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Search Results: 1 - 10 of 330508 matches for " Dominique S Meyer "
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Can phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibition ERase them all?
Dominique S Meyer, Mohamed Bentires-Alj
Breast Cancer Research , 2010, DOI: 10.1186/bcr2718
Abstract: Tamoxifen, which interferes with estrogen for receptor binding, was the first successful targeted therapy and has been the treatment of choice for estrogen receptor (ER)-positive breast cancers for more than two decades. Unfortunately, resistance occurs in approximately 30% of patients and the mechanisms of resistance act directly on the ER pathway and/or activate parallel pathways that block the anti-proliferative and pro-apoptotic actions of tamoxifen [1,2]. For example, increased mitogen-activated protein kinase (MAPK) and phosphatidyl-inositol 3-kinase (PI3K) signaling downstream of growth factor receptors (for example, ERBB2 and Insulin-like growth factor 1 receptor (IGF-1R)) has been implicated in a crosstalk with ER and in resistance to endocrine therapy [1-3].The PI3K pathway, a central regulator of diverse normal cellular functions, is very often subverted during neoplastic transformation and contributes to several hallmarks of cancer that result in a competitive advantage for cancer cells [4-6]. Not surprisingly, the PI3K cascade is an attractive therapeutic target and several inhibitors are currently in phase I/II clinical trials. Preclinical studies have shown that PI3K inhibition circumvents resistance to trastuzumab in ERBB2-positive breast cancers and this has led to clinical trials combining anti-ERBB2 and anti-PI3K therapies [7]. Although PI3K has been implicated in resistance to endocrine therapy of ER-positive tumors, several questions remain unanswered. Is PI3K inhibition, alone or in combination with tamoxifen, effective in tamoxifen-resistant ER-positive cancer cells? Does PI3K inhibition block the emergence of tamoxifen resistance? Does a PI3K hyperactivation signature in human tumors predict tamoxifen sensitivity? Two recent papers now provide some answers to these outstanding questions.Creighton and colleagues [8] investigated the relationship between the PI3K pathway and ER levels and activity using breast cancer cell lines and data sets of
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
Allelotyping identification of genomic alterations in rectal chromosomally unstable tumors without preoperative treatment
Beno?t Romain, Agnès Neuville, Nicolas Meyer, Cécile Brigand, Serge Rohr, Anne Schneider, Marie-Pierre Gaub, Dominique Guenot
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-561
Abstract: Genomic alterations of 57 rectal tumors assessed by allelotyping targeting 33 chromosomal loci, were clusterised and compared to those of 151 left colon tumors.Clustering separated the rectal tumors without preoperative treatment into three subtypes according to the allelic imbalance frequency and genomic alteration associations. The tumors without preoperative treatment displayed a significantly higher allelic imbalance frequency (54%) than the tumors with preoperative treatment (33%), suggesting that treatment could target highly altered tumor clones. Interestingly, the survival analysis identified three potential prognostic molecular survival markers, D1S197, D5S430, and D14S65, for tumors without preoperative treatment.Based on the genomic status of 33 chromosomal loci, we observed that rectal tumors without preoperative treatment segregate according to the global allelic imbalance frequency but without correlation to the tumor progression. Moreover, the detailed associations of alterations in rectal tumors are different from those described in colon tumors suggesting that rectal and left tumors should be considered as separate entities. Finally, potential prognostic genomic molecular markers for survival are proposed which status could specify the clinical course of the tumors.Colorectal cancer is the second most common cause of cancer deaths in the Western world after lung cancer for men and breast cancer for women [1]. In 2000, in France, the incidence of colorectal cancer was 36 300 patients, and there are approximately 12 000 new cases of rectal cancers diagnosed per year [2,3].A multistep process involving mutational events in both oncogenes and tumor suppressor genes is now accepted worldwide for the development of most cancers. In the current model of the stepwise progression of colorectal carcinogenesis [4], each step is initiated by the acquisition of additional genomic abnormalities that confer a growth advantage to the targeted cell. Because of the i
Cotunneling, current blockade, and backaction forces in nanobeams close to the Euler buckling instability
Guillaume Weick,Dominique M. -A. Meyer
Physics , 2011, DOI: 10.1103/PhysRevB.84.125454
Abstract: Single-electron transistors embedded in a vibrating nanoresonator such as a doubly-clamped carbon nanotube exhibit effects stemming from the coupling between electronic and vibrational degrees of freedom. In particular, a capacitive electromechanical coupling induces a blockade of the current at low bias voltage. It has been recently shown theoretically within a sequential-tunneling approximation that this current blockade can be enhanced by orders of magnitude when the suspended structure is brought to the Euler buckling instability. Here, we investigate the role of cotunneling on the predicted enhancement and show that the latter is not suppressed by cotunneling effects. We further demonstrate that despite the fact that the current blockade is difficult to measure far from the Euler instability, the backaction of the current flow on the nanobeam frequency may be easier to observe.
“We who cannot speak lived there first”: A new claim to land in My plaas se naam is Vergenoeg by George Weideman
S Meyer
Tydskrif vir letterkunde , 2012,
Abstract: My plaas se naam is Vergenoeg (“My farm’s name is Vergenoeg [‘Far Enough’]”, 2005), a published play by George Weideman, is meaningful within the context of postcolonial discourse on land ownership and ecocritical views on the use of land. The play adds viewpoints to current postcolonial claims to land through several animal characters laying claim to being the first inhabitants, further commenting critically on man’s greed and destructiveness with regard to the earth. This article undertakes an analysis of the play, firstly investigating the messages of these non-human voices, rarely remembered or heard in the historical constructions of South Africa’s past. It focuses on Weideman’s blending of aspects of different genres and periods, the animal epic and classical Greek tragedy, resulting in a powerful downplay of man’s claim to sole ownership of the land. The study, secondly, considers the notion of landscape as defined by animals’ ways of inhabiting and interaction, in addition to the notion of landscape as a cultural construct that is traditionally defined by man’s ways of inhabiting and interaction.
Heterotopiese ruimtes van krisis en die natuur se genesende invloed in "Chinchilla" (Nanette van Rooyen)
S Meyer
Tydskrif vir letterkunde , 2010,
Abstract: Crises heterotopias and nature’s healing influence in Chinchilla (Nanette van Rooyen) In this article, Michel Foucault’s term crises heterotopia is used to understand and describe the main character’s unique experience of particular places in Chinchilla. The article investigates the manner in which nature becomes part of the experience of crises heterotopias, and how the natural environment creates a space conducive to the processing of trauma within the novel. Images and experiences of nature offer the main character a “bridge” to an expressive representation of events that could not initially be otherwise verbalised. Contact with and influences from nature contribute to a new spiritual calm, energy, and perspective, as well as a rediscovery of her intuitive feminine wisdom and powers that leads to positive decisions regarding the future. Taking care of nature’s creatures leads to the recognition of some aspects of the main character’s own situation, and provides the associative stimuli for reliving the suppressed traumatic events; thereby helping to lift the silence, which aids the healing of the traumatised character in the story.
Natuur en (skrywende) mens: Petra Müller se verhaalkuns binne die raamwerk van letterkunde as kulturele ekologie
S Meyer
Tydskrif vir letterkunde , 2010,
Abstract: Nature and (writing) being: Petra Müller’s narrative art within the model of literature as cultural ecology Petra Müller’s collection of narrative works, Desembers (“Decembers”, 2007), allows for an investigation into the portrayal of identity aspects that occupy a central position in her oeuvre: the relationship between man and nature as well as the nature of authorship. These narratives reflect upon a human being’s place in the wide community of earth’s beings and forces, and elucidate the multiple levels of communication between man and other living creatures, which is possible by sensory awareness and by embracing the “voices of silence” beyond the range of human language. In this article Müller’s narratives are explored within the framework of literature as cultural ecology, including their becoming part of a re-integrative interdiscourse by means of reintegrating in the realm of imaginative literature the excluded to the cultural reality system. Müller often links natural objects to the creation of stories/art, thus integrating the spheres of nature and culture. This is done by reconstructing objects from nature, by means of imagination and by transcending reality, into symbols of the author’s/artist’s activity.
Improved 3-D Particle Tracking Velocimetry with Colored Particles  [PDF]
Christian Bendicks, Dominique Tarlet, Christoph Roloff, Robert Bordás, Bernd Wunderlich, Bernd Michaelis, Dominique Thévenin
Journal of Signal and Information Processing (JSIP) , 2011, DOI: 10.4236/jsip.2011.22009
Abstract: The present work introduces an extension to three-dimensional Particle Tracking Velocimetry (3-D PTV) in order to investigate small-scale flow patterns. Instead of using monochrome particles the novelty over the prior state of the art is the use of differently dyed tracer particles and the identification of particle color classes directly on Bayer raw images. Especially in the case of a three camera setup it will be shown that the number of ambiguities is dramatically decreased when searching for homologous points in different images. This refers particularly to the determination of spatial parti- cle positions and possibly to the linking of positions into trajectories. The approach allows the handling of tracer parti- cles in high numbers and is therefore perfectly suited for gas flow investigations. Although the idea is simple, difficult- ties may arise particularly in determining the color class of individual particle when its projection on a Bayer sensor is too small. Hence, it is not recommended to extract features from RGB images for color class recognition due to infor- mation loss during the Bayer demosaicing process. This article demonstrates how to classify the color of small sized tracers directly on Bayer raw images.
Efeito da Visita/N o-Visita na Imagem de um destino turístico: Uma aproxima o metodológica mista.
Sérgio Dominique Ferreira
Revista Turismo em Análise , 2011,
Abstract: ResumoO turismo é atualmente um dos setores mais preponderantes da economia de Portugal, representando 13% do PIB e 12% da empregabilidade gerada. Neste sentido, orientar a gest o de destinos turísticos desde um enfoque de Marketing pressup e uma análise cuidada da imagem de marca. Neste contexto, o principal objetivo do presente trabalho consiste em recorrer ao enfoque misto proposto por Echtner e Ritchie (1991, 1993), para avaliar em que medida a visita/n o-visita a um destino turístico influencia a imagem que estes desenvolvem sobre destinos turísticos. Os resultados obtidos permitem constatar que n o existem diferen as consideráveis entre a imagem formada pelos turistas que já visitaram Portugal e aqueles que nunca visitaram. Em consequência, sugere-se que, em futuros estudos, se analise o efeito da proximidade entre o local de residência dos turistas e o destino.Palavras-chave: marketing turístico; gest o turística; imagem de destinos turísticos; metodologia mista; efeito da visita na imagem. Nowadays, Tourism is one of the most important sectors of the Portuguese economy, representing 13% of GDP and generating 12% of the employability. In this sense, manage tourist destinations from a marketing approach requires a careful analysis of brand image. In this context, the main objective of this work is to use the mixed approach proposed by Echtner and Ritchie (1991, 1993), to assess the extent to which visiting / not visiting a tourist destination influences the image formed. The results
Stock and Flow of Carbon in Plant Woody Debris in Two Different Types of Natural Forests in Bateke Plateau, Central Africa  [PDF]
Averti S. Ifo, Felix Koubouana, Charlotte Jourdain, Dominique Nganga
Open Journal of Forestry (OJF) , 2015, DOI: 10.4236/ojf.2015.51005
Abstract: In order to know the role of plant woody debris in the carbon cycle, a study of carbon stocks and carbon flow of plant woody debris was conducted in the natural forests of the centre of the republic of Congo in the Bateke Plateau. Allometric equations were used to measure the carbon stock of in dead wood debris of Lesio-louna tropical rainforest. Three plots of 40 m × 40 m were delimited in each forest types. All plots were within 300 m of each other. The average stocks of carbon in coarse woody debris obtained are 10993 g·m-2 and 14172 g·m-2, respectively, in the Gallery forest (GF) and the hill-slope forest clump (HF), the difference of carbon stock between the two forests is not significant (p = 0.78). The interannual mean flow in both forests is respectively 1776 and 545 g·m-2·an-1 in the FG and the MSDS; this medium is not significant (p = 0.10). Carbon stocks of fine woody debris are respectively 965 and 83 g·m-2 in the GF and HF, difference is significant (p = 0.0013). The interannual mean flow of carbon in fine woody debris in the GF and the HF were respectively 310 g·m-2·an
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