Nonclinical Characterization of Bexmarilimab, a Clever-1-Targeting Antibody for Supporting Immune Defense Against Cancers.

Common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1) is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and metastasis formation, and its deficiency or blockage induces T-cell-dependent killing of cancer cells.

Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Importance: Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.

Objective: To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.

Comparison of the efficacy and safety of FP-1201-lyo (intravenously administered recombinant human interferon beta-1a) and placebo in the treatment of patients with moderate or severe acute respiratory distress syndrome: study protocol for a randomized controlled trial.

Background: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function.

The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study.

Background: Pulmonary vascular leakage occurs early in acute respiratory distress syndrome (ARDS). Mortality is high (35-45%), but no effective pharmacotherapy exists. Production of anti-inflammatory adenosine by ecto-5'-nucleotidase (CD73) helps maintain endothelial barrier function.

Syndecan-1 expression is upregulated in degenerating articular cartilage in a transgenic mouse model for osteoarthritis.

Objective: Mice heterozygous for the Del1 transgene locus with a short deletion mutation in the type II collagen gene develop early-onset degenerative changes in the knee joints that progress to end-stage osteoarthritis by the age of 12-15 months. This study focuses on the expression and distribution of syndecan-1, a cell-surface heparan sulfate proteoglycan, during the development of osteoarthritic cartilage degeneration, to better understand its role in this disease.

Methods: Northern analyses of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls were used to monitor changes in syndecan-1 mRNA levels during development, growth, ageing, and cartilage degeneration.

Altered expression of syndecan-1 in prostate cancer.

Syndecan-1 is a cell surface heparan sulfate proteoglycan expressed by epithelial cells. It interacts with growth factors, matrix components, and other extracellular proteins, and is thought to be involved in processes such as cell growth, differentiation and adhesion. The expression of syndecan-1 appears generally downregulated in human carcinomas and in experimental cancer models, whereas transfectional expression of syndecan-1 in cultured cancer cells has been shown to inhibit their growth and other aspects of malignant behavior.

Sulfated derivatives of Escherichia coli K5 polysaccharides as modulators of fibroblast growth factor signaling.

Heparan sulfate (HS) proteoglycans are intimately involved in the regulation of fibroblast growth factor (FGF) signaling. HS and the related glycosaminoglycan heparin interact with FGFs and FGF receptors (FGFRs), and it is believed that both interactions are required for productive FGF signaling. Attempts to inhibit FGF activity have been made with modified heparin preparations, various heparin-like polysaccharide analogues and other polyanionic molecules, which may all act by interfering with the physiological HS-FGF-FGFR interactions on the cell surface.

Protein kinase A balances the growth factor-induced Ras/ERK signaling.

Protein kinase A (PKA) has been proposed to regulate the signal transduction through the Ras/extracellular-regulated kinase (ERK) pathway. Here we demonstrate that when the PKA activity was inhibited prior to growth factor stimulus the signal flow through the Ras/ERK pathway was significantly increased. Furthermore, the data indicated that this PKA-mediated regulation was simultaneously targeted to the upstream kinase Raf-1 and to the ERK-specific phosphatase mitogen-activated protein kinase phosphatase-1 (MKP-1).

Cooperation of protein kinase A and Ras/ERK signaling pathways is required for AP-1-mediated activation of fibroblast growth factor-inducible response element (FiRE).

Recent studies suggest a crucial role for protein kinase A (PKA) in the regulation of growth factor signaling. However, the effect of PKA on the transcription of growth factor-responsive genes has drawn far less attention. Here we have investigated the signaling mechanisms involved in the activation of an activator protein-1 (AP-1)-driven, growth factor-specific enhancer element, fibroblast growth factor-inducible response element (FiRE).

Expression and characterization of minican, a recombinant syndecan-1 with extensively truncated core protein.

Syndecan-1 is an integral membrane heparan sulfate/chondroitin sulfate proteoglycan, involved in the control of cell growth and differentiation. The biological activities of syndecan-1 involve interactions with a variety of extracellular ligands, such as growth factors and matrix components, that are mainly mediated by the heparan sulfate moieties. The expression of syndecan-1 is downregulated in various malignant tumors, and low levels of expression appear to correlate with poor prognosis of some cancer types.

High syndecan-1 expression is associated with favourable outcome in squamous cell lung carcinoma treated with radical surgery.

Expression of syndecan-1 is down-regulated in many cellular transformation models. We studied the clinical significance of syndecan-1 expression in 116 squamous cell lung carcinomas treated with radical surgery. Paraffin-embedded tissue samples were immunostained with two antibodies against human syndecan-1 (B-B4 and 104-9).

Proximal promoter of the murine syndecan-1 gene is not sufficient for the developmental pattern of syndecan expression in B lineage cells.

Syndecan-1 (CD138) is a cell membrane proteoglycan that binds extracellular matrix components and various growth factors. The role of syndecan-1 in the control of cell growth and morphology has been illustrated by its altered expression in hematological malignancies such as multiple myeloma as well as some solid tumors. It has been reported that the expression of syndecan-1 in cells of the B lineage is developmentally regulated such that pre-B cells and plasma cells express syndecan-1 while mature B cells do not.

Binding of heparin/heparan sulfate to fibroblast growth factor receptor 4.

Fibroblast growth factors (FGFs) are heparin-binding polypeptides that affect the growth, differentiation, and migration of many cell types. FGFs signal by binding and activating cell surface FGF receptors (FGFRs) with intracellular tyrosine kinase domains. The signaling involves ligand-induced receptor dimerization and autophosphorylation, followed by downstream transfer of the signal.

Characterization of the D-glucuronyl C5-epimerase involved in the biosynthesis of heparin and heparan sulfate.

The murine gene for the glucuronyl C5-epimerase involved in heparan sulfate biosynthesis was cloned, using a previously isolated bovine lung cDNA fragment (Li, J.-P., Hagner-McWhirter, A.

Testosterone-induced growth of S115 mouse mammary tumor cells is dependent on heparan sulfate.

The androgen-induced proliferation of S115 mouse mammary tumor cells has been suggested to involve autocrinic fibroblast growth factor signaling. Heparan sulfate proteoglycans are required for fibroblast growth factor signaling, presumably due to their ability to alter binding of fibroblast growth factors to their receptors. We have investigated the role of heparan sulfate proteoglycans in the testosterone-induced proliferation of S115 cells.

Expression and glycosylation studies of human FGF receptor 4.

Fibroblast growth factor receptor subtype 4 (FGFR4) has been shown to have special activation properties and just one splicing form, unlike the other FGFRs. FGFR4 overexpression is correlated with breast cancer and therefore FGFR4 is a target for drug design. Our aim is to overexpress high amounts of homogeneous FGFR4 extracellular domain (FGFR4(ed)) for structural studies.

Proximal promoter-independent activation of the far-upstream FGF-inducible response element of syndecan-1 gene.

Far upstream enhancers are predicted to act by looping and activating general transcription factors on core promoters and to require proximal promoter sequences for appropriate gene activation in time and space. We have previously described an FGF-inducible response element (FiRE) located far upstream on the syndecan-1 gene. The FiRE is activated specifically by members of the fibroblast growth factor (FGF) family in NIH3T3 cells.

Transcriptional targeting of adenoviral gene delivery into migrating wound keratinocytes using FiRE, a growth factor-inducible regulatory element.

Impaired cutaneous wound healing is a common complication in diabetes, ischemia and venous insufficiency of lower extremities, and in long-term treatment with corticosteroids or other immunosuppressive agents. In development of gene therapy for wound repair, expression of therapeutic transgenes should be precisely targeted and controlled. Here, we describe a recombinant adenovirus RAdFiRE-EGFP, in which a growth factor inducible element (FiRE) of the murine syndecan-1 gene controls the expression of enhanced green fluorescent protein (EGFP) reporter gene.

Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4.

Among the members of the fibroblast growth factor receptor family the FGFR4 has demonstrated strong dependence on heparin-like material for its activation by fibroblast growth factors. We have produced and characterized a recombinant human FGFR4 extracellular domain (FGFR4ed), in order to study its biochemical properties in isolated conditions. The FGFR4ed was expressed in an insect cell system and purified from the culture medium by Ni(2+)-affinity and gel filtration chromatography.

Involvement of protein kinase A in fibroblast growth factor-2-activated transcription.

Polypeptide growth factors activate common signal transduction pathways, yet they can induce transcription of different target genes. The mechanisms that control this specificity are not completely understood. Recently, we have described a fibroblast growth factor (FGF)-inducible response element, FiRE, on the syndecan-1 gene.

Association of syndecan-1 with tumor grade and histology in primary invasive cervical carcinoma.

Objectives: The expression of syndecan-1, a cell surface heparan sulfate proteoglycan, is reduced during malignant transformation of squamous cells. Studies on squamous cell carcinoma of the head and neck have shown that syndecan-1-positive tumors are associated with longer overall and recurrence-free survival. The purpose of this study was to analyze syndecan-1 expression in invasive cervical carcinoma and to examine the association of syndecan-1 expression with prognostic factors and overall survival.

Transcriptional regulation of Syndecan-1 expression by growth factors.

Syndecan-1 is a prototype member of a family of transmembrane heparan sulfate proteoglycans. Syndecan-1 binds extracellular matrix components and fibroblast growth factors (FGFs) and modifies the function of FGFs. Syndecan-1 is constitutively expressed by several epithelial cells, but expression is also induced during many biological phenomena, such as tissue regeneration and the epithelial-mesenchymal interactions during organ development.

Extracellular matrix-dependent activation of syndecan-1 expression in keratinocyte growth factor-treated keratinocytes.

Syndecan-1 is a major heparan sulfate proteoglycan of the epidermis. Its expression is strongly induced in migrating and proliferating keratinocytes during wound healing and, on the other hand, diminished or lost in invasive squamous cell carcinoma. We have recently found in the syndecan-1 gene an enhancer (fibroblast growth factor-inducible response element (FiRE)) that activates gene expression in wound edge keratinocytes (Jaakkola, P.

Syndecan-1 expression has prognostic significance in head and neck carcinoma.

The syndecans are a family of cell-surface heparan sulphate proteoglycans that regulate cell behaviour by binding extracellular matrix molecules such as growth factors. The syndecan family has four members, of which syndecan-1 is the most studied and best characterized. We have studied the prognostic significance of syndecan-1 expression in squamous cell carcinoma (SCC) of the head and neck treated with surgery and post-operative radiotherapy.

Immunohistochemical expression of syndecan-1 in human endometrial cancer cells.

There are indications of increased frequency of endometrial cancer, one of the most common malignancies in women. Tissue samples of normal and malignant endometria were obtained post operatively from 30 women. We noted expression of syndecan-1 in 40% of investigated cancers.