Search results for "TYROSINE KINASE"
showing 10 items of 362 documents
Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells.
2006
AbstractAlthough CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIPL (cFLIPL) and PED/PEA-15, two antiapoptotic proteins whos…
From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview
2019
Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated…
Timely recognition of cardiovascular toxicity by anticancer agents: a common objective of the pharmacologist, oncologist and cardiologist.
2011
Both conventional and new anticancer drugs can frequently cause adverse cardiovascular effects, which can span from subclinical abnormalities to serious life-threatening and sometimes fatal events. This review examines the principal basic and clinical elements that may be of profit to identify, prevent and treat such toxicities. Clearly, the accomplishment of such objectives requires the strong commitment and cooperation of different professional figures including, but not limited to, pharmacologists, oncologists and cardiologists. The aspect of anticancer drug cardiotoxicity seems to be somehow underestimated, mainly due to inadequate reporting of adverse reactions from oncology drugs in t…
Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors
2020
Background:The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma.Methods:We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,46…
Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42
2005
Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…
Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.
2010
SummaryStem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocyto…
Characterization of the Receptor Protein-Tyrosine Kinase Gene from the Marine Sponge Geodia cydonium
1996
Cells are provided with well-defined receptor structures (signal receivers) which interact with their corresponding ligands (signal molecules) and initiate a signal transduction pathway resulting in a change of cellular behavior or metabolism (Stoddard et al. 1992). It is well established that cells from both eukaryotic protists (single-cell organisms) and from Metazoa (multicellular organisms) respond to signals emanating from the extracellular environment. The extracellular signals to which protists respond are mainly nutrients which diffuse to their surfaces, and in most cases cross the cell membrane. In addition, they are able to bind peptide hormones, e.g., insulin or adrenocorticotrop…
Molecular evolution of the metazoan extracellular matrix: cloning and expression of structural proteins from the demosponges Suberites domuncula and …
2000
One crucial event during evolution to multicellularity was the development of either direct cell–cell contact or indirect interaction via extracellular matrix (ECM) molecules. The identification of those polypeptides provides conclusive data on the phylogenetic relationship of metazoan phyla and helps us to understand the position of the Metazoa among the other kingdoms. Recently it became evident that the ECM of sponges is amazingly complex; it is composed of fibrous molecules, e.g., collagen, and their corresponding receptors, which are highly similar to those existing in other metazoan phyla. While these data already support the view of monophyly of Metazoa, additional studies are requir…
Activation of α-secretase cleavage
2011
Alpha-secretase-mediated cleavage of the amyloid precursor protein (APP) releases the neuroprotective APP fragment sαAPP and prevents amyloid β peptide (Aβ) generation. Moreover, α-secretase-like cleavage of the Aβ transporter 'receptor for advanced glycation end products' counteracts the import of blood Aβ into the brain. Assuming that Aβ is responsible for the development of Alzheimer's disease (AD), activation of α-secretase should be preventive. α-Secretase-mediated APP cleavage can be activated via several G protein-coupled receptors and receptor tyrosine kinases. Protein kinase C, mitogen-activated protein kinases, phosphatidylinositol 3-kinase, cAMP and calcium are activators of rece…
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
2018
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…