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Your search keyword '"Menssen, H. D."' showing total 49 results
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49 results on '"Menssen, H. D."'

1. Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Arnan, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Niolat, J, Ramos, P, Menssen, H, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan A. M., Ando K., Rauzy O., Turgut M., Wang M. -C., Cairoli R., Hou H. -A., Kwong Y. -L., Arnan M., Meers S., Pullarkat V., Santini V., Malek K., Kiertsman F., Niolat J., Ramos P. M., Menssen H. D., Fenaux P., Miyazaki Y., Platzbecker U., Zeidan, A, Ando, K, Rauzy, O, Turgut, M, Wang, M, Cairoli, R, Hou, H, Kwong, Y, Arnan, M, Meers, S, Pullarkat, V, Santini, V, Malek, K, Kiertsman, F, Niolat, J, Ramos, P, Menssen, H, Fenaux, P, Miyazaki, Y, Platzbecker, U, Zeidan A. M., Ando K., Rauzy O., Turgut M., Wang M. -C., Cairoli R., Hou H. -A., Kwong Y. -L., Arnan M., Meers S., Pullarkat V., Santini V., Malek K., Kiertsman F., Niolat J., Ramos P. M., Menssen H. D., Fenaux P., Miyazaki Y., and Platzbecker U.

Abstract

Background: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes. Methods: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m2 on day 1–5 or intravenous or subcutaneous azacitidine 75 mg/m2 on day 1–7 or day 1–5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing. Findings: Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69–77), of whom 86 (68%

Published
2024

8. 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
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11. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study

Author

Hochhaus, A, primary, Masszi, T, additional, Giles, F J, additional, Radich, J P, additional, Ross, D M, additional, Gómez Casares, M T, additional, Hellmann, A, additional, Stentoft, J, additional, Conneally, E, additional, García-Gutiérrez, V, additional, Gattermann, N, additional, Wiktor-Jedrzejczak, W, additional, le Coutre, P D, additional, Martino, B, additional, Saussele, S, additional, Menssen, H D, additional, Deng, W, additional, Krunic, N, additional, Bedoucha, V, additional, and Saglio, G, additional

Published
2017
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14. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily

Author

Hughes, T. P., primary, Hochhaus, A., additional, Kantarjian, H. M., additional, Cervantes, F., additional, Guilhot, F., additional, Niederwieser, D., additional, le Coutre, P. D., additional, Rosti, G., additional, Ossenkoppele, G., additional, Lobo, C., additional, Shibayama, H., additional, Fan, X., additional, Menssen, H. D., additional, Kemp, C., additional, Larson, R. A., additional, and Saglio, G., additional

Published
2014
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15. Phase I/II study of the tumour-targeting human monoclonal antibody–cytokine fusion protein L19-TNF in patients with advanced solid tumours

Author

Spitaleri, G., primary, Berardi, R., additional, Pierantoni, C., additional, De Pas, T., additional, Noberasco, C., additional, Libbra, C., additional, González-Iglesias, R., additional, Giovannoni, L., additional, Tasciotti, A., additional, Neri, D., additional, Menssen, H. D., additional, and de Braud, F., additional

Published
2012
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16. A dose confirmation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine in patients with metastatic melanoma.

Author

Eigentler, T. K., primary, Weide, B., additional, Spitaleri, G., additional, De Braud, F. G., additional, Romanini, A., additional, Gonzales-Inglesias, R., additional, Tasciotti, A., additional, Giovannoni, L., additional, Schwager, K., additional, Lovato, V., additional, Kaspar, M., additional, Trachsel, E., additional, Neri, D., additional, Menssen, H. D., additional, and Garbe, C., additional

Published
2011
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17. Combination of the immunocytokine F16-IL2 with doxorubicin or paclitaxel in patients with solid tumors: Results from two phase Ib trials.

Author

De Braud, F. G., primary, Catania, C., additional, Onofri, A., additional, Pierantoni, C., additional, Cascinu, S., additional, Maur, M., additional, Masini, C., additional, Conte, P. F., additional, Giovannoni, L., additional, Tasciotti, A., additional, Lovato, V., additional, Neri, D., additional, and Menssen, H. D., additional

Published
2011
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18. Preliminary evaluation of radioimmunotherapy with an 131I labelled small immunoprotein targeted against the extra domain B of fibronectin in combination with whole brain radiation therapy in patients with multiple brain metastases from solid tumors.

Author

Lastoria, S., primary, D'Ambrosio, L., additional, Aurilio, M., additional, Marreno, R., additional, Giovannoni, L., additional, Menssen, H. D., additional, Neri, D., additional, Shah, A., additional, Di Gennaro, F., additional, Caraco, C., additional, Pecori, B., additional, and Aloj, L., additional

Published
2011
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19. Preliminary evaluation of radioimmunotherapy with Tenarad, a I-131 labeled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin lymphoma.

Author

Aloj, L., primary, D'Ambrosio, L., additional, Aurilio, M., additional, Marreno, R., additional, Neri, D., additional, Menssen, H. D., additional, Giovannoni, L., additional, Di Gennaro, F., additional, Caraco, C., additional, Arcamone, M., additional, Frigeri, F., additional, Pinto, A., additional, and Lastoria, S., additional

Published
2011
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22. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

Author

Major, P, Lortholary, Alain, Hon, J., Abdi, E, Mills, Gordon B, Menssen, H D, Yunus, F, Bell, Richard H, Body, Jean-Jacques, Quebe-Fehling, E, Seaman, J, Major, P, Lortholary, Alain, Hon, J., Abdi, E, Mills, Gordon B, Menssen, H D, Yunus, F, Bell, Richard H, Body, Jean-Jacques, Quebe-Fehling, E, and Seaman, J

Abstract

Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM)., Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2001

27. Quantitative real-time RT-PCR detects elevated Wilms tumor gene (WT1) expression in autologous blood stem cell preparations (PBSCs) from acute myeloid leukemia (AML) indicating contamination with leukemic blasts.

Author

Siehl, J. M., Thiel, E., Leben, R., Reinwald, M., Knauf, W., and Menssen, H. D.

Subjects
AUTOGRAFTS, STEM cell transplantation, MYELOID leukemia, LEUKEMIA treatment, NEPHROBLASTOMA, CANCER cell growth
Abstract

Presents a study which investigated whether autologous blood stem cell preparations from patients with acute myeloid leukemia express Wilms tumor gene (WT1) compared to patients with solid cancers. Role of the zinc-finger transcription factor in the control of cellular growth; Level of WT1 expression in patients; Implications of study results.

Published
2002

28. A quantitative electron microscopic study of the effect of glucocorticoids in vivo on the early postnatal differentiation of paraneuronal cells in the carotid body and the adrenal medulla of the rat

Author

Dalnok, G. K. and Menßen, H. D.

Abstract

The postnatal differentiation of carotid body chief cells and endocrine adrenal medullary cells was comparatively examined during ontogenesis and in rats which were treated with dexamethasone for 7 days after birth. Ultrastructure and innervation of carotid body chief cells are mature in neonates according to the functional requirements of chemoreception. By the end of the first postnatal week, only an increase in number of dense core vesicles can be noticed, the concentration of which then will reach the adult level. Under the effect of dexamethasone most of the heterochromatin is transformed into finely dispersed euchromatin within the nuclei of carotid body chief cells. In the cytoplasm, the Golgi apparatus becomes larger and the granular endoplasmic reticulum hypertrophic. The number of catecholamines storing dense core vesicles increases considerably. The innervation density remains constant. In contrast to the carotid body chief cells, the adrenal medullary cells have not reached their definitive maturity at the time of birth. Besides phenotypes of adrenaline-cells, noradrenaline-cells and small granules containing cells, pheochromoblasts and intermediary cells can be seen as well. Their cytoplasm is sparse, the concentration of dense core vesicles and the innervation density very low. After 8 days of postnatal ontogenesis, pheochromoblasts and intermediary cells are no longer present in the adrenal medulla. In adrenaline-cells and noradrenaline-cells, important processes of growth can be noticed, the cytoplasm has grown in extent, the number of dense core vesicles doubled and the innervation density of single cells triplicated. Only the few small granules containing cells remain small. Under the effect of dexamethasone also in the nuclei of chromaffin cells a transformation of heterochromatin into euchromatin occurs. The increase in number of dense core vesicles is relatively lower than in carotid body chief cells. The significant growth of innervation density during the first postnatal week was inhibited. Our observations suggest that dexamethasone stimulates the synthesis of catecholamines in adrenal medullary cells of newborn rats less pronouncedly than in carotid body chief cells. This could be attributed to the inhibited formation of synapses of growing chromaffin cells and to the in vivo active endocrine counter-regulation.

Published
1986
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29. Aggressive Lymphoma after CD19 CAR T-Cell Therapy.

Author

Kobbe, G., Brüggemann, M., Baermann, B.-N., Wiegand, L., Trautmann, H., Yousefian, S., Libertini, S., Menssen, H. D., Maier, H. J., Ulrich, P., Gao, J., Bruch, P.-M., Liebers, N., Radujkovic, A., Seifert, M., Schniederjohann, C., Paramasivam, N., Fitzgerald, D., Seidel, M., and Esposito, I.

Subjects
*T-cell lymphoma, *AUTOTRANSPLANTATION, *STEM cells, *T cells, *HEMATOPOIESIS
Abstract

The development of a fatal, clonal, autonomously proli terating CD4-CD8-antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred after a patient received treatment with tisagenlecleucel for relapsed primary nervous system lymphonla. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic DNMT3A TETZ mutations ill CD34+ stem cells and their progeny were detected in the in the apheresis specimen that was obtained for CAR T-cell production, and autotransplant. The PTCL harbored an additional somatic TET2 mutation, was already detectable in the CAR T-cell apheresis product and the final CART-product at very low frequencies, providing evidence that clonal hematopoiesis contributed to lymphomagenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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31. The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: Dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer

Author

Cristina Masini, Andrea Rocca, Rossana Berardi, Giulia Zigon, Dario Neri, Michela Maur, Chiara Pierantoni, Valeria Lovato, Anna Maria Di Giacomo, Chiara Catania, Annaelisa Tasciotti, Leonardo Giovannoni, Pierfranco Conte, Giuliano Elia, Hans D. Menssen, Filippo de Braud, Gianluca Spitaleri, Stefano Cascinu, Reinerio González-Iglesias, Catania, C., Maur, M., Berardi, R., Rocca, A., Di Giacomo, A. M., Spitaleri, G., Masini, C., Pierantoni, C., Gonzalez-Iglesias, R., Zigon, G., Tasciotti, A., Giovannoni, L., Lovato, V., Elia, G., Menssen, H. D., Neri, D., Cascinu, S., Conte, P. F., and De Braud, F.

Subjects
Drug, Interleukin 2, Oncology, Adult, medicine.medical_specialty, media_common.quotation_subject, Recombinant Fusion Proteins, Immunocytokines, Breast Neoplasms, Pharmacology, Antibodies, Cellular and Molecular Neuroscience, Pharmacokinetics, Internal medicine, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Doxorubicin, In patient, Antibody, Clinical trial phase I, media_common, Aged, Breast neoplasms, Interleukin-2, biology, business.industry, Antibodies, Monoclonal, Cell Biology, Middle Aged, medicine.disease, Metastatic breast cancer, Research Papers, Treatment Outcome, Tolerability, biology.protein, Female, business, medicine.drug
Abstract

A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumors (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumors (n = 19) received escalating doses of F16-IL2 [5-25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0-25 mg/m(2)) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 10) received the drug combination at the RD. Clinical data and laboratory findings were analyzed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25 mg/m(2)). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 MIU in combination with 25 mg/m(2) doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.

Published
2015

32. Targeted ED-B fibronectin SPECT in vivo imaging in experimental atherosclerosis.

Author

Dietrich T, Berndorff D, Heinrich T, Hucko T, Stepina E, Hauff P, Dinkelborg LM, Atrott K, Giovannoni L, Neri D, Fleck E, Graf K, and Menssen HD

Subjects
Animals, Aortic Diseases diagnostic imaging, Aortic Diseases metabolism, Apolipoproteins E genetics, Biomarkers blood, Mice, Mice, Knockout, Molecular Imaging methods, Reproducibility of Results, Sensitivity and Specificity, Technetium pharmacokinetics, Antibodies, Monoclonal pharmacokinetics, Atherosclerosis diagnostic imaging, Atherosclerosis metabolism, Fibronectins metabolism, Image Enhancement methods, Tomography, Emission-Computed, Single-Photon methods
Abstract

Aim: The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions. However, functional in vivo imaging of ED-B-containing plaques has not been explored. This study evaluated whether [(99m)Tc]-conjugated AP39 ([(99m)Tc]-AP39), a single-chain antibody specific to ED-B, can be used for in vivo detection of atherosclerotic plaques in Western diet (WD)-fed, apolipoprotein E-deficient (apoE-/-) mice as compared to wildtype (WT) control mice., Methods: Using SPECT, 12-month-old WD-fed apoE-/- and WT mice were studied 4 hours after injecting [(99m)Tc]-AP39 (148 MBq). Subsequently, mice were sacrificed, thoracic aortas measured in a g-counter, and plaques analyzed using histology, immuno-histochemistry, autoradiography, and morphometry., Results: In vivo [(99m)Tc]-AP39-SPECT imaging of apoE-/- mice demonstrated a significant signal activity in the plaque-ridden thoracic aorta (52.236 ± 40.646 cpm/cm³) that co-localized with the aortic arch and the supra-aortic arteries in MRI scans. Low signal activity (9.468 ± 4.976 cpm/cm³) was observed in WT mice. In apoE-/- mice, the strongest signals were detected in the aortic root, aortic arch and along the abdominal aorta. Autoradiography analysis of aortas from apoE-/- mice confirmed the in vivo observation by demonstrating signal localization in atherosclerotic plaques. The size of autoradiography-positive plaque areas correlated significantly with the size of ED-B-positive (r=0.645, P=0.044) or macrophage-infiltrated (r=0.84, P<0.002) plaques. A significant correlation was found between the sizes of ED-B-positive and macrophage-infiltrated plaque areas (r=0.93, P<0.01)., Conclusion: [(99m)Tc]-AP39-SPECT in vivo imaging detects inflammatory plaque lesions in WD-fed apoE-/- mice.

Published
2015

33. Quantitative real-time RT-PCR detects elevated Wilms tumor gene (WT1) expression in autologous blood stem cell preparations (PBSCs) from acute myeloid leukemia (AML) patients indicating contamination with leukemic blasts.

Author

Siehl JM, Thiel E, Leben R, Reinwald M, Knauf W, and Menssen HD

Subjects
Acute Disease, Adolescent, Adult, Biomarkers, Tumor analysis, Female, Humans, Immunomagnetic Separation, Leukapheresis methods, Leukapheresis standards, Leukemia, Myeloid blood, Leukemia, Myeloid diagnosis, Male, Middle Aged, Prognosis, RNA, Messenger analysis, Recurrence, Remission Induction, Transplantation, Autologous, Genes, Wilms Tumor physiology, Hematopoietic Stem Cells metabolism, Leukemia, Myeloid therapy, Reverse Transcriptase Polymerase Chain Reaction, Stem Cell Transplantation standards
Abstract

High-dose chemotherapy with subsequent autologous stem cell transplantation is believed to be of therapeutic benefit in patients with acute myeloid leukemia (AML), especially when no allogeneic bone marrow donor is available. One of the main risks is contamination of the stem cell preparations with leukemic blasts, which may account for a higher relapse rate compared to allogeneic bone marrow transplantation. Since overexpression of WT1 is common in leukemic blasts, we investigated, whether PBSCs from AML patients express WT1 at a higher level as compared to patients with solid cancers. PBSCs of seven patients with AML and of five patients with solid cancers were investigated for WT1 expression. Total WT1 copy count was determined in a standardized quantitative real time RT-PCR. WT1 expression was found in all AML PBSCs with an average copy number of 49.99 +/- 61.09. In solid cancers WT1 expression was statistically significantly lower with a copy number of 3.51 +/- 1.92. In AML patients with sustained complete remission we found a nearly significantly lower WT1 expression than in patients who relapsed within the first year after stem cell transplantation. Our data show a higher WT1 expression in PBSCs of AML patients compared to patients with solid cancers. This finding might indicate a contamination with leukemic blasts. Quantification of WT1 in PBSCs might therefore be useful to estimate the risk of relapse after autologous stem cell transplantation in AML patients.

Published
2002
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34. The use of hirudin as universal anticoagulant in haematology, clinical chemistry and blood grouping.

Author

Menssen HD, Melber K, Brandt N, and Thiel E

Subjects
Adult, Blood Cell Count methods, Blood Chemical Analysis methods, Blood Coagulation Tests methods, Blood Specimen Collection methods, Edetic Acid pharmacology, Humans, Reproducibility of Results, Serologic Tests methods, Anticoagulants pharmacology, Blood Coagulation drug effects, Hematologic Tests methods, Hirudins pharmacology
Abstract

Undesirable interactions between anticoagulants and diagnostic test kit procedures so far have prevented the development of a single uniform blood sampling tube. Contrary to K2-EDTA, heparin and other anticoagulants, hirudin only minimally alters blood cells and dissolved blood constituents, thus qualifying as a universal anticoagulant for diagnostic purposes. Automated complete blood counts, automated analyses of clinical chemistry analytes and immunohaematology were performed from hirudinised and routinely processed blood obtained from healthy volunteers (n=35) and hospitalised patients (n=45). Hirudin (400 ATU/ml blood) sufficiently anticoagulated blood for diagnostic purposes. The measurements of automated complete blood counts obtained from K2-EDTA-anticoagulated and hirudinised blood correlated significantly as did the measurements of 24 clinical chemistry analytes from hirudinised plasma and serum. Regression analysis revealed that the results of complete blood counts and clinical chemistry tests were predictable from the respective measurements from hirudinised blood (p=0.001). Immunohaematological tests and cross-matching from hirudinised and native blood of the same donors gave identical results. Single clotting factors, but not global coagulation analytes, could be measured from hirudinised blood. Therefore, a universal hirudin-containing blood sampling tube could be designed for automated analysis of haematological, serological and clinical chemistry analytes.

Published
2001
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35. Measurement of hematological, clinical chemistry, and infection parameters from hirudinized blood collected in universal blood sampling tubes.

Author

Menssen HD, Brandt N, Leben R, Müller F, Thiel E, and Melber K

Subjects
Antibodies, Viral blood, Blood drug effects, Blood Cell Count standards, Blood Chemical Analysis standards, Blood Coagulation Tests standards, Blood Specimen Collection standards, Critical Illness, DNA, Neoplasm analysis, Edetic Acid pharmacology, Fibrinolytic Agents standards, Genes, Wilms Tumor physiology, Hirudins standards, Humans, Immunophenotyping standards, Serologic Tests standards, Blood Specimen Collection methods, Fibrinolytic Agents pharmacology, Hirudins pharmacology
Abstract

Hirudin, the anticoagulatory polypeptide of the leech Hirudo medicinalis, strongly inhibits thrombus formation by specifically interacting with thrombin. For diagnostic purposes, hirudin should be superior to other anticlotting compounds because it only minimally alters the mineral, protein, and cellular blood constituents. To test this hypothesis, hirudinized and routinely processed venous blood from 80 healthy volunteers and patients was subjected to a variety of automated blood tests. A strong correlation was found between the results of automated complete blood counts obtained from K(2)-ethylenediaminetetraacetic acid (EDTA) anticoagulated and hirudinized blood (1000 antithrombin units [ATU] hirudin/ml). In addition, clinical chemistry and serological infection parameters (asparlat amintransferase [ASAT], lactate dehydrogenase [LDH], sodium, and so on, and antibodies against hepatitis B and C and human immunodeficiency virus [HIV]1/2, respectively) correlated well when measured in serum as compared with hirudinized plasma. Contrary to single clotting factors, global coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT]) could not be measured in hirudinized blood. Recombinant hirudin neither interfered with immunophenotyping of mononuclear cells using FACScan analysis, nor did it alter the detection of Wilms' tumor gene expression by RT-PCR technology even at high doses (5000 ATU hirudin). Thus, a hirudin-containing blood sampling tube can be designed as a universal blood sampling tube (UBT) for testing the majority of diagnostic blood parameters.

Published
2001
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36. Primary tracheal leiomyosarcoma.

Author

Reichert K, Helling K, Menssen HD, Perez-Canto A, and Scherer H

Subjects
Chemotherapy, Adjuvant, Female, Humans, Leiomyosarcoma drug therapy, Leiomyosarcoma surgery, Middle Aged, Tracheal Neoplasms drug therapy, Tracheal Neoplasms surgery, Leiomyosarcoma pathology, Tracheal Neoplasms pathology
Abstract

We present the clinical course of a 56-year-old female patient with a primary tracheal leiomyosarcoma. The diagnostic approach and pathological classification of this seldom described tumour remains extremely difficult. We discuss the symptoms as well as the diagnostic and therapeutic procedures, including multimodal chemotherapy with organ-preserving surgery leading to complete remission.

Published
2000
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38. Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome by analysis of Wilms' tumour gene expression.

Author

Menssen HD, Renkl HJ, Rieder H, Bartelt S, Schmidt A, Notter M, and Thiel E

Subjects
Adult, Central Nervous System Neoplasms diagnosis, Child, Diagnosis, Differential, Female, Gene Expression, Humans, Hypereosinophilic Syndrome genetics, Leukemia, Eosinophilic, Acute genetics, Male, Middle Aged, Polymerase Chain Reaction, RNA, Messenger analysis, Genes, Wilms Tumor, Hypereosinophilic Syndrome diagnosis, Leukemia, Eosinophilic, Acute diagnosis
Abstract

In patients presenting with immature eosinophilic precursors it is notoriously difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in situ hybridization (FISH) can help in discriminating between these rare haematological disorders, but often treatment decisions cannot wait for the results of these time-consuming techniques. Recently, we and others found Wilms' tumour (WT1) gene expression to be increased in virtually all patients with acute leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much lower levels or not at all. To determine whether detection of WT1 gene expression is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR protocol, we found WT1 gene expression to be restricted to EoL patients. By detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were also able to diagnose isolated CNS-relapsed leukaemia, initially confused with bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR is a powerful complementary diagnostic tool to distinguish acute eosinophilic leukaemia from the hypereosinophilic syndromes. This observation needs confirmation in a larger series of EoL and HES patients.

Published
1998
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39. Wilms' tumor gene expression in human CD34+ hematopoietic progenitors during fetal development and early clonogenic growth.

Author

Menssen HD, Renkl HJ, Entezami M, and Thiel E

Subjects
Antigens, CD, Antigens, CD34, Cells, Cultured, Colony-Forming Units Assay, Embryonic and Fetal Development, Fetal Blood, Fetus, Gestational Age, Hematopoietic Stem Cells cytology, Humans, WT1 Proteins, Zinc Fingers, DNA-Binding Proteins biosynthesis, Gene Expression Regulation, Developmental, Genes, Wilms Tumor, Hematopoietic Stem Cells physiology, Transcription Factors biosynthesis
Published
1997

40. Detection by monoclonal antibodies of the Wilms' tumor (WT1) nuclear protein in patients with acute leukemia.

Author

Menssen HD, Renkl HJ, Rodeck U, Kari C, Schwartz S, and Thiel E

Subjects
Antibody Specificity, DNA-Binding Proteins immunology, Fluorescent Antibody Technique, Indirect, Humans, Neoplasm Proteins immunology, Transcription Factors immunology, Tumor Cells, Cultured chemistry, WT1 Proteins, Antibodies, Monoclonal, DNA-Binding Proteins analysis, Leukemia, Myeloid, Acute, Neoplasm Proteins analysis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Transcription Factors analysis
Abstract

The WT1 gene encodes a transcriptional regulator which during embryogenesis is involved in growth control and differentiation of diverse tissues. It is also expressed in few human malignancies, including acute leukemia. We tested 3 different monoclonal antibodies (MAbs H2, H7, HCl7) and the polyvalent serum WTC-19 for WT1 protein detection in mononuclear cell (MNC) preparations of 104 newly diagnosed acute leukemia patients. Using RT-PCR, these MNC preparations were also analyzed for WT1 gene expression. MAbs H2, H7 and HCl7 and the polyclonal WTC-19 exhibited nuclear immunoreactivity in 63 of 99, 28 of 56, 38 of 60 and 22 of 43 WT1 gene-expressing leukemia samples, respectively. With these antibodies, no WT1 immunoreactivity was found in MNCs from blood of healthy volunteers, from CD34+ progenitor cell-enriched leukapheresis products of patients conditioned for peripheral stem cell harvest or from reactive bone marrow. Contrary to WTC-19, all MAbs reacted highly specifically with the WT1 protein (0.71 vs. 1.0). The WT1 protein was heterogeneously detected in leukemia blast preparations by all antibodies, irrespective of cell morphology. Very few HL60 cells and blasts from newly diagnosed leukemia patients interspersed among normal blood MNCs (50 blasts among 5 x 10(5) MNCs) were easy to identify by indirect immunofluorescence using MAbs H2 and HCl7. Taken together, MAbs H2 and HCl7 were superior to MAb H7 and the polyvalent WTC-19 in detecting the WT1 nuclear protein.

Published
1997
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41. Xerocytosis with concomitant intrauterine ascites: first description and therapeutic approach.

Author

Entezami M, Becker R, Menssen HD, Marcinkowski M, and Versmold HT

Subjects
Abdominal Muscles pathology, Adult, Anemia complications, Anemia embryology, Ascites diagnosis, Ascites embryology, Ascites therapy, Blood Transfusion, Intrauterine, Cesarean Section, Exchange Transfusion, Whole Blood, Female, Fetal Diseases blood, Fetal Diseases diagnosis, Fetal Diseases embryology, Fetal Diseases therapy, Genes, Dominant, Humans, Infant, Newborn, Pre-Eclampsia, Pregnancy, Reticulocyte Count, Anemia genetics, Ascites etiology, Drainage, Fetal Diseases etiology
Published
1996

42. Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias.

Author

Menssen HD, Renkl HJ, Rodeck U, Maurer J, Notter M, Schwartz S, Reinhardt R, and Thiel E

Subjects
Adult, Base Sequence, Blast Crisis, Blotting, Northern, Cell Line, Cell Nucleus metabolism, Cell Nucleus pathology, Chromosome Mapping, Chromosomes, Human, Pair 11, DNA Primers, DNA-Binding Proteins analysis, Fluorescent Antibody Technique, Humans, Leukemia metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Leukemia, Myeloid, Acute genetics, Molecular Sequence Data, Nuclear Proteins biosynthesis, Polymerase Chain Reaction, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, RNA, Messenger analysis, RNA, Messenger biosynthesis, Transcription Factors analysis, Transcription, Genetic, Tumor Cells, Cultured, WT1 Proteins, Zinc Fingers, DNA-Binding Proteins biosynthesis, Gene Expression, Genes, Wilms Tumor, Leukemia genetics, Transcription Factors biosynthesis
Abstract

The wt1 gene is located on chromosome 11p13 and encodes a zinc finger motif-containing transcription factor involved in regulation of growth and differentiation. Its expression was shown during embryonic development in various tissues as well as in a few human malignancies including acute leukemias. Using RT-PCR, we found wt1 gene expression in blast cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) pre-pre-B-ALL patients, in 33 of 41 (80%) cALL patients, in 23 of 31 (74%) T-ALL patients, and in 53 of 57 (93%) AML patients. Additionally, mononuclear cells from CML patients expressed the wt1 gene only when diagnosed with blast crisis. In contrast to acute human leukemias, mononuclear cells from reactive bone marrow (n = 4), and peripheral blood of healthy volunteers (n = 20), as well as normal peripheral CD34+ hematopoietic progenitors (n = 6) did not express the wt1 gene at detectable levels. Using the anti-WT1 MoAb 6F-H2 in an immunofluorescence assay on single cell level, we found the translated WT1 protein only in nuclei of leukemia blast cells but not in nuclei of normal CD34+ hematopoietic progenitor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nuclear immunofluorescence. Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34+ hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan-acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.

Published
1995

43. Expression of the wt1 Wilms' tumor gene by normal and malignant human melanocytes.

Author

Rodeck U, Bossler A, Kari C, Humphreys CW, Györfi T, Maurer J, Thiel E, and Menssen HD

Subjects
Base Sequence, Blotting, Northern, DNA, Complementary chemistry, Genes, p53, Humans, Melanoma genetics, Molecular Sequence Data, Mutation, Platelet-Derived Growth Factor genetics, Polymerase Chain Reaction, RNA Splicing, RNA, Messenger metabolism, Tumor Cells, Cultured, Gene Expression, Genes, Wilms Tumor, Melanocytes metabolism, Melanoma metabolism
Abstract

We report expression of the wt1 (Wilms' tumor) gene by cultured human melanoma cells. Using RNA polymerase chain reaction analysis, wt1 transcripts were detected in 7 of 9 melanoma cell lines but not in 5 normal melanocyte strains. In Northern blot analysis, steady-state wt1 mRNA levels were found in 2 of 4 melanoma lines but not in normal melanocytes. Sequence analysis of the wt1 cDNA expressed by melanoma cell line WM 902-B revealed the presence of 4 previously published splice variants but no evidence for mutations in the coding region. Previous work has shown that WT1 modulates transcription after binding to the early growth response (EGR)-1 sites present in the platelet-derived growth factor (PDGF)-A chain promoter; the PDGF-A chain gene is known to be expressed by various melanoma cell lines. Based on these findings, we studied the relationship of wt1 and PDGF-A chain gene expression in melanoma cell lines. Co-expression of the wt1 and the PDGF-A chain genes was observed in 2 melanoma cell lines with mutated p53 but not in 2 melanoma cell lines with wild-type p53; this result is consistent with a previous report showing that, in the context of absent or mutated p53, WT1 acts as a transcriptional activator, whereas in the presence of wild-type p53 it acts as a repressor.

Published
1994
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44. Growth regulation of cultured human nevus cells.

Author

Mancianti ML, Györfi T, Shih IM, Valyi-Nagy I, Levengood G, Menssen HD, Halpern AC, Elder DE, and Herlyn M

Subjects
Base Sequence, Calcium analysis, Cell Division, Culture Media, Serum-Free chemistry, Fibroblast Growth Factor 2 analysis, Fibroblast Growth Factor 2 genetics, Humans, Melanocyte-Stimulating Hormones pharmacology, Melanoma etiology, Molecular Sequence Data, Nevus chemistry, Nevus congenital, RNA, Messenger analysis, Skin Neoplasms chemistry, Skin Neoplasms congenital, Tumor Cells, Cultured drug effects, Nevus pathology, Skin Neoplasms pathology
Abstract

Cells isolated from congenital melanocytic nevi and cultured in vitro have growth characteristics that resemble their premalignant stage in situ. A serum-free, chemically defined medium has been developed that allows continuous growth of established nevus cultures for up to several months. Like primary melanoma cells, nevus cells in high-calcium-containing W489 medium require insulin for growth. In contrast to melanoma cells, nevus cells in serum-free medium require the presence of alpha-melanocyte-stimulating hormone, which enhanced intracellular levels of cyclic adenosine monophosphate. In contrast to the requirements of normal human melanocytes from newborn foreskin, congenital nevus cells grow with less dependency on basic fibroblast growth factor (bFGF). Nevus cultures contain bFGF-like activity, and they express bFGF mRNA. Nevic cells of compound nevi also express bFGF mRNA in situ but only in the junctional areas. These results indicate that bFGF plays an important growth regulatory role for nevus cells in vitro and in vivo.

Published
1993
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45. Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes.

Author

Rodeck U, Melber K, Kath R, Menssen HD, Varello M, Atkinson B, and Herlyn M

Subjects
Blotting, Northern, ErbB Receptors genetics, ErbB Receptors immunology, Humans, Interleukin-1 genetics, Melanoma pathology, Platelet-Derived Growth Factor genetics, Platelet-Derived Growth Factor immunology, RNA, Messenger analysis, Transforming Growth Factors genetics, Transforming Growth Factors immunology, Transforming Growth Factors pharmacology, Tumor Cells, Cultured, Gene Expression, Growth Substances genetics, Melanocytes metabolism, Melanoma metabolism
Abstract

In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)- beta 1, TGF- alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1 alpha, and IL-1 beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF- beta 1 but not bFGF, PDGF, TGF- alpha , or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF- alpha, TGF- beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF- beta inhibited melanoma growth at concentrations greater than 10 ng/ml, suggesting that bioactive TGF- beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF- alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF- alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.

Published
1991
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46. [Growth factors in the pathogenesis of malignant diseases].

Author

Rodeck U, Menssen HD, and Herlyn M

Subjects
Animals, Culture Techniques, Epidermal Growth Factor physiology, Fibroblast Growth Factors physiology, Growth Inhibitors therapeutic use, Humans, Insulin-Like Growth Factor I physiology, Insulin-Like Growth Factor II physiology, Neoplasms pathology, Neoplasms therapy, Neoplasms, Experimental therapy, Platelet-Derived Growth Factor physiology, Growth Substances physiology, Neoplasms etiology
Published
1988
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47. Rapid dissociation of adherent human tumor cells by ultrasound.

Author

Menssen HD, Herlyn M, Rodeck U, and Koprowski H

Subjects
Antibodies, Monoclonal, Antibodies, Neoplasm immunology, Cell Division, Fluorescent Antibody Technique, Humans, Trypsin, Cell Adhesion, Tumor Cells, Cultured cytology, Ultrasonics
Abstract

Cultured human melanoma and gastrointestinal carcinoma cells were detached from substrate and further dissociated by placing the culture vessel into a water-filled ultrasonic cleaner (43 kHz) and sonicating it for 10-50 s. Plating efficiency and long-term growth of three melanoma cell lines were similar after ultrasound or trypsin detachment. Binding of monoclonal antibodies that define normal and tumor-associated antigens on melanoma and colorectal carcinoma cells was not affected by ultrasound in 21 out of 23 cases. The 40 kDa colorectal carcinoma-associated antigen defined by monoclonal antibody CO 17-1A was more highly expressed after ultrasonication than trypsinization. The antigen defined by antibody CO 44.1 on these cells was more sensitive to sonication. This method represents a rapid, effective and gentle alternative to trypsin detachment of cultured cells, especially when repeated cell washing or centrifugation steps are required.

Published
1987
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48. Tumor progression in the human melanocytic system.

Author

Kath R, Rodeck U, Menssen HD, Mancianti ML, Linnenbach AJ, Elder DE, and Herlyn M

Subjects
Animals, Cell Line, Cells, Cultured, Chromosome Aberrations, Chromosome Disorders, Genes, Growth Substances genetics, Humans, Melanocytes cytology, Melanoma genetics, Mice, Neoplasm Metastasis, Nevus pathology, Protein Kinase C genetics, Proto-Oncogenes, Receptors, Cell Surface genetics, Skin cytology, Skin pathology, Skin Neoplasms genetics, Tumor Cells, Cultured cytology, Melanocytes pathology, Melanoma pathology, Skin Neoplasms pathology
Abstract

The isolation and routine tissue culture of melanocytic cells from normal skin, precursor nevi, primary and metastatic melanomas has allowed the experimental study of different stages of tumor progression. Characteristic differences between cultured normal melanocytes and highly malignant metastatic melanoma cells were: 1) limited life span for normal melanocytes and non-malignant nevus cells versus infinite growth for malignant melanoma cells; 2) inability to grow anchorage-independently versus high colony forming-efficiency in soft agar; 3) non-tumorigenicity versus tumorigenicity in athymic nude mice; 4) dependence on exogenous growth factors and other mitogens versus autonomous growth in protein-free medium; 5) expression of melanocyte-associated antigens versus expression of melanoma-associated antigens; and 6) diploid karyotype versus non-random chromosomal abnormalities. The only major distinction found between advanced primary and metastatic melanomas was that only metastatic melanoma cells proliferated continuously in the absence of growth factors or other proteins. However, advanced primary melanoma cells could be clearly distinguished from dysplastic nevus cells by their growth behavior and growth factor requirements. Only limited information is available on the biologic, genetic, immunologic and molecular properties of dysplastic nevus cells and early (radial growth phase) primary melanoma cells but these cells appear to differ markedly from advanced primary and metastatic cells. The availability of cells from sequential steps of tumor progression in the human melanocytic system offers a unique experimental model for the study of malignant transformation.

Published
1989

49. Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors.

Author

Rodeck U, Herlyn M, Menssen HD, Furlanetto RW, and Koprowsk H

Subjects
Cell Division drug effects, Cell Line, Culture Media, Epidermal Growth Factor pharmacology, Humans, Insulin pharmacology, Insulin-Like Growth Factor I pharmacology, Transferrin pharmacology, Tumor Cells, Cultured drug effects, Growth Substances pharmacology, Melanoma secondary
Abstract

Five out of 6 cell lines derived from metastatic melanoma lesions grew in a chemically defined base medium consisting of a mixture of calcium-supplemented MCDB 153 and L 15 media in the absence of any polypeptide growth factors. In contrast, under these conditions no growth was seen in any of 5 primary melanoma cell lines tested, including 2 cell lines from patients whose metastatic cells proliferated well in base medium. Growth stimulation of all 11 melanoma cell lines by epidermal growth factor (EGF), transferrin, insulin, and insulin-like growth factor (IGF)-1 alone and in various combinations was studied. Insulin represented the strongest single growth factor for primary and metastatic melanoma cell lines. The metastatic cell lines remained growth-responsive to EGF, insulin and transferrin and responded more vigorously to these exogenously provided mitogens than the primary cell lines. No synergistic or additive growth effects of insulin, transferrin, or EGF for primary and metastatic cell lines were observed. Cross-linking studies with 125I-IGF-1 demonstrate surface expression of the type-I IGF receptor on melanoma cells. Growth stimulation by insulin and IGF-1 was inhibited by adding to the culture medium a monoclonal antibody to the type-I IGF receptor. Our studies indicate that IGF-1 and insulin are major growth factors for melanoma cells and act via the type-I IGF receptor.

Published
1987
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