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Search Results: 1 - 10 of 5141 matches for " Erik HJ Danen "
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Integrins and Oncogenes: Partners in Crime
Jordi Carreras Puigvert,Louise von Stechow,Bob van de Water,Erik HJ Danen
Molecular and Cellular Pharmacology , 2009,
Abstract: Metastatic spread and acquired or intrinsic resistance to existing therapies form the two major obstacles in cancer treatment. Accumulating evidence indicates that cancer growth, metastasis, and the response to therapy are strongly affected by integrin-mediated interactions with the extracellular matrix (ECM) in the tumor microenvironment. Indeed, altered expression levels of various integrins has been associated with poor differentiation, increased metastasis, and decreased overall and recurrence-free survival after radio- or chemotherapy in different types of cancer. Recent evidence indicates that the role of specific integrins in cancer progression and treatment response depends on the spectrum of oncogenic mutations present in cancer cells. In this PharmSight, we discuss several examples of such cross talk between integrins and oncogenes that may point to new avenues for cancer therapy.
Integrin Signaling as a Cancer Drug Target
Erik H. J. Danen
ISRN Cell Biology , 2013, DOI: 10.1155/2013/135164
Abstract: Integrins are transmembrane receptors that mediate cell adhesion to neighboring cells and to the extracellular matrix. Here, the various modes in which integrin-mediated adhesion regulates intracellular signaling pathways impinging on cell survival, proliferation, and differentiation are considered. Subsequently, evidence that integrins also control crucial signaling cascades in cancer cells is discussed. Lastly, the important role of integrin signaling in tumor cells as well as in stromal cells that support cancer growth, metastasis, and therapy resistance indicates that integrin signaling may be an attractive target for (combined) cancer therapy strategies. Current approaches to target integrins in this context are reviewed. 1. Integrin-Mediated Cell Adhesion 1.1. Cell Adhesion Cells within multicellular organisms are typically attached to each other and to the extracellular matrix (ECM). ECM is a meshwork of various glycoproteins that exists in many forms, including laminin-rich basement membranes that align tissues, pliable matrices made from fibrilar networks of collagens, rigid collagen-based bone matrices, and provisional fibronectin-containing matrices associated with active processes such as wound healing and angiogenesis [1]. Various adhesion molecules, such as those belonging to the cadherin family, mediate cell-cell contacts. Likewise, interactions with the ECM also occur through a variety of receptors, including syndecans, dystroglycans, and integrins. 1.2. Integrins Integrin cell adhesion receptors participate in cell-cell and cell-ECM interactions [2]. This large family of heterodimeric transmembrane receptors recognizes a plethora of extracellular ligands, including transmembrane receptors on other cells and ECM proteins. The common integrin-binding motif, Arg-Gly-Asp (RGD), is shared by several ECM proteins, including fibronectin, vitronectin, and fibrinogen. Integrin binding to laminins and collagens occurs at other recognition motifs. Integrins participating in cell-cell adhesion bind counter receptors such as a disintegrin and metalloproteases (ADAMs), or immunoglobulin-type receptors such as intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecules (VCAMs) that are expressed on leukocytes and endothelial cells. 1.3. Integrin Evolution Clearly, integrins are essential receptors in mammalian development, and adult life. Studies in mice have attributed roles to certain integrins already at very early stages of development while others play specific roles later in the adult. In fact, integrins are found throughout
The Interaction of Src Kinase with β3 Integrin Tails: A Potential Therapeutic Target in Thrombosis and Cancer
Stephan Huveneers,Erik H. J. Danen
The Scientific World Journal , 2010, DOI: 10.1100/tsw.2010.114
Identification of Cisplatin-Regulated Metabolic Pathways in Pluripotent Stem Cells
Louise von Stechow, Ainhoa Ruiz-Aracama, Bob van de Water, Ad Peijnenburg, Erik Danen, Arjen Lommen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076476
Abstract: The chemotherapeutic compound, cisplatin causes various kinds of DNA lesions but also triggers other pertubations, such as ER and oxidative stress. We and others have shown that treatment of pluripotent stem cells with cisplatin causes a plethora of transcriptional and post-translational alterations that, to a major extent, point to DNA damage response (DDR) signaling. The orchestrated DDR signaling network is important to arrest the cell cycle and repair the lesions or, in case of damage beyond repair, eliminate affected cells. Failure to properly balance the various aspects of the DDR in stem cells contributes to ageing and cancer. Here, we performed metabolic profiling by mass spectrometry of embryonic stem (ES) cells treated for different time periods with cisplatin. We then integrated metabolomics with transcriptomics analyses and connected cisplatin-regulated metabolites with regulated metabolic enzymes to identify enriched metabolic pathways. These included nucleotide metabolism, urea cycle and arginine and proline metabolism. Silencing of identified proline metabolic and catabolic enzymes indicated that altered proline metabolism serves as an adaptive, rather than a toxic response. A group of enriched metabolic pathways clustered around the metabolite S-adenosylmethionine, which is a hub for methylation and transsulfuration reactions and polyamine metabolism. Enzymes and metabolites with pro- or anti-oxidant functions were also enriched but enhanced levels of reactive oxygen species were not measured in cisplatin-treated ES cells. Lastly, a number of the differentially regulated metabolic enzymes were identified as target genes of the transcription factor p53, pointing to p53-mediated alterations in metabolism in response to genotoxic stress. Altogether, our findings reveal interconnecting metabolic pathways that are responsive to cisplatin and may serve as signaling modules in the DDR in pluripotent stem cells.
Automated Whole Animal Bio-Imaging Assay for Human Cancer Dissemination
Veerander P. S. Ghotra, Shuning He, Hans de Bont, Wietske van der Ent, Herman P. Spaink, Bob van de Water, B. Ewa Snaar-Jagalska, Erik H. J. Danen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031281
Abstract: A quantitative bio-imaging platform is developed for analysis of human cancer dissemination in a short-term vertebrate xenotransplantation assay. Six days after implantation of cancer cells in zebrafish embryos, automated imaging in 96 well plates coupled to image analysis algorithms quantifies spreading throughout the host. Findings in this model correlate with behavior in long-term rodent xenograft models for panels of poorly- versus highly malignant cell lines derived from breast, colorectal, and prostate cancer. In addition, cancer cells with scattered mesenchymal characteristics show higher dissemination capacity than cell types with epithelial appearance. Moreover, RNA interference establishes the metastasis-suppressor role for E-cadherin in this model. This automated quantitative whole animal bio-imaging assay can serve as a first-line in vivo screening step in the anti-cancer drug target discovery pipeline.
Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value
Martinus AM van Boekel, Erik R Vossenaar, Frank HJ van den Hoogen, Walther J van Venrooij
Arthritis Research & Therapy , 2001, DOI: 10.1186/ar395
Abstract: RA is a common systemic autoimmune disease with a prevalence of about 1% worldwide. Although the etiology of the disease is still unknown, several risk factors have been identified. Like many autoimmune diseases, RA occurs more frequently in women than in men (3:1 ratio), suggesting a role for sex hormones. Genetic studies have demonstrated that a genetic predisposition resides in the HLA-DR locus. There is also evidence that environmental factors, such as infectious agents, oral contraceptives and smoking, may play a role [1].RA is characterized by inflammation of the synovial membrane of diarthrodial joints. Early indications of RA are swelling and pain of the proximal interphalangeal and metacarpophalangeal joints. Later, the larger joints become affected, especially those of the knee, elbow and ankle. Large numbers of activated leukocytes infiltrate the synovial membrane, causing hyperplasia and inflammation, which in most cases leads to progressive destruction of cartilage and bone. Since RA is a systemic autoimmune disease, other parts/organs of the body may become affected at a later stage. An example of this is the formation of rheumatoid noduli. Peak onset typically occurs in the fourth and fifth decades of life.With more sophisticated types of therapy becoming available, it is becoming more important to diagnose RA at an early stage of the disease, so that earlier treatment can be applied and major damage of joint tissue can be prevented. It is during the first period of the disease, when not all clinical parameters are manifest, that a specific and sensitive serological test is needed. Even more helpful would be the serological test being able to predict, in an early phase of RA, the erosive or nonerosive progression of the disease.Over the past 25 years, many autoantibody activities in RA have been described. This review summarizes the most relevant, and attempts to discuss their specificity and possible diagnostic and prognostic value. We shall distingu
DYNA , 2011,
Abstract: the major sources of water pollution can be classified as municipal, industrial, and agricultural. different types of polluted aqueous effluents and sediments may be produced, which contain relatively high levels of heavy metals. during the 1990s, the large-scale development of constructed wetlands around the world drew much attention from public and environmental groups. the present study looks at the use of an integrated remediation system using zeolites for the treatment of wastewater and sediments. zeolites have been widely studied in the past 10 years due to their attractive properties such as molecular-sieving, high cation exchange capacities, and their affinity for heavy metals. coal industry by-products-based zeolites (faujasite type) have been tested as an effective and low-cost novel alternative for wastewater treatment, particularly their removing of heavy metals. on the other hand, a preliminary laboratory-scale experiment was conducted on the use of natural zeolites (clinoptilolite type) for the retention of heavy metals from canal sediments. experimental work revealed promising results, which could be replicated on a bigger scale. although this has been developed for canal sediments, the remediation strategy can be adapted to different waterways such as rivers. the development of the proposed remediation system in a specific experimental site as the major part of an innovation park can provide great benefits to a population living near contaminated effluents. it provides not only opportunities for the mitigation of environmental impact, improving water quality and landscape amenity, but also allows for several recreational opportunities.
DYNA , 2011,
Abstract: Las principales fuentes de contaminación del agua pueden ser clasificadas como urbanas, industriales y agrícolas. Diferentes tipos de efluentes acuosos y sedimentos contaminados pueden ser producidos, los cuales contienen niveles relativamente altos de metales pesados. Durante la década de los 90s, el desarrollo a gran escala global de humedales construidos dirigió la atención de grupos públicos y ambientalistas. El presente estudio examina el uso de un sistema de remediación integrado usando zeolitas para el tratamiento de aguas residuales y sedimentos. Las zeolitas han sido ampliamente estudiadas en la última década debido a sus propiedades atractivas como tamizado molecular, alta capacidad de intercambio catiónico y afinidad por metales pesados. Zeolitas (tipo faujasita) sintetizadas a partir de sub-productos de la industria del carbón han sido probadas como una novedosa alternativa eficaz y de bajo costo para el tratamiento de aguas residuales, en particular en la eliminación de metales pesados. Por otra parte, una experimentación preliminar a escala de laboratorio se llevó a cabo sobre el uso de las zeolitas naturales (tipo clinoptilolita) para la eliminación de metales pesados de sedimentos de canal. El trabajo experimental revelo resultados prometedores, que podrían reproducirse en una mayor escala. Aunque esto se ha desarrollado para los sedimentos de canal, la estrategia de remediación se puede adaptar a diferentes cursos de agua tales como ríos. El desarrollo del sistema de remediación propuesto en un sitio experimental específico, representando la parte más importante de un parque de innovación, puede proporcionar grandes beneficios a la población que vive cerca de efluentes contaminados. Ofrece no sólo oportunidades para la mitigación del impacto ambiental, la mejora de la calidad del agua y la amenidad del paisaje, sino también varias oportunidades de recreación.
Molecular epidemiology and evolution of avian infectious bronchitis virus
Montassier, HJ;
Revista Brasileira de Ciência Avícola , 2010, DOI: 10.1590/S1516-635X2010000200003
Abstract: mutation and recombination processes are involved in the genetic and phenotypic variations of rna viruses, leading to the emergence of new variant strains, and give rise to virus population diversity to be modeled by the host, particularly by the immune system, as occurred with infectious bronchitis virus (ibv) in chickens. the consequence is a continuous emergence of new ibv variants with regard to pathotypes, serotypes, and protectotypes. nucleotide sequencing and subsequent genetic analysis of the s1 and n protein gene sequences provide a fast and accurate method to classify and predict ibv genotype, and a powerful instrument to monitor phylogenetic and epidemiological evolution of ibv variants. despite the use of vaccination programmes, infectious bronchitis has become a serious problem in brazil. thus, a significant number of ibv field variants have been identified circulating in the brazilian commercial poultries between 2000 to 2006 and more recently in argentina. these viruses seem to be indigenous, because they demonstrated a low genetic relatedness with the majority of the reference strains from north america, europe and asia, but were moderately to highly related one to another. in summary, indigenous field ibv variants were evolving and circulating in the field in brazil and argentina, and should be considered as initial candidates for protection against current ibv infectious in chickens. however, in vitro and in vivo studies are needed to determine the pathogenicity and immunogenecity of these new isolates, before defining a new vaccine strain.
Missional theology and social development
HJ Hendriks
HTS Theological Studies/Teologiese Studies , 2007,
Abstract: The article describes a theological paradigm shift taking place in congregations in South Africa that empower them to become involved in development work as a way of serving their neighbor. It also opens the possibility of working interdisciplinary without compromising theological and faith values. The perspectives and assumptions of the new paradigm are outlined and the basic methodology of doing theology is described. The new paradigm is a missional one, taking the focus on God as its point of departure and describing the identity and purpose of the church by looking at God's identity and plan or mission with creation and humankind. Social development is seen as being in line with God's mission and as such the church should not have difficulty in working with those who pursue the same goals. HTS Theological Studies Vol. 63 (3) 2007: pp. 999-1016
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