Search results for "Cell adhesion molecule"

A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refract…

2018

ABSTRACT We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): e…

Differential VASP phosphorylation controls remodeling of the actin cytoskeleton

2009

Proteins of the Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family link signal transduction pathways to actin cytoskeleton dynamics. VASP is substrate of cAMP-dependent, cGMP-dependent and AMP-activated protein kinases that primarily phosphorylate the sites S157, S239 and T278, respectively. Here, we systematically analyzed functions of VASP phosphorylation patterns for actin assembly and subcellular targeting in vivo and compared the phosphorylation effects of Ena/VASP family members. Methods used were the reconstitution of VASP-null cells with `locked' phosphomimetic VASP mutants, actin polymerization of VASP mutants in vitro and in living cells, site-specific kinase-mediated…

Monoclonal antibodies to polysialic acid reveal epitope sharing between invasive pathogenic bacteria, differentiating cells and tumor cells

1987

Monoclonal antibodies (mAb) for rapid diagnosis and detection of invasive bacteria and identification of pathogenic factors in infectious disease are equally important in medical microbiology and clinical pathology and may even provide a breakthrough in basic medical and cell biology research. Such a situation evolved from the application of a unique mAb against the poorly immunogenic homopolymers of alpha 2,8-linked sialic acid of Escherichia coli K1 and meningococci group B capsules which could be derived from immune-hyperreactive NZB-autoimmune mice. The cross-reactivity of this mAb with identical polysialic acid (polySA) units of the neural cell adhesion molecule (N-CAM) revealed antige…

Antibodies to cell surface ganglioside GD3 perturb inductive epithelial-mesenchymal interactions

1988

Abstract Most epithelial sheets emerge during embryogenesis by a branching and growth of the epithelium. The surrounding mesenchyme is crucial for this process. We report that branching morphogenesis and the formation of a new epithelium from the mesenchyme in the embryonic kidney can be blocked by a monoclonal antibody reacting with a surface glycolipid, disialoganglioside G D3 . In contrast, a more than 10-fold excess of antibodies to adhesive glycoproteins (N-CAM, L -CAM, fibronectin) fails to inhibit morphogenesis. Although the anti-G D3 antibody affected epithelial development, the disialoganglioside G D3 was expressed not in the epithelium, but in the mesenchyme surrounding the develo…

Effects of soy isoflavones on endothelial function in healthy postmenopausal women.

2005

Objective: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. Design: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity par…

IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus; induction of adhesion molecule expression in cultured endothelial cells

1998

SUMMARYAECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of < 1 year duration and those with long-standing disease had the highest levels of these antibodies. Inhibition studies suggest that at least part of the AECA reactivity is due to cross-reactive anti-ssDNA antibodies. AECA-positive sera were able to increase intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was also found to accompany raised E-selectin expression. Soluble ICAM-1 and E-selectin were also found to be increased in the sera of AE…

Embryo effects in human implantation: embryonic regulation of endometrial molecules in human implantation.

2001

: Embryonic implantation requires coordinated development of the blastocyst and the maternal endometrium. Considerable advances have been made in the understanding of the cell biology of human embryo and maternal endometrium as separate entities. Nevertheless, communication between them and their reciprocal effects on each other constitute an exciting and as-yet unsolved problem in reproductive medicine. Cross-talk among the embryo, endometrium, and the corpus luteum are known to occur in ruminants and primates; more specifically, endometrial-embryonic interactions have been reported in rodents and primates. Here, we present updated information in humans on the embryonic regulation of endom…

Cytokines, Selectins and Adhesion Molecules Plasma Levels in Acute Ischaemic Stroke: Relationship with Stroke Subtype, Ischaemic Lesion Site and Clin…

2007

Changes in lymphocyte subsets after cardiac surgery in children.

2001

Children undergoing cardiopulmonary bypass (CPB) operations have an increased risk of developing severe infections. Impairment of the immune system may contribute to the development of sequelae such as capillary leaks, pulmonary dysfunction and auto-immune reactions. The objective of this study was to investigate the impact of cardiac surgery with CPB on the immune system of infants and young children. We conducted a prospective study to investigate the changes in circulating lymphocyte subpopulations in a sample of 21 consecutive infants and young children undergoing cardiac surgery for congenital heart disease. The following statistically significant (P<0.05) results were obtained: leucoc…

Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus

2003

Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural c…