1,721,040 research outputs found
Un metodo per la diagnosi , il monitoraggio dell'efficacia di una terapia e per lo sviluppo di un trattamento per la Sclerosi Multipla Method for diagnosis, monitoring the efficacy of a therapy and for development of treatment for Multiple Sclerosis
No full textThe present invention relates to a method for diagnosis and/or prognosis of multiple sclerosis or to monitor the efficacy of a therapy and/or to screen for a treatment for multiple sclerosis comprising measuring the amount or assessing the cellular localization of one or more specific molecular species in stimulated oligodendrocyte cells. Changes of expression or localization of specific proteins involved in oligodendrocyte differentiation are measured after incubation of differentiating cells with cerebrospinal fluid, immunoglobulins extracted from blood serum or blood of patients with multiple sclerosis
cAMP signaling selectively influences Ras effectors pathways
No full textAbstract
Thyrotropin (TSH) stimulates survival and growth of thyroid cells via a seven transmembrane G protein-coupled receptor. TSH elevates the intracellular cyclic AMP (cAMP) levels activating protein kinase A (PKA). Recent evidence indicates that p21 Ras is required for TSH-induced mitogenesis, but the molecular mechanism(s) is not known. Here we report that Ras p21 activity is necessary for the Go- G1 transition in TSH induced cycle and that the downstream effector of Ras upon TSH signaling is p85-p110 PI3K. We show that PI3K inhibitors block TSH-induced DNA synthesis, cAMP-PKA stimulate the formation of the complex PI3K-p21 Ras and reduce the complex Ras-Raf1 in thyroid and other cells types. Moreover, PKA phosphorylates immunoprecipitated p85 and PKA phosphorylation of cell extracts significantly stimulates the formation of the complex PI3K-Ras. We suggest that PKA phosphorylates p85 and stabilizes the complex p110-p85, enhancing the interaction PI3K and p21 Ras. Simultaneously, cAMP inhibits Raf-1-ERK signaling by decreasing Raf1 availability to Ras. Under these circumstances PI3K signaling is favored. These results indicate that PI3K is an important mediator of Ras effects in cAMP-induced proliferation and illustrates how cAMP can selectively influence Ras effector pathways
Mutations of thyrotropin receptor isolated from thyroid autonomous adenomas confer TSH-indepedent growth to thyroid cells.
No full textRetinoic acid impairs estrogen signaling in breast cancer cells by interfering with activation of LSD1 via PKA.
No full text"More than 70% of breast cancers in women require estrogens for cell proliferation and survival. 17β-estradiol (E2) effect on mammary target cells is almost exclusively mediated by its binding to the estrogen receptor-α (ERα) that joins chromatin where it assembles active transcription complexes. The proliferative and pro-survival action of estrogens is antagonized in most cases by retinoic acid (RA), even though the cognate retinoic acid receptor-α (RARα) cooperates with ERα on promoters of estrogen-responsive genes. We have examined at the molecular level the crosstalk between these nuclear receptors from the point of view of their control of cell growth and show here that RA reverts estrogen-stimulated transcription of the pivotal anti-apoptotic bcl-2 gene by preventing demethylation of dimethyl lysine 9 in histone H3 (HeK9me2). As we previously reported, this is obtained by means of E2-triggered activation of the lysine-specific demethylase 1 (LSD1), an enzyme that manages chromatin plasticity in order to allow specific movements of chromosomal regions within the nucleus. We find that E2 fuels LSD1 by inducing migration of the catalytic subunit of protein kinase A (PKA) into the nucleus, where it targets estrogen-responsive loci. RA rescues LSD1-dependent disappearance of H3K9me2 at bcl-2 regulatory regions upon the prevention of PKA assembly to the same sites.
STYMULATORY AUTO-AUTO-ANTIBODIES TO THE PDGF RECEPTOR AS PATHOLOGY MARKER AND THERAPEUTIC TARGET
No full textThe present invention relates to a method for the diagnosis and prognosis of the systemic sclerosis, and for discriminating between Raynaud phenomenon and systemic sclerosis, based on the presence of IgG auto-antibodies directed to the PDGF receptor (PDGFR) in systemic sclerosis patients. Therefore it is an object of the invention an in vitro method for detecting the presence in a body sample of auto-antibodies for the PDGF receptor by incubating the body sample with an effective amount of a specific ligand for such auto-antibodies in conditions allowing the binding and the formation of a complex and detecting the bound auto-antibodies, or the complex, if present. It is another object of the invention a diagnostic kit for the method describe
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