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151. Perioperative chemotherapy with ECX +/- panitumumab in locally advanced gastroesophageal adenocarcinomas (GEA): A randomized study of the Arbeitsgemeinschaft Internistische Onkologie and the Chirurgische Arbeitsgemeinschaft Onkologie of the German Cancer Society.

Author

Stahl, Michael, primary, Mihaljevic, Andre L., additional, Moehler, Markus, additional, Kanzler, Stephan, additional, Hoehler, Thomas, additional, Thuss-Patience, Peter C., additional, Moenig, Stefan Paul, additional, Kunzmann, Volker, additional, Schroll, Sebastian, additional, Lordick, Florian, additional, Meyer, Hans-Joachim, additional, Sandermann, Andreas, additional, Schumacher, Christoph, additional, and Wilke, Hansjochen, additional

Published
2015
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154. Azacitidine Followed By Intensive Induction/Consolidation Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML): Results from the Randomized AML-AZA Trial of the Study Alliance Leukemias (SAL)

Author

Müller-Tidow, Carsten, primary, Tschanter, Petra, additional, Krug, Utz, additional, Goellner, Stefanie, additional, Röllig, Christoph, additional, Thiede, Christian, additional, Koschmieder, Anja, additional, Dugas, Martin, additional, Gerss, Joachim, additional, Butterfaß-Bahloul, Trude, additional, Wagner, Ruth, additional, Krause, Stefan W., additional, Kaiser, Ulrich, additional, Kunzmann, Volker, additional, Steffen, Björn, additional, Noppeney, Richard, additional, Herr, Wolfgang, additional, Baldus, Claudia D, additional, Schmitz, Norbert, additional, Götze, Katharina, additional, Reichle, Albrecht, additional, Kaufmann, Martin, additional, Neubauer, Andreas, additional, Schäfer-Eckart, Kerstin, additional, Hänel, Mathias, additional, Peceny, Rudolf, additional, Bea, Haack, additional, Meredith, Lilly, additional, Frickhofen, Norbert, additional, Kiehl, Michael G, additional, Giagounidis, Aristoteles A.N., additional, Görner, Martin, additional, Repp, Roland, additional, Naumann, Ralph, additional, Link, Hartmut, additional, Kiani, Alexander, additional, Koschmieder, Steffen, additional, Brümmendorf, Tim H., additional, Serve, Hubert, additional, Ehninger, Gerhard, additional, and Berdel, Wolfgang E, additional

Published
2014
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155. Sorafenib Versus Placebo in Addition to Standard Therapy in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia: Results from 267 Patients Treated in the Randomized Placebo-Controlled SAL-Soraml Trial

Author

Röllig, Christoph, primary, Müller-Tidow, Carsten, additional, Hüttmann, Andreas, additional, Noppeney, Richard, additional, Kunzmann, Volker, additional, Baldus, Claudia D, additional, Brandts, Christian H., additional, Krämer, Alwin, additional, Schäfer-Eckart, Kerstin, additional, Neubauer, Andreas, additional, Krause, Stefan W., additional, Giagounidis, Aristoteles, additional, Aulitzky, Walter E., additional, Bornhäuser, Martin, additional, Schaich, Markus, additional, Parmentier, Stefani B, additional, Thiede, Christian, additional, von Bonin, Malte, additional, Schetelig, Johannes, additional, Kramer, Michael, additional, Serve, Hubert, additional, Berdel, Wolfgang E, additional, and Ehninger, Gerhard, additional

Published
2014
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156. Elektrophysiologischer Nachweis langsam leitender Pyramidenbahnfasern

Author

Kunzmann, Volker

Subjects
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
Abstract

Nur der kleine Bruchteil (10%) der Pyramidenbahnfasern des Menschen mit Leitgeschwindigkeiten größer als 30 m/s vermittelt die überschwellige, als Muskelantwort registrierbare Wirkung eines transkraniellen magnetelektrischen Reizes auf spinale Motoneurone. Die unterschwellige Wirkung der durch den transkraniellen Reiz gleichzeitig aktivierten langsamer leitenden Neurone (90%) erzeugt keine Muskelantwort, jedoch eine Bahnung von H-Reflexen. Wenn man das Intervall zwischen konditionierendem Magnetpuls und elektrischem H-Reflexreiz zwischen Δt = -5 und Δt = 35 ms variiert, so erhält man in der distalen Muskulatur bis zu 35 ms dauernde triphasische Bahnungskurven mit einem frühen und späten Maximum. Mit den aus Autopsien gewonnenen Schätzwerten der Abstände zwischen kortikalem Reizort und spinalem Wirkort und dem jeweiligen Intervall zwischen konditionierendem und Testreiz lassen sich die Geschwindigkeiten der bahnenden Komponenten des Kortikospinaltraktes berechnen. Die Maxima werden durch Komponenten gebildet, die mit 30 m/s, bzw. 15 m/s leiten, die langsamsten Komponenten mit bahnender Wirkung leiten mit 6 m/s. Im Einklang mit unserer Hypothese, dass die Abszissenwerte der Bahnungskurve den Ankunftszeiten von bahnenden kortikospinalen Erregungen unterschiedlicher Leitgeschwindigkeit entsprechen, nimmt der zeitliche Abstand zwischen den Bahnungsgipfeln, die jeweils durch Komponenten gleicher Leitgeschwindigkeiten gebildet werden, und die Dauer der Bahnung an der unteren Extremität im Vergleich zur oberen Extremität zu. Die triphasische Bahnungskurve mit einem frühen und späten Gipfel und die Gipfel trennenden intermodalen Minimum erhält man nur aus der distalen Muskulatur. Bei proximalen Antischwerkraftsmuskeln bricht die Bahnung nach dem ersten frühen Gipfel ab, um in eine Phase normaler oder gehemmter H-Reflex Erregbarkeit überzugehen. Als Erklärung können eine durch den Magnetreiz gleichzeitig aktivierte, überwiegend spinale, Hemmkomponente oder vorwiegend disynaptische kortikomotoneuronale Verbindungen langsam leitender Pyramidenbahnfasern, die für eine direkte bahnende Interaktion mit der Ia-Afferenz am Motoneuron nicht zur Verfügung stehen, dienen. Die summierende Interaktion des peripheren und zentralen Inputs am Motoneuron lässt sich durch Modelle analytisch simulieren. Aus diesen Modellen gewinnt man auch Näherungen der empirischen Beziehungen zwischen Verstärkungswirkungen und Reizstärken. Triphasische Bahnungskurven mit zwei Maxima und intermodalem Minimum erhält man, wenn man das Produkt aus Faserzahl und Faserquerschnitt, d.h. den Anteil einer bestimmten Leitgeschwindigkeitskomponente am Gesamtquerschnitt der Pyramidenbahn, über der Leitgeschwindigkeit verteilt. Die so erhaltenen Verteilungen gleichen den empirischen Verteilungen der Bahnungsstärken. Faserzahl und auch Faserdurchmesser einer Komponente des Pyramidenbahnspektrums bestimmen also ihre Bahnungsstärke., The small fraction (10%) of the pyramidal tract fibres with conduction velocities of more than 30 m/s provides the above threshold effect of the transcranial magnetic stimulation on spinal motoneurones which is measurable as a muscular response. The 90% of slow conduction pyramidal tract fibres don’t provide a muscular response after transcranial magnetic stimulation, although they facilitate H-Reflexes. Varying the interval of conditioning magnet impulse and electric H-Reflex stimulus between Δt = -5 and Δt = 35 ms results in a triphasic facilitated curve of 35ms duration with an early and a late maximum in distal muscles. On the basis of autopsies we estimated the values of the distances between the area of cortical stimulation and spinal motoneurons in the anterior horn. Together with the intervals between conditioning magnet stimulus and electric test stimulus we calculated the conduction velocities of the respective facilitating components of the pyramidal tract. The two maxima were formed of pyramidal components conducting with 30m/s, rsp. 15m/s; the slowest facilitating components conducted with 6m/s. Consistent with our hypothesis, that the x-coordinates of our facilitated curves represent arrival times of excitating corticospinal fibres of different conduction velocities, the time-lag between the two maxima representing the same conduction velocities in upper and lower extremity grows. Additionally the overall period of facilitation is longer in the lower than in the upper extremity. The triphasic curve with an early and late peak and the separative dip is only available in the distal muscles. Concerning proximal anti gravity muscles the facilitation ends after the first peak. For longer Δts the H-reflexes were unaffected or suppressed. Explanations for this could be inhibiting spinal elements activated via the magnetic impulse or disynaptic corticomotoneuronal connections in proximal muscles which are not able to facilitate the Ia-afferents at the spinal motoneurons. In analytic models the accumulative interaction of the central and peripheral input on the spinal motoneuron can be simulated. We find approximations of the empiric relations between amplifying effects and stimulus intensities based on these models. The product of number of fibres and cross sectional area gives us the fraction of a fibre group with a distinct conduction velocity in the overall cross section area of the pyramidal tract. If we administer this product evenly across the conduction velocities, the result is a triphasic curve with two maxima and a separative minimum which resemble our empiric results. That means that the number of fibres and the diameter of a component of the pyramidal tract determine their strength of facilitation.

Published
2008

160. Analyses of updated overall survival (OS) and prognostic effect of neutrophil-to-lymphocyte ratio (NLR) and CA 19-9 from the phase III MPACT study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem for patients (pts) with metastatic pancreatic cancer (PC).

Author

Goldstein, David, primary, El-Maraghi, Robert Hassan, additional, Hammel, Pascal, additional, Heinemann, Volker, additional, Kunzmann, Volker, additional, Sastre, Javier, additional, Scheithauer, Werner, additional, Siena, Salvatore, additional, Macarulla, Teresa, additional, Teixeira, Luis, additional, Tortora, Giampaolo, additional, Van Laethem, Jean Luc, additional, Penenberg, Darryl Neil, additional, Lu, Brian, additional, Romano, Alfredo, additional, and Von Hoff, Daniel D., additional

Published
2014
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161. HER-FLOT: Trastuzumab in combination with FLOT as perioperative treatment for patients with HER2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the AIO Gastric Cancer Study Group.

Author

Hofheinz, Ralf, primary, Hegewisch-Becker, Susanna, additional, Thuss-Patience, Peter C., additional, Kunzmann, Volker, additional, Fuchs, Martin, additional, Graeven, Ullrich, additional, Homann, Nils, additional, Heinemann, Volker, additional, Pohl, Michael, additional, Tannapfel, Andrea, additional, and Al-Batran, Salah-Eddin, additional

Published
2014
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162. Updated survival from a randomized phase III trial (MPACT) of nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients (pts) with metastatic adenocarcinoma of the pancreas.

Author

Goldstein, David, primary, El Maraghi, Robert Hassan, additional, Hammel, Pascal, additional, Heinemann, Volker, additional, Kunzmann, Volker, additional, Sastre, Javier, additional, Scheithauer, Werner, additional, Siena, Salvatore, additional, Tabernero, Josep, additional, Teixeira, Luis, additional, Tortora, Giampaolo, additional, Van Laethem, Jean-Luc, additional, Young, Rosemary, additional, Wei, Xinyu, additional, Lu, Brian, additional, Romano, Alfredo, additional, and Von Hoff, Daniel D., additional

Published
2014
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164. Sorafenib In Combination with Standard Induction and Consolidation Therapy In Elderly AML Patients: Results From a Randomized, Placebo-Controlled Phase II Trial

Author

Serve, Hubert, Wagner, Ruth, Sauerland, Cristina, Brunnberg, Uta, Krug, Utz, Schaich, Markus, Ottmann, Oliver G., Duyster, Justus, Wandt, Hannes, Herr, Wolfgang, Giagounidis, Aristoteles A. N., Neubauer, Andreas, Reichle, Albrecht, Aulitzky, Walter E., Noppeney, Richard, Blau, Igor Wolfgang, Kunzmann, Volker, Schmitz, Norbert, Kreuzer, Karl-Anton, Kraemer, Alwin, Brandts, Christian, Steffen, Bjoern, Heinecke, Achim, Thiede, Christian, Mueller-Tidow, Carsten, Ehninger, Gerhard, Berdel, Wolfgang E., Serve, Hubert, Wagner, Ruth, Sauerland, Cristina, Brunnberg, Uta, Krug, Utz, Schaich, Markus, Ottmann, Oliver G., Duyster, Justus, Wandt, Hannes, Herr, Wolfgang, Giagounidis, Aristoteles A. N., Neubauer, Andreas, Reichle, Albrecht, Aulitzky, Walter E., Noppeney, Richard, Blau, Igor Wolfgang, Kunzmann, Volker, Schmitz, Norbert, Kreuzer, Karl-Anton, Kraemer, Alwin, Brandts, Christian, Steffen, Bjoern, Heinecke, Achim, Thiede, Christian, Mueller-Tidow, Carsten, Ehninger, Gerhard, and Berdel, Wolfgang E.

Published
2010

165. Sorafenib in Combination With Intensive Chemotherapy in Elderly Patients With Acute Myeloid Leukemia: Results From a Randomized, Placebo-Controlled Trial

Author

Serve, Hubert, primary, Krug, Utz, additional, Wagner, Ruth, additional, Sauerland, M. Cristina, additional, Heinecke, Achim, additional, Brunnberg, Uta, additional, Schaich, Markus, additional, Ottmann, Oliver, additional, Duyster, Justus, additional, Wandt, Hannes, additional, Fischer, Thomas, additional, Giagounidis, Aristoteles, additional, Neubauer, Andreas, additional, Reichle, Albrecht, additional, Aulitzky, Walter, additional, Noppeney, Richard, additional, Blau, Igor, additional, Kunzmann, Volker, additional, Stuhlmann, Reingard, additional, Krämer, Alwin, additional, Kreuzer, Karl-Anton, additional, Brandts, Christian, additional, Steffen, Björn, additional, Thiede, Christian, additional, Müller-Tidow, Carsten, additional, Ehninger, Gerhard, additional, and Berdel, Wolfgang E., additional

Published
2013
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166. CA19-9 Decrease and Kinetics in a Randomized Phase III Trial (MPACT) of Weekly Nab-Paclitaxel Plus Gemcitabine in Metastatic Pancreatic Cancer

Author

Reni, Michele, primary, Von Hoff, Daniel, additional, Chiorean, E., additional, Ervin, Thomas, additional, Arena, Francis, additional, Infante, Jeffrey, additional, Bathini, Venu, additional, Clingan, Philip, additional, Kunzmann, Volker, additional, Ramanathan, Ramesh, additional, Tabernero, Josep, additional, Goldstein, David, additional, Ko, Amy, additional, and Lu, Brian, additional

Published
2013
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168. CA19-9 decrease at 8 weeks as a predictor of overall survival (OS) in a randomized phase III trial (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (G) versus G alone in patients with metastatic pancreatic cancer (MPC).

Author

Chiorean, E. Gabriela, primary, Von Hoff, Daniel D., additional, Ervin, Thomas J., additional, Arena, Francis P., additional, Infante, Jeffrey R., additional, Bathini, Venu Gopal, additional, Wood, Tina Evans, additional, Mainwaring, Paul N., additional, Muldoon, Robert T., additional, Clingan, Philip R., additional, Kunzmann, Volker, additional, Ramanathan, Ramesh K., additional, Tabernero, Josep, additional, Goldstein, David, additional, Ko, Amy, additional, and Lu, Brian, additional

Published
2013
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170. Sorafenib Versus Placebo in Addition to Standard Therapy in Adult Patients ≥60 Years with Newly Diagnosed Acute Myeloid Leukemia: Results From the Randomized-Controlled Soraml Trial

Author

Röllig, Christoph, primary, Müller-Tidow, Carsten, additional, Hüttmann, Andreas, additional, Kunzmann, Volker, additional, Baldus, Claudia D, additional, Brandts, Christian H., additional, Krämer, Alwin, additional, Schäfer-Eckart, Kerstin, additional, Neubauer, Andreas, additional, Krause, Stefan W., additional, Krug, Utz, additional, Giagounidis, Aristoteles, additional, Aulitzky, Walter E., additional, Bornhäuser, Martin, additional, Schaich, Markus, additional, Parmentier, Stefani, additional, Thiede, Christian, additional, von Bonin, Malte, additional, Illmer, Thomas, additional, Schetelig, Johannes, additional, Kramer, Michael, additional, Serve, Hubert, additional, Berdel, Wolfgang E, additional, and Ehninger, Gerhard, additional

Published
2012
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171. Results of the first interim analysis of the CARMA study to investigate efficacy and safety profile of catumaxomab in clinical practice.

Author

Kunzmann, Volker, primary, Sehouli, Jalid, additional, Schmalfeldt, Barbara, additional, Wimberger, Pauline, additional, Kurbacher, Christian M., additional, Tempelhoff, G.-F., additional, Vanhoefer, Udo J., additional, Ebeling, P., additional, Breuer, F., additional, Schulz, Holger, additional, Welslau, Manfred, additional, Finas, Dominique, additional, Sagasser, Jaqueline, additional, Kiehl, M., additional, and Fruehauf, S., additional

Published
2012
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172. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma.

Author

Schulz, Christoph, primary, Kullmann, Frank, additional, Kunzmann, Volker, additional, Schepp, Wolfgang, additional, Geissler, Michael, additional, Vehling-Kaiser, Ursula, additional, Stauder, Heribert, additional, Wein, Axel, additional, Al-Batran, Salah-Eddin, additional, Kubin, Thomas, additional, Schaefer, Claus, additional, Held, Swantje, additional, Stintzing, Sebastian, additional, Boeck, Stefan Hubert, additional, Haas, Michael, additional, Forstpointner, Roswitha, additional, Ridwelski, Karsten, additional, and Heinemann, Volker, additional

Published
2012
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175. Sorafenib In Combination with Standard Induction and Consolidation Therapy In Elderly AML Patients: Results From a Randomized, Placebo-Controlled Phase II Trial

Author

Serve, Hubert, primary, Wagner, Ruth, additional, Sauerland, Cristina, additional, Brunnberg, Uta, additional, Krug, Utz, additional, Schaich, Markus, additional, Ottmann, Oliver G., additional, Duyster, Justus, additional, Wandt, Hannes, additional, Herr, Wolfgang, additional, Giagounidis, Aristoteles A.N., additional, Neubauer, Andreas, additional, Reichle, Albrecht, additional, Aulitzky, Walter E., additional, Noppeney, Richard, additional, Blau, Igor Wolfgang, additional, Kunzmann, Volker, additional, Schmitz, Norbert, additional, Kreuzer, Karl-Anton, additional, Krämer, Alwin, additional, Brandts, Christian, additional, Steffen, Björn, additional, Heinecke, Achim, additional, Thiede, Christian, additional, Müller-Tidow, Carsten, additional, Ehninger, Gerhard, additional, and Berdel, Wolfgang E., additional

Published
2010
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179. Bortezomib, Intravenous Cyclophosphamide and Dexamethasone (VelCD) for Previously Untreated Multiple Myeloma: An Interim Analysis of the German DSMM XIa Trial

Author

Knop, Stefan, primary, Liebisch, Peter, primary, Wandt, Hannes, primary, Kropff, Martin, primary, Kunzmann, Volker, primary, Weisel, Katja, primary, Franke, Daniel, primary, Engelhardt, Monika, primary, Truemper, Lorenz H., primary, Kroeger, Nikolaus, primary, Hennemann, Burkhard, primary, Pfreundschuh, Michael, primary, Gramatzki, Martin, primary, Metzner, Bernd, primary, Peschel, Christian, primary, Sayer, Herbert G., primary, Sezer, Orhan, primary, Duerk, Heinz A, primary, Hertenstein, Bernd, primary, Mergenthaler, Hans-Guenther, primary, Gollasch, Hella, primary, Wolf, Hans-Heinrich, primary, Schilling, Georgia, primary, Frohn, Claas, primary, and Einsele, Hermann, primary

Published
2008
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180. Neo FLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors.

Author

Schulz, Christoph, Kullmann, Frank, Kunzmann, Volker, Fuchs, Martin, Geissler, Michael, Vehling‐Kaiser, Ursula, Stauder, Heribert, Wein, Axel, Al‐Batran, Salah‐Eddin, Kubin, Thomas, Schäfer, Claus, Stintzing, Sebastian, Giessen, Clemens, Modest, Dominik Paul, Ridwelski, Karsten, and Heinemann, Volker

Abstract

Perioperative treatment is a standard of care in locally advanced gastroesophageal cancer (GEC) (gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma). While preoperative treatment can be applied to the majority of patients, postoperative chemotherapy can be given only to a fraction. The NeoFLOT-study therefore investigates the application of prolonged neoadjuvant chemotherapy (NACT). Patients with T3, T4, and/or node-positive adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-fluorouracil 2600 mg/m2 and docetaxel 50 mg/m2 (FLOT) applied q 2 wks. Application of adjuvant chemotherapy was explicitly not part of the protocol. R0-resection rate was evaluated as a primary endpoint. Of 59 enrolled patients, 50 patients underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). Pathologic complete response (pCR) was 20.0% (10/50) and a further 20% (10/50) of patients achieved near complete histological remission (<10% residual tumor). Among these very good responders, 85% (17/20) had intestinal type tumors, 10% (2/20) had diffuse and 5% (1/20) had mixed type tumors. After 3 cycles of NACT, 6.9% (4/58) of patients developed progressive disease. Median disease-free survival was 32.9 months. The 1-year survival-rate was 79.3%. Grade 3-4 toxicities included neutropenia 29.3%, febrile neutropenia 1.7%, diarrhea 12.1% and mucositis 6.9%. This study indicates that intensified NACT with 6 cycles of FLOT is highly effective and tolerable in resectable GEC. Very good response (pCR and <10% residual tumor) was predominantly observed in patients with intestinal type tumors. [ABSTRACT FROM AUTHOR]

Published
2015
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188. Activation of Vγ9Vδ2 T Cells by NKG2D

Author

Rincon-Orozco, Bladimiro, primary, Kunzmann, Volker, additional, Wrobel, Philine, additional, Kabelitz, Dieter, additional, Steinle, Alexander, additional, and Herrmann, Thomas, additional

Published
2005
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191. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study

Author

Reimer, Peter, primary, Schertlin, Tobias, additional, Rüdiger, Thomas, additional, Geissinger, Eva, additional, Roth, Sabine, additional, Kunzmann, Volker, additional, Weissinger, Florian, additional, Nerl, Christoph, additional, Schmitz, Norbert, additional, Müller-Hermelink, Hans Konrad, additional, and Wilhelm, Martin, additional

Published
2004
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197. Primary cutaneous marginal zone lymphoma with sequential development of nodal marginal zone lymphoma in a patient with selective immunoglobulin A deficiency.

Author

Wobser, Marion, Kerstan, Andreas, Kneitz, Hermann, Goebeler, Matthias, Kunzmann, Volker, Rosenwald, Andreas, and Geissinger, Eva

Subjects
LYMPHOMAS, IMMUNOGLOBULIN A, B cells, CANCER research, DERMATOPATHOLOGY, IMMUNOHISTOCHEMISTRY
Abstract

Multiple lymphoma subtypes occurring within one patient is rare in the context of B-cell lymphoma, and only few such cases have been reported in association with primary cutaneous marginal zone lymphoma ( PCMZL). We herein describe the case of a 43-year-old patient who was diagnosed with PCMZL and subsequently developed a clonally unrelated nodal marginal zone lymphoma ( MZL). At the time of diagnosis of PCMZL, multiple skin lesions were present. The atypical lymphoid infiltrate showed monotypic expression of immunoglobulin light chain lambda and heavy chain ( IgM) on immunohistochemistry and an identical B-cell clone. No sign of systemic lymphoma was present in staging examinations. Complete remission was achieved utilizing rituximab. After a 3-year clinical course of repetitive cutaneous relapses and remissions, the patient additionally developed nodal lymphoma involvement by MZL which, however, harbored an immunophenotype and a genetic clone distinct from the cutaneous lymphoma counterpart. Therefore, the rare occurrence of two different types of MZL with sequential evolution was diagnosed. In this uncommon case, we hypothesize that selective immunoglobulin A deficiency may play a promoting role for the metachronous development of the two MZL that occurred in our patient. [ABSTRACT FROM AUTHOR]

Published
2013
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200. Inhibition of phosphoantigen-mediated γδ T-cell proliferation by CD4+ CD25+ FoxP3+ regulatory T cells.

Author

Kunzmann, Volker, Kimmel, Brigitte, Herrmann, Thomas, Einsele, Hermann, and Wilhelm, Martin

Subjects
*TUMOR growth, *CELL proliferation, *T cells, *CELL-mediated cytotoxicity, *CANCER patients, *IMMUNOTHERAPY
Abstract

Tumour growth promotes the expansion of CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) which suppress various arms of immune responses and might therefore contribute to tumour immunosurveillance. In this study, we found an inverse correlation between circulating Treg frequencies and phosphoantigen-induced γδ T-cell proliferation in cancer patients, which prompted us to address the role of Tregs in controlling the γδ T-cell arm of innate immune responses. In vitro, human Treg–peripheral blood mononuclear cell (PBMC) co-cultures strongly inhibited phosphoantigen-induced proliferation of γδ T cells and depletion of Tregs restored the impaired phosphoantigen-induced γδ T-cell proliferation of cancer patients. Tregs did not suppress other effector functions of γδ T cells such as cytokine production or cytotoxicity. Our experiments indicate that Tregs do not mediate their suppressive activity via a cell–cell contact-dependent mechanism, but rather secrete a soluble non-proteinaceous factor, which is independent of known soluble factors interacting with amino acid depletion (e.g. arginase-diminished arginine and indolamine 2,3-dioxygenase-diminished tryptophan) or nitric oxide (NO) production. However, the proliferative activity of αβ T cells was not affected by this cell–cell contact-independent suppressive activity induced by Tregs. In conclusion, these findings indicate a potential new mechanism by which Tregs can specifically suppress γδ T cells and highlight the strategy of combining Treg inhibition with subsequent γδ T-cell activation to enhance γδ T cell-mediated immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2009
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