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  • 1
    Keywords: IN-VITRO ; INDUCED APOPTOSIS ; CELL-CYCLE CONTROL ; DNA-DAMAGE ; MAMMALIAN-CELLS ; ABL TYROSINE KINASE ; TUMOR-SUPPRESSOR ; HUMAN CANCER ; ACUTE MYELOID-LEUKEMIA ; C-ABL
    Abstract: Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by erufosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status.
    Type of Publication: Journal article published
    PubMed ID: 24987858
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  • 2
    Keywords: brain ; EXPRESSION ; CELL ; Germany ; IN-VIVO ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PROTEIN ; PROTEINS ; transcription ; METABOLISM ; ACCUMULATION ; MICE ; ACTIVATION ; INDUCTION ; BINDING ; BIOLOGY ; MOLECULAR-BIOLOGY ; PHOSPHORYLATION ; STIMULATION ; ACID ; CAMP ; CELL-SURVIVAL ; DELETION ; hippocampus ; MUTANT ; NERVOUS-SYSTEM ; PATTERNS ; gene expression ; MUTATION ; cholesterol ; INSIGHTS ; BINDING PROTEIN ; molecular biology ; molecular ; RE ; PATTERN ; GENOME-WIDE ANALYSIS ; NEURONS ; FOREBRAIN ; USA ; neurodegeneration ; HOMEOSTASIS ; synthesis ; PLASTICITY ; CELL BIOLOGY ; cocaine plasticity ; Cre/loxP
    Abstract: Induction of specific gene expression patterns in response to activity confers functional plasticity to neurons. A principal role in the regulation of these processes has been ascribed to the cAMP responsive element binding protein (CREB). Using genome-wide expression profiling in mice lacking CREB in the forebrain, accompanied by deletion of the cAMP responsive element modulator gene (CREM), we here show that the role of these proteins in activity-induced gene expression is surprisingly selective and highly context dependent. Thus, only a very restricted subset of activity-induced genes (i.e., Gadd45b or Nr4a2) requires these proteins for their induction in the hippocampus after kainic acid administration, while they are required for most of the cocaine-induced expression changes in the striatum. Interestingly, in the absence of CREB, CREM is able to rescue activity-regulated transcription, which strengthens the notion of overlapping functions of the two proteins. In addition, we show that cholesterol metabolism is dysregulated in the brains of mutant mice, as reflected coordinated expression changes in genes involved in cholesterol synthesis and neuronal accumulation of cholesterol. These findings provide novel insights into the role of CREB and CREM in stimulus-dependent transcription and neuronal homeostasis
    Type of Publication: Journal article published
    PubMed ID: 18424767
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  • 3
    Keywords: RECEPTOR ; EXPRESSION ; CELL ; Germany ; GENERATION ; SYSTEM ; GENE-EXPRESSION ; RNA ; EFFICIENCY ; MICE ; TRANSCRIPTION FACTOR ; BIOLOGY ; MOLECULAR-BIOLOGY ; ACIDS ; TRANSGENIC MICE ; NUCLEAR-FACTOR ; DESIGN ; VECTOR ; LINE ; DELIVERY ; MAMMALIAN-CELLS ; STEM-CELLS ; NETHERLANDS ; molecular biology ; molecular ; RE ; INTERFERENCE ; RNA INTERFERENCE ; GAMMA ; LENTIVIRAL VECTOR ; methods ; NUCLEAR ; function ; TRANSMISSION ; microbiology ; lentiviral vectors ; MicroRNAs ; mosaicism ; biotechnology ; INTERFERING RNAS ; SIRNAS ; Transgenesis ; TRANSGENIC RATS
    Abstract: We have used a lentiviral delivery system (LentiLox3.7) to generate transgenic mice harbouring RNA interference (RNAi) against the hepatocyte nuclear factor 4 gamma (HNF4(gamma)). HNF4(gamma) is a nuclear receptor with unknown function. Our analyses performed on founder (F-0) and first generation (F-1) mice revealed mosaicism in F-0 founders and a low efficiency of transgenesis (6%) in F-1 mice. These data, together with the observation of multiple silenced transgenes, do not favour the use of LentiLox3.7 lentivirus for transgenesis. Despite the low efficiency of transgenesis, we achieved a tissue-dependent knockdown of HNF4(gamma) expression in some mice
    Type of Publication: Journal article published
    PubMed ID: 17682835
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  • 4
    Keywords: CANCER ; CELLS ; GROWTH ; IN-VITRO ; tumor ; CELL ; Germany ; human ; LUNG ; THERAPY ; TOOL ; liver ; POPULATION ; GENE ; GENES ; PROTEIN ; DIFFERENTIATION ; gene therapy ; MICE ; TRANSDUCTION ; gene transfer ; GENE-TRANSFER ; kidney ; BONE-MARROW ; MOUSE ; NUMBER ; genetics ; NUDE-MICE ; FUSION ; MIGRATION ; STEM-CELLS ; PROGENITOR CELLS ; SELECTION ; GENE-THERAPY ; RETROVIRAL VECTORS ; pancreatic cancer ; heredity ; VELOCITY ; ONCOLOGY ; homing ; XENOGRAFTS ; THERAPIES ; EX-VIVO ; HUMAN BONE-MARROW ; stem cells ; BONE ; EXTENT ; microbiology ; ENGLAND ; STEM ; UMBILICAL-CORD BLOOD ; MEDICINE ; biotechnology ; modification ; mesenchymal stem cells ; DELIVERY VEHICLES ; INDUCIBLE RNA INTERFERENCE ; lentiviral transduction ; TARGETED-DELIVERY
    Abstract: Genetic modification of human bone marrow mesenchymal stem cells ( MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 mu mh(-1) was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy
    Type of Publication: Journal article published
    PubMed ID: 18202717
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  • 5
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 69 (1996), S. 1579-1581 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: This letter presents a study of intermixing in ZnSe/ZnCdSe quantum well structures, using repetitive thermal annealing with photoluminescence measurements. An improvement in the optical quality of the samples was found for anneals at temperatures (∼500 °C) for which macroscopic intermixing is not observed. The interdiffusion process of this system was found to be Fickian with no dependence on alloy composition or strain. An activation energy of 2.3±0.2 eV was obtained for the interdiffusion process over a 250 K temperature range and four decades of interdiffusion coefficient. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 44 (1989), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Physics and chemistry of minerals 23 (1996), S. 470-475 
    ISSN: 1432-2021
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: Abstract The thermal diffusivity tensors at ambient pressure and temperature of three silicate mineral phases abundant in the upper mantle (San Carlos olivine [Mg0.89Fe0.11]2SiO4, Kilbourne Hole orthopyroxene [Mg1.63Fe0.17Ca0.04Mn0.01] [Cr0.01 Al0.12] [Si1.89Al0.11]O6 and a garnet of intermediate composition Py51Al32Gr16Sp1 are reported. The extension to high pressure and temperature of the experimental technique employed here is discussed and, for olivine, data at high pressure are also reported. The diffusivity in the two orthorhombic minerals is highly anisotropic, the components of the tensor along the a, b, and c crystallographic axes, in units of mm2/sec, being [2.16 1.25 1.87] in the case of olivine and [1.26 1.05 1.66] in the case of the orthopyroxene. The isotropic thermal diffusivity in garnet is 1.06 mm2/ sec. The experimental uncertainty is approximately 2%. The pressure dependence of thermal diffusivity is approximately 4% per GPa. The relation of thermal to elastic anisotropy is briefly considered. A model incorporating elastic anisotropy, anharmonicity described by acoustic Grüneisen parameters, Brillouin zone structure, and the increased phase volume for the scattering of short wavelength phonons provides a qualitatively reasonable description of the thermal diffusivity anisotropy. Since both olivine and orthopyroxene are aligned by flow deformation processes, the upper mantle is expected to be thermally anisotropic.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 76 (2000), S. 715-717 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Amorphous disilicides of the refractory metals chromium and molybdenum have been formed at room temperature in hydrogenated amorphous silicon. The silicides are produced by radiation-enhanced diffusion during bombardment through a thin metal film on the surface of the amorphous silicon. The properties of the layers are similar to those produced by thermal annealing at temperatures 〈300 °C. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 4842-4846 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We present data of the interdiffusion coefficient of AlGaAs/GaAs over the temperature range 750–1150 °C, and obtain EA and D0 values of 3.6±0.2 eV and 0.2 (with an uncertainty from 0.04 to 1.1) cm2/s, respectively. These data are compared with those from the literature taken under a wide range of experimental conditions. We show that despite the range of activation energies quoted in the literature all the data can be described using a single activation energy. Using this value of EA to fit the published data and then determining D0 for each data point we find that the published data fall into two clusters. One, for samples annealed under a gallium rich overpressure and a second for As rich or capped anneals. This result can be explained by the diffusion in all cases being governed by a single mechanism, vacancy-controlled second-nearest-neighbor hopping. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
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