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Targeting tyrosine kinases: a novel therapeutic strategy for systemic sclerosis.

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OBJECTIVE This article reviews the current evidence and rationale for the use of tyrosine kinase inhibitors as potential therapeutic interventions for systemic sclerosis. RESULTS The signaling cascades of the profibrotic cytokines transforming growth factor-β and platelet-derived growth factor

MiRNAs from DLK1-DIO3 Imprinted Locus at 14q32 are Associated with Multiple Sclerosis: Gender-Specific Expression and Regulation of Receptor Tyrosine Kinases Signaling.

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Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent course of multiple sclerosis. It is an autoimmune inflammatory disease of the central nervous system. To investigate the gender-specific involvement of microRNAs (miRNAs) in RRMS pathogenesis, we compared miRNA profiles in

Tyrosine kinase inhibitors for the treatment of fibrotic diseases such as systemic sclerosis: towards molecular targeted therapies.

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Systemic sclerosis (SSc) is a fibrosing connective tissue disease with significantly increased mortality. Therapeutic options to treat fibrosis are limited. The small molecule tyrosine kinase inhibitor imatinib and related drugs such as dasatinib and nilotinib target simultaneously two of the major

Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.

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The levels of the antioxidants ascorbic acid, cysteine, reduced glutathione and alpha-tocopherol, of the free-radical marker uric acid and of the amino acids tyrosine and tryptophan were measured by means of high-pressure liquid chromatography in plaques, adjacent white matter and distant white

Protein Tyrosine Phosphatases in Systemic Sclerosis: Potential Pathogenic Players and Therapeutic Targets.

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OBJECTIVE The pathogenesis of systemic sclerosis depends on a complex interplay between autoimmunity, vasculopathy, and fibrosis. Reversible phosphorylation on tyrosine residues, in response to growth factors and other stimuli, critically regulates each one of these three key pathogenic processes.

Receptor Tyrosine Kinase and Tyrosine Kinase Inhibitors: New Hope for Success in Multiple Sclerosis Therapy.

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Receptor tyrosine kinases (RTKs) are essential components of signal transduction pathways that mediate cell-to-cell communication and their function as relay points for signaling pathways. They have a key role in numerous processes that control cellular proliferation and differentiation, regulate

Induction of multiple sclerosis and response to tyrosine kinase inhibitors.

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The goal of this work is to determine the role of the autoimmune cells in multiple sclerosis (MS) induction and the immunomodulatory mechanism of therapy with tyrosine kinase inhibitors (TKIs) in MS attenuation. Samples (5 × 10(5) cells per well) of C6 and primary rat astrocytes were stimulated with

Protein tyrosine phosphatase receptor-type C exon 4 gene mutation distribution in an Italian multiple sclerosis population.

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In this study, we investigate the role of the C-->G mutation in position 77 of exon 4 of the protein tyrosine phosphatase receptor-type C (PTPRC) gene, coding for the CD45 molecule, for the development of multiple sclerosis (MS) in an Italian continental population. The PTPRC mutated genotype has

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: The Difficulty in Interpreting Proof-of-Concept Studies.

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Tyrosine kinase inhibitors (TKIs) have emerged as a targeted therapy of interest for the treatment of systemic sclerosis (SSc). Recently, several groups have performed pilot or "proof-of-concept" studies to determine the feasibility of this approach for the treatment of the cutaneous and pulmonary

Functional tyrosine kinase inhibitor profiling: a generally applicable method points to a novel role of platelet-derived growth factor receptor-beta in tuberous sclerosis.

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Tumors often exhibit activation of specific tyrosine kinases, which may allow targeting of therapy through inhibition of tyrosine kinase signaling. This strategy has been used successfully in the development of STI571 (gleevec), an inhibitor of bcr-abl tyrosine kinase that has been used successfully

A potential role for imatinib and other small molecule tyrosine kinase inhibitors in the treatment of systemic and localized sclerosis.

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Small molecule tyrosine kinase (TK) inhibitor, such as imatinib, is well established in the treatment of malignancy. Oral administration, high efficacy, and an excellent safety profile have made imatinib a drug of choice for several malignancies and benign conditions. Recent progress in the

Preserved phosphorylation of RET receptor protein in spinal motor neurons of patients with amyotrophic lateral sclerosis: an immunohistochemical study by a phosphorylation-specific antibody at tyrosine 1062.

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Ret oncoprotein is a functional receptor for the glial cell line-derived neurotrophic factor (GDNF) family and it is expressed in motor neurons, playing an important role in the motor neuron function. In this study, we examined the expression of the phosphorylation state of tyrosine residue 1062

Therapeutic inhibition of tyrosine kinases in systemic sclerosis: a review of published experience on the first 108 patients treated with imatinib.

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OBJECTIVE Experimental and clinical evidence suggest a therapeutic role for the tyrosine kinase inhibitor imatinib in fibrosing conditions. We evaluated published data on the safety and efficacy of imatinib for patients with systemic sclerosis (SSc), a severe autoimmune disease with significant

An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with multiple sclerosis in an Australian population.

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Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The disease generally manifests in early to middle adulthood and causes various neurological deficits. Autoreactive T lymphocytes and their associated antigens have long been presumed important features of MS

Disturbed balance between serum levels of receptor tyrosine kinases Tie-1, Tie-2 and angiopoietins in systemic sclerosis.

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OBJECTIVE The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands--angiopoietins--in systemic sclerosis (SSc) patients. METHODS Serum levels of

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