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Search Results: 1 - 10 of 3546 matches for " Stephan Duss "
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Hippo inactivation feeds tumor-initiating cells
Stephan Duss, Adrian Britschgi, Mohamed Bentires-Alj
Breast Cancer Research , 2012, DOI: 10.1186/bcr3190
Abstract: The Hippo signaling pathway was discovered more than 17 years ago in Drosophila mutant screens as a major regulator of organ size controlling proliferation and cell death [1]. This pathway is conserved and equally important in mammals and, not surprisingly, deregulation of the Hippo pathway plays fundamental roles in cancer [2,3]. Whereas the upstream components of the Hippo pathway (NF2, MST1/2, SAV1, LATS1/2, and MOB1A) are tumor suppressors, the downstream components (YAP1, TAZ and TEAD) are oncogenes [4]. The mammalian Hippo homolog kinases MST1/2 (macrophage stimulating 1/2) in complex with the scaffold protein SAV1 (salvador homolog 1), phosphorylate and activate the kinases LATS1/2 (large tumor suppressor homolog 1/2). LATS1/2 phosphorylate and inactivate the transcription co-activators YAP1 (Yes-associated protein 1) [5] and TAZ (transcriptional coactivator with PDZ-binding motif) [6]. Unphosphorylated YAP1/TAZ associate with TEAD (TEA domain family member 1) and activate their target genes [7] (Figure 1). TAZ binds heteromeric SMAD2/3-4, activates transforming growth factor-beta target genes and maintains human embryonic stem cell self-renewal [8]. Furthermore, TAZ enhances epithelial-to-mesenchymal transition (EMT), migration, invasion and tumorigenesis of breast cancer cell lines [6,9].Whereas many upstream components of the Hippo pathway in Drosophila [10] and zebrafish [11] have been identified, those in mammals remain poorly defined. The work of Cordenonsi and colleagues [12] indicates a role for EMT and the polarity gatekeeper Scribble upstream of the Hippo cascade in human breast tumor-initiating cells.To identify signaling pathways that drive breast tumorigenesis and heterogeneity, Cordenonsi and colleagues [12] analyzed a gene expression metadataset of breast tumors and found a TAZ/YAP signature to be correlated with high-grade (poorly differentiated) tumors. These tumors were previously shown to express embryonic and mammary stem cell signatures.
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion
Nicola Aceto, Stephan Duss, Gwen MacDonald, Dominique S Meyer, Tim-C Roloff, Nancy E Hynes, Mohamed Bentires-Alj
Breast Cancer Research , 2012, DOI: 10.1186/bcr3329
Abstract: Three-dimensional (3D) cultures, invasion and migration assays were used to determine the effects of HER2 and HER3 co-expression and activation. Gene expression analysis was performed to identify the gene network induced by HER2/HER3 in 3D cultures. Bioinformatic analysis and neutralizing antibodies were used to identify key mediators of HER2/HER3-evoked invasion.Co-expression of the tyrosine kinase receptors HER2 and HER3 induced migration and invasion of MCF10A cells. Microarray analysis of these cells revealed a specific "HER2/HER3 signature" comprising 80 upregulated transcripts, with IL8 being the highest (11-fold upregulation). Notably, examination of public datasets revealed high levels of IL8 transcripts in HER2-enriched as well as basal-like primary breast tumors, two subtypes characterized by a particularly poor prognosis. Moreover, IL8 expression correlated with high tumor grade and ER-negative status. Importantly, treatment with IL8-neutralizing antibodies prevented invasion of MCF10A-HER2/HER3 and BT474 cells in 3D cultures, highlighting the importance of IL8 autocrine signaling upon HER2/HER3 activation.Our findings demonstrate that HER2 and HER3 co-expression induces IL8 autocrine signaling, leading to the invasion of mammary cells. Agents targeting IL8 or its receptor CXCR1 may be useful for the treatment of HER2/HER3/IL8-positive breast cancers with invasive traits.HER2 (ErbB2) and HER3 (ErbB3) are members of a family of four receptor tyrosine kinases that also includes the epidermal growth factor receptor (HER1/EGFR) and HER4 (ErbB4) [1]. HER2 overexpression accounts for approximately 20% of all breast cancers and is commonly associated with a poor prognosis [2]. The importance of HER2 in cancer is highlighted by the clinical efficacy of the anti-HER2 humanized monoclonal antibody trastuzumab (Herceptin), especially when combined with chemotherapy, for the treatment of HER2-overexpressing breast cancers [3,4]. HER3 has been strongly implicated as a
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells
Stephan Duss, Sylvie André, Anne-Laure Nicoulaz, Maryse Fiche, Hervé Bonnefoi, Cathrin Brisken, Richard D Iggo
Breast Cancer Research , 2007, DOI: 10.1186/bcr1734
Abstract: Candidate genes were selected based on breast cancer microarray data and cloned into lentiviral vectors. Primary HMECs prepared from reduction mammoplasty tissue were infected with lentiviral particles. Infected HMECs were characterised by Western blotting, immunofluorescence microscopy, microarray analysis, growth curves, karyotyping and SNP chip analysis. The tumorigenicity of the modified HMECs was tested after orthotopic injection into the inguinal mammary glands of NOD/SCID mice. Cells were marked with a fluorescent protein to allow visualisation in the fat pad. The growth of the graft was analysed by fluorescence microscopy of the mammary glands and pathological analysis of stained tissue sections. Oestrogen dependence of tumour growth was assessed by treatment with the oestrogen antagonist fulvestrant.Microarray analysis of ERα-positive tumours reveals that they commonly overexpress the Polycomb-group gene BMI1. Lentiviral transduction with ERα, BMI1, TERT and MYC allows primary HMECs to be expanded in vitro in an oestrogen-dependent manner. Orthotopic xenografting of these cells into the mammary glands of NOD/SCID mice results in the formation of ERα-positive tumours that metastasise to multiple organs. The cells remain wild type for TP53, diploid and genetically stable. In vivo tumour growth and in vitro proliferation of cells explanted from tumours are dependent on oestrogen.We have created a genetically defined model of ERα-positive human breast cancer based on normal HMECs that has the potential to model human oestrogen-dependent breast cancer in a mouse and enables the study of mechanisms involved in tumorigenesis and metastasis.Classic epidemiological studies on the increase in cancer incidence with age predicted that from three to six independent events would be required to convert a normal cell into a tumour cell [1]. Experimental studies have now proven that it is indeed possible to transform a cell in culture by modifying the activity of only a few
H.H. Jakobs, Come per cagione di femine si rovina uno stato
Marco Duss
Forum Historiae Iuris , 2005,
Abstract:
Marie Theres F gen, Das Lied vom Gesetz.
Marco Duss
Forum Historiae Iuris , 2008,
Abstract:
El cadáver como texto estético: Avatares semióticos de la necroscopia
García Dussá,Eder;
Folios , 2007,
Abstract: taking the artistic performance "bodily worlds" as a principal reference from the german doctor gunther von hagens, an effort is advanced to interpret the textual event inside some conceptual tracks of the psychoanalysis. the museum-like vision of the corpse acts as a mirror of the human body across which the spectator satisfies his/her drive of death. the enjoyment, that surplus of the visual clash with this type of esthetic text, provokes a close relationship with a wish to know about the human being that its accepted or rejected by the spectator desires.
Rorty como el escéptico del giro lingüístico: la discusión con Habermas en torno a la comprensión del pragmatismo y los presupuestos para una política democrática
Prada Dussán,Maximiliano;
Folios , 2008,
Abstract: from the second half of twentieth century, with the driving force of authors like perelman and toulmin, the importance of rhetoric argument has been shown, in general, and of arguments by analogies, particularly, in the field of philosophy. more than being considered as literary figures, analogies serve to persuade in the field of line of argument, to comprehend philosophical problems, and to clarify questions of public worrying. in this paper, a case in which the discussion about inclusive democratic policies turns around an argument by analogy, will be analyzed. talking about the assumptions of a democratic policy, habermas and rorty discuss if it is required and possible to go to universal scenes of justification, in a way that may be possible to have a neutral criterion to validate interindividually the positions of the groups which are part of the current societies or if it can be only possible to appeal to contexts of justification and to contextual criteria for this goal. habermas 's argument, in order to disqualify to context of rorty as a solid position in the inclusive democracy, consists of tracing an analogy between pragmatism and skepticism, in a way that knowing in advance critics to this last idea, the first falls inside them too. from the image of the modern skeptical analogy proposes to create a image of pragmatism in order to disqualify it. discussion is centered, for that, in breaking the proposed analogy by habermas. in this paper is shown how it is build and shattered that analogy and what role argument plays by analogy there.
Crítica moral de Francis Bacon a la filosofía
Prada Dussán,Maximiliano;
Folios , 2009,
Abstract: this paper is about bacon's moral critique to philosophy. this critique is present in his youth work and it is developed in three levels: first, charges against philosophy because of its uselessness; second, accusations against philosophy's lack of truth and method; and, finally, charges against philosophy's lack of charity and humility. briefly, this study will state and support two hypotheses. 1. bacon′s reform is not restricted to a new method neither a new theory of matter; beyond this; it is a new moral position about man in relation to nature. 2. his epistemological project makes sense in the moral background.
Crítica moral de Francis Bacon a la filosofía Francis Bacon's moral critique to philosophy
Maximiliano Prada Dussán
Folios , 2009,
Abstract: Este escrito muestra la crítica moral de Bacon a la filosofía, presente en sus obras de juventud, la cual es desarrollada en tres niveles: primero, los cargos a la filosofía por su inutilidad, segundo, las acusaciones a la falta de verdad y de método y, finalmente, la denuncia de falta de caridad y humildad. En conclusión, este estudio intentará sustentar que 1. La reforma baconiana no se restringe a un nuevo método ni a una nueva teoría de la materia; más allá de esto, encuentra un sustento en una nueva posición moral del hombre frente a la naturaleza, y 2. Que su proyecto epistemológico encuentra sentido en el trasfondo moral. This paper is about Bacon's moral critique to philosophy. This critique is present in his youth work and it is developed in three levels: first, charges against philosophy because of its uselessness; second, accusations against philosophy's lack of truth and method; and, finally, charges against philosophy's lack of charity and humility. Briefly, this study will state and support two hypotheses. 1. Bacon′s reform is not restricted to a new method neither a new theory of matter; beyond this; it is a new moral position about man in relation to nature. 2. His epistemological project makes sense in the moral background.
Rorty como el escéptico del giro lingüístico: la discusión con Habermas en torno a la comprensión del pragmatismo y los presupuestos para una política democrática Rorty as a Sceptic of the Linguistic Turn: A discussion with Habermas related to the Pragmatism Comprehension and some presuppositions for the Democratic Policies
Maximiliano Prada Dussán
Folios , 2008,
Abstract: A partir de la segunda mitad del siglo XX, bajo el impulso de autores como Perelman y Toulmin, ha venido mostrándose la importancia de la argumentación retórica, en general, y de los argumentos por analogías, en particular, en el campo de la filosofía. Más que ser consideradas como figura literaria, las analogías sirven en el campo de la argumentación para persuadir, para comprender los problemas filosóficos y esclarecer cuestiones de preocupación pública. En este escrito se analiza un caso en el que la discusión acerca de las políticas democráticas inclusivistas gira en torno a un argumento por analogía. Al tratar sobre los presupuestos de una política democrática, Habermas y Rorty discuten si se requiere y si es posible acudir a escenarios universales de justificación, de modo que se tenga un criterio neutro para validar intersubjetivamente las posturas de los grupos que hacen parte de las sociedades actuales, o si podemos apelar solo a contextos de justificación y a criterios contextuales para este fin. El argumento de Habermas, para descalificar el contextualismo de Rorty como postura sólida en la democracia inclusivista, consiste en trazar una analogía entre el pragmatismo y el escepticismo, de modo que, al saber de antemano las críticas a esto último, el primero caiga también dentro de ellas. A partir de la imagen del escéptico moderno, la analogía propone crear una imagen del pragmatismo para descalificarlo. La discusión se centra, por ello, en romper la analogía propuesta por Habermas. En este escrito se muestra cómo se construye y cómo se deshace dicha analogía y qué papel juega allí el argumento por analogía. From the second half of twentieth century, with the driving force of authors like Perelman and Toulmin, the importance of rhetoric argument has been shown, in general, and of arguments by analogies, particularly, in the field of philosophy. More than being considered as literary figures, analogies serve to persuade in the field of line of argument, to comprehend philosophical problems, and to clarify questions of public worrying. In this paper, a case in which the discussion about inclusive democratic policies turns around an argument by analogy, will be analyzed. Talking about the assumptions of a democratic policy, Habermas and Rorty discuss if it is required and possible to go to universal scenes of justification, in a way that may be possible to have a neutral criterion to validate interindividually the positions of the groups which are part of the current societies or if it can be only possible to appeal to contexts of justification
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