Search results for "JUNCTION"
showing 10 items of 862 documents
FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric …
2021
Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms.The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/mIn the overall population, both PFS [hazard ratio (HR) = 0…
GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks.
2017
The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide…
Expression of Claudin 18.2 and HER2 in gastric, gastroesophageal junction, and esophageal cancers : Results from the FAST study
2017
4038 Background: Claudin 18.2 (CLDN18.2), a gastric mucosa tight junction protein, is aberrantly expressed in various cancers. In the FAST Phase 2 trial (NCT01630083), IMAB362, an anti-CLDN18.2 monoclonal antibody, administered in combination with EOX chemotherapy, prolonged survival compared to EOX alone in patients with advanced/recurrent gastric, gastroesophageal junction (GEJ), and esophageal cancers ineligible for trastuzumab. The aim of the present analysis was to assess tumor CLDN18.2 expression and co-expression with HER2 in the FAST population. Methods: Tumor tissue samples from patients screened for inclusion into the FAST trial were analyzed for CLDN18.2 expression using a CE-ma…
Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells
2021
Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including…
Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics
2016
AbstractBioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects …
The Drosophila Hox gene Ultrabithorax acts both in muscles and motoneurons to orchestrate formation of specific neuromuscular connections
2016
Hox genes are known to specify motoneuron pools in the developing vertebrate spinal cord and to control motoneuronal targeting in several species. However, the mechanisms controlling axial diversification of muscle innervation patterns are still largely unknown. We present data showing that the Drosophila Hox gene Ultrabithorax (Ubx) acts in the late embryo to establish target specificity of ventrally projecting RP motoneurons. In abdominal segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner. In Ubx mutants, these motoneurons fail to make correct contacts with muscle VL1, a phenotype partially resembling t…
E-Cadherin is Dispensable to Maintain Langerhans Cells in the Epidermis.
2019
The cell adhesion molecule E-cadherin is a major component of adherens junctions and marks Langerhans cells (LC), the only dendritic cell (DC) population of the epidermis. LC form a dense network and attach themselves to the surrounding keratinocytes via homophilic E-cadherin binding. LC activation, mobilization, and migration require a reduction in LC E-cadherin expression. To determine whether E-cadherin plays a role in regulating LC homeostasis and function, we generated CD11c-specific E-cadherin knockout mice (CD11c-Ecaddel). In the absence of E-cadherin−mediated cell adhesion, LC numbers remained stable and similar as in control mice, even in aged animals. Intriguingly, E-cadherin−defi…
Neuronal LRP4 regulates synapse formation in the developing CNS
2017
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific kno…
Complexity of gap junctions between horizontal cells of the carp retina.
2016
In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. We have cloned four carp connexins designated Cx49.5, Cx55.5, Cx52.6 and Cx53.8 with a close relationship to connexins previously reported in HCs of mouse, rabbit and zebrafish, respectively. Using in s…
Macrophage-induced reactive oxygen species promote myometrial contraction and labor-associated mechanisms
2020
AbstractAt labor, the myometrium is infiltrated by a massive influx of macrophages that secrete high levels of pro-inflammatory cytokines inducing the expression of specific labor-associated markers. However, the interactions between myocytes and macrophages and the role of macrophages in the myometrium at labor remain to be elucidated. In this work, we studied the role of myometrium-infiltrated macrophages and their interaction with myocytes in lipopolysaccharide-induced preterm labor. A co-culture model of human primary myometrial cells and macrophages was developed and validated. Collagen lattices were used to evaluate myocyte contraction. Differentiation steps were assessed by (i) phall…