S Seeber

Kliniken Essen-Mitte Knappschafts-Krankenhaus, Essen, North Rhine-Westphalia, Germany

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Publications (455)1529.24 Total impact

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    ABSTRACT: Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50mg/m(2) day 1+8) and paclitaxel (175mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45Gy (1.5Gy bid) with cisplatin 50mg/m(2) day 2+9 and etoposide 100mg/m(2) d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20Gy; 2Gy qd) followed. Here we report 10-year-LTS for this cohort. All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).
    No preview · Article · Aug 2013 · Lung cancer (Amsterdam, Netherlands)

  • No preview · Article · Apr 2011 · Cancer Research
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    ABSTRACT: Background: we have already reported cumulative probability (prob) of brain relapse as first site of failure within our randomized trial that investigated TRIMODALITY + prophylactic cranial irradiation (PCI) versus SURG + RTx alone in operable IIIA NSCLC (Pöttgen, JCO 2007). Here we report LTS for these arms, look for exploratory subgroups and investigate competing risks. Methods: Pts with histopathologically (mediastinoscopy) proven operable IIIA (1-2 LN involved, no clinical N2, no bulky/extranodal disease, central T3N0-1, WHO 0,1) NSCLC were stratified (TN-group, center) and randomized. Arm B received three CTx cycles cis (60 mg/m2 d 1+7 or 8) and eto (150 mg/m2 d 3,4,5) qd 22. This was followed by cc CTx/RTx including cis 50 mg/m2 d 2 + 9 and eto 100 mg/m2 d 4-6 cc with 45 Gy (1.5 Gy bid). 3-5 weeks after end of RTx SURG was performed if possible and PCI given thereafter. Arm A had local treatment alone (SURG + RTx) and no PCI. Results: Pts accrual 1/95 to 10/01; eligible 106/112 randomized; Pts characteristics: gender m 90; f 16; age median 57 (37-71); PS 0-1; histo: adeno (ADC) 35; squamous cell (SCC) 50; large cell (LCC) 16; ADSCC 5 TN-groups: T3N0-1 6 T1-2N2 83 T3N2 17. Med S of pts still alive on f-up: 130 mo. LT exploratory OS analysis (2-y-OS %; 5-y-OS %, 10-y-OS %); B: 54.6 20.0 12.5; A: 44.2 23.5 10.0 (ns log rank, Wilcoxon); PFS: B: 36.4 14.6 12.7 A: 29.4 17.3 10.4 (p = 0.30/0.14 log rank/Wilcoxon) Disease-specific survival: B: 40.5 25.0 25.0 A: 32.5 23.1 18.5 (p = 0.16/0.059 log rank/Wilcoxon), Cumulative 10-y prob %: non-disease-related events (tox, comorbidity, second cancer): B: 56.3 A: 67.7 (ns); brain relapse as first site of failure: B: 16.6 A: 30.4 (p = 0.059/0.020 log rank/Wilcoxon). Conclusions: LTS after Tx in stage IIIA is significantly hampered by cumulative competing risks (toxicities, comorbidities, second cancers) regardless of Tx intensity. Initial pts selection based on comorbidity profiles may be most important in improving LTS with aggressive protocols based on TRIMODALITY (+/- PCI).
    No preview · Article · Jan 2011 · Journal of Clinical Oncology
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    ABSTRACT: Background: The use of autologous peripheral blood progenitor/stem cells as part of dose-intensified treatment protocols for patients with acute myeloid leukemia (AML) is under current clinical investigation. Methods: We analyzed the frequency of CD 34+ 381 and CD 34+DR 1 subpopulations, clonogenic cells and long-term culture-derived clonogenic cells (LTC-DC) in peripheral blood (PB) samples from patients with AML after chemotherapy and G-CSF given for mobilization in comparison to a control population of patients with non-hematological malignancies. Results: We observed a lower number of CD 34+ cells (31.2 ± 14.8 vs. 114 ± 36 /μ l) and a reduction to less than 15 % for clonogenic progenitors (CFU) and LTC-DC in peripheral blood mononuclear cells from AML patients after consolidation therapy. In contrast, the quality of these CD 34+ cells was not significantly impaired after consolidation therapy determined by a moderately reduced frequency of CFU/CD34+ cells (5.0 ± 1.5 % vs. 10.0 ± 2.8 %), a nearly identical frequency of LTC-DC/CD34+ cells (0.5 ± 0.1 % vs. 0.6 ± 0.2 %), and a higher percentage of CD 34+381 cells/CD34+ cells (8.4 ± 1.8 % vs. 3.8 ± 1.1 %) in comparison to the control population. Conclusion: Our data confirm that it is possible to mobilize CD 34+ cells into the peripheral blood of AML patients using chemotherapy and G-CSF. Nevertheless, the low absolute number of CFU and LTC-DC after high-dose ara-C treatment for AML has to be taken into consideration for the design of treatment protocols using autologous progenitor/stem cell transplantation.
    No preview · Article · Oct 2010 · TumorDiagnostik & Therapie
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    ABSTRACT: Die vorliegende retrospektive Untersuchung befaßt sich mit der sequentiell-alternierenden Chemotherapie metastasierender, nicht-seminomatöser Hodentumoren. Die therapeutische Wertigkeit der Zytostatikakombinationen Adriamycin/Cisplatin (Kombination A) und Bleomycin/Vinblastin (Kombination B) wurde in Abhängigkeit von Tumorhistologie und Tumorstadium bestimmt. Untersucht wurden 180 Patienten, die die Kombination A entweder während der beiden ersten Therapiekurse (n = 63) oder nach zweimaliger Vorbehandlung mit der Kombination B (n = 117) erhalten hatten. 151 von 180 (84%) der mit Adriamycin/Cisplatin behandelten Patienten wiesen ein Tumoransprechen auf, wobei die Ansprechrate bei den unvor-behandelten Patienten 95 % (60/63 Patienten) und bei den vorbehan-delten Patienten 78% (91/117 Patienten) betrug. Die Gruppe der mit der Kombination B behandelten Patienten (n = 157) umfaßt 116 unvorbehandelte und 41 mit Adriamycin/Cisplatin vorbehandelte Patienten. Bei 131 von 157 Patienten (84%) zeigte sich ein Tumoransprechen; eine Abhängigkeit von der Vorbehandlung war hier nicht nachweisbar. Die Analyse der Therapieversager im Hinblick auf die Tumorhistologie ergab eine etwa 2,5fach höhere Versagerrate der Kombination A bei embryonalen Tumoren (Klasse II nach Dixon und Moore) als bei vorwiegend chorealen Tumoren (Klasse V). Die Kombination B versagte in den Histologieklassen II, III und IV mit durchschnittlich 14% weniger häufig als bei Tumoren der Klasse V (22%). Neben der Tumorhistologie war auch ein Einfluß des Tumor-stadiums auf das Therapieansprechen zu verzeichnen. Beide Therapiekombinationen versagten in den Stadien II C und IV D häufiger als in den Stadien geringerer Tumormasse. Die Ergebnisse sprechen für eine nur partielle Kreuzresistenz zwischen beiden Zytostatikakombinationen. Bei Resistenz von Bleomycin/Vinblastin war die Kombination A noch bei 18 von 26 Patienten (69%) wirksam. Die Kombination B erwies sich nach Versagen von Adriamycin/Cisplastin bei 14 von 24 Patienten (58%) als effektiv. Eine Therapieresistenz war zu 93% bereits nach dem ersten Therapiekurs einer Zytostatikakombination erkennbar und ermöglichte damit in der Regel noch einen rechtzeitigen Therapiewechsel auf die jeweils alternative Zytostatikakombination.
    No preview · Article · Apr 2009 · Oncology Research and Treatment
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    ABSTRACT: ImmunoRNases represent a highly attractive alternative to conventional immunotoxins for cancer therapy. Quantitative production of immunoRNases in appropriate expression systems, however, remains a major challenge for further clinical development of these novel compounds. Here we describe a method for high-level production and purification of a fully functional immunoRNase fusion protein from supernatants of stably transfected mammalian cells.
    No preview · Article · Feb 2009 · Methods in Molecular Biology
  • O Kloke · N Niederle · B Opalka · I Hawig · S Seeber · R Becher
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    ABSTRACT: To evaluate the long-term impact of the reduction of Philadelphia chromosome (Ph)-positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha, we examined the outcome of 62 patients who had been enrolled between 1984 and 1990 into 2 IFN trials at our institution. As best cytogenetic response, 9 patients had achieved a complete remission and an additional 9 patients a partial remission. The remaining 44 patients had obtained either a minimal (n=29) or no cytogenetic response (n=15). Of the total of 62 patients, 9 were still on schedule and responsive to IFN in January 1995, including 7 patients in ongoing complete cytogenetic remission. The overall 5-year survival rate after a median follow-up from diagnosis of 51 months (range 3-102 months) was 62% and the median survival was reached at month 87. The effect of cytogenetic remission on survival was examined by "landmark" studies showing a significant survival advantage for patients with karyotype responses. In conclusion, in the patients studied, cytogenetic improvement was found to translate into improved survival expectancy. Long-term control by IFN alpha of CML, however, was restricted to a small minority of patients, predominantly to those attaining a complete suppression of the leukaemic cell clone as judged by cytogenetic criteria.
    No preview · Article · Jan 2009 · European Journal Of Haematology
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    Siegfried Seeber

    Preview · Article · Oct 2008 · Onkologie
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    ABSTRACT: Anthracyline-based chemotherapy is the treatment of choice for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL). However, anthracyclines have been associated with long-term cardiac toxicity. We conducted a study using a sequential combination chemotherapy with a reduced cumulative dose of anthracyclines in younger patients with good-prognosis aggressive NHL. Chemotherapy consisted of one cycle of vincristine, ifosfamide, etoposide, and dexamethasone, followed by three cycles of epirubicin, cyclophosphamide, vincristine, and dexamethasone, and a fifth cycle containing carboplatin, etoposide, and dexamethasone. 86 patients were treated, 65 without and 21 with additional rituximab. Consolidating involved-field irradiation was applied in patients with stage I/II, bulky disease, or localized residual lymphoma. Complete and partial remissions were achieved in 67 and 27% of patients, respectively, and the 3-year event-free and overall survival estimates were 75 and 87%. The survival estimates were substantially better in patients who received rituximab. Main toxicity was grade 3/4 leukocytopenia in 89% patients with neutropenic fever in 30%. Two patients died of septic shock. The treatment appears to be effective in this group of patients. The hematological toxicities, particularly after the first and fifth cycle, require the use of G-CSF and/or a dose reduction in selected patients.
    No preview · Article · Sep 2008 · Journal of Cancer Research and Clinical Oncology
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    S. Seeber · A. Welt
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    ABSTRACT: Eine vielfältige klinische und zellbiologisch-experimentelle Forschungslandschaft trägt dazu bei, dass gerade beim metastasierten Mammakarzinom die zunehmenden therapeutischen Alternativen einer medikamentösen Behandlung nicht nur einem steten Wandel unterworfen sind, sondern glücklicherweise auch zu einer schrittweisen Verbesserung der Langzeitergebnisse führen [1]. Wie bei der einzelnen Patientin zu verfahren ist, wird durch die onkologischen Therapeuten oft recht unterschiedlich beurteilt. Auch aus Sicht der Autoren sind bei den zahlreichen unterschiedlichen Situationen eines Langzeitverlaufs die Behandlungsmöglichkeiten heterogen. Diese können durch die gegenwärtige Studienmedizin nur teilweise abgebildet werden [2]. Deshalb sind Vorgaben durch vereinfachende Leitlinien von Fachgesellschaften auch nicht immer befriedigend.
    Preview · Article · Jun 2008 · best practice onkologie
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    ABSTRACT: The genes MTS1/p16 and MTS2/p15 located in 9p21 encoding cyclin-dependent kinase-4 inhibitors are homozygously deleted in a number of different tumour cell lines. By PCR analysis of 30 cell lines, including 10 acute lymphoblastic leukaemia (ALL) and 20 lymphoma cell lines, we found homozygous deletions of at least one locus in 11 (37%) cell lines. MTS1-speciflc sequences were deleted in 70% of ALL (reaching 86% in T-cell ALL) but in none of the non-Hodgkin's lymphoma (NHL) cell lines. MTS2-specific sequences were deleted in 40% of ALL and 17% of NHL cell lines. We observed a higher frequency of MTS1 deletions in ALL than in NHL (P< 0.001) and in T-cell neoplasms compared to B-cell neoplasms (67%v 6%; P= 0.001). In ALL-derived cell lines deletions of the MTS2 gene only occurred in cases with MTS1 deletions but in NHL only in cases without MTS1 deletions.
    No preview · Article · Mar 2008 · British Journal of Haematology
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    ABSTRACT: Advanced stage/metastatic soft tissue sarcoma (STS) has a poor prognosis especially after failure of the established first-line treatment. In patients with relapsed leiomyosarcoma, however, the combination of gemcitabine (G) and docetaxel (D) recently has emerged as a valuable salvage therapy. A retrospective analysis of G (900 mg/m2, days 1+8) and D (100 mg/m2, day 8) was performed in 34 patients with STS, and response rate (RR), overall survival (OS), time to progression (TTP), and toxicities were evaluated. Analysis of these 34 patients revealed a RR of 15% with no complete remission (CR) and 5 partial remissions (PR). Of note, 4/5 PR were achieved in patients with leiomyosarcoma. In 13 patients (38%) disease stabilization (SD) could be achieved resulting in a clinical benefit rate (CBR), defined as CR+PR+SD, of 53%. Median OS was 12.5 and TTP was 2.4 months for the whole group and 2.8 months for patients with leiomyosarcoma. A progression- free rate at 3 months of 38% and 45%, respectively, was observed in these 2 groups. Major side effects were 47% hematological and 26% grade 3/4 nonhematological toxicity. With regard to the observed CBR further use of GD seems to be warranted even in pretreated patients with STS.
    No preview · Article · Mar 2008 · Onkologie
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    ABSTRACT: Because of the variable clinical course of multiple myeloma, the identification of prognostic parameters is of clinical interest. Therefore, we analyzed the clinical significance of serum levels of soluble human leukocyte antigen class I molecules (sHLA-I), carboxy-terminal telopeptide of type-I collagen (ICTP), and receptor activator of nuclear factor kappa B ligand (RANKL). Compared with controls, sHLA-I were threefold (p < 0.001) elevated in multiple myeloma. Increased levels of ICTP and RANKL were demonstrated in 50 and 43% of patients, respectively. sHLA-I correlated significantly with stage of disease. Serial determination of sHLA-I in 11 patients revealed significantly higher sHLA-I levels (median [range] mug/l) during active disease than during remission (700 [250-2090] versus 380 [130-920]). ICTP demonstrated an association with stages of disease and the presence of osteolytic lesions, whereas there were no differences with respect to active/remittent disease. Importantly, levels of sHLA-I > or = 1000 microg/l and ICTP > or = 5 microg/l were significantly associated with a poor overall survival. For RANKL, no significant associations were observed with disease stages, disease status, osteolytic lesions, and survival. In conclusion, sHLA-I and ICTP serum levels seem to be of prognostic significance in multiple myeloma and might be helpful to identify patients of poor prognosis.
    No preview · Article · Mar 2008 · Human Immunology
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    ABSTRACT: Introduction: Advanced stage/metastatic soft tissue sarcoma (STS) has a poor prognosis especially after failure of the established first-line treatment. In patients with relapsed leiomyosarcoma, however, the combination of gemcitabine (G) and docetaxel (D) recently has emerged as a valuable salvage therapy. Patients and Methods: A retrospective analysis of G (900 mg/m2, days 1+8) and D (100 mg/m2, day 8) was performed in 34 patients with STS, and response rate (RR), overall survival (OS), time to progression (TTP), and toxicities were evaluated. Results: Analysis of these 34 patients revealed a RR of 15% with no complete remission (CR) and 5 partial remissions (PR). Of note, 4/5 PR were achieved in patients with leiomyosarcoma. In 13 patients (38%) disease stabilization (SD) could be achieved resulting in a clinical benefit rate (CBR), defined as CR+PR+SD, of 53%. Median OS was 12.5 and TTP was 2.4 months for the whole group and 2.8 months for patients with leiomyosarcoma. A progression- free rate at 3 months of 38% and 45%, respectively, was observed in these 2 groups. Major side effects were 47% hematological and 26% grade 3/4 nonhematological toxicity. Conclusion: With regard to the observed CBR further use of GD seems to be warranted even in pretreated patients with STS.
    No preview · Article · Jan 2008 · Onkologie
  • Siegfried Seeber · Anja Welt

    No preview · Article · Dec 2007 · Breast Care

  • No preview · Article · Sep 2007 · EJC Supplements
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    ABSTRACT: To improve the survival of patients with aggressive non-Hodgkin's lymphoma, we evaluated a risk-adapted therapeutic approach using high-dose (HD) or conventional-dose (CD) chemotherapy (CT) for poor-risk and good-risk patients, respectively. Twenty patients were treated in each group. In both groups, the first chemotherapy cycle consisted of dexamethasone, vincristine, ifosfamide, and etoposide. Thereafter, the CD or HD patients received 3 or 2 cycles of dexamethasone, vincristine, epirubicin, and cyclophosphamide, respectively, followed by 1 cycle of dexamethasone, carboplatin, and etoposide. In the HD group cyclophosphamide, epirubicin, carboplatin, and etoposide were dose-escalated by a factor of 6, 3, 3, and 3, respectively, as compared to the CD group, and autologous peripheral blood stem cells were administered after each HD-CT cycle. Grade III-IV toxicities were neutropenia and thrombocytopenia (100%), anemia (55%), and stomatitis (30%) in patients with HD-CT, and neutropenia (90%) in patients with CD-CT. One toxic death occurred in a patient with HD-CT. The overall response rate was 100% in HD-CT patients, including 70% complete remissions, and 80% in CD-CT patients, including 60% complete remissions. The 10-year overall survival was 55% for patients with HD-CT and 80% for patients with CD-CT. The risk-adapted treatment approach showed tolerable toxicities and was associated with encouraging results.
    Preview · Article · Sep 2007 · Tumori
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    ABSTRACT: We here describe a novel xenograft model of chronic lymphocytic leukemia (CLL) generated by infusion of human primary CLL cells into immunodeficient nonobese/severe combined immunodeficient (NOD/SCID) mice. Combined i.v. and i.p. injection of peripheral blood mononuclear cells (PBMC) from 39 patients with CLL resulted in highly reproducible splenic (37 of 39) and peritoneal (35 of 39) engraftment, which remained stable over a time span of 4 to 8 weeks. By comparison, recovery of leukemic cells from bone marrow (21 of 39) or peripheral blood (8 of 22) was substantially lower. The engraftment pattern of CLL PBMC 4 weeks posttransplant was correlated with clinical disease activity: infusion of PBMC from donors with Binet stage A, lymphocyte doubling time of >12 months, and normal lactate dehydrogenase (LDH) serum levels led to marked engraftment of T cells whereas comparably few tumor cells could be detected. In contrast, NOD/SCID mice receiving PBMC from donors with advanced stage Binet C, lymphocyte doubling time of <12 months, and elevated LDH serum levels exhibited predominant engraftment of tumor cells and comparably low numbers of T cells. These results suggest that this model reflects the heterogeneity and important clinical characteristics of the disease, and thus may serve as a tool for preclinical drug testing and investigation of the pathophysiology of CLL.
    Full-text · Article · Sep 2007 · Cancer Research
  • S Müller · A Welt · S Seeber · R Kimmig · S Kasimir-Bauer

    No preview · Article · Jun 2007 · Senologie - Zeitschrift für Mammadiagnostik und -therapie
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    ABSTRACT: Although gene transfer with retroviral vectors has shown distinct clinical success in defined settings, efficient genetic manipulation of hematopoietic progenitor cells remains a challenge. To address this issue we have evaluated different transduction protocols and retroviral constructs in the non-obese diabetes (NOD)/severe combined immunodeficiency disease (SCID) xenograft model. An extended transduction protocol requiring 144 h of in vitro manipulation was compared to a more conventional protocol requiring 96 h only. While pretransplantation analysis of cells transduced with a retroviral vector, expressing the enhanced green fluorescent protein (EGFP) marker gene, demonstrated significantly higher overall transduction rates for the extended protocol (33.6 +/- 2.3 vs. 22.1 +/- 3.8%), EGFP expression in CD34+ cells before transplantation (4.0 +/- 0.9 vs. 11.6 +/- 2.5%), engraftment of human cells in NOD/SCID bone marrow 4 weeks after transplantation (4.5 +/- 1.7 vs. 36.5 +/- 9.4%) and EGFP expression in these cells (0 +/- 0 vs. 11.3 +/- 2.8%) were significantly impaired. When the 96 h protocol was used in combination with the spleen focus forming virus (SFFV)/murine embryonic stem cell (MESV) hybrid vector SFbeta11-EGFP, high transduction rates for CD45+ (41.0 +/- 5.3%) and CD34+ (38.5 +/- 3.7%) cells prior to transplantation, as well as efficient human cell engraftment in NOD/SCID mice 4 weeks after transplantation (32.4 +/- 3.5%), was detected. Transgene expression was observed in B-lymphoid (15.9 +/- 2.0%), myeloid (36.5 +/- 3.5%) and CD34+ cells (10.1 +/- 1.5%). Our data show that CD34+ cells maintained in cytokines for multiple days may differentiate and loose their capacity to contribute to the haematological reconstitution of NOD/SCID mice. In addition, the SFFV/MESV hybrid vector SFbeta11-EGFP allows efficient transduction of and gene expression in haematopoietic progenitor cells.
    No preview · Article · Apr 2007 · Journal of Cancer Research and Clinical Oncology

Publication Stats

9k Citations
1,529.24 Total Impact Points

Institutions

  • 2007-2008
    • Kliniken Essen-Mitte Knappschafts-Krankenhaus
      Essen, North Rhine-Westphalia, Germany
  • 1992-2008
    • University of Duisburg-Essen
      • • Faculty of Medicine
      • • Department of Internal and Integrative Medicine
      Essen, North Rhine-Westphalia, Germany
    • Institute of Molecular Biology
      Mayence, Rheinland-Pfalz, Germany
  • 1974-2008
    • University Hospital Essen
      • • Institute of Immunology
      • • Clinic for Internal Medicine (Tumor Research)
      Essen, North Rhine-Westphalia, Germany
  • 2006
    • Kinki University
      Ōsaka, Ōsaka, Japan
  • 2005
    • Institut Jules Bordet
      Bruxelles, Brussels Capital, Belgium
  • 1986-2005
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
  • 2004
    • University Hospital Vall d'Hebron
      Barcino, Catalonia, Spain
  • 2001
    • Roswell Park Cancer Institute
      • Grace Cancer Drug Center
      Buffalo, New York, United States
  • 1999
    • Universitätsklinikum des Saarlandes
      Homburg, Saarland, Germany
  • 1997
    • LungenClinic Grosshansdorf
      Hamburg, Hamburg, Germany
  • 1996
    • Katholisches Klinikum Essen
      Essen, North Rhine-Westphalia, Germany
  • 1995
    • medac GmbH
      Wedel, Schleswig-Holstein, Germany
    • Mitsubishi Pharma Germany GmbH
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1993
    • Friedrich Schiller University Jena
      • Clinic of Internal Medicine II
      Jena, Thuringia, Germany
  • 1992-1993
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1988-1990
    • Städtisches Krankenhaus Kiel
      Kiel, Schleswig-Holstein, Germany
  • 1984
    • Universität Regensburg
      Ratisbon, Bavaria, Germany
  • 1981
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 1971-1979
    • Baylor College of Medicine
      • • Department of Pharmacology
      • • Department of Pediatrics
      Houston, Texas, United States