The role of bone morphogenetic proteins and their signalling in human cancers

Both endogenous and exogenous GDF-9 led to a promotion in prostate cancer cell adhesion, invasion, motility, and growth. GDF-9 mediated growth promotion was shown to correlate with an increase in cell cycle progression via up-regulation of Cyclin D1, and protection from apoptosis in a Smad-independent manner. Furthermore, GDF-9 associated cell adhesion, motility, and invasion was shown to involve FAK, paxillin, and Rho-ROCK signalling, as well as EMT and its associated inducers. These effects promote the aggressiveness of PC-3 cells, aiding in their progression and possibly metastasis. These results suggest that GDF-9 is involved in prostate cancer progression by activation of a complex network of signalling pathways and molecules. This provides further proof of the importance of BMP signalling, and suggests that perhaps novel treatments for prostate cancer based on BMPs should be investigated. In addition, it sheds some light on the use of BMPs as prognostic indicators of disease, aiding in diagnosis, and perhaps future forms of treatment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Les didascalies dans Le Fils Naturel de Diderot

Dans cet article, Michèle Bokobza Kahan étudie les multiples aspects formels et fonctionnels du discours didascalique dans Le Fils naturel. Initialement destiné à indiquer les modalités du jeu de l’acteur, la didascalie déborde sa fonction première. Destinée à la fois au lecteur et au comédien, elle cumule dans le théâtre diderotien des fonctions utilitaires et des fonctions poétiques. L’appareil didascalique devient une couche énonciative supplémentaire à travers laquelle Diderot déploie un espace discursif qui révèle par des jeux de contrastes et de résonances les non-dits des personnages tout en développant une pensée plus nuancée d’ordre socio-culturel. Motivée par la volonté d’étudier l’actualisation dans le texte théâtral des idées que Diderot développe dans ses essais théoriques sur le théâtre, cette étude pose la question du rapport entre la matérialisation de l’espace, tributaire des didascalies, qui gouverne l’organisation matérielle des situations d’énonciation, et une problématique d’ordre idéologique qui parcourt et anime l’action dramatique à travers cette mise en place spatialeStage Directions in Diderot’s Fils naturelThis article studies the various formal and functional aspects of the stage directions in Le fils naturel, which go beyond their original purpose of directing the acting. In Diderot’s theatre they are for both the actor and the reader and have both utilitarian and poetic functions. They become a new level of enunciation, which the author uses to show, by means of contrasts and echoes, what the characters are leaving unsaid, while developing a more nuanced socio-cultural reflection. The present article, which aims at studying the way Diderot staged the ideas he developed in his theoretical writings on theatre, investigates, through this spatial disposition, the relationship between the materialisation of space (dependent on the stage instructions), governing the material organisation of the spoken word, and the ideological issues at the basis of the dramatic actio

Lire “Les Liaisons dangereuses” de Laclos par le prisme de l’œuvre quignardienne

The last short text in Pascal Quignard’s La Haine de la musique is called «Sur la fin des liaisons». By reinventing a happy ending to Laclos’ Liaisons dangereuses, Quignard offers a key for interpreting both his own work and that of Laclos. Far from being a simple exercise in dismantling the classic dramatic conclusion of a moral novel or being a ludic game of rewriting a famous scene of fiction, Quignard’s version opens up an unexpected path to a deepened interpretation of both authors. The aim of this article is to throw a light on the vital reciprocal literary relationship between Quignard and Laclos and to analyse the complexity of this precise intertextual relationship. Three main points that emerge from this literary confluence will be discussed here: both writers develop a deep concern with language and its impossible transparency; both maintain a climate of indecidability in their works; and the similarities between Quignard’s fragmentary and Laclos’ epistolary writing invite the reader to rethink the issues of both forms

The role of bone morphogenetic proteins and their signalling in human cancers

Both endogenous and exogenous GDF-9 led to a promotion in prostate cancer cell adhesion, invasion, motility, and growth. GDF-9 mediated growth promotion was shown to correlate with an increase in cell cycle progression via up-regulation of Cyclin D1, and protection from apoptosis in a Smad-independent manner. Furthermore, GDF-9 associated cell adhesion, motility, and invasion was shown to involve FAK, paxillin, and Rho-ROCK signalling, as well as EMT and its associated inducers. These effects promote the aggressiveness of PC-3 cells, aiding in their progression and possibly metastasis. These results suggest that GDF-9 is involved in prostate cancer progression by activation of a complex network of signalling pathways and molecules. This provides further proof of the importance of BMP signalling, and suggests that perhaps novel treatments for prostate cancer based on BMPs should be investigated. In addition, it sheds some light on the use of BMPs as prognostic indicators of disease, aiding in diagnosis, and perhaps future forms of treatmen

Introduction

Qu’est-ce qu’un auteur ? La question, d’une simplicité provocante (Foucault 1994 [1968]), fait rebondir un débat que Barthes pensait clore en tuant l’auteur (Barthes 1984 [1967]). Les deux textes, on le sait, constituent le point d’orgue de la fameuse querelle qui déchire le champ littéraire du 20e siècle entre ceux qui attribuent à l’auteur la pleine maîtrise de son texte (les « intentionnalistes » dans le jargon de la critique américaine) et ceux qui au contraire veulent penser la littératu..

Bone morphogenetic proteins in development and progression of breast cancer and therapeutic potential (review)

Bone morphogenetic proteins (BMPs) belong to the TGF-beta superfamily, which plays important roles in foetal and postnatal development and also maintains the homeostasis of various tissues and organs. Due to the critical role played by BMPs in bone formation and bone turnover, the implication of these molecules in bone metastasis has been intensively studied over the past decade. BMPs have been implicated in the development and progression of solid tumours, particularly the disease-specific bone metastasis. In breast cancer, a tumour type which most commonly metastasizes to bones, aberrations of both BMP expression and their signalling have been recently demonstrated. These aberrations have certain correlations with the development and progression of the disease. Recent in vitro studies have also demonstrated that BMPs can regulate a range of biological functions of breast cancer cells. Targeting BMPs or BMP signalling may provide novel therapeutic approaches for breast cancer. In the current review, we discuss the present knowledge on BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis

Phenotypic consequences of somatic mutations in the ataxia-telangiectasia mutated gene in non-small cell lung cancer

Mutations in the Ataxia-telangiectasia mutated (ATM) gene are frequently found in human cancers, including non-small cell lung cancer (NSCLC). Loss of ATM function confers sensitivity to ionising radiation (IR) and topoisomerase inhibitors and may thus define a subset of cancer patients that could get increased benefit from these therapies. In this study, we evaluated the phenotypic consequences of ATM missense changes reported in seven NSCLC cell lines with regard to radiosensitivity and functionality of ATM signalling. Our data demonstrate that only 2/7 NSCLC cell lines (H1395 and H23) harbouring ATM missense mutations show a functional impairment of ATM signalling following IR-exposure. In these two cell lines, the missense mutations caused a significant reduction in ATM protein levels, impairment of ATM signalling and marked radiosensitivity. Of note, only cell lines with homozygous mutations in the ATM gene showed significant impairment of ATM function. Based on these observations, we developed an immunohistochemistry-based assay to identify patients with loss or reduction of ATM protein expression in a clinical setting. In a set of 137 NSCLC and 154 colorectal cancer specimens we identified tumoral loss of ATM protein expression in 9.5% and 3.9% of cases, respectively, demonstrating the potential utility of this method

Tuning the Mechanical Properties in Model Nanocomposites: Influence of the Polymer-Filler Interfacial Interactions

This paper presents a study of the polymer-filler interfacial effects on filler dispersion and mechanical reinforcement in Polystyrene (PS) / silica nanocomposites by direct comparison of two model systems: un-grafted and PS-grafted silica dispersed in PS matrix. The structure of nanoparticles has been investigated by combining Small Angle Neutron Scattering (SANS) measurements and Transmission Electronic Microscopic (TEM) images. The mechanical properties were studied over a wide range of deformation by plate/plate rheology and uni-axial stretching. At low silica volume fraction, the particles arrange, for both systems, in small finite size non-connected aggregates and the materials exhibit a solid-like behavior independent of the local polymer/fillers interactions suggesting that reinforcement is dominated by additional long range effects. At high silica volume fraction, a continuous connected network is created leading to a fast increase of reinforcement whose amplitude is then directly dependent on the strength of the local particle/particle interactions and lower with grafting likely due to deformation of grafted polymer.Comment: Journal Polymer Science (2011