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53. Irradiation system for pre-clinical studies with laser accelerated electrons

Author

Schürer, M., primary, Baumann, M., additional, Beyreuther, E., additional, Brüchner, K., additional, Enghardt, W., additional, Kaluza, M., additional, Karsch, L., additional, Laschinsky, L., additional, Leßmann, E., additional, Nicolai, M., additional, Oppelt, M., additional, Reuter, M., additional, Richter, C., additional, Sävert, A., additional, Schnell, M., additional, Woithe, J., additional, and Pawelke, J., additional

Published
2012
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57. DEGRO 2004

Author

Wendt, Thomas G., primary, Gademann, G., additional, Pambor, C., additional, Grießbach, I., additional, von Specht, H., additional, Martin, T., additional, Baltas, D., additional, Kurek, R., additional, Röddiger, S., additional, Tunn, U. W., additional, Zamboglou, N., additional, Eich, H. T., additional, Staar, S., additional, Gossmann, A., additional, Hansemann, K., additional, Semrau, R., additional, Skripnitchenko, R., additional, Diehl, V., additional, Müller, R.-P., additional, Sehlen, S., additional, Willich, N., additional, Rühl, U., additional, Lukas, P., additional, Dühmke, E., additional, Engel, K., additional, Tabbert, E., additional, Bolck, M., additional, Knaack, S., additional, Annweiler, H., additional, Krempien, R., additional, Hoppe, H., additional, Harms, W., additional, Daeuber, S., additional, Schorr, O., additional, Treiber, M., additional, Debus, J., additional, Alber, M., additional, Paulsen, F., additional, Birkner, M., additional, Bakai, A., additional, Belka, C., additional, Budach, W., additional, Grosser, K.-H., additional, Kramer, R., additional, Kober, B., additional, Reinert, M., additional, Schneider, P., additional, Hertel, A., additional, Feldmann, H., additional, Csere, P., additional, Hoinkis, C., additional, Rothe, G., additional, Zahn, P., additional, Alheit, H., additional, Cavanaugh, S. X., additional, Kupelian, P., additional, Reddy, C., additional, Pollock, B., additional, Fuss, M., additional, Roeddiger, S., additional, Dannenberg, T., additional, Rogge, B., additional, Drechsler, D., additional, Herrmann, T., additional, Alberti, W., additional, Schwarz, R., additional, Graefen, M., additional, Krüll, A., additional, Rudat, V., additional, Huland, H., additional, Fehr, C., additional, Baum, C., additional, Glocker, S., additional, Nüsslin, F., additional, Heil, T., additional, Lemnitzer, H., additional, Knips, M., additional, Baumgart, O., additional, Thiem, W., additional, Kloetzer, K.-H., additional, Hoffmann, L., additional, Neu, B., additional, Hültenschmidt, B., additional, Sautter-Bihl, M.-L., additional, Micke, O., additional, Seegenschmiedt, M. H., additional, Köppen, D., additional, Klautke, G., additional, Fietkau, R., additional, Schultze, J., additional, Schlichting, G., additional, Koltze, H., additional, Kimmig, B., additional, Glatzel, M., additional, Fröhlich, D., additional, Bäsecke, S., additional, Krauß, A., additional, Strauß, D., additional, Buth, K.-J., additional, Böhme, R., additional, Oehler, W., additional, Bottke, D., additional, Keilholz, U., additional, Heufelder, K., additional, Wiegel, T., additional, Hinkelbein, W., additional, Rödel, C., additional, Papadopoulos, T., additional, Munnes, M., additional, Wirtz, R., additional, Sauer, R., additional, Rödel, F., additional, Lubgan, D., additional, Distel, L., additional, Grabenbauer, G. G., additional, Sak, A., additional, Stüben, G., additional, Pöttgen, C., additional, Grehl, S., additional, Stuschke, M., additional, Müller, K., additional, Pfaffendorf, C., additional, Mayerhofer, A., additional, Köhn, F. M., additional, Ring, J., additional, van Beuningen, D., additional, Meineke, V., additional, Neubauer, S., additional, Keller, U., additional, Wittlinger, M., additional, Riesenbeck, D., additional, Greve, B., additional, Exeler, R., additional, Ibrahim, M., additional, Liebscher, C., additional, Severin, E., additional, Ott, O., additional, Pötter, R., additional, Hammer, J., additional, Hildebrandt, G., additional, Beckmann, M. W., additional, Strnad, V., additional, Fehlauer, F., additional, Tribius, S., additional, Bajrovic, A., additional, Höller, U., additional, Rades, D., additional, Warszawski, A., additional, Baumann, R., additional, Madry-Gevecke, B., additional, Karstens, J. H., additional, Grehn, C., additional, Hensley, F., additional, Berns, C., additional, Wannenmacher, M., additional, Semrau, S., additional, Reimer, T., additional, Gerber, B., additional, Ketterer, P., additional, Koepcke, E., additional, Hänsgen, G., additional, Strauß, H. G., additional, Dunst, J., additional, Füller, J., additional, Kalb, S., additional, Wendt, T., additional, Weitmann, H. D., additional, Waldhäusl, C., additional, Knocke, T.-H., additional, Lamprecht, U., additional, Classen, J., additional, Kaulich, T. W., additional, Aydeniz, B., additional, Bamberg, M., additional, Wiezorek, T., additional, Banz, N., additional, Salz, H., additional, Scheithauer, M., additional, Schwedas, M., additional, Lutterbach, J., additional, Bartelt, S., additional, Frommhold, H., additional, Lambert, J., additional, Hornung, D., additional, Swiderski, S., additional, Walke, M., additional, Siefert, A., additional, Pöllinger, B., additional, Krimmel, K., additional, Schaffer, M., additional, Koelbl, O., additional, Bratengeier, K., additional, Vordermark, D., additional, Flentje, M., additional, Hero, B., additional, Berthold, F., additional, Combs, S. E., additional, Gutwein, S., additional, Schulz-Ertner, D., additional, van Kampen, M., additional, Thilmann, C., additional, Kocher, M., additional, Kunze, S., additional, Schild, S., additional, Ikezaki, K., additional, Müller, B., additional, Sieber, R., additional, Weiß, C., additional, Wolf, I., additional, Wenz, F., additional, Weber, K.-J., additional, Schäfer, J., additional, Engling, A., additional, Laufs, S., additional, Veldwijk, M. R., additional, Milanovic, D., additional, Fleckenstein, K., additional, Zeller, W., additional, Fruehauf, S., additional, Herskind, C., additional, Weinmann, M., additional, Jendrossek, V., additional, Rübe, C., additional, Appold, S., additional, Kusche, S., additional, Hölscher, T., additional, Brüchner, K., additional, Geyer, P., additional, Baumann, M., additional, Kumpf, R., additional, Zimmermann, F., additional, Schill, S., additional, Geinitz, H., additional, Nieder, C., additional, Jeremic, B., additional, Molls, M., additional, Liesenfeld, S., additional, Petrat, H., additional, Hesselmann, S., additional, Schäfer, U., additional, Bruns, F., additional, Horst, E., additional, Wilkowski, R., additional, Assmann, G., additional, Nolte, A., additional, Diebold, J., additional, Löhrs, U., additional, Fritz, P., additional, Hans-Jürgen, K., additional, Mühlnickel, W., additional, Bach, P., additional, Wahlers, B., additional, Kraus, H.-J., additional, Wulf, J., additional, Hädinger, U., additional, Baier, K., additional, Krieger, T., additional, Müller, G., additional, Hof, H., additional, Herfarth, K., additional, Brunner, T., additional, Hahn, S. M., additional, Schreiber, F. S., additional, Rustgi, A. K., additional, McKenna, W. G., additional, Bernhard, E. J., additional, Guckenberger, M., additional, Meyer, K., additional, Willner, J., additional, Schmidt, M., additional, Kolb, M., additional, Li, M., additional, Gong, P., additional, Abdollahi, A., additional, Trinh, T., additional, Huber, P. E., additional, Christiansen, H., additional, Saile, B., additional, Neubauer-Saile, K., additional, Tippelt, S., additional, Rave-Fränk, M., additional, Hermann, R. M., additional, Dudas, J., additional, Hess, C. F., additional, Schmidberger, H., additional, Ramadori, G., additional, Andratschke, N., additional, Price, R., additional, Ang, K.-K., additional, Schwarz, S., additional, Kulka, U., additional, Busch, M., additional, Schlenger, L., additional, Bohsung, J., additional, Eichwurzel, I., additional, Matnjani, G., additional, Sandrock, D., additional, Richter, M., additional, Wurm, R., additional, Budach, V., additional, Feussner, A., additional, Gellermann, J., additional, Jordan, A., additional, Scholz, R., additional, Gneveckow, U., additional, Maier-Hauff, K., additional, Ullrich, R., additional, Wust, P., additional, Felix, R., additional, Waldöfner, N., additional, Seebass, M., additional, Ochel, H.-J., additional, Dani, A., additional, Varkonyi, A., additional, Osvath, M., additional, Szasz, A., additional, Messer, P. M., additional, Blumstein, N. M., additional, Gottfried, H.-W., additional, Schneider, E., additional, Reske, S. N., additional, Röttinger, E. M., additional, Grosu, A.-L., additional, Franz, M., additional, Stärk, S., additional, Weber, W., additional, Heintz, M., additional, Indenkämpen, F., additional, Beyer, T., additional, Lübcke, W., additional, Levegrün, S., additional, Hayen, J., additional, Czech, N., additional, Mbarek, B., additional, Köster, R., additional, Thurmann, H., additional, Todorovic, M., additional, Schuchert, A., additional, Meinertz, T., additional, Münzel, T., additional, Grundtke, H., additional, Hornig, B., additional, Hehr, T., additional, Dilcher, C., additional, Chan, R. C., additional, Mintz, G. S., additional, Kotani, J.-I., additional, Shah, V. M., additional, Canos, D. A., additional, Weissman, N. J., additional, Waksman, R., additional, Wolfram, R., additional, Bürger, B., additional, Schrappe, M., additional, Timmermann, B., additional, Lomax, A., additional, Goitein, G., additional, Schuck, A., additional, Mattke, A., additional, Int-Veen, C., additional, Brecht, I., additional, Bernhard, S., additional, Treuner, J., additional, Koscielniak, E., additional, Heinze, F., additional, Kuhlen, M., additional, von Schorlemer, I., additional, Ahrens, S., additional, Hunold, A., additional, Könemann, S., additional, Winkelmann, W., additional, Jürgens, H., additional, Gerstein, J., additional, Polivka, B., additional, Sykora, K.-W., additional, Bremer, M., additional, Thamm, R., additional, Höpfner, C., additional, Gumprecht, H., additional, Jäger, R., additional, Leonardi, M. A., additional, Frank, A. M., additional, Trappe, A. E., additional, Lumenta, C. B., additional, Östreicher, E., additional, Pinsker, K., additional, Müller, A., additional, Fauser, C., additional, Arnold, W., additional, Henzel, M., additional, Groß, M. W., additional, Engenhart-Cabillic, R., additional, Schüller, P., additional, Palkovic, S., additional, Schröder, J., additional, Wassmann, H., additional, Block, A., additional, Bauer, R., additional, Keffel, F.-W., additional, Theophil, B., additional, Wisser, L., additional, Rogger, M., additional, Niewald, M., additional, van Lengen, V., additional, Mathias, K., additional, Welzel, G., additional, Bohrer, M., additional, Steinvorth, S., additional, Schleußner, C., additional, Leppert, K., additional, Röhrig, B., additional, Strauß, B., additional, van Oorschot, B., additional, Köhler, N., additional, Anselm, R., additional, Winzer, A., additional, Schneider, T., additional, Koch, U., additional, Schönekaes, K., additional, Mücke, R., additional, Büntzel, J., additional, Kisters, K., additional, Scholz, C., additional, Keller, M., additional, Winkler, C., additional, Prause, N., additional, Busch, R., additional, Roth, S., additional, Haas, I., additional, Willers, R., additional, Schultze-Mosgau, S., additional, Wiltfang, J., additional, Kessler, P., additional, Neukam, F. W., additional, Röper, B., additional, Nüse, N., additional, Auer, F., additional, Melzner, W., additional, Geiger, M., additional, Lotter, M., additional, Kuhnt, T., additional, Müller, A. C., additional, Jirsak, N., additional, Gernhardt, C., additional, Schaller, H.-G., additional, Al-Nawas, B., additional, Klein, M. O., additional, Ludwig, C., additional, Körholz, J., additional, Grötz, K. A., additional, Huppers, K., additional, Kunkel, M., additional, Olschewski, T., additional, Bajor, K., additional, Lang, B., additional, Lang, E., additional, Kraus-Tiefenbacher, U., additional, Hofheinz, R., additional, von Gerstenberg-Helldorf, B., additional, Willeke, F., additional, Hochhaus, A., additional, Roebel, M., additional, Oertel, S., additional, Riedl, S., additional, Buechler, M., additional, Foitzik, T., additional, Ludwig, K., additional, Klar, E., additional, Meyer, A., additional, Meier zu Eissen, J., additional, Schwab, D., additional, Meyer, T., additional, Höcht, S., additional, Siegmann, A., additional, Sieker, F., additional, Pigorsch, S., additional, Milicic, B., additional, Acimovic, L., additional, Milisavljevic, S., additional, Radosavljevic-Asic, G., additional, Presselt, N., additional, Baum, R. P., additional, Treutler, D., additional, Bonnet, R., additional, Schmücking, M., additional, Sammour, D., additional, Fink, T., additional, Ficker, J., additional, Pradier, O., additional, Lederer, K., additional, Weiss, E., additional, Hille, A., additional, Welz, S., additional, Sepe, S., additional, Friedel, G., additional, Spengler, W., additional, Susanne, E., additional, Kölbl, O., additional, Hoffmann, W., additional, Wörmann, B., additional, Günther, A., additional, Becker-Schiebe, M., additional, Güttler, J., additional, Schul, C., additional, Nitsche, M., additional, Körner, M. K., additional, Oppenkowski, R., additional, Guntrum, F., additional, Malaimare, L., additional, Raub, M., additional, Schöfl, C., additional, Averbeck, T., additional, Hacker, I., additional, Blank, H., additional, Böhme, C., additional, Imhoff, D., additional, Eberlein, K., additional, Weidauer, S., additional, Böttcher, H. D., additional, Edler, L., additional, Tatagiba, M., additional, Molina, H., additional, Ostertag, C., additional, Milker-Zabel, S., additional, Zabel, A., additional, Schlegel, W., additional, Hartmann, A., additional, Wildfang, I., additional, Kleinert, G., additional, Hamm, K., additional, Reuschel, W., additional, Wehrmann, R., additional, Kneschaurek, P., additional, Münter, M. W., additional, Nikoghosyan, A., additional, Didinger, B., additional, Nill, S., additional, Rhein, B., additional, Küstner, D., additional, Schalldach, U., additional, Eßer, D., additional, Göbel, H., additional, Wördehoff, H., additional, Pachmann, S., additional, Hollenhorst, H., additional, Dederer, K., additional, Evers, C., additional, Lamprecht, J., additional, Dastbaz, A., additional, Schick, B., additional, Fleckenstein, J., additional, Plinkert, P. K., additional, Rübe, Chr., additional, Merz, T., additional, Sommer, B., additional, Mencl, A., additional, Ghilescu, V., additional, Astner, S., additional, Martin, A., additional, Momm, F., additional, Volegova-Neher, N. J., additional, Schulte-Mönting, J., additional, Guttenberger, R., additional, Buchali, A., additional, Blank, E., additional, Sidow, D., additional, Huhnt, W., additional, Gorbatov, T., additional, Heinecke, A., additional, Beckmann, G., additional, Bentia, A.-M., additional, Schmitz, H., additional, Spahn, U., additional, Heyl, V., additional, Prott, P.-J., additional, Galalae, R., additional, Schneider, R., additional, Voith, C., additional, Scheda, A., additional, Hermann, B., additional, Bauer, L., additional, Melchert, F., additional, Kröger, N., additional, Grüneisen, A., additional, Jänicke, F., additional, Zander, A., additional, Zuna, I., additional, Schlöcker, I., additional, Wagner, K., additional, John, E., additional, Dörk, T., additional, Lochhas, G., additional, Houf, M., additional, Lorenz, D., additional, Link, K.-H., additional, Prott, F.-J., additional, Thoma, M., additional, Schauer, R., additional, Heinemann, V., additional, Romano, M., additional, Reiner, M., additional, Quanz, A., additional, Oppitz, U., additional, Bahrehmand, R., additional, Tine, M., additional, Naszaly, A., additional, Patonay, P., additional, Mayer, Á., additional, Markert, K., additional, Mai, S.-K., additional, Lohr, F., additional, Dobler, B., additional, Pinkawa, M., additional, Fischedick, K., additional, Treusacher, P., additional, Cengiz, D., additional, Mager, R., additional, Borchers, H., additional, Jakse, G., additional, Eble, M. J., additional, Asadpour, B., additional, Krenkel, B., additional, Holy, R., additional, Kaplan, Y., additional, Block, T., additional, Czempiel, H., additional, Haverkamp, U., additional, Prümer, B., additional, Christian, T., additional, Benkel, P., additional, Weber, C., additional, Gruber, S., additional, Reimann, P., additional, Blumberg, J., additional, Krause, K., additional, Fischedick, A.-R., additional, Kaube, K., additional, Steckler, K., additional, Henzel, B., additional, Licht, N., additional, Loch, T., additional, Krystek, A., additional, Lilienthal, A., additional, Alfia, H., additional, Claßen, J., additional, Spillner, P., additional, Knutzen, B., additional, Souchon, R., additional, Schulz, I., additional, Grüschow, K., additional, Küchenmeister, U., additional, Vogel, H., additional, Wolff, D., additional, Ramm, U., additional, Licner, J., additional, Rudolf, F., additional, Moog, J., additional, Rahl, C. G., additional, Mose, S., additional, Vorwerk, H., additional, Weiß, E., additional, Engert, A., additional, Seufert, I., additional, Schwab, F., additional, Dahlke, J., additional, Zabelina, T., additional, Krüger, W., additional, Kabisch, H., additional, Platz, V., additional, Wolf, J., additional, Pfistner, B., additional, Stieltjes, B., additional, Wilhelm, T., additional, Schmuecking, M., additional, Junker, K., additional, Treutier, D., additional, Schneider, C. P., additional, Leonhardi, J., additional, Niesen, A., additional, Hoeffken, K., additional, Schmidt, A., additional, Mueller, K.-M., additional, Schmid, I., additional, Lehmann, K., additional, Blumstein, C. G., additional, Kreienberg, R., additional, Freudenberg, L., additional, Kühl, H., additional, Stahl, M., additional, Elo, B., additional, Erichsen, P., additional, Stattaus, H., additional, Welzel, T., additional, Mende, U., additional, Heiland, S., additional, Salter, B. J., additional, Schmid, R., additional, Stratakis, D., additional, Huber, R. M., additional, Haferanke, J., additional, Zöller, N., additional, Henke, M., additional, Lorenzen, J., additional, Grzyska, B., additional, Kuhlmey, A., additional, Adam, G., additional, Hamelmann, V., additional, Bölling, T., additional, Job, H., additional, Panke, J. E., additional, Feyer, P., additional, Püttmann, S., additional, Siekmeyer, B., additional, Jung, H., additional, Gagel, B., additional, Militz, U., additional, Piroth, M., additional, Schmachtenberg, A., additional, Hoelscher, T., additional, Verfaillie, C., additional, Kaminski, B., additional, Lücke, E., additional, Mörtel, H., additional, Eyrich, W., additional, Fritsch, M., additional, Georgi, J.-C., additional, Plathow, C., additional, Zieher, H., additional, Kiessling, F., additional, Peschke, P., additional, Kauczor, H.-U., additional, Licher, J., additional, Schneider, O., additional, Henschler, R., additional, Seidel, C., additional, Kolkmeyer, A., additional, Nguyen, T. P., additional, Janke, K., additional, Michaelis, M., additional, Bischof, M., additional, Stoffregen, C., additional, Lipson, K., additional, Weber, K., additional, Ehemann, V., additional, Jürgen, D., additional, Achanta, P., additional, Thompson, K., additional, Martinez, J. L., additional, Körschgen, T., additional, Pakala, R., additional, Pinnow, E., additional, Hellinga, D., additional, O’Tio, F., additional, Katzer, A., additional, Kaffer, A., additional, Kuechler, A., additional, Steinkirchner, S., additional, Dettmar, N., additional, Cordes, N., additional, Frick, S., additional, Kappler, M., additional, Taubert, H., additional, Bartel, F., additional, Schmidt, H., additional, Bache, M., additional, Frühauf, S., additional, Wenk, T., additional, Litzenberger, K., additional, Erren, M., additional, van Valen, F., additional, Liu, L., additional, Yang, K., additional, Palm, J., additional, Püsken, M., additional, Behe, M., additional, Behr, T. M., additional, Marini, P., additional, Johne, A., additional, Claussen, U., additional, Liehr, T., additional, Steil, V., additional, Moustakis, C., additional, Griessbach, I., additional, Oettel, A., additional, Schaal, C., additional, Reinhold, M., additional, Strasssmann, G., additional, Braun, I., additional, Vacha, P., additional, Richter, D., additional, Osterham, T., additional, Wolf, P., additional, Guenther, G., additional, Miemietz, M., additional, Lazaridis, E. A., additional, Forthuber, B., additional, Sure, M., additional, Klein, J., additional, Saleske, H., additional, Riedel, T., additional, Hirnle, P., additional, Horstmann, G., additional, Schoepgens, H., additional, Van Eck, A., additional, Bundschuh, O., additional, Van Oosterhut, A., additional, Xydis, K., additional, Theodorou, K., additional, Kappas, C., additional, Zurheide, J., additional, Fridtjof, N., additional, Ganswindt, U., additional, Weidner, N., additional, Buchgeister, M., additional, Weigel, B., additional, Müller, S. B., additional, Glashörster, M., additional, Weining, C., additional, Hentschel, B., additional, Sauer, O. A., additional, Kleen, W., additional, Beck, J., additional, Lehmann, D., additional, Ley, S., additional, Fink, C., additional, Puderbach, M., additional, Hosch, W., additional, Schmähl, A., additional, Jung, K., additional, Stoßberg, A., additional, Rolf, E., additional, Damrau, M., additional, Oetzel, D., additional, Maurer, U., additional, Maurer, G., additional, Lang, K., additional, Zumbe, J., additional, Hahm, D., additional, Fees, H., additional, Robrandt, B., additional, Melcher, U., additional, Niemeyer, M., additional, Mondry, A., additional, Kanellopoulos-Niemeyer, V., additional, Karle, H., additional, Jacob-Heutmann, D., additional, Born, C., additional, Mohr, W., additional, Kutzner, J., additional, Thelen, M., additional, Schiebe, M., additional, Pinkert, U., additional, Piasswilm, L., additional, Pohl, F., additional, Garbe, S., additional, Wolf, K., additional, Nour, Y., additional, Barwig, P., additional, Trog, D., additional, Schäfer, C., additional, Herbst, M., additional, Dietl, B., additional, Cartes, M., additional, Schroeder, F., additional, Sigingan-Tek, G., additional, Feierabend, R., additional, Theden, S., additional, Schlieck, A., additional, Gotthardt, M., additional, Glowalla, U., additional, Kremp, S., additional, Hamid, O., additional, Riefenstahl, N., additional, Michaelis, B., additional, Schaal, G., additional, Liebermeister, E., additional, Niewöhner-Desbordes, U., additional, Kowalski, M., additional, Franz, N., additional, Stahl, W., additional, Baumbach, C., additional, Thale, J., additional, Wagner, W., additional, Justus, B., additional, Huston, A. L., additional, Seaborn, R., additional, Rai, P., additional, Rha, S.-W., additional, Sakas, G., additional, Wesarg, S., additional, Zogal, P., additional, Schwald, B., additional, Seibert, H., additional, Berndt-Skorka, R., additional, Seifert, G., additional, Schoenekaes, K., additional, Bilecen, C., additional, Ito, W., additional, Matschuck, G., additional, and Isik, D., additional

Published
2004
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59. Selective inhibition of the epidermal growth factor receptor tyrosine kinase by BIBX1382BS and the improvement of growth delay, but not local control, after fractionated irradiation in human FaDu squamous cell carcinoma in the nude mouse

Author

Baumann, M., primary, Krause, M., additional, Zips, D., additional, Eicheler, W., additional, Dörfler, A., additional, Ahrens, J., additional, Petersen, C., additional, Brüchner, K., additional, and Hilberg, F., additional

Published
2003
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64. An optimized small animal tumour model for experimentation with low energy protons.

Author

Beyreuther E, Brüchner K, Krause M, Schmidt M, Szabo R, and Pawelke J

Subjects
Animals, Cell Line, Tumor, Cell Proliferation radiation effects, Disease Models, Animal, Dose-Response Relationship, Radiation, Female, Humans, Male, Mice, Particle Accelerators, Ear Neoplasms pathology, Ear Neoplasms radiotherapy, Proton Therapy
Abstract

Background: The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out., Methods: To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation., Results: Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities., Conclusion: The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

Published
2017
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65. Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours.

Author

Jentsch C, Bergmann R, Brüchner K, Mosch B, Yaromina A, Krause M, Zips D, Troost EGC, Löck S, Kotzerke J, Steinbach J, Thames H, Baumann M, and Beuthien-Baumann B

Subjects
Animals, Carcinoma, Squamous Cell pathology, Dose Fractionation, Radiation, Dose-Response Relationship, Radiation, Female, Fluorodeoxyglucose F18, Humans, Hypopharyngeal Neoplasms pathology, Male, Mice, Nude, Neoplasm Recurrence, Local, Proportional Hazards Models, Radiotherapy Dosage, Xenograft Model Antitumor Assays, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell radiotherapy, Hypopharyngeal Neoplasms diagnostic imaging, Hypopharyngeal Neoplasms radiotherapy, Positron-Emission Tomography methods
Abstract

Objective: To investigate local tumour control after dose-escalation based on [ 18 F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation., Materials and Methods: 85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1&#95;0) and second after 18°Gy (PET2&#95;18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60°Gy; n=31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25°Gy [α/β-value: 10]; n=25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116°Gy; n=29). The effects of SUV max 0°Gy, SUV max 18°Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUV max values and dose. Second, the Kaplan-Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUV max ) at PET1&#95;0 and PET2&#95;18, or (2) the cut-off value 2.5., Results: The multivariate Cox analysis revealed a significant negative association between higher SUV max determined before start of treatment and local control (HR=1.59, [95% CI 1.04, 2.42], p=0.031), whereas higher dose had a significant positive effect (HR=0.95, [0.93, 0.98], p<0.001). In contrast, FDG uptake at 18Gy did not correlate with local control (HR=1.14, [0.53, 2.45], p=0.73). Neither FDG uptake prior to irradiation nor at 18Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUV max values for stratification (SUV max 0Gy: 60Gy: p=0.25, 86.25Gy: p=0.47, 116Gy: p=0.88 and SUV max 18Gy: 60Gy: p=0.42, 86.25Gy: p=0.34, 116Gy: p=0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1&#95;0 reveals a significant difference in local control for the 60Gy group (p=0.034), but not for the other dose groups. At PET2&#95;18, no significant effect for any dose group was detected., Conclusions: The multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUV max determined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Published
2016
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66. Comparison study of in vivo dose response to laser-driven versus conventional electron beam.

Author

Oppelt M, Baumann M, Bergmann R, Beyreuther E, Brüchner K, Hartmann J, Karsch L, Krause M, Laschinsky L, Leßmann E, Nicolai M, Reuter M, Richter C, Sävert A, Schnell M, Schürer M, Woithe J, Kaluza M, and Pawelke J

Subjects
Animals, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell radiotherapy, Cell Line, Tumor, Cell Proliferation radiation effects, Cell Transformation, Neoplastic, Dose-Response Relationship, Radiation, Female, Humans, Male, Mice, Radiometry, Electrons therapeutic use, Lasers, Particle Accelerators, Radiotherapy instrumentation
Abstract

The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.

Published
2015
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67. BAY 87-2243, a novel inhibitor of hypoxia-induced gene activation, improves local tumor control after fractionated irradiation in a schedule-dependent manner in head and neck human xenografts.

Author

Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Baumann M, Zips D, and Yaromina A

Subjects
Animals, Antineoplastic Agents pharmacology, Blotting, Western, Cell Hypoxia drug effects, Chemoradiotherapy methods, Dose Fractionation, Radiation, Humans, Mice, Mice, Nude, Squamous Cell Carcinoma of Head and Neck, Xenograft Model Antitumor Assays, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms pathology, Hypoxia-Inducible Factor 1, alpha Subunit antagonists & inhibitors, Oxadiazoles pharmacology, Pyrazoles pharmacology, Radiation-Sensitizing Agents pharmacology
Abstract

Background: The transcription factor hypoxia-inducible factor-1 (HIF-1) pathway plays an important role in tumor response to cytotoxic treatments. We investigated the effects of a novel small molecule inhibitor of mitochondrial complex I and hypoxia-induced HIF-1 activity BAY-87-2243, on tumor microenvironment and response of human squamous cell carcinoma (hSCC) to clinically relevant fractionated radiotherapy (RT) with and without concomitant chemotherapy., Methods: When UT-SCC-5 hSCC xenografts in nude mice reached 6 mm in diameter BAY-87-2243 or carrier was administered before and/or during RT or radiochemotherapy with concomitant cisplatin (RCT). Local tumor control was evaluated 150 days after irradiation and the doses to control 50% of tumors (TCD50) were compared between treatment arms. Tumors were excised at different time points during BAY-87-2243 or carrier treatment for western blot and immunohistological investigations., Results: BAY-87-2243 markedly decreased nuclear HIF-1α expression and pimonidazole hypoxic fraction already after 3 days of drug treatment. BAY-87-2243 prior to RT significantly reduced TCD50 from 123 to 100 Gy (p=0.037). Additional BAY-87-2243 application during RT did not decrease TCD50. BAY-87-2243 before and during radiochemotherapy did not improve local tumor control., Conclusions: Pronounced reduction of tumor hypoxia by application of BAY-87-2243 prior to RT improved local tumor control. The results demonstrate that radiosensitizing effect importantly depends on treatment schedule. The data support further investigations of HIF-1 pathway inhibitors for radiotherapy and of predictive tests to select patients who will benefit from this combined treatment.

Published
2014
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68. Effect of [(18)F]FMISO stratified dose-escalation on local control in FaDu hSCC in nude mice.

Author

Schütze C, Bergmann R, Brüchner K, Mosch B, Yaromina A, Zips D, Hessel F, Krause M, Thames H, Kotzerke J, Steinbach J, Baumann M, and Beuthien-Baumann B

Subjects
Animals, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Hypoxia radiation effects, Cell Line, Tumor, Dose-Response Relationship, Radiation, Female, Head and Neck Neoplasms diagnostic imaging, Head and Neck Neoplasms metabolism, Head and Neck Neoplasms pathology, Humans, Hypopharyngeal Neoplasms diagnostic imaging, Hypopharyngeal Neoplasms metabolism, Hypopharyngeal Neoplasms pathology, Mice, Mice, Nude, Misonidazole administration & dosage, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local radiotherapy, Radionuclide Imaging, Random Allocation, Squamous Cell Carcinoma of Head and Neck, Xenograft Model Antitumor Assays, Carcinoma, Squamous Cell radiotherapy, Fluorine Radioisotopes administration & dosage, Head and Neck Neoplasms radiotherapy, Hypopharyngeal Neoplasms radiotherapy, Misonidazole analogs & derivatives, Radiation-Sensitizing Agents administration & dosage, Radiopharmaceuticals administration & dosage
Abstract

Objective: To investigate the effect of radiation dose-escalation on local control in hypoxic versus non-hypoxic hypoxic tumours defined using [(18)F]fluoromisonidazole ([(18)F]FMISO) PET., Materials and Methods: FaDu human squamous cell carcinomas (hSCCs) growing subcutaneously in nude mice were subjected to [(18)F]FMISO PET before irradiation with single doses of 25 or 35Gy under normal blood flow conditions. [(18)F]FMISO hypoxic volume (HV) and maximum standardised uptake value (SUVmax) were used to quantify tracer uptake. The animals were followed up for at least 120days after irradiation. The endpoints were permanent local tumour control and time to local recurrence., Results: HV varied between 38 and 291mm(3) (median 105mm(3)). Non-hypoxic tumours (HV below median) showed significantly better local control after single dose irradiation than hypoxic tumours (HV above median) (p=0.046). The effect of dose was significant and not different in non-hypoxic and in hypoxic tumours (HR=0.82 [95% CI 0.71; 0.93], p=0.002 and HR=0.86 [0.78; 0.95], p=0.001, respectively). Dose escalation resulted in an incremental increase of local tumour control from low-dose hypoxic, over low-dose non-hypoxic and high-dose hypoxic to high-dose non-hypoxic tumours. SUVmax did not reveal significant association with local control at any dose level., Conclusions: The negative effect of [(18)F]FMISO HV on permanent local tumour control supports the prognostic value of the pre-treatment [(18)F]FMISO HV. Making the assumption that variable [(18)F]FMISO uptake in different FaDu tumours which all have the same genetic background may serve as an experimental model of intratumoural heterogeneity, the data support the concept of dose-escalation with inhomogeneous dose distribution based on pre-treatment [(18)F]FMISO uptake. This result needs to be confirmed in other tumour models and using fractionated radiotherapy schedules., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Published
2014
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69. Establishment of a small animal tumour model for in vivo studies with low energy laser accelerated particles.

Author

Brüchner K, Beyreuther E, Baumann M, Krause M, Oppelt M, and Pawelke J

Subjects
Animals, Equipment Design, Female, Ions therapeutic use, Lasers, Male, Mice, Mice, Nude, Neoplasms pathology, Proton Therapy, Radiotherapy Dosage, Tumor Cells, Cultured, X-Rays, Disease Models, Animal, Low-Level Light Therapy instrumentation, Low-Level Light Therapy methods, Neoplasms radiotherapy, Particle Accelerators instrumentation
Abstract

Background: The long-term aim of developing a laser based acceleration of protons and ions towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short pulsed particle beams. Recent in vitro data showed similar effects of laser-accelerated versus "conventional" protons on clonogenic cell survival. As the proton energies currently achieved by laser driven acceleration are too low to penetrate standard tumour models on mouse legs, the aim of the present work was to establish a tumour model allowing for the penetration of low energy protons (~ 20 MeV) to further verify their effects in vivo., Methods: KHT mouse sarcoma cells were injected subcutaneously in the right ear of NMRI (nu/nu) mice and the growing tumours were characterized with respect to growth parameters, histology and radiation response. In parallel, the laser system JETI was prepared for animal experimentation, i.e. a new irradiation setup was implemented and the laser parameters were carefully adjusted. Finally, a proof-of-principle experiment with laser accelerated electrons was performed to validate the tumour model under realistic conditions, i.e. altered environment and horizontal beam delivery., Results: KHT sarcoma on mice ears showed a high take rate and continuous tumour growth after reaching a volume of ~ 5 mm(3). The first irradiation experiment using laser accelerated electrons versus 200 kV X-rays was successfully performed and tumour growth delay was evaluated. Comparable tumour growth delay was found between X-ray and laser accelerated electron irradiation. Moreover, experimental influences, like anaesthesia and positioning at JETI, were found to be negligible., Conclusion: A small animal tumour model suitable for the irradiation with low energy particles was established and validated at a laser based particle accelerator. Thus, the translation from in vitro to in vivo experimentation was for the first time realized allowing a broader preclinical validation of radiobiological characteristics and efficacy of laser driven particle accelerators in the future.

Published
2014
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70. Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential.

Author

Koi L, Bergmann R, Brüchner K, Pietzsch J, Pietzsch HJ, Krause M, Steinbach J, Zips D, and Baumann M

Subjects
Animals, Antibodies, Monoclonal, Humanized immunology, Antibodies, Monoclonal, Humanized pharmacokinetics, Carcinoma, Squamous Cell immunology, Cell Line, Tumor, Cetuximab, Female, Humans, Immunotoxins immunology, Immunotoxins pharmacokinetics, Isothiocyanates chemistry, Male, Mice, Mice, Nude, Pentetic Acid analogs & derivatives, Pentetic Acid chemistry, Radioimmunotherapy, Radiopharmaceuticals administration & dosage, Radiopharmaceuticals immunology, Random Allocation, Tissue Distribution, Yttrium Radioisotopes chemistry, Yttrium Radioisotopes pharmacokinetics, Antibodies, Monoclonal, Humanized administration & dosage, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy, ErbB Receptors immunology, Immunotoxins administration & dosage, Yttrium Radioisotopes administration & dosage
Abstract

Purpose: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined., Methods: Growth delay was evaluated in three human squamous cell carcinoma models after RIT with [(90)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD₅₀) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([(86)Y]Y-(CHX-A''-DTPA)₄-cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab., Results: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD₅₀ after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT., Conclusion: EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Published
2014
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71. Hypoxia-inducible factor pathway inhibition resolves tumor hypoxia and improves local tumor control after single-dose irradiation.

Author

Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Pruschy M, Baumann M, Yaromina A, and Zips D

Subjects
Animals, Bromodeoxyuridine metabolism, Carcinoma, Squamous Cell metabolism, Cell Hypoxia physiology, Cell Nucleus metabolism, Dose Fractionation, Radiation, Female, Heterografts, Humans, Ki-67 Antigen metabolism, Male, Mice, Mice, Nude, Neoplasm Transplantation methods, Nitroimidazoles pharmacology, Radiation Tolerance physiology, Radiation-Sensitizing Agents pharmacology, Random Allocation, Tumor Microenvironment, Amines pharmacology, Cell Hypoxia drug effects, Electron Transport Complex I antagonists & inhibitors, Hypoxia-Inducible Factor 1 antagonists & inhibitors, Radiation Tolerance drug effects
Abstract

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors., Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD50) was calculated., Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD50, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD50., Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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72. Prognostic value of radiobiological hypoxia during fractionated irradiation for local tumor control.

Author

Zips D, Böke S, Kroeber T, Meinzer A, Brüchner K, Thames HD, Baumann M, and Yaromina A

Subjects
Animals, Cell Line, Tumor, Dose Fractionation, Radiation, Female, Humans, Male, Mice, Mice, Nude, Neoplasms pathology, Predictive Value of Tests, Random Allocation, Transplantation, Heterologous, X-Rays, Cells radiation effects, Hypoxia pathology, Neoplasms radiotherapy
Abstract

Background and Purpose: Previous experiments showed that the fraction of radiobiologically hypoxic tumor cells (rHF) in un-treated tumors did not accurately predict local tumor control after fractionated irradiation. Thus, the prognostic value of rHF determined during fractionated irradiation was investigated., Materials and Methods: Six human squamous cell carcinoma lines were transplanted into nude mice and then irradiated with 15 fractions over 3 weeks. Thereafter, single dose irradiation under normal and clamped blood flow was given. Local tumor control rates were used to calculate the rHF and the TCD₅₀, i.e., the radiation dose necessary to control 50% of the tumors, after single dose irradiation. These values were compared with the in parallel determined TCD₅₀ after 30 fractions in 6 weeks., Results: The rHF after 15 fractions varied between 28% and 100%. No correlation was found with the TCD₅₀ after 30 fractions in 6 weeks. Single dose top-up TCD₅₀ under ambient and clamp conditions after 15 fractions significantly correlated with TCD₅₀ after 30 fractions in 6 weeks., Conclusion: rHF after 15 fractions is not a prognostic parameter for the outcome after fractionated irradiation. In contrast, the radiobiological parameters number of tumor stem cells, intrinsic radiosensitivity, and number of radiobiologically hypoxic tumor cells appear promising to predict outcome after fractionated irradiation.

Published
2011
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73. Experimental evaluation of functional imaging for radiotherapy.

Author

Zips D, Yaromina A, Schütze C, Wüllrich K, Krause M, Krause M, Hessel F, Eicheler W, Dörfler A, Brüchner K, Menegakis A, Zhou X, Bergmann R, van den Hoff J, Beuthien-Baumann B, and Baumann M

Subjects
Animals, Biomarkers, Tumor, Dose Fractionation, Radiation, Humans, Mice, Mice, Nude, Nitroimidazoles metabolism, Proportional Hazards Models, Radiation-Sensitizing Agents metabolism, Radiotherapy Dosage, Fluorodeoxyglucose F18, Neoplasms, Experimental diagnostic imaging, Neoplasms, Experimental radiotherapy, Neoplastic Stem Cells radiation effects, Positron-Emission Tomography, Radiopharmaceuticals, Radiotherapy methods, Xenograft Model Antitumor Assays
Published
2007
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74. [Not Available].

Author

Wendt TG, Gademann G, Pambor C, Grießbach I, von Specht H, Martin T, Baltas D, Kurek R, Röddiger S, Tunn UW, Zamboglou N, Eich HT, Staar S, Gossmann A, Hansemann K, Semrau R, Skripnitchenko R, Diehl V, Müller RP, Sehlen S, Willich N, Rühl U, Lukas P, Dühmke E, Engel K, Tabbert E, Bolck M, Knaack S, Annweiler H, Krempien R, Hoppe H, Harms W, Daeuber S, Schorr O, Treiber M, Debus J, Alber M, Paulsen F, Birkner M, Bakai A, Belka C, Budach W, Grosser KH, Kramer R, Kober B, Reinert M, Schneider P, Hertel A, Feldmann H, Csere P, Hoinkis C, Rothe G, Zahn P, Alheit H, Cavanaugh SX, Kupelian P, Reddy C, Pollock B, Fuss M, Roeddiger S, Dannenberg T, Rogge B, Drechsler D, Herrmann T, Alberti W, Schwarz R, Graefen M, Krüll A, Rudat V, Huland H, Fehr C, Baum C, Glocker S, Nüsslin F, Heil T, Lemnitzer H, Knips M, Baumgart O, Thiem W, Kloetzer KH, Hoffmann L, Neu B, Hültenschmidt B, Sautter-Bihl ML, Micke O, Seegenschmiedt MH, Köppen D, Klautke G, Fietkau R, Schultze J, Schlichting G, Koltze H, Kimmig B, Glatzel M, Fröhlich D, Bäsecke S, Krauß A, Strauß D, Buth KJ, Böhme R, Oehler W, Bottke D, Keilholz U, Heufelder K, Wiegel T, Hinkelbein W, Rödel C, Papadopoulos T, Munnes M, Wirtz R, Sauer R, Rödel F, Lubgan D, Distel L, Grabenbauer GG, Sak A, Stüben G, Pöttgen C, Grehl S, Stuschke M, Müller K, Pfaffendorf C, Mayerhofer A, Köhn FM, Ring J, van Beuningen D, Meineke V, Neubauer S, Keller U, Wittlinger M, Riesenbeck D, Greve B, Exeler R, Ibrahim M, Liebscher C, Severin E, Ott O, Pötter R, Hammer J, Hildebrandt G, Beckmann MW, Strnad V, Fehlauer F, Tribius S, Bajrovic A, Höller U, Rades D, Warszawski A, Baumann R, Madry-Gevecke B, Karstens JH, Grehn C, Hensley F, Berns C, Wannenmacher M, Semrau S, Reimer T, Gerber B, Ketterer P, Koepcke E, Hänsgen G, Strauß HG, Dunst J, Füller J, Kalb S, Wendt T, Weitmann HD, Waldhäusl C, Knocke TH, Lamprecht U, Classen J, Kaulich TW, Aydeniz B, Bamberg M, Wiezorek T, Banz N, Salz H, Scheithauer M, Schwedas M, Lutterbach J, Bartelt S, Frommhold H, Lambert J, Hornung D, Swiderski S, Walke M, Siefert A, Pöllinger B, Krimmel K, Schaffer M, Koelbl O, Bratengeier K, Vordermark D, Flentje M, Hero B, Berthold F, Combs SE, Gutwein S, Schulz-Ertner D, van Kampen M, Thilmann C, Kocher M, Kunze S, Schild S, Ikezaki K, Müller B, Sieber R, Weiß C, Wolf I, Wenz F, Weber KJ, Schäfer J, Engling A, Laufs S, Veldwijk MR, Milanovic D, Fleckenstein K, Zeller W, Fruehauf S, Herskind C, Weinmann M, Jendrossek V, Rübe C, Appold S, Kusche S, Hölscher T, Brüchner K, Geyer P, Baumann M, Kumpf R, Zimmermann F, Schill S, Geinitz H, Nieder C, Jeremic B, Molls M, Liesenfeld S, Petrat H, Hesselmann S, Schäfer U, Bruns F, Horst E, Wilkowski R, Assmann G, Nolte A, Diebold J, Löhrs U, Fritz P, Hans-Jürgen K, Mühlnickel W, Bach P, Wahlers B, Kraus HJ, Wulf J, Hädinger U, Baier K, Krieger T, Müller G, Hof H, Herfarth K, Brunner T, Hahn SM, Schreiber FS, Rustgi AK, McKenna WG, Bernhard EJ, Guckenberger M, Meyer K, Willner J, Schmidt M, Kolb M, Li M, Gong P, Abdollahi A, Trinh T, Huber PE, Christiansen H, Saile B, Neubauer-Saile K, Tippelt S, Rave-Fränk M, Hermann RM, Dudas J, Hess CF, Schmidberger H, Ramadori G, Andratschke N, Price R, Ang KK, Schwarz S, Kulka U, Busch M, Schlenger L, Bohsung J, Eichwurzel I, Matnjani G, Sandrock D, Richter M, Wurm R, Budach V, Feussner A, Gellermann J, Jordan A, Scholz R, Gneveckow U, Maier-Hauff K, Ullrich R, Wust P, Felix R, Waldöfner N, Seebass M, Ochel HJ, Dani A, Varkonyi A, Osvath M, Szasz A, Messer PM, Blumstein NM, Gottfried HW, Schneider E, Reske SN, Röttinger EM, Grosu AL, Franz M, Stärk S, Weber W, Heintz M, Indenkämpen F, Beyer T, Lübcke W, Levegrün S, Hayen J, Czech N, Mbarek B, Köster R, Thurmann H, Todorovic M, Schuchert A, Meinertz T, Münzel T, Grundtke H, Hornig B, Hehr T, Dilcher C, Chan RC, Mintz GS, Kotani JI, Shah VM, Canos DA, Weissman NJ, Waksman R, Wolfram R, Bürger B, Schrappe M, Timmermann B, Lomax A, Goitein G, Schuck A, Mattke A, Int-Veen C, Brecht I, Bernhard S, Treuner J, Koscielniak E, Heinze F, Kuhlen M, von Schorlemer I, Ahrens S, Hunold A, Könemann S, Winkelmann W, Jürgens H, Gerstein J, Polivka B, Sykora KW, Bremer M, Thamm R, Höpfner C, Gumprecht H, Jäger R, Leonardi MA, Frank AM, Trappe AE, Lumenta CB, Östreicher E, Pinsker K, Müller A, Fauser C, Arnold W, Henzel M, Groß MW, Engenhart-Cabillic R, Schüller P, Palkovic S, Schröder J, Wassmann H, Block A, Bauer R, Keffel FW, Theophil B, Wisser L, Rogger M, Niewald M, van Lengen V, Mathias K, Welzel G, Bohrer M, Steinvorth S, Schleußner C, Leppert K, Röhrig B, Strauß B, van Oorschot B, Köhler N, Anselm R, Winzer A, Schneider T, Koch U, Schönekaes K, Mücke R, Büntzel J, Kisters K, Scholz C, Keller M, Winkler C, Prause N, Busch R, Roth S, Haas I, Willers R, Schultze-Mosgau S, Wiltfang J, Kessler P, Neukam FW, Röper B, Nüse N, Auer F, Melzner W, Geiger M, Lotter M, Kuhnt T, Müller AC, Jirsak N, Gernhardt C, Schaller HG, Al-Nawas B, Klein MO, Ludwig C, Körholz J, Grötz KA, Huppers K, Kunkel M, Olschewski T, Bajor K, Lang B, Lang E, Kraus-Tiefenbacher U, Hofheinz R, von Gerstenberg-Helldorf B, Willeke F, Hochhaus A, Roebel M, Oertel S, Riedl S, Buechler M, Foitzik T, Ludwig K, Klar E, Meyer A, Meier Zu Eissen J, Schwab D, Meyer T, Höcht S, Siegmann A, Sieker F, Pigorsch S, Milicic B, Acimovic L, Milisavljevic S, Radosavljevic-Asic G, Presselt N, Baum RP, Treutler D, Bonnet R, Schmücking M, Sammour D, Fink T, Ficker J, Pradier O, Lederer K, Weiss E, Hille A, Welz S, Sepe S, Friedel G, Spengler W, Susanne E, Kölbl O, Hoffmann W, Wörmann B, Günther A, Becker-Schiebe M, Güttler J, Schul C, Nitsche M, Körner MK, Oppenkowski R, Guntrum F, Malaimare L, Raub M, Schöfl C, Averbeck T, Hacker I, Blank H, Böhme C, Imhoff D, Eberlein K, Weidauer S, Böttcher HD, Edler L, Tatagiba M, Molina H, Ostertag C, Milker-Zabel S, Zabel A, Schlegel W, Hartmann A, Wildfang I, Kleinert G, Hamm K, Reuschel W, Wehrmann R, Kneschaurek P, Münter MW, Nikoghosyan A, Didinger B, Nill S, Rhein B, Küstner D, Schalldach U, 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Published
2004
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75. Experimental study on different combination schedules of VEGF-receptor inhibitor PTK787/ZK222584 and fractionated irradiation.

Author

Zips D, Krause M, Hessel F, Westphal J, Brüchner K, Eicheler W, Dörfler A, Grenman R, Petersen C, Haberey M, and Baumann M

Subjects
Animals, Carcinoma, Squamous Cell blood supply, Cell Line, Tumor, Chemotherapy, Adjuvant, Dose Fractionation, Radiation, Drug Administration Schedule, Female, Humans, Male, Mice, Mice, Nude, Neoadjuvant Therapy, Xenograft Model Antitumor Assays, Angiogenesis Inhibitors administration & dosage, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell radiotherapy, Phthalazines administration & dosage, Pyridines
Abstract

Background: Inhibition of the vascular endothelial growth factor receptor (VEGFR) has been shown to improve the radiation response of several experimental tumors. The present experimental study compares the effect of neoadjuvant, concomitant and adjuvant treatment with PTK787/ZK222584, a specific inhibitor of the VEGFR, in combination with fractionated irradiation., Materials and Methods: Growth delay after daily oral application of 50 mg per kg bodyweight PTK787/ZK222584 or carrier was tested in five different human squamous cell carcinoma growing in nude mice. Two of these tumor models, a responder (UT-SCC-14) and a non-responder (FaDu), were selected for the irradiation experiments (15 fractions of 2 Gy within 15 days). PTK787/ZK222584 was applied daily for 4-18 days and stopped before start of irradiation (neoadjuvant), for 15 days during fractionated irradiation (concomitant) or for 45 days after the course of irradiation (adjuvant)., Results: Adjuvant application of PTK787/ZK222584 after fractionated irradiation retarded regrowth of UT-SCC-14 tumors and, surprisingly, also of FaDu tumors which did not respond to the agent when given alone. No effects on radiation response were observed after short-term neoadjuvant or concomitant PTK787/ZK222584 application., Conclusion: Combined with fractionated irradiation, only adjuvant application of PTK787/ZK222584 retarded regrowth of UT-SCC-14 and FaDu tumors. The data suggest that preirradiated vasculature might be more sensitive to VEGFR inhibition compared to unirradiated vasculature. Whether the effect of adjuvant VEGFR inhibition on growth delay translates into improved local tumor control after irradiation needs further investigation.

Published
2003

76. Selection of genetically distinct, rapidly proliferating clones does not contribute to repopulation during fractionated irradiation in FaDu squamous cell carcinoma.

Author

Zips D, Petersen C, Junghanns S, Eicheler W, Brüchner K, and Baumann M

Subjects
Animals, Cell Differentiation, Cell Division radiation effects, Dose Fractionation, Radiation, Dose-Response Relationship, Radiation, Female, Humans, Hypoxia, Male, Mice, Mice, Nude, Neoplasm Transplantation, Pharyngeal Neoplasms radiotherapy, Time Factors, Tumor Cells, Cultured, Carcinoma, Squamous Cell radiotherapy
Abstract

Acceleration of clonogen repopulation during fractionated irradiation after about 3 weeks has been demonstrated previously in FaDu human squamous cell carcinoma in nude mice (Petersen et al., Int. J. Radiat. Oncol. Biol. Phys. 51, 483-493, 2001). Selection of genetically distinct, rapidly proliferating clones might contribute to this phenomenon. To address this question, three sublines (R1-R3) were established from FaDu tumors that recurred locally after fractionated irradiation. The tumors were retransplanted and irradiated under clamp hypoxia with single doses or with 18 x 3 Gy within 18 days or 36 days, followed by graded top-up doses. The results were compared with data obtained after the same treatment schedules in the parental tumor line. Histologies, tumor volume doubling times, and potential doubling times of FaDu sublines R1-R3 were not different from those of the parental line. The radiation dose required to control 50% of the tumors (TCD(50)) after single-dose irradiation of 37-38 Gy was the same for the FaDu sublines R1-R3 and the parental tumor. The top-up TCD(50) values for the FaDu sublines R1-R3 after 18 fractions within 36 days were 14-17 Gy higher than those after 18 fractions within 18 days, indicating significant repopulation. The magnitude of this effect was not significantly different between the sublines R1-R3 or between these sublines and the parental FaDu tumors. The results indicate that selection of genetically distinct, rapidly proliferating clones does not contribute to the acceleration of repopulation during fractionated irradiation in poorly differentiated FaDu tumors.

Published
2003
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