer an…

Gating Harmonization Guidelines for Intracellular Cytokine Staining Validated in Second International Multiconsortia Proficiency Panel Conducted by C…

2020

Results from the first gating proficiency panel of intracellular cytokine staining (ICS) highlighted the value of using a consensus gating approach to reduce the variability across laboratories in reported %CD8+ or %CD4+ cytokine-positive cells. Based on the data analysis from the first proficiency panel, harmonization guidelines for a consensus gating protocol were proposed. To validate the recommendations from the first panel and to examine factors that were not included in the first panel, a second ICS gating proficiency panel was organized. All participants analyzed the same set of Flow Cytometry Standard (FCS) files using their own gating protocol. An optional learning module was provi…

Harnessing the potential of noninvasive in vivo preclinical imaging of the immune system: challenges and prospects.

2016

Preclinical imaging has become a powerful method for investigation of in vivo processes such as pharmacokinetics of therapeutic substances and visualization of physiologic and pathophysiological mechanisms. These are important aspects to understand diseases and develop strategies to modify their progression with pharmacologic interventions. One promising intervention is the application of specifically tailored nanoscale particles that modulate the immune system to generate a tumor targeting immune response. In this complex interaction between immunomodulatory therapies, the immune system and malignant disease, imaging methods are expected to play a key role on the way to generate new thera…

Lawsone derivatives target the Wnt/β-catenin signaling pathway in multidrug-resistant acute lymphoblastic leukemia cells.

2017

Abstract Multidrug resistance (MDR) represents a serious problem in cancer treatment. One strategy to overcome this obstacle is to identify agents that are selectively lethal to MDR cells. The aim of this study was to discover novel compounds against MDR leukemia and to determine the molecular mechanisms behind collateral sensitivity. A library of 1162 compounds was tested against parental, drug-sensitive CCRF-CEM cells using the resazurin assay. A total of 302 compounds showed reasonable activity (less than 50% cell viability). Eleven out of 30 lawsone derivatives revealed considerable collateral sensitivity in MDR P-glycoprotein (Pgp)-overexpressing CEM/ADR5000 cells. They reduced β-caten…

2019

Purpose: Clear resection margins are paramount for good outcome in children undergoing solid tumor resections. Multiphoton microscopy (MPM) can provide high-resolution, real-time, intraoperative microscopic images of tumor tissue. Objective: This prospective international multicenter study evaluates the diagnostic accuracy, feasibility, and interobserver congruence of MPM in diagnosing solid pediatric tissue and tumors for the first time. Material and methods: Representative fresh sections from six different neonatal solid tissues (liver, lung, kidney, adrenal gland, heart muscle, testicle) and two types of typical pediatric solid tumors (neuroblastoma, rhabdomyosarcoma) with adjacent nonne…

Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

2020

Abstract HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of m…