Global ETD Search

61	Étude des propriétés oncogéniques des membres de la famille SNAIL / Analysis of the oncogenic properties of the SNAIL family members Gras, Baptiste 19 December 2012 (has links) En parallèle à son rôle dans l’initiation de la cascade métastatique, la transition épithéliomésenchymateuse est capable de faciliter la transformation néoplasique par le biais de mécanismes encore indéfinis. Nous avons démontré que, comme SNAIL1 et SNAIL2, l’expression de SNAIL3 est réactivée de façon aberrante dans les cancers humains, en particulier dans les carcinomes mammaires, établissant un lien entre l’ensemble des membres de la famille SNAIL et la tumorigénèse. Expérimentalement, les trois protéines SNAIL induisent une EMT avec des efficacités différentes. Ce différentiel reflète leur capacité à protéger les cellules de l’anoikis et à favoriser la prolifération dans des conditions de faible adhérence en absence d’altération oncogénique. La réversion partielle du processus d’EMT en réponse à l’expression ectopique des protéines ST14/Matriptase ou de l’E-cadhérine inhibe le potentiel oncogénique des protéines SNAIL. Nous avons donc démontré que la perte de protéines responsables du maintien de l’intégrité de l’épithélium contribue à l’activité pro-tumorale des inducteurs d’EMT / Beyond its role in initiating the metastatic cascade, cell commitment to the epithelial-to-mesenchymal transition program has been shown to facilitate neoplastic transformation, the underlying mechanisms yet remaining elusive. We herein demonstrate that likewise SNAI1 and SNAI2, the expression of SNAI3 is aberrantly reactivated in human cancers, mainly in breast carcinomas, linking all members of the SNAIL family to tumorigenesis. Experimentally, the three SNAIL proteins trigger EMT with unequal efficiencies. This differential mirrors their ability to protect cells from anoikis and to sustain proliferation in low-adherent conditions in absence of an oncogenic insult. Partial reversion of the EMT-process, achieved through forced expression of the ST14/Matriptase or E-cadherin proteins, alleviates the SNAIL oncogenic potential. We thus demonstrate that loss of epithelial integrity gatekeepers contributes to the tumor promoting activity of embryonic EMT-inducers Cancer Transition épithélio-mésenchymateuse Facteurs de transcription embryonnaires Transformation Initiation tumorale Famille SNAIL Jonctions cellulaires Cancer Epithelial-to-mesenchymal transition Embryonic transcription factors Transformation Tumor initiation SNAIL family Cell junctions 616.994
62	CLUSTERING AND VISUALIZATION OF GENOMIC DATA Sutharzan, Sreeskandarajan 26 July 2019 (has links) No description available. Bioinformatics Biology Botany RNA-Seq Gene Ontology network clustering nucleotide sequence clustering Self Organizing Map SOM NGS Influenza A virus HA Segment 4 retina regeneration epithelial to mesenchymal transition hypoxia prime number algorithm machine learning
63	Modeling cancer predisposition: Profiling Li-Fraumeni syndrome patient-derived cell lines using bioinformatics and three-dimensional culture models Phatak, Amruta Rajendra 07 October 2015 (has links) Indiana University-Purdue University Indianapolis (IUPUI) / Although rare, classification of over 200 hereditary cancer susceptibility syndromes accounting for ~5-10% of cancer incidence has enabled the discovery and understanding of cancer predisposition genes that are also frequently mutated in sporadic cancers. The need to prevent or delay invasive cancer can partly be addressed by characterization of cells derived from healthy individuals predisposed to cancer due to inherited "single-hits" in genes in order to develop patient-derived samples as preclinical models for mechanistic in vitro studies. Here, we present microarray-based transcriptome profiling of Li-Fraumeni syndrome (LFS) patient-derived unaffected breast epithelial cells and their phenotypic characterization as in vitro three-dimensional (3D) models to test pharmacological agents. In this study, the epithelial cells derived from the unaffected breast tissue of a LFS patient were cultured and progressed from non-neoplastic to a malignant stage by successive immortalization and transformation steps followed by growth in athymic mice. These cell lines exhibited distinct transcriptomic profiles and were readily distinguishable based upon their gene expression patterns, growth characteristics in monolayer and in vitro 3D cultures. Transcriptional changes in the epithelial-to-mesenchymal transition gene signature contributed to the unique phenotypes observed in 3D culture for each cell line of the progression series; the fully transformed LFS cells exhibited invasive processes in 3D culture with disorganized morphologies due to cell-cell miscommunication, as seen in breast cancer. Bioinformatics analysis of the deregulated genes and pathways showed inherent differences between these cell lines and targets for pharmacological agents. After treatment with small molecule APR-246 that restores normal function to mutant p53, we observed that the neoplastic LFS cells had reduced malignant invasive structure formation from 73% to 9%, as well as an observance of an increase in formation of well-organized structures in 3D culture (from 27% to 91%) by stereomicroscopy and confocal microscopy. Therefore, the use of well-characterized and physiologically relevant preclinical models in conjunction with transcriptomic profiling of high-risk patient derived samples as a renewable laboratory resource can potentially guide the development of safer and more effective chemopreventive approaches. Breast cancer progression Epithelial-to-mesenchymal transition Genomics Li-Fraumeni syndrome Preclinical in vitro models Three-dimensional culture Cancer -- Susceptibility Cancer -- Genetic aspects p53 protein p53 antioncogene Genetic transcription Cancer -- Molecular diagnosis
64	DIVERSE ROLES FOR EGF RECEPTOR SIGNALING IN THE BREAST CANCER TUMOR MICROENVIRONMENT Balanis, Nikolas G. January 2013 (has links) No description available. Bioinformatics Biochemistry Microbiology Molecular Biology breast cancer EGFR EGF Receptor Triple Negative Breast Cancer Epithelial-to-Mesenchymal Transition EMT focal adhesion fibronectin IL-6 JAK2 MIG6 STAT3 TNBC FN PYK2 FAK NMUMG Basal-like
65	Exploring the Neural-Tumor Synapse: The Effects of Serotonin on C6 Glioma Cells Coulson, Katarina Michelle 02 August 2017 (has links) No description available. Biology Cellular Biology Experiments Health Sciences Molecular Biology Morphology Neurobiology Neurosciences Oncology neural-tumor synapse serotonin 5-HT circadian rhythms epithelial-to-mesenchymal transition EMT C6 glioma cell morphology serotonin circadian rhythm serotonin dose response
66	Understanding the role of the matricellular protein SMOC-2 in renal cell carcinoma Feng, Daniel 08 1900 (has links) Les proteins matricellulaires (MPs) sont des macromolécules non structurales de la matrice extracellulaire (ECM) qui sont induites de façon transitoire lors du développement, de la réparation et du remodelage tissulaire et lors de l’inflammation. L’expression des MPs peut être déclenchée par des dommages tissulaires aigus, et leur expression à long terme peut contribuer à certaines maladies chroniques. Les MPs agissent principalement pour médier les événements du remodelage tissulaire en facilitant les interactions et les signaux à partir de l’ECM vers l’environnement cellulaire avoisinant. En utilisant des données de RNA-seq provenant de deux modèles distincts de dommages rénaux, soit l’Acide Folique (FA) ou l’Obstruction Urétérale Unilatérale (UUO), nous avons analysé les profils d’expressions de plusieurs familles bien connues de MPs lors des blessures aigues et chroniques. Nous révélons de nouvelles MPs impliquées dans les dommages rénaux et présentons de nouveaux réseaux entre les membres de chaque famille de MPs, en utilisant des outils bioinformatiques. L’expression de l’ARNm de certaines MPs a été confirmée par immuno-buvardage de type Western (WB). Afin d’approfondir notre connaissance des mécanismes de réparation tissulaire et de remodelage de la matrice, nous avons choisi SMOC-2 comme MP modèle dans l’étude des carcinomes cellulaires rénaux (RCC), cancers qui présentent de fortes tendances métastatiques. Nous avons démontré que la surexpression de SMOC-2 ainsi que le traitement avec la protéine recombinante de lignées cellulaires RCC (786-O, et ACHN) induisent un profil métastatique de transition épithélio-mésenchymateuse (EMT) par WB et des tests fonctionnels. Nous avons également démontré que l’inhibition de SMOC-2 par siRNA donne les résultats opposés. L’ensemble de nos travaux utilise la compréhension des patrons d’expressions temporels des MPs pour améliorer notre compréhension des mécanismes et conditions qui supportent une activation persistante dans des états pathologiques chroniques. Globalement, notre étude sur SMOC-2 offre une perspective ainsi qu’un modèle intéressant pour l’étude et la caractérisation de nouvelles MPs dans des maladies impliquant le remodelage et la réparation de la matrice. / Matricellular proteins (MPs) are non-structural ECM macromolecules induced transiently during development, tissue repair and remodeling, and inflammation. Expression of MPs can be triggered by acute tissue injury and their sustained expression can contribute to chronic disease. MPs primarily act to mediate tissue remodeling events by facilitating interactions and signals from the ECM to the surrounding cellular niche. Using published RNA-seq data from two distinct models of kidney injury, Folic Acid (FA) and Unilateral Ureteral Obstruction (UUO), we analyzed the expression profile of various members of well-known MP families during the acute and fibrotic injury phases. We reveal novel MPs implicated in renal injury and present informative networks between members of each MP family using bioinformatic tools. mRNA expression of select candidate MPs were confirmed by Western blot. To extend our understanding of translatable mechanisms in repair and matrix remodeling, we chose SMOC-2 as our MP model to study in Renal Cell Carcinoma (RCC) which has strong metastatic tendencies. SMOC-2 overexpression and recombinant protein treatment of RCC cell lines (786-O, ACHN) were shown to induce a metastatic EMT profile by Western blot analysis, supported by functional assays (proliferation, migration). Silencing SMOC-2 by siRNA showed the contrary results. Taken together, our work utilizes the understanding of temporal expression patterns of MPs to gain insight into mechanisms and conditions that support persistent activation in chronic injury states. Overall, our work with SMOC-2 provides a valuable perspective and template to approach studying and characterizing novel MPs in diseases involving pathological matrix remodeling and repair. protéine matricellulaire acide folique obstruction unilatérale de l'uretère matrice extracellulaire carcinome à cellules rénales métastase du cancer matricellular protein epithelial-to-mesenchymal transition folic acid unilateral ureteral obstruction extracellular matrix renal cell carcinoma cancer metastasis
67	Role of Ring1B in ephitelial to mesenchimal transition, invasion and migration of mammary epithelial cells Bosch Gutiérrez, Almudena 21 December 2009 (has links) The Polycomb group (PcG) family of proteins form chromatin-modifying complexes essential for embryonic development, and stem cell renewal and are commonly deregulated in cancer. There are several reports that address the possible implication of PcG proteins in tumor progression and metastasis, but very little is known about the specific role of these proteins in tumor progression and invasion. On the other hand, the molecular processes of the worst cancer prognosis, metastasis, which leads to an incurable disease, are yet incompletely elucidated. Here we show a role for Ring1B, a PcG protein, in three processes related to metastasis: in the Epithelial-mesenchymal transition (EMT), a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors, an in the migration and the invasion of mammary epithelial cells. / Las proteínas del grupo Polycomb (PcG) forman complejos modificadores de la cromatina esenciales en el desarrollo embrionario y en la renovación de las células madre, y su desregulación ha sido asociada al cáncer. Varios estudios muestran la posible implicación de las proteínas de PcG en la progresión tumoral y en la metástasis, pero a pesar de ello se sabe muy poco de los procesos moleculares en los que estas proteínas están participando. Por otro lado, los procesos moleculares responsables del peor pronóstico en cáncer, la metástasis, que continua siendo una enfermedad incurable, siguen sin estar completamente elucidados. En esta disertación mostramos el papel de Ring1B, una proteína del PcG, en tres procesos implicados en la metástasis: en la transición epitelio-mesénquima (EMT), un proceso morfogénico crítico en el desarrollo embrionario y durante la progresión de varios cánceres epiteliales, y en la migración y la invasión de las células epiteliales mamarias. Tgf- SIS3 (inhibidor específico de Smad3) Egf Hgf Tgf-β citoquina xenografo Kaplan-meier cáncer de mama humano inmunocitofluorescencia inmunohistoquímica ChIP (immunoprecipitación de cromatina) western blot ADN proteína ARN DCIS (carcinoma ductal in situ) IDC (carcinoma ductal infiltrante) E-caderina célula epitelial glándula mamaria invasión migración metástasis transición epitelio mesénquima cancer mama familia p53 Fak epigenética p63 Ring1b Polycomb SIS3 (specific inhibitor of smad3) Egf Tgf- Hgf Tgf-β cytokine xenograft Kaplanmeier human breast cancer immunocytofluorescence immunohistochemistry ChIP (chromatin immunoprecipitation) DNA protein western blot RNA IDC (infiltrating ductal carcinoma) DCIS (ductal carcinoma in situ) E-cadherin epithelial cell mammary gland invasion migration metastasis epithelial to mesenchymal transition cancer breast p53 family Fak p63 Ring1B epigenetic Polycomb 57 61

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