16 results on '"Zafferani M"'
Search Results
2. Abstract
- Author
-
Mache, Ch., Urban, Ch., Sauer, H., Brandesky, G., Meßner, H., Grienberger, H., Becker, H., Slave, I., Hauer, Ch., Pakisch, B., Oberbauer, R., Mokry, M., Ebner, F., Kleinert, R., Schiller, D., Kasparu, H., Schneider, G., Sega, W., Lutz, D., Mader, R. M., Steger, G. G., Sieder, A. E., Ovissi, L., Roth, E., Hamilton, G., Jakesz, R., Rainer, H., Schenk, T., Kornek, G., Schulz, F., Depisch, D., Rosen, H., Sebesta, Ch., Scheithauer, W., Locker, G. J., Czernin, J., Derfler, K., Gnant, M., Schiessel, R., Petru, E., Pickel, H., Heydarfadai, M., Lahousen, M., Haas, J., Sagaster, P., Flamm, J., Umek, H., Essl, R., Teich, G., Micksche, M., Ludwig, H., Ambros, P. F., Lestou, V., Strehl, S., Mann, G., Gadner, H., Eibl, B., Greiter, E., Grünewald, K., Gastl, G., Thaler, J., Aulitzky, W., Lion, T., Henn, T., Gaiger, A., Hofmann, J., Wolf, A., Spitaler, M., Ludescher, Christof, Grunicke, H., Mitterbauer, G., Stangl, E., Geissler, K., Jäger, U., Lechner, K., Mannhalter, C., Haas, Oskar A., Tirita, Anthi, Kahls, P., Haas, O., Hinterberger, W., Linkesch, W., Pober, Michael, Fae, Ingrid, Kyrle, Alexander, Neumeister, Andrea, Panzer, Simon, Kandioler, D., End, A., Grill, R., Karlic, H., Inhauser, T., Chott, A., Pirc-Danoewinata, H., Klepetko, W., Heinz, R., Hopfinger-Limberger, G., Koller, E., Schneider, B., Pittermann, E., Lorber, C., Eichinger, S., Neumann, E., Weidinger, J., Gisslinger, H., Bedford P., Jones D., Cawley J., Catovsky D., Bevan P., Scherrer, R., Bettelheim, P., Knöbl, P., Kyrie, P. A., Lazcika, K., Schwarzinger, I., Sillaber, C., Watzke, H., Dávid, M., Losonczy, H., Matolcsy, A., Papp, M., Prischl, F. C., Schwarzmeier, J. D., Zoubek, Andreas, Harbott, Jochen, Ritterbach, Jutta, Ritter, Jörg, Sillaber, Ch., Agis, H., Spanblöchl, E., Sperr, W. R., Valent, P., Czerwenka, K., Virgolini, I., Li, S. R., Müller, M., Wrann, M., Gaggl, S., Fasching, B., Herold, M., Geissler, D., Nachbaur, D., Huber, Ch., Schwaighofer, H., Pichl, M., Niederwieser, D., Gilly, B., Weissel, H., Lorber, Ch., Schwarzmeier, J., Gasché, C., Reinisch, W., Hilgarth, M., Keil, F., Thomssen, C., Kolb, H. J., Holler, E., Wilmanns, W., Tilg, H., Gächter, A., Panzer-Grümayer, E. R., Majdic, O., Kersey, J. H., Petzer, A. L., Bilgeri, R., Zilian, U., Geisen, F. H., Haun, M., Konwalinka, G., Fuchs, D., Zangerle, R., Artner-Dworzak, E., Weiss, G., Fritsch, P., Tilz, G. P., Dierich, M. P., Wachter, H., Schüller, J., Czejka, M. J., Jäger, W., Meyer, B., Weiss, C., Schernthaner, G., Marosi, Ch., Onderka, E., Schlögl, B., Maca, T., Hanak, R., Mannhalter, Ch., Brenner, B., Mayer, R., Langmann, A., Langmann, G., Slave, J., Poier, E., Stücklschweiger, G., Hackl, A., Fritz, A., Pabinger, I., Willfort, A., Groiss, E., Bernhart, M., Waldner, R., Krieger, O., Nowotny, H., Strobl, H., Michlmayr, G., Mistrik, M., lstvan, L., Kapiotis, S., Laczika, K., Speiser, W., Granena, A., Hermans, J., Zwaan, F., Gratwohl, A., Labar B., Mrsić M., Nemet D., Bogdanić V., Radman I., Zupančić-Šalek Silva, Kovačević-Metelko Jasna, Aurer I., Forstinger, C., Scholten, C., Kier, P., Kalhs, P., Schwinger, W., Slavc, I., Lackner, H., Nussbaumer, W., Fritsch, E., Fink, M., Zechner, O., Kührer, I., Kletter, V., Frey, S., Leitgeb, C., Fritz, E., Silly, H., Brezinschek, R., Kuss, I., Stöger, H., Schmid, M., Samonigg, H., Wilders-Truschnig, M., Schmidt, F., Bauernhofer, T., Kasparek, A. K., Ploner, F., Stoeger, H., Moser, R., Leikauf, W., Klemm, F., Pfeffel, F., Niessner, H., Poschauko, H., Pojer, E., Locker, G. J., Braun, J., Gnant, M. F. X., Michl, I., Pirker, R., Liebhard, A., Zielinski, C., Dittrich, C., Bernát, S. I., Pongrácz, E., Kastner, J., Raderer, M., Jorbenyi, Z., Yilmaz, A., Suardet, L., Lahm, H., Odartchenko, N., Varga, Gy., Sréter, L. A., Oberberg, D., Berdel, W. E., Budiman, R., Brand, C., Berkessy, S., Radványi, G., Pauker, Zs., Nagy, Zs., Karádi, Å., Serti, S., Hainz, R., Kirchweger, P., Prager, C., Prada, J., Neifer, S., Bienzle, U., Kremsner, P., Kämmerer, B., Vetterlein, M., Pohl, W., Letnansky, K., Imre, S. G., Parkas, T., Lakos, Zs., Kiss, A., Telek, B., Felszeghy, E., Kelemen, E., Rak, K., Pfeilstöcker, M., Reisner, R., Salamon, J., Georgopoulos, A., Feistauer, S., Georgopoulos, M., Graninger, W., Klinda, F., Hrubisko, M., Sakalova, A., Weißmann, A., Röhle, R., Fortelny, R., Gutierrez, F., Fritsch, G., Printz, D., Buchinger, P., Buchinger, P., Hoecker, P., Peters, C., Gebauer, E., Katanić, D., Nagy, Á., Szomor, Á., Med. J., Batinić D., Užaervić B., Marušić M., Kovačoević-Metelko Jasminka, Jakić-Razumović Jasminka, Kovačević-Metelko Jasminka, Zuoancić-Šalek Silva, Ihra, G. C., Reinisch, W. W., Hilgarth, M. F., Schwarzmeier, I. D., Várady, E., Molnár, Z. S., Fleischmann, T., Borbényi, Z., Bérczi, M., István, L., Szerafin, L., Jakó, J., Bányai, A., Dankó, K., Szegedi, Gy., Neubauer, M., Frudinger, A., Scholten, Ch., Forstinger, Ch., Dobrić I., Willheim, M., Szépfalusi, Z., Mader, R., Boltz, G., Schwarzmeier, J. D., Nahajevszky, S., Téri, N., Póth, I., Nagy, P., Smanykó, D., Babicz, T., Ujj, Gy., Iványi, J. L., Tóth, F. D., Kiss, J., Konja, J., Petković, I., Kardum, I., Kaštelan, M., Kelečić, J., Feminić, R., Djermanović, M., Bilić, E., Jakovljević, G., Peter, B., Gredelj, G., Senji, P., Thalhammer, F., Floth, A., Etele-Hainz, A., Kainberger, F., Radaszkiewicz, T., Kierner, H., Mód, Anna, Pitlik, E., Gottesman, M., Magócsi, Mária, Sarkadi, B., Knapp, S., Purtscher, B., DelleKarth, G., Jaeger, U., Krieger, O., Berger, W., Elbling, L., Ludescher, C., Hilbe, W., Eisterer, W., Preuß, E., Izraeli, S., Janssen, J. W. G., Walther, J. U., Kovar, H., Ludwig, W. D., Rechavi, G., Bartram, C. R., Rehberger, A., Mittermayer, F., Schauer, E., Kokoschka, E. M., Kammerer, B., Kokron, E., Desser, L., Abdul-Hamid, G., Kroschinksky, F., Luther, Th., Fischer, H., Nowak, R., Wolf, H., Fleischer, J., Wichmann, G., Albercht, S., Adorf, D., Kaboth, W., Nerl, C., Aman, J., Rudolf, G., Peschel, C., Anders, O., Burstein, Ch., Ernst, B., Steiner, H., Konrad, H., Annaloro, U. P., Mozzana, C., Butti, R., Della, C., Volpe A., Soligo D., Uderzo M., Lambertenghi-Deliliers G., Ansari, H., Dickson, D., Hasford, J., Hehlmann, R., Anyanwu, E., Krysa, S., Bülzebrück, H., Vogt-Moykopf, I., Arning, M., Südhoff, Th., Kliche, K. O., Wehmeier, A., Schneider, W., Arnold, R., Bunjes, D., Hertenstein, B., Hueske, D., Stefanic, M., Theobald, M., Wiesneth, M., Heimpel, H., Waldmann, H., Arseniev, L., Bokemeyer, C., Andres, J., Könneke, A., Papageorgiou, E., Kleine, H. -D., Battmer, K., Südmeyer, I., Zaki, M., Schmoll, H. -J., Stangel, W., Poliwoda, H., Link, H., Aul, C., Runde, V., Heyll, A., Germing, U., Gattermann, N., Ebert, A., Feinendegen, L. E., Huhn, D., Bergmann, L., Dönner, H., Hartlapp, J. H., Kreiter, H., Schuhmacher, K., Schalk T., Sparwasser C., Peschel U., Fraaß C. Huber, HIadik, F., Kolbe, K., Irschick, E., Bajko, G., Wozny, T., Hansz, J., Bares, R., Buell, U., Baumann, I., Harms, H., Kuse, R., Wilms, K., Müller-Hermelink, H. K., Baurmann, H., Cherif, D., Berger, R., Becker, K., Zeller, W., Helmchen, U., Hossfeld, D. K., Bentrup, I., Plusczyk, T., Kemkes-Matthes, B., Matthes, K., Bentz, M., Speicher, M., Schröder, M., Moos, M., Döhner, H., Lichter, P., Stilgenbauer, S., Korfel, A., Harnoss, B. -M., Boese-Landgraf, J., May, E., Kreuser, E. -D., Thiel, E., Karacas, T., Jahn, B., Lautenschläger, G., Szepes, S., Fenchel, K., Mitrou, P. S., Hoelzer, D., Heil, G., Lengfelder, E., Puzicha, E., Martin, H., Beyer, J., Kleiner, S., Strohscheer, I., Schwerdtfeger, R., Schwella, N., Schmidt-Wolf, I., Siegert, W., Weyer, C., arzen, G., Risse, G., Miksits, K., Farshidfar, G., Birken, R., Schilling, C. v., Brugger, W., Holldack, J., Mertelsmann, R., Kanz, L., Blanz, J., Mewes, K., Ehninger, G., Zeller, K. -P., Böhme. A., Just G., Bergmann. L., Shah P., Hoelzer D., Stille W., Bohlen, H., Hopff, T., Kapp, U., Wolf, J., Engert, A., Diehl, V., Tesch, H., Schrader, A., van Rhee, J., Köhne-Wömpner, H., Bokemeyer', C., Gonnermann, D., Harstrick, A., Schöffski, P., van Rhee, J., Schuppert, F., Freund, M., Boos, J., Göring, M., Blaschke, G., Borstel, A., Franke, A., Hüller, G., Uhle, R., Weise, W., Brach, Marion A., Gruss, Hans-Jürgen, Herrmann, Friedhelm, deVos, Sven, Brennscheidt, Ulrich, Riedel, Detlev, Klch, Walter, Bonlfer, Renate, Mertelsmann, Roland, Brieaer, J., Appelhans, H., Brückner, S., Siemens, HJ., Wagner, T., Moecklin, W., Mertelsmann, R., Bertz, H., Hecht, T., Mertelsmann, R., Bühl, K., Eichelbaum, M. G., Ladda, E., Schumacher, K., Weimer, A., Bühling, F., Kunz, D., Lendeckel, U., Reinhold, D., Ulmer, A. J., Flad, H. -D., Ansorge, S., Bühring, Hans-Jörg, Broudy¶, Virginia C., Ashman§, Leonie K., Burk, M., Kunecke, H., Dumont, C., Meckenstock, G., Volmer, M., Bucher, M., Manegold, C., Krenpien, B., Fischer, J. R., Drings, P., Bückner, U., Donhuijsen-Ant, R., Eberhardt, B., Westerhausen, M., Busch, F. W., Jaschonek, K., Steinke, B., Calavrezos, A., Hausmann, K., Solbach, M., Woitowitz, H. -P., Hilierdal, G., Heilmann, H. -P., Chen, Z. J., Frickhofen, N., Ellbrück, D., Schwarz, T. F., Körner, K., Wiest, C., Kubanek, B., Seifried, E., Claudé, R., Brücher, J., Clemens, M. R., Bublitz, K., Bieger, O., Schmid, B., Clemetson, K. J., Clemm, Ch., Bamberg, M., Gerl, A., Weißbach, L., Danhauser-Riedl, S., Schick, H. D., Bender, R., Reuter, M., Dietzfelbinger, H., Rastetter, J., Hanauske, A. -R., Decker, Hans-Jochen, Klauck, Sabine, Seizinger, Bernd, Denfeld, Ralf, Pohl, Christoph, Renner, Christoph, Hombach, Andreas, Jung, Wolfram, Schwonzen, Martin, Pfreundschuh, Michael, Derigs, H. Günter, Boswell, H. Scott, Kühn, D., Zafferani, M., Ehrhardt, R., Fischer, K., Schmitt, M., Witt, B., Ho, A. D., Haas, R., Hunstein, W., Dölken, G., Finke, J., Lange, W., Held, M., Schalipp, E., Fauser, A. A., Mertelsmann, R., Donhuijsen, K., Nabavi, D., Leder, L. D., Haedicke, Ch., Freund, H., Hattenberger, S., Dreger, Peter, Grelle, Karen, Schmitz, Norbert, Suttorp, Meinolf, Müller-Ruchholtz, Wolfgang, Löffler, Helmut, Dumoulin, F. L., Jakschies, D., Walther, M., Hunger, P., Deicher, H., von Wussow, P., Dutcher, J. P., Ebell, W., Bender-Götze, C., Bettoni, C., Niethammer, D., Reiter, A., Sauter, S., Schrappe, M., Riehm, H., Niederle, N., Heidersdorf, H., Müller, M. R., Mengelkoch, B., Vanhoefer, U., Stahl, M., Budach, V., loehren, B., Alberti, W., Nowrousian, M. R., Seeber, S., Wilke, H., Stamatis, G., Greschuchna, D., Sack, H., Konietzko, N., Krause, B., Dopfer, R., Schmidt, H., Einsele, H., Müller, C. A., Goldmann, S. F., Grosse-Wilde, H., Waller, H. D., Libal, B., Hohaus, S., Gericke, G., von Eiff, M., Oehme, A., Roth, B., van de Loo, J., von Eiff, K., Pötter, R., Weiß, H., Suhr, B., Koch, P., Roos, H., van de Loo, J., Meuter, V., Heissig, B., Schick, F., Duda, S., Saal, J. G., Klein, R., Steidle, M., Eisner, S., Ganser, A., Seipelt, G., Leonhardt, M., Engelhard, M., Brittinger, G., Gerhartz, H., Meusers, P., Aydemir, Ü., Tintrup, W., Tiemann, H., Lennert, K., Esser, B., Hirsch, F. W., Evers, C., Riess, H., Lübbe, A., Greil, R., Köchling, A., Digel, D., Bross, K. J., Dölken, G., Mertelsmann, R., Gencic S., Ostermann, M., Baum, R. P., Fiebig, H. H., Berger, D. P., Dengler, W. A., Winterhalter, B. R., Hendriks, H., Schwartsmann, G., Pinedo, H. M., Ternes, P., Mertelsmann, R., Dölken, G., Fischbach, W., Zidianakis, Z., Lüke, G., Kirchner, Th., Mössner, J., Fischer, Thomas, Haque, Saikh J., Kumar, Aseem, Rutherford, Michael N., Williams, Bryan R. G., Flohr, T., Decker, T., Thews, A., Hild, F., Dohmen, M., von Wussow, P., Grote-Metke, A., Otremba, B., Fonatsch, C., Binder, T., Imhof, C., Feller, A. C., Fruehauf, S., Moehle, R., Hiddemann Th., Büchner M. Unterhalt, Wörmann, B., Ottmann, O. G., Verbeek, G. W., Seipelt A. Maurer, Geissler, G., Schardt, C., Reutzel, R., Hiddemann, W., Maurer, A., Hess, U., Lindemann, A., Frisch, J., Schulz, G., Mertelsmann, R., Hoelzer, P., Gassmann, W., Sperling, C., Uharek, L., Becher, R., Weh, H. J., Tirier, C., Hagemann, F. G., Fuhr, H. G., Wandt, H., Sauerland, M. C., Gause, A., Spickermann, D., Klein, S., Pfreund-schuh, M., Gebauer, W., Fallgren-Gebauer, E., Geissler, R. G., Mentzel, U., Kleiner, K., Rossol, R., Guba, P., Kojouharoff, G., Gerdau, St., Körholz, D., Klein-Vehne, A., Burdach, St., Gerdemann M., Maurer J., Gerhartz, H. H., Schmetzer, H., Mayer, P., Clemm, C., Hentrich, M., Hartenstein, R., Kohl, P., Gieseler, F., Boege, F., Enttmann, R., Meyer, P., Glass, B., Zeis, M., Loeffler, H., Mueller-Ruchholtz, W., Görg, C., Schwerk, W. B., Köppler, H., Havemann, K., Goldschmitt, J., Goldschmidt, H., Nicolai, M., Richter, Th., Blau, W., Hahn, U., Kappe, R., Leithäuser, F., Gottstein, Claudia, Schön, Gisela, Dünnebacke, Markus, Berthold, Frank, Gramatzki, M., Eger, G., Geiger, M., Burger, R., Zölch, A., Bair, H. J., Becker, W., Griesinger, F., Elfers, H., Griesser, H., Grundner-Culemann, E., Neubauer, V., Fricke, D., Shalitin, C., Benter, T., Mertelsmann, R., Dölken, Gottfried, Mertelsmann, Roland, Günther, W., Schunmm, M., Rieber, P., Thierfelder, S., Gunsilius, E., Kirstein, O., Bommer, M., Serve, H., Hülser, P. -J., Del Valle F., Fischer J. Th., Huberts H., Kaplan E., Haase, D., Halbmayer, W. -M., Feichtinger, Ch., Rubi, K., Fischer, M., Hallek, M., Lepislo, E. M., Griffin, J. D., Emst, T. J., Druker, B., Eder, M., Okuda, K., D.Griffin, J., Kozłowska-Skrzypczak, K., Meyer, B., Reile, D., Scharnofske, M., Hapke, G., Aulenbacher, P., Havemann, K., Becker, N., Scheller, S., Zugmaier, G., Pralle, H., Wahrendorf, J., Heide, Immo, Thiede, Christian, de Kant, Eric, Neubauer, Andreas, Herrmann, Richard, Rochlitz, Christoph, Heiden, B., Depenbrock, H., Block, T., Vogelsang, H., Schneider, P., Fellbaum, Ch., Heidtmann, H. -H., Blings, B., Havemann, K., Fackler-Schwalbe, E., Schlimok, G., Lösch, A., Queißer, W., Löffler, B., Kurrle, E., Chadid, L., Lindemann, A., Mertelsmann, R., Nicolay, U., Gaus, W., Heinemann, V., Jehn, U., Gleixner, B., Wachholz, W., Scholz, P., Plunkett, W., Heinze, B., Novotny, J., Hess, Georg, Gamm, Heinold, Seliger, Barbara, Heuft, H. G., Oettle, H., Zeiler, T., Eckstein, R., Heymanns, J., Havemann, K., Hladik, F., Hoang-Vu, C., Horn, R., Cetin, Y., Scheumann, G., Dralle, H., Köhrle, J., von zur Mühlen, A., Brabant, G., Hochhaus, A., Mende, S., Simon, M., Fonatsch, Ch., Heinze, B., Georgii, A., Hötzl, Ch., Hintermeier-Knabe, R., Kempeni, J., Kaul, M., Hoetzl, Ch., Clemm, Ch., Lauter, H., Hoffknecht, M. M., Eckardt, N., Hoffmann-Fezer, G., Gall, C., Kranz, B., Zengerle, U., Pfoersich, M., Birkenstock, U., Pittenann, E., Heinz, B., Hosten, N., Schörner, W., Kirsch, A., Neumann, K., Felix, R., Humpe, A., Kiss, T., Trümper, L. H., Messner, H. A., Hundt, M., Zielinska-Skowronek, M., Schubert, J., Schmidt, R. E., Huss, R., Storb, R., Deeg, H. J., Issels, R. D., Bosse, D., Abdel-Rahman, S., Jaeger, M., Söhngen, D., Weidmann, E., Schwulera, U., Jakab, I., Fodor, F., Pecze, K., Jaques, G., Schöneberger, H. -J., Wegmann, B., Grüber, A., Bust, K., Pflüger, K. -H., Havemann, K., Faul, C., Wannke, B., Scheurlen, M., Kirchner, M., Dahl, G., Schmits, R., Fohl, C., Kaiser, U., Tuohimaa, P., Wollmer, E., Aumüller, G., Havemann, K., Kolbabek, H., Schölten, C., Popov-Kraupp, B., Emminger, W., Hummel, M., Pawlita, M., v.Kalle, C., Dallenbach, F., Stein, H., Krueger, G. R. F., Müller-Lantzsch, N., Kath, R., Höffken, K., Horn, G., Brockmann, P., Keilholz, U., Stoelben, E., Scheibenbogen, C., Manasterski, M., Tilgen, W., Schlag, P., Görich, J., Kauffmann, G. W., Kempter, B., Rüth, S., Lohse, P., Khalil, R. M., Hültner, L., Mailhammer, R., Luz, A., Hasslinger, M. -A., Omran, S., Dörmer, P., Kienast, J., Kister, K. P., Seifarth, W., Klaassen, U., Werk, S., Reiter, W. W., Klein, G., Beck-Gessert, S., Timpl, R., Hinrichs, H., Lux, E., Döring, G., Scheinichen, D., Döring, G., Wernet, P., Vogeley, K. T., Richartz, G., Südhoff, T., Horstkotte, D., Klocker, J., Trotsenburg, M. v., Schumer, J., Kanatschnig, M., Henning, K., Knauf, W. U., Pottgießer, E., Raghavachar, A., Zeigmeister, B., Bollow, M., Schilling, A., König, H., Koch, M., Volkenandt, M., Seger, Andrea, Banerjee, D., Vogel, J., Bierhoff, E., Heidi, G., Neyses, L., Bertino, J., Kocki, J., Rozynkowa, D. M., M.Rupniewska, Z., Wojcierowski, J., König, V., Hopf, U., Koenigsmann, M., Streit, M., Koeppen, K. M., Martini, I., Poppy, U., Hardel, M., Havemann, K., Havemann, K., Clemm, Ch., Wendt, Th., Gauss, J., Kreienberg, R., Hohenfellner, R., Krieger, O., Istvan, L., Komarnicki, M., Kazmierczak, M., Haertle, D., Korossy, P., Haus, S. Kotlarek, Gabryś, K., Kuliszkiewicz-Janus, M., Krauter, J., Westphal, C., Werner, K., Lang, P., Preissner, K. T., Völler, H., Schröder, K., Uhrig, A., Behles, Ch., Seibt-Jung, H., Besserer, A., Kreutzmann, H., Kröning, H., Kähne, T., Eßbach, U., Kühne, W., Krüger, W. H., Krause, K., Nowicki, B., Stockschläder, M., Peters, S. O., Zander, A. R., Kurowski, V., Schüler, C., Höher, D., Montenarh, M., Lang, W., Schweiger, H., Dölken, Gottfried, Lege, H., Dölken, G., Wex, Th., Frank, K., Hastka, J., Bohrer, M., Leo, R., Peest, D., Tschechne, B., Atzpodien, J., Kirchner, H., Hein, R., Hoffmann, L., Stauch, M., Franks, C. R., Palmer, P. A., Licht, T., Mertelsmann, R., Liersch, T., Vehmeyer, K., Kaboth, U., Maschmeyer, G., Meyer, P., Helmerking, M., Schmitt, J., Adam, D., Prahst, A., Hübner, G., Meisner, M., Seifert, M., Richard, D., Yver, A., Spiekermann, K., Brinkmann, L., Battmer, K., Krainer, M., Löffel, J., Stahl, H., Wust, P., Lübbert, M., Schottelius, A., Mertelsmann, R., Henschler, R., Mertelsmann, R., Mapara, M. Y., Bargou, R., Zugck, C., Krammer, P. H., Dörken, B., Maschek, Hansjörg, Kaloutsi, Vassiliki, Maschek, Hansjörg, Gormitz, Ralf, Meyer, P., Kuntz, B. M. E., Mehl, B., Günther, I., Bülzebruck, H., Menssen, H. D., Mergenthaler, H. -G., Dörmer, P., Heusers, P., Zeller, K. -P., Enzinger, H. M., Neugebauer, T., Klippstein, T., Burkhardt, K. L., Putzicha, E., Möller, Peter, Henne, Christof, Eichelmann, Anette, Brüderlein, Silke, Dhein, Jens, Möstl, M., Krieger, O., Mucke, H., Schinkinger, M., Moiling, J., Daoud, A., Willgeroth, Ch., Mross K., Bewermeier P., Krüger W., Peters S., Berger C., Bohn, C., Edler, L., Jonat, W., Queisser, W., Heidemann, E., Goebel, M., Hamm, K., Markovic-Lipkovski, J., Bitzer, G., Müller, H., Oethinger, M., Grießhammer, M., Tuner, I., Musch E., Malek, M., Peter-Katalinic, J., Hügl, E., Helli, A., Slanicka, M., Filipowicz, A., Nissen, C., Speck, B., Nehls, M. C., Grass, H. -J., Dierbach, H., Mertelsmann, R., Thaller, J., Fiebeler, A., Schmidt, C. A., O'Bryan, J. P., Liu, E., Ritter, M., de Kant, E., Brendel, C., He, M., Dodge, R., George, S., Davey, F., Silver, R., Schiffer, C., Mayer, R., Ball, E., Bloomfield, C., Ramschak, H., Tiran, A., Truschnig-Wilders, M., Nizze, H., Bühring, U., Oelschlägel, U., Jermolow, M., Oertel, J., Weisbach, V., Zingsem, J., Wiens, M., Jessen, J., Osthoff, K., Timm, H., Wilborn, F., Bodak, K., Langmach, K., Bechstein, W., Blumhardt, G., Neuhaus, P., Olek, K., Ottinger, H., Kozole, G., Belka, C., Meusers, P., Hense, J., Papadileris, Stefan, Pasternak, G., Pasternak, L., Karsten, U., Pecherstorfer, M., Zimmer-Roth, I., Poloskey, A., Petrasch, S., Kühnemund, O., Uppenkamp, M., Lütticken, R., Kosco, M., Schmitz, J., Petrides, Petro E., Dittmann, Klaus H., Krieger, O., Pflueger, K. -H., Grueber, A., Schoeneberger, J., Wenzel, E., Havemann, K., Pies, A., Kneba, M., Edel, G., Pohl, S., Bulgay-Mörschel, M., Polzin, R., Issing, W., Clemm, Ch., Schorn, K., Ponta, H., Zöller, M., Hofmann, M., Arch, R., Heider, K. -H., Rudy, W., Tölg, C., Herrlich, P., Prümmer, O., Scherbaum, W. A., Porzsolt, F., Prümmer, O., Krüger, A., Schrezenmeier, H., Schlander, H., Pineo, G., Marin, P., Gluckman, E., Shahidi, N. T., Bacigalupo, A., Ratajczak, M. Z., Gewirtz, A. M., Ratei, R., Borner, K., Bank, U., Bühling, F., Reisbach, G., Bartke, L., Kempkes, B., Kostka, G., Ellwart, X., Birner, A., Bornkamm, G. W., Ullrich, A., Dörmer, P., Henze, G., Parwaresch, R., Müller-Weihrich, S. T., Klingebiel, Th., Odenwald, E., Brandhorst, D., Tsuruo, T., Wetter, O., Renner, C., Pohl, C., Sahin, U., Renner, U., Zeller, K. -P., Repp, R., Valerius, Th., Sendler, A., Kalden, J. R., PIatzer, E., Reuss-Borst, M. A., Bühring, H. J., Reuter, C., der Landwehr, II, U. Auf, der Landwehr, II, U. Auf, Schleyer, E., Rolf, C., Ridwelski, K., Matthias, M., Preiss, R., Riewald, M., Puzo, A., Serke, S., Rohrer, B., Pfeiffer, D., Hepp, H., Romanowski, R., Schött, C., Rüther, U., Rothe, B., Pöllmann, H., Nunnensiek, C., Schöllhammer, T., Ulshöfer, Th., Bader, H., Jipp, P., Müller, H. A. G., Rupp, W., Lüthgens, M., Eisenberger, F., Afflerbach, C., Höller, A., Schwamborn, J. S., Daus, H., Krämer, K., Pees, H., Salat, C., Reinhardt, B., Düll, T., Knabe, H., Hiller, E., Sawinski, K., Schalhorn, A., Kühl, M., Heil, K., Schardt, Ch., Drexler, H. G., Scharf, R. E., Suhijar, D., del Zoppo, G. J., Ruggeri, Z. M., Roll, T., Möhler, T., Giselinger, H., Knäbl, P., Kyrie, P. A., Lazcíka, K., Lechner, X., Scheulen, M. E., Beelen, D. W., Reithmayer, H., Daniels, R., Weiherich, A., Quabeck, K., Schaefer, U. W., Reinhardt J., Grimm M., Unterhalt M., Schliesser, G., Lohmeyer, J., Schlingheider, O., von Eiff, M., Schulze, F., Oehme, C., van de Loo, J., Schlögl E., Bemhart M., Schmeiser, Th., Rozdzinski, E., Kern, W., Reichle, A., Moritz, T., Merk, Bruno, Schmid, R. M., Perkins, N. D., Duckett, C. S., Leung, K., Nabel, G. J., Pawlaczyk-Peter, B., Kellermann-Kegreiß, Schmidt E., Steiert, I., Schmidt-Wolf, G., Schmidt-Wolf, I. G. H., Schlegel, P., Blume, K. G., Chao, N. J., Lefterova, P., Laser, J., Schmitz, G., Rothe, G., Schönfeld, S., Schulz, S., Nyce, J. W., Graf, N., Ludwig, R., Steinhauser, I., Brommer, A. E., Qui, H., Schroeder, M., Grote-Kiehn, J., Bückner, U., Rüger, I., Schröder, J., Meusers, P., Weimar, Ch., Schoch, C., Schröter, G., Stern, H., Buchwald, B., Schick, K., Avril, N., Flierdt, E. v. d., Langhammer, H. R., Pabst, H. W., Alvarado, M., Witte, T., Vogt, H., Schuler, U., Brammer, K., Klann, R. C., Schumm, M., Hahn, J., Günther, W., Wullich, B., Moringlane, J. R., Schöndorf, S., Schwartz, S., Bühring, H. -J., Notter, M., Böttcher, S., Martin, M., Schmid, H., Lübbe, A. S., Leib-Mösch C., Wankmüller, H., Eilbrück, D., Funke, I., Cardoso, M., Duranceyk, H., Seitz, R., Rappe, N., Kraus, H., Egbring, R., Haasberg, M., Havemann, K., Seibach, J., Wollscheid, Ursula, Serke, St., Zimmermann, R., Shirai, T., Umeda, M., Anno, S., Kosuge, T., Katoh, M., Moro, S., Su, C. -Y., Shikoshi, K., Arai, N., Schwieder, G., Silling-Engelhardt, G., Zühlsdorf, M., Aguion-Freire-Innig, E., van de Loo, J., Stockdreher, K., Gatsch, L., Tischler, H. -J., Ringe, B., Diedrich, H., Franzi, A., Kruse, E., Lück, R., Trenn, G., Sykora, J., Wen, T., Fung-Leung, W. P., Mak, T. W., Brady, G., Loke, S., Cossman, J., Gascoyne, R., Mak, T., Urasinski, I., Zdziarska, B., Usnarska-Zubkiewicz, L., Kotlarek-Haus, S., Sciborskl, R., Nowosad, H., Kummer, G., Schleucher, N., Preusser, P., Niebel, W., Achterrath, W., Pott, D., Eigler, F. -W., Venook, A., Stagg, R., Frye, J., Gordon, R., Ring, E., Verschuer, U. v., Baur, F., Heit, W., Corrons, J. L. L. Vives, Vogel, M., Nekarda, H., Remy, W., Bissery, M. C., Aapro, M., Buchwald-Pospiech, A., Kaltwasser, J. P., Jacobi, V., de Vos, Sven, Asano, Yoshinobu, Voss, Harald, Knuth, Alexander, Wiedemann, G., Komischke, B., Horisberger, R., Wussow, P. v., Wanders, L., Senekowitsch, R., Strohmeyer, S., Emmerich, B., Selbach, J., Gutensohn, K., Wacker-Backhaus, G., Winkeimann, M., Send, W., Rösche, J., Weide, R., Parviz, B., Havemann, K., Weidmann, B., Henss, H., Engelhardt, R., Bernards, P., Zeidler, D., Jägerbauer, E., Colajori, E., Kerpel-Fronius, S., Weiss, A., Buchheidt, D., Döring, A., D.Saeger, H., Weissbach, L., Emmler, J., Wermes, R., Meusers, P., Flasshove, M., Skorzec, M., Käding, J., Platow, S., Winkler, Ute, Thorpe, Philip, Winter, S. F., Minna, J. D., Nestor, P. J., Johnson, B. E., Gazdar, A. F., Havemann, K., Carbone, D. P., Wit, M. de, Bittner, S., Hossfeld, D., Wittmann, G., Borchelt, M., Steinhagen-Thiessen, E., Koch, K., Brosch, T., Haas, N., Wölfel, C., Knuth, A., Wölfel, T., Safford, M., Könemann, S., Zurlutter, K., Schreiber, K., Piechotka, K., Drescher, M., Toepker, S., Terstappen, L. W. M. M., Bullerdiek, J., Jox, A., zur Hausen, H., Wolters, B., Stenzinger, W., Woźny, T., Sawiński, K., Kozłowska-Skrzypczak, M., Wussow, P. v., Hochhaus, T., Ansarl, H., Prümmer, O., Zapf, H., Thorban, S., Präuer, H., Zeller, W., Stieglitz, J. v., Dürken, M., Greenshaw, C., Kabisch, H., Reuther, C., Knabbe, C., Lippman, M., Havemann, K., Wellstein, A., Degos, L., Castaigne, S., Fenaux, P., Chomienne, C., Raza, A., Preisler, H. D., PEG Interventional Antimicrobial Strategy Study Group, Interventional Antimicrobial Strategy Study Group of the Paul Ehrlich Society (PEG), and H. Riehm for the BFM study group
- Published
- 1992
- Full Text
- View/download PDF
3. Effect of interleukin-3 and granulocyte-macrophage colony-stimulating factor on growth of xenotransplanted human tumour cell lines in nude mice
- Author
-
Berdel, W.E., primary, Kreuser, E.D., additional, Thiel, E., additional, Zafferani, M., additional, and Senekowitsch, R., additional
- Published
- 1992
- Full Text
- View/download PDF
4. Daily Oral Miltefosine (Hexadecyl-Phosphocholine) in Patients with Advanced Non-Small Cell Lung Cancer. A Phase II Study
- Author
-
Berdel, W.E., primary, Becher, R., additional, Edler, L., additional, Bremer, K., additional, Essers, U., additional, Drozd, A., additional, Zafferani, M., additional, Klee, M.A.G., additional, Bachmann, P., additional, Korfel, A., additional, and Westerhausen, M., additional
- Published
- 1992
- Full Text
- View/download PDF
5. Phase I Study of Weekly Oral Miltefosine (Hexadecyl-Phosphocholine) in Cancer Patients
- Author
-
Danhauser-Riedl, S., primary, Drozd, A., additional, Zafferani, M., additional, Bruntsch, U., additional, Peukert, M., additional, Sindermann, H., additional, Präuer, H.W., additional, and Siewert, J.R., additional
- Published
- 1991
- Full Text
- View/download PDF
6. Lack of therapeutic effects of platelet activating factor antagonists in WEHI-3B leukemia, human xenotransplanted colorectal and lung cancer and Lewis-lung tumor in vivo
- Author
-
Koenigsmann, M., Zafferani, M., Danhauser-Riedl, S., and Reufi, B.
- Published
- 1992
- Full Text
- View/download PDF
7. Multiassay Profiling of a Focused Small Molecule Library Reveals Predictive Bidirectional Modulation of the lncRNA MALAT1 Triplex Stability In Vitro .
- Author
-
Zafferani M, Martyr JG, Muralidharan D, Montalvan NI, Cai Z, and Hargrove AE
- Subjects
- Calorimetry, Diminazene, Gene Library, Humans, Nucleic Acid Conformation, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
The rapidly accelerating characterization of RNA tertiary structures has revealed their pervasiveness and active roles in human diseases. Small molecule-mediated modulation of RNA tertiary structures constitutes an attractive avenue for the development of tools for therapeutically targeting and/or uncovering the pathways associated with these RNA motifs. This potential has been highlighted by targeting of the triple helix present at the 3'-end of the noncoding RNA MALAT1, a transcript implicated in several human diseases. This triplex has been reported to decrease the susceptibility of the transcript to degradation and promote its cellular accumulation. While small molecules have been shown to bind to and impact the stability of the MALAT1 triple helix, the small molecule properties that lead to these structural modulations are not well understood. We designed a library utilizing the diminazene scaffold, which is underexplored but precedented for nucleic acid binding, to target the MALAT1 triple helix. We employed multiple assays to holistically assess what parameters, if any, could predict the small molecule affinity and effect on triplex stability. We designed and/or optimized competition, calorimetry, and thermal shift assays as well as an enzymatic degradation assay, the latter of which led to the discovery of bidirectional modulators of triple helix stability within the scaffold-centric library. Determination of quantitative structure-activity relationships afforded predictive models for both affinity- and stability-based assays. This work establishes a suite of powerful orthogonal biophysical tools for the evaluation of small molecule:RNA triplex interactions that generate predictive models and will allow small molecule interrogation of the growing body of disease-associated RNA triple helices.
- Published
- 2022
- Full Text
- View/download PDF
8. RT-qPCR as a screening platform for mutational and small molecule impacts on structural stability of RNA tertiary structures.
- Author
-
Zafferani M, Muralidharan D, Montalvan NI, and Hargrove AE
- Abstract
The exponential increase in the discovery and characterization of RNA tertiary structures has highlighted their active role in a variety of human diseases, yet often their interactome and specific function remain unknown. Small molecules offer opportunities to both decode these cellular roles and develop therapeutics, however there are few examples of small molecules that target biologically relevant RNA tertiary structures. While RNA triple helices are a particularly attractive target, discovery of triple helix modulators has been hindered by the lack of correlation between small molecule affinity and effect on structural modulation, thereby limiting the utility of affinity-based screening as a primary filtering method. To address this challenge, we developed a high-throughput RT-qPCR screening platform that reports on the effect of mutations and additives, such as small molecules, on the stability of triple helices. Using the 3'-end of the oncogenic long non-coding RNA MALAT1 as a proof-of-concept, we demonstrated the applicability of both a two-step and a one-pot method to assess the impact of mutations and small molecules on the stability of the triple helix. We demonstrated the adaptability of the assay to diverse RNA tertiary structures by applying it to the SARS-CoV-2 pseudoknot, a key viral RNA structure recently identified as an attractive therapeutic target for the development of antivirals. Employment of a functional high-throughput assay as a primary screen will significantly expedite the discovery of probes that modulate the structural landscape of RNA structures and, consequently, help gain insight into the roles of these pervasive structures., Competing Interests: Nothing to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2022
- Full Text
- View/download PDF
9. Quantitative Structure-Activity Relationship (QSAR) Study Predicts Small-Molecule Binding to RNA Structure.
- Author
-
Cai Z, Zafferani M, Akande OM, and Hargrove AE
- Subjects
- Drug Discovery, Humans, Models, Biological, Quantitative Structure-Activity Relationship, RNA
- Abstract
The diversity of RNA structural elements and their documented role in human diseases make RNA an attractive therapeutic target. However, progress in drug discovery and development has been hindered by challenges in the determination of high-resolution RNA structures and a limited understanding of the parameters that drive RNA recognition by small molecules, including a lack of validated quantitative structure-activity relationships (QSARs). Herein, we develop QSAR models that quantitatively predict both thermodynamic- and kinetic-based binding parameters of small molecules and the HIV-1 transactivation response (TAR) RNA model system. Small molecules bearing diverse scaffolds were screened against TAR using surface plasmon resonance. Multiple linear regression (MLR) combined with feature selection afforded robust models that allowed direct interpretation of the properties critical for both binding strength and kinetic rate constants. These models were validated with new molecules, and their accurate performance was confirmed via comparison to ensemble tree methods, supporting the general applicability of this platform.
- Published
- 2022
- Full Text
- View/download PDF
10. Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures.
- Author
-
Zafferani M, Haddad C, Luo L, Davila-Calderon J, Chiu LY, Mugisha CS, Monaghan AG, Kennedy AA, Yesselman JD, Gifford RJ, Tai AW, Kutluay SB, Li ML, Brewer G, Tolbert BS, and Hargrove AE
- Abstract
The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals.
- Published
- 2021
- Full Text
- View/download PDF
11. Small molecule targeting of biologically relevant RNA tertiary and quaternary structures.
- Author
-
Zafferani M and Hargrove AE
- Subjects
- Humans, Ligands, Nucleic Acid Conformation, RNA chemistry, Small Molecule Libraries chemistry, RNA drug effects, Small Molecule Libraries pharmacology
- Abstract
Initial successes in developing small molecule ligands for non-coding RNAs have underscored their potential as therapeutic targets. More recently, these successes have been aided by advances in biophysical and structural techniques for identification and characterization of more complex RNA structures; these higher-level folds present protein-like binding pockets that offer opportunities to design small molecules that could achieve a degree of selectivity often hard to obtain at the primary and secondary structure level. More specifically, identification and small molecule targeting of RNA tertiary and quaternary structures have allowed researchers to probe several human diseases and have resulted in promising clinical candidates. In this review we highlight a selection of diverse and exciting successes and the experimental approaches that led to their discovery. These studies include examples of recent developments in RNA-centric assays and ligands that provide insight into the features responsible for the affinity and biological outcome of RNA-targeted chemical probes. This report highlights the potential and emerging opportunities to selectively target RNA tertiary and quaternary structures as a route to better understand and, ultimately, treat many diseases., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
12. Regulation of MALAT1 triple helix stability and in vitro degradation by diphenylfurans.
- Author
-
Donlic A, Zafferani M, Padroni G, Puri M, and Hargrove AE
- Subjects
- Exoribonucleases metabolism, Furans chemical synthesis, Ligands, Molecular Docking Simulation, Nucleic Acid Conformation, RNA Stability, RNA, Long Noncoding metabolism, Furans chemistry, RNA, Long Noncoding chemistry
- Abstract
Small molecule-based modulation of a triple helix in the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been proposed as an attractive avenue for cancer treatment and a model system for understanding small molecule:RNA recognition. To elucidate fundamental recognition principles and structure-function relationships, we designed and synthesized nine novel analogs of a diphenylfuran-based small molecule DPFp8, a previously identified lead binder of MALAT1. We investigated the role of recognition modalities in binding and in silico studies along with the relationship between affinity, stability and in vitro enzymatic degradation of the triple helix. Specifically, molecular docking studies identified patterns driving affinity and selectivity, including limited ligand flexibility, as observed by ligand preorganization and 3D shape complementarity for the binding pocket. The use of differential scanning fluorimetry allowed rapid evaluation of ligand-induced thermal stabilization of the triple helix, which correlated with decreased in vitro degradation of this structure by the RNase R exonuclease. The magnitude of stabilization was related to binding mode and selectivity between the triple helix and its precursor stem loop structure. Together, this work demonstrates the value of scaffold-based libraries in revealing recognition principles and of raising broadly applicable strategies, including functional assays, for small molecule-RNA targeting., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2020
- Full Text
- View/download PDF
13. Photoresponsive azo-combretastatin A-4 analogues.
- Author
-
Rastogi SK, Zhao Z, Barrett SL, Shelton SD, Zafferani M, Anderson HE, Blumenthal MO, Jones LR, Wang L, Li X, Streu CN, Du L, and Brittain WJ
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Azo Compounds chemical synthesis, Azo Compounds chemistry, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Kinetics, Ligands, Molecular Structure, Photochemical Processes, Stilbenes chemical synthesis, Stilbenes chemistry, Structure-Activity Relationship, Ultraviolet Rays, Antineoplastic Agents pharmacology, Azo Compounds pharmacology, Stilbenes pharmacology
- Abstract
Colchicine analogues in which an azo group is incorporated into a molecule containing the key pharmacophore of colchicine, have found particular utility as switchable tubulin binding chemotherapeutics. Combretastatin is a related compound containing a stilbene fragment that shows different bioactivity for the cis and trans isomers. We have performed cell assays on 17 new compounds structurally related to a previously reported azo-analogue of combretastatin. One of these compounds showed enhanced potency against HeLa (IC
50 = 0.11 μM) and H157 cells (IC50 = 0.20 μM) for cell studies under 400 nm irradiation and the highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have performed docking and physicochemical studies of this new compound (7). Kinetic studies in water reveal a longer half-life for the cis isomer of 7 which may be one factor responsible for the better IC50 values in cell assays and the improved photoresponsive behavior., (Published by Elsevier Masson SAS.)- Published
- 2018
- Full Text
- View/download PDF
14. Removal of breast cancer cells from bone marrow by in vitro purging with ether lipids and cryopreservation.
- Author
-
Dietzfelbinger HF, Kühn D, Zafferani M, Hanauske AR, Rastetter JW, and Berdel WE
- Subjects
- Breast Neoplasms surgery, Female, Humans, Transplantation, Autologous, Tumor Cells, Cultured, Antineoplastic Agents, Bone Marrow Purging, Bone Marrow Transplantation, Breast Neoplasms pathology, Cryopreservation, Phospholipid Ethers
- Abstract
Four cell lines from human breast cancer (HTB 19, HTB 133, IZB B, and MCF 7M) were investigated for in vitro growth before and after incubation with the ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) for 4 h and at increasing concentrations (25, 50, 75, and 100 micrograms/ml), as well as with and without cryopreservation. When measured with the human tumor cloning assay in agar or methyl-cellulose the surviving fraction showed an inverse correlation with the concentrations of ET-18-OCH3. After a 4-h exposure with 75 micrograms/ml ET-18-OCH3 at a cell density of 2 x 10(5)/ml the number of colonies of HTB 19 decreased from 75 +/- 10/10(3) cells (100%) to 1 +/- 0/10(3) cells (1%), and after subsequent cryopreservation no remaining colonies were found. In order to simulate the situation in autologous bone marrow transplantation we contaminated normal human bone marrow cells with malignant HTB 19 breast cancer cells at a ratio of 100:1. After incubation with 75 micrograms/ml ET-18-OCH3 for 4 h and subsequent cryopreservation there was a considerable reduction of HTB 19 colonies whereas the majority of normal human hematopoietic progenitors recovered. We conclude that ET-18-OCH3, in combination with cryopreservation, can remove breast cancer cells from bone marrow by up to 1 log and may be useful for purging bone marrow for autologous bone marrow transplantation not only in acute leukemia and non-Hodgkin's lymphoma but also in breast cancer.
- Published
- 1993
15. Effects of hematopoietic growth factors on malignant nonhematopoietic cells.
- Author
-
Berdel WE, Danhauser-Riedl S, Oberberg D, and Zafferani M
- Subjects
- Animals, Drug Screening Assays, Antitumor, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Recombinant Proteins pharmacology, Tumor Cells, Cultured, Hematopoietic Cell Growth Factors pharmacology, Neoplasms pathology, Tumor Stem Cell Assay
- Abstract
We have assayed modulation of clonal growth of cell lines from human solid tumors in vitro by recombinant human interleukin-6 (rhIL-6), rhIL-3, rh granulocyte-macrophage colony-stimulating factor (GM-CSF), rhG-CSF, rhM-CSF, and rh erythropoietin. Effects of hematopoietic growth factors were also tested in the tritiated thymidine uptake assay. No reproducible and significant modulation of clonal growth was found with rhIL-6, rhM-CSF, and rhEPO. The other cytokines showed stimulation of colony formation in some cell lines from colorectal adenocarcinomas and bladder and lung cancers with the following order of activity: rhIL-3 greater than or equal to rhGM-CSF greater than rhG-CSF. Growth stimulation was only found in clonal assays; it was abolished by neutralizing antibodies and was highly dependent on culture conditions. Stimulation could be masked by elevation of serum concentration and there was an inverse correlation between spontaneous plating efficacy of the control cells and growth stimulation by the factor with the highest activity of the colony-stimulating factor at suboptimal growth conditions. Growth inhibition by the cytokines was not observed. We could not establish autocrine loops for the growth modulation by the cytokines in the cell lines tested so far. Furthermore, we xenotransplanted some responsive cell lines into athymic mice and observed their in vivo growth under systemic application of rhIL-3 and rhGM-CSF or vehicle. There was no significant alteration of the tumor growth by these cytokines at plasma levels sufficient for in vitro growth stimulation. In conclusion, tumor growth stimulation by rhGM-CSF and rhIL-3 as potential hazards for their clinical application in cancer patients in conjunction with cytotoxic chemotherapy is unlikely.
- Published
- 1992
16. Some antagonists of platelet activating factor are cytotoxic for human malignant cell lines.
- Author
-
Danhauser-Riedl S, Felix SB, Houlihan WJ, Zafferani M, Steinhauser G, Oberberg D, Kalvelage H, Busch R, Rastetter J, and Berdel WE
- Subjects
- Humans, Imidazoles pharmacology, Isoquinolines pharmacology, Piperidines pharmacology, Platelet Aggregation drug effects, Antineoplastic Agents pharmacology, Cell Survival drug effects, Platelet Activating Factor antagonists & inhibitors, Tumor Cells, Cultured drug effects
- Abstract
Nine new platelet activating factor (PAF) antagonists from 4 different chemical classes (thiopyrimidines: SDZ 59-015; thioimidazolines: SDZ 61-813; imidazoisoquinolines: SDZ 62-434, SDZ 62-759, SDZ 63-135, SDZ 63-596; and imidazopiperidines: SDZ 61-638, SDZ 62-293, SDZ 62-694) have been tested for cytostatic/antiproliferative ([3H]thymidine uptake) and cytotoxic (trypan blue dye exclusion) activity in neoplastic human cell lines of different histology in vitro. The antiproliferative activity of 3 of the 9 PAF antagonists (SDZ 61-638, SDZ 61-813, SDZ 62-694) was not stable after freezing and thawing. SDZ 59-015 showed only minor cytotoxic or antiproliferative effects in a dose range of 2-40 microns after 24, 48, and 72 h of incubation. SDZ 62-434 showed varying activity. There were no significant differences between the activities of the other 3 PAF antagonists from the imidazoisoquinoline class, which showed drug concentrations inhibiting 50% of the activity studied (IC50) and drug concentrations yielding a 50% decrease of trypan blue dye exclusion (LC50) of less than or equal to 20 microM at greater than or equal to 48 h, even in the K-562 cell line, which is known to be rather resistant for a variety of cytotoxic drugs related to PAF. SDZ 62-293 showed the best antineoplastic properties with IC50 and LC50 values less than or equal to 10 microM at greater than or equal to 48 h including K-562. SDZ 62-434, SDZ 62-759, SDZ 63-135, SDZ 63-596, and SDZ 62-293 have been further tested in a human tumor cloning assay in 5 cell lines. Colony formation was reproducibly suppressed to less than 30% of the controls only by SDZ 63-135 (less than or equal to 40 microM) and SDZ 62-293 (less than or equal to 20 microM) during continuous exposure. There was no correlation between the IC50 values for the antiproliferative activity of the test compounds and their IC50 values for PAF-induced human platelet aggregation. Furthermore, the antiproliferative activity of the most active compound, SDZ 62-293, could not be antagonized by preincubation with the specific PAF antagonists WEB 2170 or WEB 2086 or PAF itself in noncytotoxic doses.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1991
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.