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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  22. Internationaler Kongress der Deutschen Ophthalmochirurgen; 20090618-20090621; Nürnberg; DOC09docVI 4.3 /20090709/
    Publication Date: 2009-08-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; INHIBITOR ; SURVIVAL ; tumor ; carcinoma ; CELL ; COMBINATION ; Germany ; IN-VIVO ; MODEL ; MODELS ; THERAPY ; VITRO ; VIVO ; PROTEINS ; SAMPLE ; SAMPLES ; TIME ; NF-KAPPA-B ; ACTIVATION ; LIGAND ; INDEX ; TISSUES ; CONTRAST ; ANTITUMOR-ACTIVITY ; TARGET ; MOUSE ; resistance ; CARCINOMA CELLS ; CELL-DEATH ; MEMBRANE ; CARCINOMA-CELLS ; adenocarcinoma ; NORMAL TISSUE ; REVEALS ; CHILDREN ; pancreatic cancer ; pancreatic carcinoma ; TRAIL ; HUMAN PROSTATE-CANCER ; TRAIL-INDUCED APOPTOSIS ; APOPTOSIS-INDUCING LIGAND ; DRUG-INDUCED APOPTOSIS ; INHIBITORS ; PANCREATIC-CANCER ; THERAPIES ; DECOY RECEPTORS ; development ; X-LINKED INHIBITOR ; pancreatic adenocarcinoma ; USA ; ANTAGONISTS ; pancreatic tumor ; IRRADIATION-INDUCED APOPTOSIS ; XIAP ; therapeutic ; ALPHA-DEPENDENT APOPTOSIS
    Abstract: Evasion of apoptosis is a characteristic feature of pancreatic cancer, a prototypic cancer that is refractory to current treatment approaches. Hence, there is an urgent need to design rational strategies that counter apoptosis resistance. To explore X-linked inhibitor of apoptosis (XIAP) as a therapeutic target in pancreatic cancer, we analyzed the expression of XIAP in pancreatic tumor samples and evaluated the effect of small molecule XIAP inhibitors alone and in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against pancreatic carcinoma in vitro and in vivo. Here, we report that XIAP is highly expressed in pancreatic adenocarcinoma samples compared with normal pancreatic ducts. Small molecule XIAP inhibitors synergize with TRAIL to induce apoptosis and to inhibit long-term clonogenic survival of pancreatic carcinoma cells. In contrast, they do not reverse the lack of toxicity of TRAIL on nonmalignant cells in vitro or normal tissues in vivo, pointing to a therapeutic index. Most importantly, XIAP inhibitors cooperate with TRAIL to trigger apoptosis and suppress pancreatic carcinoma growth in vivo in two preclinical models, i.e., the chorioallantoic membrane model and a mouse xenograft model. Parallel immunohistochemical analysis of tumor tissue under therapy reveals that the XIAP inhibitor acts in concert with TRAIL to cause caspase-3 activation and apoptosis. In conclusion, our findings provide, for the first time, evidence in vivo that XIAP inhibitors prime pancreatic carcinoma cells for TRAM-induced apoptosis and potentiate the antitumor activity of TRAIL against established pancreatic carcinoma. These findings build the rationale for further (pre)clinical development of XIAP inhibitors and TRAIL against pancreatic cancer. [Cancer Res 2009;69(6):2425-34]
    Type of Publication: Journal article published
    PubMed ID: 19258513
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  • 3
    ISSN: 0013-4686
    Keywords: XPS ; carbon ; fluorine ; graphite intercalation compound ; impedance
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Using a flight-time-difference method we measured the energy distributions of H-H+ and H+-H+ fragment pairs arising from collisional dissociation of 10keV H 2 + ions incident on He. The distributions measured at an angle of 0.28° with respect to the beam direction have maxima at 4.3eV for H-H+ and at 8.7eV for H+-H+ in the center-of-mass frame. The sharp maximum of the angle distribution in the CM frame at right angles to the beam direction observed in experiments in which only protons are detected does not appear in this coincidence experiment. This supports an earlier assumption that this sharp maximum can be ascribed to dissociation by vibrational-rotational excitation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    The European physical journal 210 (1968), S. 337-360 
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The angular and energy distribution of protons produced by collision-induced dissociations of H 2 + ions with energies of 10 and 20 keV were measured in a parabola spectrograph. From these measurements the velocity distribution of the protons in the center of mass system of the H 2 + ion can be calculated. This gives information about the type, the abundance, and the anisotropy of the processes involved. The most frequent transitions leading to dissociations are the excitation of the 2pσu state, the ionisation of the H 2 + ion, the transition into the vibrational continuum, and the electron capture into the 13 σ u + state of the hydrogen. It is shown that the cross section for an electronic transition depends on the velocity of the ion, the distance of the nuclei in the ion, the angle between the internuclear axis and the direction of the primary ion beam, and the excitation energy of the target. The fraction of protons produced by vibrational excitation increases with increasing atomic number of the target. Concerning electronic transitions D 2 + ions equal H 2 + ions of the same velocity.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The collision-induced dissociation of 10 keV H 2 + ions incident on H2 has been studied in this paper. Total cross sections and angle distributions for the H+-H, H+-H+ and H-H fragmentations are given. Distributions over both angle and velocity have been measured for the H-H+ and H-H fragmentation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The velocity distributions of H-H fragment pairs arising from dissociative collisions of 10keV H 2 + ions incident on H2, He, and Ar were measured using a flight-time-difference method. The H 2 + ions were produced in an electron impact ion source at two different electron energies, at 100eV and 18eV. The influence of the electron energy on the fragment velocity distributions is studied. Conclusions are drawn on the processes which lead to the formation of neutral fragment pairs. Electron capture into the repulsive b3 Σ u + state of H2 plays a dominant role.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1434-601X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Using a photon-particle delayed coincidence method the energy distributions of H +H(2p) and H++H(2p) fragment pairs have been measured arising from collisional dissociation of 10 keV H 2 + ions incident on various target gases. H fragments in their 2p state are identified by the Lymanα radiation emitted. The distribution of H+H(2p) fragment pairs arising from dissociative charge exchange reveals a sharp increase below 0.2 eV in the center-of-mass frame of the H 2 + ion. This is ascribed to predissociation of vibrational levels of higher H2 Rydberg states close above then=2 dissociation limit by those H2 Rydberg states which separate into H+H(2p) fragments. Only direct transitions into the continuum of theGK 1 ∑ g + state may compete. Some structure at 0.3–0.5 eV is attributed to the three statesI 1 П g,i 3 П g, andh 3 bE g + having potential barriers of this height. The distributions for H++H(2p) have maxima at 3.4, 3.8, and 4.2 eV for a H2, Ar, and He target, respectively, indicating that the 2pπ u state as well as the 3dσ g state ofH 2 + is excited. The H+H(2p) process has a greater probability than the H++H(2p) process for Ar and H2 targets, though all electronic H2 states under consideration are bound.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1572-8838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Improvements in the fluorine production process may be obtained by forming a ternary conducting layer CF x M y at the surface of the carbon anodes (M is a metal: Li, Mg, Al,...). Electron transfer at the interface is thus enhanced and the wettability of the electrode by the KF-2HF melt is improved. In this paper, we show that polishing the carbon electrodes with alumina or magnesia actually dopes the carbon by mechanical insertion of the latter compound. Scanning electron microscopy experiments show that particles of aluminium oxide or magnesium oxide are inserted during the polishing process; they give the corresponding fluorides during electrolysis in the KF-2HF melt. A surfacic ternary conducting compound is formed, as in the case of electrodes doped by additions of LiF or AlF3 into the melt. The electrochemical behavior of the polished electrodes has been studied by cyclic voltammetry experiments and impedance measurements.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1572-8838
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract The modification of raw carbon electrodes by a nitrate-based treatment improves the fluorine evolution process on carbon anodes. In the case of Al(NO3)3-impregnated electrodes, these improvements are attributed to the formation, at the electrode/KF-2HF interface, of a ternary conducting compound C x (AIF3) y F, i.e. a GIC, instead of insulating graphite fluorides, CF x . In addition, the effect of the NO3 anions of the impregnation solution is demonstrated by impedance spectroscopy, scanning electron microscopy and mercury porosimetry. Impregnation of crude carbon electrodes by nitrate salts, followed by heat treatment, induces smoothing of the electrode surfaces and an increase in the diameter of the pores. This treatment also improves the electronic transfer at the interface and enhances the wet-ability of the electrode by the melt.
    Type of Medium: Electronic Resource
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