Search results for "C2"
showing 10 items of 879 documents
Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-dr…
2017
Background Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. Methods 3-dimens…
Synthesis and Antitumor Activity of 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-Phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles
2011
Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ∼60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exh…
A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells
2021
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpressed in PDAC tissues and has been correlated to the aggressive nature of these tumors because of its key role in cell cycle progression and resistance to the induction of apoptosis. For these reasons, CDK1 is one of the main causes of chemoresistance, representing a promising pharmacological target. In this study, we report the synthesis of new 1,2,4…
β1D Integrin Inhibits Cell Cycle Progression in Normal Myoblasts and Fibroblasts
1998
Integrins are alphabeta heterodimeric transmembrane receptors involved in the regulation of cell growth and differentiation. The beta1 integrin subunit is widely expressed in vivo and is represented by four alternatively spliced cytoplasmic domain isoforms. beta1D is a muscle-specific variant of beta1 integrin and a predominant beta1 isoform in striated muscles. In the present study we showed that expression of the exogenous beta1D integrin in C2C12 myoblasts and NIH 3T3 or REF 52 fibroblasts inhibited cell proliferation. Unlike the case of the common beta1A isoform, adhesion of beta1D-transfected C2C12 myoblasts specifically via the expressed integrin did not activate mitogen-activated pro…
A SIMPLE PARTICLE MODEL FOR A SYSTEM OF COUPLED EQUATIONS WITH ABSORBING COLLISION TERM
2011
We study a particle model for a simple system of partial differential equations describing, in dimension $d\geq 2$, a two component mixture where light particles move in a medium of absorbing, fixed obstacles; the system consists in a transport and a reaction equation coupled through pure absorption collision terms. We consider a particle system where the obstacles, of radius $\var$, become inactive at a rate related to the number of light particles travelling in their range of influence at a given time and the light particles are instantaneously absorbed at the first time they meet the physical boundary of an obstacle; elements belonging to the same species do not interact among themselves…
LAS REDES SOCIALES VIRTUALES Y LAS MARCAS: INFLUENCIA DEL INTERCAMBIO DE EXPERIENCIAS eC2C SOBRE LA ACTITUD DE LOS USUARIOS HACIA LA MARCA
2013
RESUMENFrente a la irrupción de los nuevos medios de comunicación digital, las marcas se enfrentan al desafio de encontrar nuevos formatos, tonos y contenidos que capturen la atención de los usuarios que navegan por las redes sociales. Este artículo indaga la eficacia publicitaria de las campañas en redes sociales virtuales (actitud hacia el anuncio, actitud hacia la marca e intención de compra) utilizando el Modelo de Mediación Dual y el MOA (motivación, oportunidad, habilidad). Los resultados constatan la influencia que el intercambio de experiencias eC2C (experiencias online entre consumidores) tiene en la actitud hacia la marca y de ésta en la intención de compra y en el eWOM (boca a oí…
Variations of lipid and apolipoprotein content in lipoproteins during fasting in European sea bass (Dicentrarchus labrax L.)
1997
Lipoproteins are involved in transport of exogenous and endogenous lipids. For this reason, the lipoprotein pattern undergoes drastic variation during fasting. In D. labrax, observed variations concern, the relative content of the five lipoproteins and their composition, both in lipid and apolipoprotein content. These data indicate the presence of a cascade mechanism of maturation involving very-low-density lipoprotein, (VLDL), low-density lipoprotein (LDL)-1 and LDL-2. In addition, a metabolic correlation involves VLDL and high-density lipoprotein (HDL). VLDL are functionally comparable with mammalian chylomicrons; in fact, they disappear rapidly after feeding from the chromatographic patt…
Internet-based perioperative exercise program in patients with Barrett’s carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomize…
2017
Abstract Background Patients undergoing surgery for esophageal cancer have a high risk for postoperative deterioration of lung function and pulmonary complications. This is partly due to one-lung ventilation during thoracotomy. This often accounts for prolonged stay on intensive care units, delayed postoperative reconvalescence and reduced quality of life. Socioeconomic disadvantages can result from these problems. Physical preconditioning has become a crucial leverage to optimize fitness and lung function in patients scheduled for esophagectomy, in particular during the time period of neoadjuvant therapy. Methods/Study design We designed a prospective multicenter randomized-controlled tria…
Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.
2001
AbstractThe bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S-phase. Use of wortmannin and caffeine suggests that this effect is no…
Satisfacción laboral de los asalariados en España
2012
El objetivo de este trabajo es identificar los factores determinantes del nivel de satisfacción laboral de los asalariados en España, haciendo especial hincapié en las diferencias de género y de nacionalidad. Para ello, se estima un modelo de respuesta múltiple ordenada, utilizando los datos de la Encuesta de Calidad de Vida en el Trabajo, para el período que abarca desde 2006 a 2010. Los resultados obtenidos muestran que, después de controlar por las características personales y laborales de los asalariados, se obtiene un diferencial positivo en la satisfacción laboral en favor de las mujeres, mientras que no se evidencia la existencia de un efecto diferencial entre los asalariados nativos…