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  • 11
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  35. Jahrestagung der Deutschsprachigen Arbeitsgemeinschaft für Verbrennungsbehandlung (DAV 2017); 20170111-20170114; Chur, Schweiz; DOC17dav10.7 /20170118/
    Publication Date: 2017-01-18
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 12
    Keywords: NF-KAPPA-B ; EPITHELIAL-CELLS ; HUMAN LIVER ; KINASE CASCADE ; PHASE-II ; tumor microenvironment ; TARGETED THERAPY ; RAF/MEK/ERK PATHWAY ; AZD6244 ARRY-142886 ; RAF INHIBITOR
    Abstract: PURPOSE: Small molecule inhibitors of the mitogen-activated protein kinase (MAPK) pathway, such as sorafenib, represent novel treatment options for advanced hepatocellular carcinoma. The aim of our study was to identify downstream targets as biomarker candidates that are directly linked to the oncogenic MAPK pathway in hepatocellular carcinoma and correlate with inhibition of this pathway by multikinase inhibitors. EXPERIMENTAL DESIGN: Hepatocellular carcinoma cell lines and fresh tumor and tumor-free liver tissues from patients with hepatocellular carcinoma were incubated with different BRaf or MEK inhibitors and analyzed for kinase phosphorylation, proliferation, induction of apoptosis, and chemokine secretion. RESULTS: Hepatocellular carcinoma cell lines responded differentially to these inhibitors in a dose-dependent manner, even those targeting the same kinase. Sorafenib inhibited both MEK1 and ERK1/2 phosphorylation at high but increased signaling at low concentrations. Similarly, PLX4720 increased MEK/ERK signaling independently from mutations in BRaf or NRas. MEK inhibitors decreased ERK1/2 phosphorylation in a dose-dependent manner. These signaling characteristics correlated with inhibition of proliferation, induction of apoptosis, and chemokine secretion. Fresh tissues derived from patients diagnosed with primary hepatocellular carcinoma responded to these inhibitors with changes in their microenvironment following the patterns observed in hepatocellular carcinoma cells. CONCLUSIONS: Oncogenic signaling of the MAPK pathway influences hepatocellular carcinoma sensitivity to treatment with BRaf and MEK inhibitors about cell fate independently from mutations in BRaf and NRas. MAPK inhibitors have a strong impact on chemokine secretion as a consequence of interference with oncogenic signaling. Therefore, novel biomarker candidates associated with the hepatocellular carcinoma microenvironment may be developed for prediction and monitoring of treatment response to small molecule inhibitors.
    Type of Publication: Journal article published
    PubMed ID: 24573550
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  • 13
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  124. Kongress der Deutschen Gesellschaft für Chirurgie; 20070501-20070504; München; DOC07dgch6804 /20071001/
    Publication Date: 2007-10-02
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 14
    ISSN: 1420-9136
    Keywords: Coherent phase transformation ; Nonhydrostatic thermodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract It is shown that in diffusionless coherent first-order phase transformations in stressed solids an energy-momentum tensor appears in the role of a chemical potential. A thermodynamic equilibrium condition is derived in terms of this tensor from balance relations and a dissipation inequality, and its use in formulating linear phenomenological relations for irreversible phase transformations in nonhydrostatic systems is pointed out.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Pure and applied geophysics 122 (1984), S. 53-85 
    ISSN: 1420-9136
    Keywords: Phase transformation ; solution/precipitation creep ; grain boundaries
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract This paper is concerned with the thermodynamic theory of solution and precipitation processes in wet crustal rocks and with the mechanism of steady pressure-solution slip in ‘contact zones,’ such as grain-to-grain contacts, fracture surfaces, and permeable gouge layers, that are infiltrated by a mobile aqueous solution phase. A local dissipation jump condition at the phase boundary is fundamental to identifying the thermodynamic force driving the solution and precipitation process and is used here in setting up linear phenomenological relations to model near-equilibrium phase transformation kinetics. The local thermodynamic equilibrium of a stressed pure solid in contact with its melt or solution phase is governed by Gibbs's relation, which is rederived here, in a manner emphasizing its independence of constitutive assumptions for the solid while neglecting surface tension and diffusion in the solid. Fluid-infiltrated contact zones, such as those formed by rough surfaces, cannot generally be in thermodynamic equilibrium, especially during an ongoing process of pressure-solution slip, and the existing equilibrium formulations are incorrect in overlooking dissipative processes tending to eliminate fluctuations in superficial free energies due to stress concentrations near asperities, defects, or impurities. Steady pressure-solution slip is likely to exhibit a nonlinear dependence of slip rate on shear stress and effective normal stress, due to a dependence of the contact-zone state on the latter. Given that this dependence is negligible within some range, linear relations for pressure-solution slip can be derived for the limiting cases of diffusion-controlled and interface-reaction-controlled rates. A criterion for rate control by one of these mechanisms is set by the magnitude of the dimensionless quantitykδ/2C pD, wherek is the interfacial transfer coefficient, δ is the mean diffusion path length,C p is the solubility at pressurep, andD is the mass diffusivity.
    Type of Medium: Electronic Resource
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