88 results on '"Gunter Schuch"'
Search Results
2. Data from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Purpose: Angiogenesis and lymphangiogenesis are important steps in tumor growth and dissemination and are of prognostic importance in solid tumors. The determination of microvessel density (MVD) by immunohistology is subject to considerable variability between different laboratories and observers. We compared MVD determination by immunohistology and quantitative real-time PCR and correlated the results with clinical variables.Experimental Design: The expression of endothelial antigens vascular endothelial cadherin (CD144), P1H12 (CD146), tie-2, and VEGFR-2, and lymphatic endothelial markers VEGFR-3, Prox, and LYVE was assessed by quantitative PCR (qPCR) in primary surgical samples. The expression of angiogenetic growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1, and angiopoietin-2 was quantified by PCR and correlated with MVD and clinical variables.Results: The expression of endothelial antigens vascular endothelial cadherin (CD144), P1H12 (CD146), tie-2, and VEGFR-2 correlated with each other in 54 samples of primary esophageal cancer (P < 0.0001 for all comparisons). MVD determined immunohistologically by CD31 staining in a subgroup of 35 patients correlated significantly with the qPCR method. The expression of angiogenetic growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1, and angiopoietin-2 was significantly associated with MVD (P < 0.0001 for all comparisons). Analysis of the expression of lymphendothelial markers VEGFR-3, Prox, and LYVE revealed concordant results, indicating that quantification of lymphendothelial cells is possible by qPCR. The presence of lymph node metastasis on surgical specimens was significantly correlated with MVD (P < 0.003), VEGFR-2 (P < 0.048), and VEGF-C (P < 0.042) expression.Conclusions: These results indicate that quantification of MVD by qPCR in surgical samples of esophageal carcinoma yields similar results with immunohistology. Interestingly, the extent of angiogenesis and lymphangiogenesis was not related in individual tumor samples. Lymph node metastases could be predicted by MVD and VEGF-C expression.
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- 2023
3. Supplementary Data Figure 10 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 10 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
4. Supplementary Data Figure 13 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 13 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
5. Supplementary Data Figure 3 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 3 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
6. Supplementary Data Figure 7 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 7 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
7. Supplementary Data Figure 4 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 4 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
8. Supplementary Data Figure 8 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 8 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
9. Supplementary Data Figure 12 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 12 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
10. Supplementary Data Figure 5 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 5 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
11. Supplementary Data Figure 6 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 6 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
12. Supplementary Data Figure 2 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 2 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
13. Supplementary Data Figure 11 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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Walter Fiedler, Carsten Bokemeyer, Klaus Pantel, Jakob Izbicki, Gunter Schuch, Emre Yekebas, Paulus Schurr, Andreas Erbersdobler, Michael Bubenheim, Uta Reichelt, Henning Clausen, and Sonja Loges
- Abstract
Supplementary Data Figure 11 from Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis
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- 2023
14. FOLFOX versus FOLFOX plus nivolumab and ipilimumab administered in parallel or sequentially versus FLOT plus nivolumab administered in parallel in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: A randomized phase 2 trial of the AIO
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Sylvie Lorenzen, Peter C. Thuss-Patience, Jorge Riera Knorrenschild, Eray Goekkurt, Tobias Nicolaas Dechow, Ralf-Dieter Hofheinz, Kim Barbara Luley, Thomas Jens Ettrich, Daniel Pink, Udo Lindig, Gunnar Folprecht, Gunter Schuch, Michael Bitzer, Claus Bolling, Nils Homann, Sabine Junge, Claudia Pauligk, Timo Gaiser, Thorsten Oliver Goetze, and Salah-Eddin Al-Batran
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Cancer Research ,Oncology - Abstract
4043 Background: FOLFOX plus nivolumab (nivo) has become standard of care for first-line therapy of patients (pts) with esophagogastric adenocarcinomas. The aim of Moonlight trial is to generate signals for whether (a) dual checkpoint inhibition or (b) a triplet chemotherapy is beneficial in the context of nivolumab therapy in this setting. Methods: The AIO-STO-0417 trial (Moonlight) is a four-arm investigator-initiated trial. Pts were randomized to FOLFOX alone (Arm B) or FOLFOX plus nivo 240 mg; q2w and ipilimumab (ipi) 1 mg/kg; q6w administered in parallel (Arm A/A1) or sequentially (Arm A2) or pts were treated in a non-randomized fashion with FLOT plus nivo 240 mg; q2w (Arm C). PD-L1 expression was centrally assessed. Primary endpoint is progression-free survival (PFS). Results: The study completed enrollment with 260 pts. Arms A1/A2 and C started later and will be analyzed in Mar 2022 and presented at the meeting. The abstract, therefore, focuses on Arms A (n = 60) vs B (n = 60). Baseline characteristics were: median age 62.5y, GEJ, 55%, intestinal type, 36%. Forty-one percent had PD-L1 CPS≥1 (available in 79% of pts). Pts received a median of 10 and 9 cycles Arms A and B. Adverse events of grade 3/4 were seen in 86% for Arm A and 60% for Arm B, respectively, and serious adverse events (SAE) in 78% in Arm A and 50% in Arm B. Median follow-up was 9.7 mo. No difference in PFS (5.7 and 6.6 mo), OS (10 vs. 12 mo) or objective response rate (45% and 48%) was seen in Arms A and B, respectively. The results were similar in the PD-L1+ group. Conclusions: FOLFOX plus dual checkpoint inhibition administered in parallel is associated with an increase in toxicity but not activity. This portion of the moonlight trial does not generate a signal for further trials on FOLFOX plus nivo and ipi for adenocarcinoma of stomach and GEJ. Clinical trial information: NCT03647969.
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- 2022
15. Quality of life and outcome of patients with metastatic pancreatic cancer receiving first-line chemotherapy with nab-paclitaxel and gemcitabine: Real-life results from the prospective QOLIXANE trial of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer registry
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Salah-Eddin, Al-Batran, Ralf-Dieter, Hofheinz, Alexander, Reichart, Claudia, Pauligk, Caroline, Schönherr, Rudolf, Schlag, Gabriele, Siegler, Steffen, Dörfel, Michael, Koenigsmann, Mark-Oliver, Zahn, Jörg, Schubert, Ali, Aldaoud, Heinz-Gert, Höffkes, Holger, Schulz, Lars, Hahn, Jens, Uhlig, Wolfgang, Blau, Martina, Stauch, Jörg, Weniger, Martin, Wolf, Lutz, Jacobasch, Stephan, Bildat, Jürgen, Wehmeyer, Nils, Homann, Jörg, Trojan, Oliver, Waidmann, Thomas, Fietz, Hans-Peter, Feustel, Matthias, Groschek, Jan, Wierecky, Karin, Waibel, Stefan, Mahlmann, Uwe, Schwindel, Uwe, Peters, Gunter, Schuch, Daniel, Pink, Henning, Eschenburg, Marcus-A, Wörns, Hans-Detlev, Harich, Ludwig Fischer, von Weikersthal, Klaus-Ulrich, Däßler, Dirk M, Behringer, Helmut, Messmann, Albrecht, Kretzschmar, Eike, Gallmeier, Helmut, Forstbauer, Volker, Kunzmann, Jens, Papke, Petra, Büchner-Steudel, Ursula, Vehling-Kaiser, Christoph, Springfeld, Arndt, Vogel, Thomas J, Ettrich, Marina, Schaaf, Gerrit Zur, Hausen, and Thorsten Oliver, Götze
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Adult ,Aged, 80 and over ,Male ,Paclitaxel ,Adenocarcinoma ,Middle Aged ,Deoxycytidine ,Gemcitabine ,Pancreatic Neoplasms ,Treatment Outcome ,Albumins ,Antineoplastic Combined Chemotherapy Protocols ,Quality of Life ,Humans ,Female ,Registries ,Aged - Abstract
Few data exist on health-related quality of life (QoL) in patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy (Awad L ZE, Mesbah M Boston, MA. Applying survival data methodology to analyze quality of life data, in Mesbah M, Cole BF, Ting Lee M-L (eds): Statistical Methods for Quality of Life Studies: Design, Measurements and Analysis. Kluwer Academic Publishers 2002). The QOLIXANE study is a prospective, noninterventional, multicenter substudy of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer (PARAGON) registry, which evaluated QoL in patients with mPC receiving first-line gemcitabine and nab-paclitaxel chemotherapy in real-life setting. QoL was prospectively measured via EORTC QLQ-C30 questionnaires at baseline and every month thereafter. Therapy and efficacy parameters were prospectively collected. Main objectives were the rate of patients without deterioration of Global Health Status/QoL (GHS/QoL) at 3 and 6 months. Six hundred patients were enrolled in 95 German study sites. Median progression-free survival was 5.9 months (95% confidence interval [CI], 5.2-6.3). Median overall survival (OS) was 8.9 months (95% CI, 7.9-10.2), while median time to deterioration of GHS/QoL was 4.7 months (95% CI, 4.0-5.6). With a baseline GHS/QoL score of 46 (SD, 22.8), baseline QoL of the patients was severely impaired, in most cases due to loss in role functioning and fatigue. In the Kaplan-Meier analysis, 61% and 41% of patients had maintained GHS/QoL after 3 and 6 months, respectively. However, in the QoL response analysis, 35% and 19% of patients had maintained (improved or stable) GHS/QoL after 3 and 6 months, respectively, while 14% and 9% had deteriorated GHS/QoL with the remaining patients being nonevaluable. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a hazard ratio of 0.86 (P .0001). Patients with mPC have poor QoL at baseline that deteriorates within a median of 4.7 months. Treatment with gemcitabine and nab-paclitaxel is associated with maintained QoL in relevant proportions of patients. However, overall, results remain poor, reflecting the aggressive nature of the disease.
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- 2020
16. Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies
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Peter Bannas, Timon Hansen, Nicolaus Kröger, Björn Rissiek, Katharina Petry, Friedrich Koch-Nolte, Mascha Binder, Boris Fehse, Julia Koenigsdorf, Levin Schriewer, Birte Albrecht, William Fumey, Jana Larissa Röckendorf, Francis Ayuk, Kerstin Schütze, Gunter Schuch, Friedrich Haag, Stephan Menzel, Gerhard Adam, Hans O. Pinnschmidt, Kristoffer Riecken, Joanna Schmid, Natalie Baum, and Julia Hambach
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0301 basic medicine ,Male ,medicine.drug_class ,Medicine (miscellaneous) ,Mice, SCID ,Monoclonal antibody ,Antibodies, Monoclonal, Humanized ,Epitope ,03 medical and health sciences ,Epitopes ,Mice ,0302 clinical medicine ,In vivo ,immune system diseases ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Aged ,Isatuximab ,Antibody-dependent cell-mediated cytotoxicity ,Membrane Glycoproteins ,biology ,business.industry ,Daratumumab ,Middle Aged ,Single-Domain Antibodies ,ADP-ribosyl Cyclase 1 ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Immunoglobulin G ,biology.protein ,Cancer research ,Female ,Antibody ,business ,Immunoglobulin Heavy Chains ,Multiple Myeloma ,Ex vivo ,Research Paper - Abstract
Rationale: CD38 is a target for the therapy of multiple myeloma (MM) with monoclonal antibodies such as daratumumab and isatuximab. Since MM patients exhibit a high rate of relapse, the development of new biologics targeting alternative CD38 epitopes is desirable. The discovery of single-domain antibodies (nanobodies) has opened the way for a new generation of antitumor therapeutics. We report the generation of nanobody-based humanized IgG1 heavy chain antibodies (hcAbs) with a high specificity and affinity that recognize three different and non-overlapping epitopes of CD38 and compare their cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. Methods: We generated three humanized hcAbs (WF211-hcAb, MU1067-hcAb, JK36-hcAb) that recognize three different non-overlapping epitopes (E1, E2, E3) of CD38 by fusion of llama-derived nanobodies to the hinge- and Fc-domains of human IgG1. WF211-hcAb shares the binding epitope E1 with daratumumab. We compared the capacity of these CD38-specific hcAbs and daratumumab to induce CDC and ADCC in CD38-expressing tumor cell lines in vitro and in patient MM cells ex vivo as well as effects on xenograft tumor growth and survival in vivo. Results: CD38-specific heavy chain antibodies (WF211-hcAb, MU1067-hcAb, JK36-hcAb) potently induced antibody-dependent cellular cytotoxicity (ADCC) in CD38-expressing tumor cell lines and in primary patient MM cells, but only little if any complement-dependent cytotoxicity (CDC). In vivo, CD38-specific heavy chain antibodies significantly reduced the growth of systemic lymphomas and prolonged survival of tumor bearing SCID mice. Conclusions: CD38-specific nanobody-based humanized IgG1 heavy chain antibodies mediate cytotoxicity against CD38-expressing hematological cancer cells in vitro, ex vivo and in vivo. These promising results of our study indicate that CD38-specific hcAbs warrant further clinical development as therapeutics for multiple myeloma and other hematological malignancies.
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- 2019
17. The metabolite 3-hydroxiglutaric acid effectively reduces glioblastoma growth in vivo by affecting the structural integrity of tumor vasculature
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Süleyman Ergün, Walter Fiedler, Jessica Hauschild, Jasmin Wellbrock, Carsten Bokemeyer, Marianne Klokow, Gunter Schuch, Melanie Braig, and Leticia Oliveira-Ferrer
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Cancer Research ,DNA, Complementary ,Endothelium ,Angiogenesis ,Metabolite ,Mice, Nude ,Biology ,Glutarates ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Glioma ,medicine ,Animals ,Humans ,Mitosis ,Oligonucleotide Array Sequence Analysis ,Neovascularization, Pathologic ,medicine.disease ,Immunohistochemistry ,In vitro ,medicine.anatomical_structure ,Oncology ,Biochemistry ,chemistry ,Cancer research ,Blood Vessels ,VE-cadherin ,Glioblastoma ,Cell Division - Abstract
3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
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- 2012
18. Elevated pretreatment serum concentration of YKL-40-An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer
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Lutz Edler, Iris Burkholder, I. Thoem, B. Andritzky, Carsten Bokemeyer, Julia S. Johansen, Udo Schumacher, Gunter Schuch, and E. Laack
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Adult ,Male ,Oncology ,musculoskeletal diseases ,Cancer Research ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,macromolecular substances ,Vinorelbine ,Gastroenterology ,Disease-Free Survival ,Metastasis ,Adipokines ,Carcinoma, Non-Small-Cell Lung ,Lectins ,Internal medicine ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,Malignant pleural effusion ,Chitinase-3-Like Protein 1 ,Neoplasm Metastasis ,Lung cancer ,Aged ,Glycoproteins ,Cisplatin ,Chemotherapy ,business.industry ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Chemotherapy regimen ,Gemcitabine ,Tumor progression ,Cancer cell ,Female ,business ,medicine.drug - Abstract
BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 has not been established in nonsmall cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV disease. Ninety-eight patients received combined gemcitabine and vinorelbine, and 91 received combined gemcitabine, vinorelbine, and cisplatin as first-line chemotherapy. The median overall survival was 37 weeks. RESULTS: Patients had a median serum YKL-40 level of 209 ng/mL (range, 19-2153 ng/mL). No correlation was observed between overall survival and the type of chemotherapy regimen used, tumor stage, sex, or histologic types. Patients with high serum YKL-40 levels (greater than the median level for all patients [209 ng/mL]) had a significantly shorter survival than patients with serum YKL-40 levels below the median (median survival, 32 weeks vs 41 weeks; P = .007). In multivariate analysis, the serum YKL-40 level, the presence of bone lesions, and the serum lactate dehydrogenase level were independent, statistically significant prognostic factors. CONCLUSIONS: The pretreatment serum YKL-40 level was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010. © 2010 American Cancer Society.
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- 2010
19. Lama-Antikörper helfen bei der Erforschung neuer Krebs-Therapie
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Gunter Schuch and Peter Bannas
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Gynecology ,medicine.medical_specialty ,business.industry ,Surgical oncology ,Medicine ,business - Published
- 2018
20. TAE226-mediated inhibition of focal adhesion kinase interferes with tumor angiogenesis and vasculogenesis
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Sebastian Decker, Andrea Kristina Horst, Alexander Schultze, Walter Fiedler, Sonja Loges, Gunter Schuch, Carsten Bokemeyer, Gabi Vohwinkel, and Jasmin Otten
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Angiogenesis ,Morpholines ,Organogenesis ,Mice, SCID ,Biology ,Neovascularization ,Focal adhesion ,Mice ,Vasculogenesis ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Everolimus ,Progenitor cell ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sirolimus ,Pharmacology ,Tube formation ,Neovascularization, Pathologic ,Endothelial Cells ,Cell Differentiation ,Cell biology ,Endothelial stem cell ,Oncology ,Focal Adhesion Protein-Tyrosine Kinases ,Blood Vessels ,medicine.symptom - Abstract
Neoangiogenesis plays an important role in tumor growth and metastasis. Evaluation of new anti-angiogenic targets may broaden the armament for future therapeutic concepts. Focal adhesion kinase (FAK), expressed in endothelial and tumor cells, is essential for adhesion and mobility of adherent cells. In the current study we analyzed the anti-angiogenic properties of the FAK inhibitor TAE226 on the proliferation of blood outgrowth endothelial cell (OEC) and differentiation of endothelial progenitor cells (EPC), derived from peripheral blood CD133(+) cells, tube formation and on neovascularization in a HT29 xenotransplant model. The effects of TAE226 were compared to those of the rapamycin analogue RAD001. The combination of both drugs was also studied. We showed that HT29 tumor cells and OEC were most sensitive to the action of TAE226 compared to EPC in vitro. In contrast, RAD001 affected the proliferation of both types of endothelial cells stronger than that of HT29 cells. Furthermore we could show that TAE226 inhibited tube formation in a dose dependent manner. In a HT29 subcutaneous tumor model TAE226 and RAD001 diminished MVD at commonly employed doses to a similar degree. Combination of both compounds did not show synergy in vitro or in vivo. Since TAE226 has been shown to inhibit the PI3 kinase, Akt kinase, mTor pathway, addition of RAD001 may not increase this effect. In conclusion, we have shown that treatment with TAE leads to a reduction of neoangiogenesis in vitro and in a mouse model. The effects are mediated by inhibition of angiogenesis and vasculogenic OEC and EPC.
- Published
- 2009
21. Pharmacogenetic Analyses of a Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma With Fluorouracil and Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie
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Jan Stoehlmacher, Eray Goekkurt, Elke Jaeger, Salah-Eddin Al-Batran, Michael Kramer, Ulrike Mogck, Jörg T. Hartmann, Carsten Bokemeyer, Gerhard Ehninger, and Gunter Schuch
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Organoplatinum Compounds ,medicine.drug_class ,medicine.medical_treatment ,Adenocarcinoma ,Gastroenterology ,Antimetabolite ,Thymidylate synthase ,Stomach Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Aged ,Cisplatin ,Clinical Trials as Topic ,Chemotherapy ,biology ,business.industry ,Cancer ,Combination chemotherapy ,Middle Aged ,medicine.disease ,Oxaliplatin ,Surgery ,Clinical Trials, Phase III as Topic ,Oncology ,Pharmacogenetics ,Fluorouracil ,biology.protein ,Female ,business ,medicine.drug - Abstract
Purpose To evaluate the association of germ-line polymorphisms of genes that may impact treatment outcome of platinum and fluorouracil combination chemotherapy in advanced gastric cancer (AGC). Patients and Methods Blood samples of 156 patients enrolled onto a phase III study comparing fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin were collected. Polymorphisms within genes of TS, MTHFR, MTR, OPRT, XPD, ERCC1, XRCC1, XPA, GSTP1, GSTT1, and GSTM1 were genotyped using polymerase chain reaction–based techniques. Results Median overall survival (OS) was 11.8 months (95% CI, 9.75 to 13.79 months) and median progression-free survival (PFS) was 5.8 months (95% CI, 4.99 to 6.61 months). The TS-3R/+6 haplotype (P = .004), the GSTT1 deletion polymorphism (P = .015), and genotypes of OPRT-Gly213Ala (P = .003) and XRCC1-Arg399Gln (P = .023) could be identified as independent predictors of OS. For PFS analyses, the TS-3R/+6 haplotye (P = .003) and MTR-A2756G (P = .01) were identified as independent positive predictors. The association between the GSTT1 deletion polymorphism and PFS showed only borderline significance (P = .053). Treatment related hematotoxicity in terms of grade 3/4 leukopenia was lowest among TS-3R/+6 haplotype carriers (P = .037). Grade 3/4 neutropenia was directly associated with the MTR-2756G/G genotype (P = .011), GSTP1-105Ile/Ile genotype (P = .02), and with the ERCC1-118T/8092C-haplotype (P = .042). In addition, significant associations between GSTP1-105Ile/Ile genotype and neurotoxicity and between the XPD-Asn312/751Gln haplotype and nephrotoxicity could be identified (P = .028 and P = .005, respectively). Conclusion These findings underline the hypothesis that germ-line polymorphisms may play an important role in individualizing chemotherapy in AGC and deserve further prospective evaluation in AGC patients.
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- 2009
22. Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer
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Heinz Ludwig, Anja H. Loos, A. Makhson, Carsten Bokemeyer, Gunter Schuch, Christopher Stroh, Serban Donea, A. Zubel, Joerg T. Hartmann, Igor Bondarenko, Jorge Aparicio, Filippo de Braud, and Piotr Koralewski
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Organoplatinum Compounds ,Colorectal cancer ,Leucovorin ,Cetuximab ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,medicine.disease_cause ,Lower risk ,Gastroenterology ,Proto-Oncogene Proteins p21(ras) ,Proto-Oncogene Proteins ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Panitumumab ,Neoplasm Metastasis ,Aged ,Aged, 80 and over ,business.industry ,Antibodies, Monoclonal ,Cancer ,Middle Aged ,medicine.disease ,digestive system diseases ,Surgery ,Oxaliplatin ,Oncology ,Fluorouracil ,Mutation ,ras Proteins ,Patient Compliance ,Female ,KRAS ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Purpose This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated. Patients and Methods Patients received cetuximab (400 mg/m2 initial dose followed by 250 mg/m2/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, plus leucovorin 200 mg/m2 and fluorouracil as a 400 mg/m2 bolus followed by a 600 mg/m2 infusion during 22 hours on days 1 and 2; n = 169) or FOLFOX-4 alone (n = 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n = 233). Results The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio = 1.52; P = .064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR = 61% v 37%; odds ratio = 2.54; P = .011) and a lower risk of disease progression (hazard ratio = 0.57; P = .0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. Conclusion KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.
- Published
- 2009
23. Inhalt Band 32, 2009
- Author
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Michael Pfreundschuh, Susanne Albrecht, Gunter Schuch, Thomas Hany, Wolfgang Schmitt, Thorsten Fischer, Martin Pölcher, Qingyuan Zhang, Michael Zünd, Niels Murawski, George H. Sakorafas, Karl T.M. Schneider, Sabine Balmer-Majno, Wenjie Ma, Jingxuan Wang, Ina Thöm, Nikolaus de Gregorio, Spiros Christodoulou, Thomas Kubin, Christos Lappas, Rolf Kreienberg, Isabell Witzel, Shu Zhao, Egbert Nitzsche, Zhengyan Yu, Christine Wulff, Carsten Bokemeyer, Peter Brauchli, Antonia Dimitrakopoulou-Strauss, Clemens Caspar, Dieter Köberle, Gisela Walgenbach-Bruenagel, Michael Braun, Roger von Moos, Corinne Cescato-Wenger, Thorleif Etgen, Bernd Klaeser, Ruediger Hein, Nikolaos Antoniou, Eva Wardelmann, Christian Rudlowski, Shi Jin, Reinhard Büttner, Eckart Laack, Thomas Ruhstaller, Hanne Stensheim, Athanasios N. Chalazonitis, Manuel Debald, Nina Gottschalk, Ludwig G. Strauss, Flora Zagouri, Claudia Rogers, Meletios-Athanasios Dimopoulos, Aristotle Bamias, Jan C. Schuller, Maria Papaefthimiou, Birte Andritzky, Tobias Höller, Volker R. Jacobs, Bernhard C. Pestalozzi, Walther Kuhn, Stephanie Pildner von Steinburg, Georg Weidenhöfer, Axel Sauerwald, Lucas Widmer, Michael Safioleas, Matthias Wolfgarten, Yongzhi Zhuang, and Dieter K. Hossfeld
- Subjects
Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2009
24. Contents Vol. 32, 2009
- Author
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Antonia Dimitrakopoulou-Strauss, Eckart Laack, Christine Wulff, Karl Schneider, Bernhard C. Pestalozzi, Eva Wardelmann, Hanne Stensheim, Maria Papaefthimiou, Birte Andritzky, Shu Zhao, Nikolaus de Gregorio, Michael Braun, Roger von Moos, Clemens B. Caspar, Athanasios N. Chalazonitis, Tobias Höller, Volker R. Jacobs, Niels Murawski, Spiros Christodoulou, Peter Brauchli, Yongzhi Zhuang, Susanne Albrecht, Nikolaos Antoniou, Jingxuan Wang, Wolfgang Schmitt, Zhengyan Yu, George H. Sakorafas, Nina Gottschalk, Flora Zagouri, Claudia Rogers, Michael Zünd, Axel Sauerwald, Carsten Bokemeyer, Aristotle Bamias, Thomas Kubin, Jan C. Schuller, Ruediger Hein, Corinne Cescato-Wenger, Dieter Köberle, Georg Weidenhöfer, Wenjie Ma, Gisela Walgenbach-Bruenagel, Dieter K. Hossfeld, Meletios-Athanasios Dimopoulos, Bernd Klaeser, Ludwig G. Strauss, Martin Pölcher, Isabell Witzel, Manuel Debald, Rolf Kreienberg, Ina Thöm, Sabine Balmer-Majno, Thorsten Fischer, Egbert Nitzsche, Christos Lappas, Shi Jin, Reinhard Büttner, Thorleif Etgen, Matthias Wolfgarten, Thomas F. Hany, Lucas Widmer, Michael Safioleas, Qingyuan Zhang, Stephanie Pildner von Steinburg, Gunter Schuch, Michael Pfreundschuh, Christian Rudlowski, Thomas Ruhstaller, and Walther Kuhn
- Subjects
Cancer Research ,Oncology ,Hematology ,General Medicine - Published
- 2009
25. Single-Center Management of 136 Patients with Cancer of Unknown Primary Site (CUP Syndrome) Over a Period of 10 Years
- Author
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Gunter Schuch, Dieter K. Hossfeld, Birte Andritzky, Ina Thöm, Claudia Rogers, Eckart Laack, Carsten Bokemeyer, and Isabell Witzel
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Pediatrics ,Single Center ,Young Adult ,Germany ,medicine ,Retrospective analysis ,Humans ,Longitudinal Studies ,Aged ,Aged, 80 and over ,business.industry ,Incidence ,Cancer ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Survival Rate ,Oncology ,Cancer of unknown primary ,Neoplasms, Unknown Primary ,Female ,business - Abstract
Cancer of unknown primary site (CUP syndrome) is a particular challenge in oncology which occurs in about 5-10% of cancer patients. Here, we investigated clinicopathological and prognostic factors in patients with CUP syndrome in a retrospective analysis.136 patients with CUP syndrome who were treated in our Department of Oncology and Hematology were analyzed over a period of 10 years. Clinical and histopathological characteristics, response to chemotherapy, survival and prognostic factors were investigated in a retrospective analysis.83 of the patients (61%) received first-line chemotherapy, which induced an overall response rate of 19%. Altogether 37 different chemotherapy regimens were used. Median overall survival of all patients was 7.9 months. In multivariate Cox regression analysis, gender, Karnofsky performance status, treatment modality and extent of disease were identified as independent prognostic factors.Our analysis showed a poor prognosis for patients with CUP syndrome. The response rate to chemotherapy was low with no significant benefit for any of the investigated cytotoxic agents. Newer diagnostic and therapeutical approaches might contribute to an improvement of prognosis, and their value is currently investigated in prospective studies.
- Published
- 2009
26. Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie
- Author
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Salah-Eddin, Al-Batran, Joerg Thomas, Hartmann, Stephan, Probst, Harald, Schmalenberg, Stephan, Hollerbach, Ralf, Hofheinz, Volker, Rethwisch, Gernot, Seipelt, Nils, Homann, Gerhard, Wilhelm, Gunter, Schuch, Jan, Stoehlmacher, Hans Günter, Derigs, Susanna, Hegewisch-Becker, Johannes, Grossmann, Claudia, Pauligk, Akin, Atmaca, Carsten, Bokemeyer, Alexander, Knuth, Elke, Jäger, Wolfgang, Dippold, and University of Zurich
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,Organoplatinum Compounds ,Nausea ,medicine.drug_class ,medicine.medical_treatment ,Leucovorin ,610 Medicine & health ,Kaplan-Meier Estimate ,Adenocarcinoma ,Gastroenterology ,Antimetabolite ,Thymidylate synthase ,Drug Administration Schedule ,Stomach Neoplasms ,Germany ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,1306 Cancer Research ,Aged ,Aged, 80 and over ,Cisplatin ,Chemotherapy ,biology ,business.industry ,Middle Aged ,Surgery ,Oxaliplatin ,Treatment Outcome ,Oncology ,Fluorouracil ,10032 Clinic for Oncology and Hematology ,Vomiting ,biology.protein ,2730 Oncology ,Female ,Esophagogastric Junction ,medicine.symptom ,business ,medicine.drug - Abstract
Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. Conclusion FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.
- Published
- 2008
27. Hydraulische Untersuchungen zur Steigerung der Kapazität von Böden in Destillationskolonnen
- Author
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Gunter Schuch, Michael Jodecke, and Thorsten Friese
- Subjects
General Chemical Engineering ,General Chemistry ,Industrial and Manufacturing Engineering - Abstract
Experimentelle Untersuchungen zur Hydraulik von Hochleistungsbodenelementen wurden in einer mit Luft und Wasser betriebenen Versuchskolonne mit einem Durchmesser von 0,5 m durchgefuhrt. Die Untersuchungen beinhalteten hydraulische Messungen von neuen Ventiltypen, von abgeschnittenen Schachten und von Abscheideelementen auf den Boden. Auserdem wurde der Einfluss der Tragerorientierung auf die Kapazitatsgrenzen eines Bodens analysiert sowie die Belastungsgrenzen einiger spezieller Typen von Hochleistungsboden bestimmt. Die experimentellen Ergebnisse zu den abgeschnittenen Schachten belegen einen grosen Arbeitsbereich dieser Bauarten von Ablaufschachten. Untersuchungen zum Einsatz von Abscheideelementen auf Boden ergaben, dass die obere Belastungsgrenze der Boden signifikant erhoht werden kann. Dies ist aber nur bei geringen spezifischen Flussigkeitslasten moglich. Das optimale Design eines Abscheideelements und der optimale Luckengrad sind Gegenstand weiterer Untersuchungen. Die Exploration zum Einfluss der Tragerorientierung eines Kolonnenbodens auf die Kapazitat des Bodens fuhrte zu dem Ergebnis, das kein Einfluss auf die obere Belastungsgrenze zu beobachten ist, wenn die Trager in Richtung der Flussigkeitsstromung gerichtet sind. Bei quer zur Flussigkeitsstromung angeordneten Tragern ist ein Einfluss auf die Belastungsgrenze der Boden zu erkennen.
- Published
- 2008
28. Combined Antiangiogenic Therapy is Superior to Single Inhibitors in a Model of Renal Cell Carcinoma
- Author
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Richard E. Hautmann, Shay Soker, Gunter Schuch, Katharina Eggert, Carsten Bokemeyer, and Georg Bartsch
- Subjects
medicine.medical_specialty ,Urology ,Angiogenesis Inhibitors ,Mice ,chemistry.chemical_compound ,In vivo ,Internal medicine ,Tumor Cells, Cultured ,Carcinoma ,medicine ,Animals ,Cytotoxic T cell ,Carcinoma, Renal Cell ,Kidney ,business.industry ,medicine.disease ,Kidney Neoplasms ,Neuropilin-1 ,Endostatins ,Vascular endothelial growth factor ,Endothelial stem cell ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,chemistry ,cardiovascular system ,Cancer research ,Drug Therapy, Combination ,Endostatin ,Thrombospondins ,business ,Fetal bovine serum - Abstract
Similar to cytotoxic drugs, a combination of antiangiogenic factors may lead to an improved treatment response and minimize resistance by targeting different pathways. Therefore, we investigated the effects of a combination of endogenous inhibitors using endostatin, soluble neuropilin-1 and thrombospondin-2 in a renal cell carcinoma model.Microencapsulated porcine aortic endothelial cells producing endostatin, soluble neuropilin-1 or thrombospondin-2 were tested in vitro and in a murine renal cell carcinoma alone or as a combination of the all 3 factors. Renca cells were applied subcutaneously for local therapy or injected intravenously in a metastatic model.Factors released from microbeads inhibited endothelial cell function but did not affect tumor cell proliferation in vitro. In vivo tumor growth was inhibited similarly by each angiogenic inhibitor alone (0.17, 0.18 and 0.18 gm in endostatin, soluble neuropilin-1 and thrombospondin-2 treated mice vs 1.3 gm in controls). The combination of all 3 inhibitors further decreased tumor weight (0.03 gm). In the metastatic model treatment with angiogenic inhibitors induced a significant reduction in the size and number of lung metastases with additive effects when factors were used in combination.The combination of angiogenic inhibitors was superior to single factors, suggesting additive activity. These data support the strategy of combining angiogenic inhibitors to accomplish a complete angiogenic blockade.
- Published
- 2008
29. Acute psychological stress alerts the adaptive immune response: Stress-induced mobilization of effector T cells
- Author
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Julia Schulze, Katrin Bartels, Monika C. Brunner-Weinzierl, Christiane Faltz, Benjamin Schnee, Gunter Schuch, Djordje Atanackovic, Cora Weber, Carsten Bokemeyer, Philippe Schafhausen, and Hans Christian Deter
- Subjects
Adult ,Antigens, Differentiation, T-Lymphocyte ,Male ,Receptors, CCR7 ,Receptors, CCR5 ,T-Lymphocytes ,T cell ,Immunology ,chemical and pharmacologic phenomena ,Interleukin 21 ,Antigens, Neoplasm ,Cell Movement ,immune system diseases ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Membrane Glycoproteins ,CD40 ,biology ,virus diseases ,CD28 ,hemic and immune systems ,Acquired immune system ,Natural killer T cell ,CD56 Antigen ,Killer Cells, Natural ,medicine.anatomical_structure ,Neurology ,Acute Disease ,biology.protein ,Leukocyte Common Antigens ,Receptors, Chemokine ,Neurology (clinical) ,Immunologic Memory ,Stress, Psychological - Abstract
Influences of psychological stress on the acquired immune system have not consequently been investigated. We found acute psychological stress to cause an increase in CD56+ and CCR5+ effector T cells in the peripheral blood of healthy human subjects (N=22), while skin-homing CLA+ T cells decreased. At the same time, we observed a stress-induced decrease in CD45RA+/CCR7+ naive and CD45RA-/CCR7+ central memory T cells, while CD45RA-/CCR7- effector memory and CD45RA+/CCR7- terminally differentiated T cells increased. This T cell redistribution translated into an increase in T cells expressing perforin/granzyme B and in Epstein-Barr virus-specific, cytomegalovirus-specific and influenza virus-specific CD8+ T cells. Thus, acute stress seems to promote the retention of less mature T cells within lymphoid tissue or skin while effector-type T cells are mobilized into the blood in order to be able to rapidly migrate into peripheral tissues.
- Published
- 2006
30. Significance of vascular stabilization for tumor growth and metastasis
- Author
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Leticia Oliveira-Ferrer, Nerbil Kilic, Derya Tilki, Süleyman Ergün, and Gunter Schuch
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Pathology ,medicine.medical_specialty ,Angiogenesis ,business.industry ,Tumor therapy ,Angiogenesis Inhibitors ,Vascular permeability ,Tumor vascularization ,medicine.disease ,Mini review ,Metastasis ,Oncology ,Neoplasms ,cardiovascular system ,Animals ,Humans ,Medicine ,Tumor growth ,Neoplasm Metastasis ,Endostatin ,business - Abstract
This mini review highlights the role of vascular stabilization which is apparently mediated by factors belonging to both the pro- and anti-angiogenic group. Knowingly angiopoietin-1 has pro-angiogenic properties while endostatin acts anti-angiogenic. But both factors suppress tumor growth in experimental tumor models. The crossing points of mechanisms of their action are the parameters vascular stabilization and vascular permeability, which are of high importance not only for tumor vascularization, but also for tissue vascularization in general. Both angiopoietin-1 and endostatin reduce the vascular permeability, but promote vascular stabilization. Vascular stabilization is significantly increased under experimental treatment of tumors with angiogenesis inhibitors such as endostatin. It inhibits tumor growth and probably tumor metastasis. The understanding of temporal and spatial sequences of vascular stabilization is an important challenge for scientists working on tumor vascularization and anti-angiogenic tumor therapy.
- Published
- 2006
31. CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer
- Author
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Martin G. Friedrich, Derya Tilki, Christian G. Stief, Hartwig Huland, Süleyman Ergün, Leticia Oliveira-Ferrer, Ergin Kilic, R Galalae, Gunter Schuch, P Hammerer, K Miethe, Ster Irmak, H Atakaya, and Jessica Hauschild
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Cancer Research ,Angiogenic Switch ,Angiogenesis ,Down-Regulation ,Biology ,Prostate cancer ,chemistry.chemical_compound ,Downregulation and upregulation ,Antigens, CD ,Cell Movement ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Gene Silencing ,Cell adhesion ,Molecular Biology ,Neovascularization, Pathologic ,Cell adhesion molecule ,Prostatic Neoplasms ,medicine.disease ,Immunohistochemistry ,Vascular endothelial growth factor ,chemistry ,Immunology ,Cancer research ,Endothelium, Vascular ,Endostatin ,Cell Adhesion Molecules - Abstract
We demonstrate here that epithelial carcinoembryonic antigen (CEA)-related cell adhesion molecule-1 (CEACAM1) downregulation in prostate intraepithelial neoplasia (PIN) is inversely correlated with its upregulation in adjacent blood vessels. CEACAM1 silencing in prostate cancer cell line DU-145 via small interfering ribonucleic acid (siRNA) increased but its overexpression suppressed the expression of angiogenic/lymphangiogenic factors such as vascular endothelial growth factor (VEGF)-A, -C and -D, and angiogenic inhibitor collagen 18/endostatin. Furthermore, CEACAM1 overexpression in DU-145 cells increased but CEACAM1 silencing reduced angiopoietin-1 expression. Inverse relation was found for angiopoietin-2. Supernatant of CEACAM1-overexpressing DU-145 suppressed but that of CEACAM1-silenced increased the VEGF-induced endothelial tubes. Electron microscopically the majority of PIN-associated blood vessels was structurally destabilized exhibiting endothelial fenestration, trans- and inter-endothelial gaps. In some PIN areas, invasion of single tumor cells into the destabilized blood vessels was observed. These data show that disappearance of epithelial CEACAM1 in PIN is accompanied by its upregulation in adjacent vasculature which apparently correlates with vascular destabilization and increased vascularization of prostate cancer. Strategies to either conserve the epithelial CEACAM1 or to target endothelial CEACAM1 might be useful for an anti-angiogenic therapy of prostate cancer.
- Published
- 2006
32. Downregulation of VEGF-A, STAT5 and AKT in acute myeloid leukemia blasts of patients treated with SU5416
- Author
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Anja Metzner, Heike Tinnefeld, Elena Draab, Melanie Bruweleit, Manfred Jücker, Martin Butzal, Gunter Schuch, Anne Marie O'-Farrel, Uta Fischer, Carsten Bokemeyer, Walter Fiedler, Sonja Loges, and Dieter K. Hossfeld
- Subjects
Vascular Endothelial Growth Factor A ,Cancer Research ,Indoles ,Angiogenesis ,Angiogenesis Inhibitors ,Cell Separation ,Receptor tyrosine kinase ,Downregulation and upregulation ,Cell Line, Tumor ,hemic and lymphatic diseases ,STAT5 Transcription Factor ,Humans ,Medicine ,Pyrroles ,Autocrine signalling ,Protein Kinase Inhibitors ,Protein kinase B ,STAT5 ,DNA Primers ,biology ,Kinase ,business.industry ,Myeloid leukemia ,Hematology ,Flow Cytometry ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,Oncology ,Disease Progression ,biology.protein ,Cancer research ,business ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
In acute myeloid leukemia (AML), autocrine or paracrine activation of receptor tyrosine kinases such as c-kit and FLT3 contributes to proliferation and apoptosis resistance of leukemic blasts. This provided the rationale for a multicenter clinical trial in patients with refractory AML with SU5416, a small molecule kinase inhibitor which blocks phosphorylation of c-kit, FLT3, VEGFR-1, VEGFR-2 (KDR) and VEGFR-3. The levels of VEGF mRNA expression were investigated in peripheral blood leukemic blasts taken from AML patients before and during treatment with SU5416. Rapid down regulation of VEGF was observed in AML blasts from 72% (13 of 18) of patients analysed. Patients initially expressing high VEGF-levels had a stronger downregulation and a higher clinical response rate (mean 865-fold, n = 10, P = 0,01) than patients initially expressing low VEGF-levels (mean four-fold, n = 8). These results suggest that abnormal high VEGF expression is downregulated by SU5416 treatment, and furthermore that decreases in VEGF mRNA levels may provide an early marker of therapeutic response with anti-angiogenic therapy. Additionally, protein expression of STAT5 and AKT was assessed by western blotting in these patient samples, as well as in the leukemia cell line, M-07e, treated in vitro with SU5416 as a model system. In the AML patient samples, parallel downregulation of both STAT5 and AKT was observed in several cases (STAT5 in four of 15; AKT in three of six examined patients). These effects were confirmed with the cell line M-07e after incubation with SU5416 in vitro using concentrations that are achievable in patients. In summary, our data show suppression of the expression of VEGF and key signal transduction intermediates in AML blasts during treatment with SU5416.
- Published
- 2006
33. Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)
- Author
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Walter Fiedler, Ina Boeters, Dieter K. Hossfeld, Lutz Edler, Gunter Schuch, Birte Andritzky, Eckart Laack, Gaby Vohwinkel, Iris Burkholder, Michael Görn, and Antje Scheffler
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,VEGF receptors ,non-small cell lung cancer (NSCLC) ,Enzyme-Linked Immunosorbent Assay ,Matrix metalloproteinase ,Metastasis ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Lung cancer ,Aged ,biology ,business.industry ,Proportional hazards model ,Respiratory disease ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Vascular endothelial growth factor ,Matrix Metalloproteinase 9 ,chemistry ,biology.protein ,Female ,business ,Follow-Up Studies - Abstract
Summary Purpose: In the present study, we investigated the prognostic value of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 serum levels in patients with metastatic non-small cell lung cancer (NSCLC). Patients and methods: From September 1999 to June 2001, pretreatment serum levels of VEGF and MMP-9 were analysed in 194 patients of a randomized phase III trial with enzyme-linked immunoassays. Results: Patients with a VEGF serum level higher than the median serum level (10,995 pg/ml) had a significantly shorter overall survival than those with a lower serum level ( P = 0.04). The MMP-9 serum level did not correlate with survival. In a multivariate Cox regression analysis, only the pretreatment serum level of VEGF, the Karnofsky performance status, and the presence of bone metastases were identified as independent prognostic factors. Conclusions: The pretreatment VEGF serum level was identified as independent prognostic factor in this study and may help to assess individual risk and treatment profiles in patients with metastatic NSCLC.
- Published
- 2005
34. Antiangiogenic treatment with endostatin inhibits progression of AML in vivo
- Author
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Gunter Schuch, Leticia Oliveira-Ferrer, Dieter K. Hossfeld, Sonja Loges, Walter Fiedler, Süleyman Ergün, Carsten Bokemeyer, and E. Laack
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Drug Compounding ,Genetic enhancement ,Angiogenesis Inhibitors ,Mice, SCID ,Mice ,Cell Line, Tumor ,Internal medicine ,Animals ,Medicine ,Progenitor cell ,Cell Proliferation ,Hematology ,Neovascularization, Pathologic ,business.industry ,Myeloid leukemia ,Bone Marrow Examination ,Neoplasms, Experimental ,medicine.disease ,Endostatins ,Platelet Endothelial Cell Adhesion Molecule-1 ,Survival Rate ,Leukemia ,medicine.anatomical_structure ,Oncology ,Leukemia, Myeloid ,Acute Disease ,Cancer research ,Bone marrow ,Endostatin ,business - Abstract
Increased vessel density in the bone marrow of patients with acute myeloid leukemia as well as elevated expression of proangiogenic factors by leukemic cells implies a central role of angiogenesis in hematological malignancies. Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis that has shown therapeutic activity in solid tumors in various preclinical models. Using microencapsulation technology, we studied the therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 murine leukemic cells in vitro, ES producing microbeads significantly inhibited growth of subcutaneous chloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with ES microbeads prolonged median survival significantly. Histological analysis revealed a decreased microvessel density and a reduced number of CD31-positive single cells, putatively endothelial progenitor cells, in the bone marrow of treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis in the bone marrow and on progression of leukemia in vivo. These experiments suggest a possible therapeutic role of antiangiogenic gene therapy with ES in AML.
- Published
- 2005
35. Docetaxel and Cisplatin as First-Line Treatment for Patients with Metastatic Esophageal Cancer: A Pilot Study
- Author
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Dieter K. Hossfeld, Rainer Lipp, Lutz Edler, Johann Popp, Gunter Schuch, Birte Andritzky, Eckart Laack, Hartmut Horst, Iris Burkholder, Heinz Dürk, Michael Görn, and Ina Boeters
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,medicine.medical_treatment ,Pilot Projects ,Docetaxel ,Germany ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Prevalence ,medicine ,Humans ,Aged ,Cisplatin ,Chemotherapy ,Taxane ,business.industry ,Cancer ,Hematology ,Middle Aged ,Esophageal cancer ,medicine.disease ,Regimen ,Treatment Outcome ,Lymphatic Metastasis ,Adenocarcinoma ,Female ,Taxoids ,business ,medicine.drug - Abstract
Background: We investigated the combination of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic esophageal cancer. Patients and Methods: 16 chemotherapy-naive patients with distant metastases were included in the study (15 male, 1 female; median age: 58.5 years (range 37-69); median ECOG performance status: 1). 11 patients (69%) had esophageal cancer, and 5 patients (31%) had cancer of the gastroesophageal junction. Patients received docetaxel 75 mg/m2 and cisplatin 80 mg/m2 on day 1 every 3 weeks. A total of 55 chemotherapy cycles was administered. The median number of cycles was 3 (range 1-6). Results: The overall response rate was 31.3%. 4 out of 10 patients (40%) with squamous cell carcinoma and 1 out of 5 patients (20%) with adenocarcinoma responded to chemotherapy. The median overall survival was 29.6 weeks, and the median progression-free survival was 18.6 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 42.9%, alopecia grade II/III: 64.3%, nausea/vomiting grade II/III: 57.2%, neurotoxicity grade II: 14.3%). Conclusion: The combination of docetaxel and cisplatin is an active regimen with moderate toxicity in the treatment of patients with metastatic esophageal cancer. This pilot study demonstrates the feasibility of a combination treatment containing a taxane and cisplatin in metastatic esophageal cancer.
- Published
- 2005
36. In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo
- Author
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Gunter Schuch, Masashi Nomi, Marcelle Machluf, Georg Bartsch, Anthony Atala, Shay Soker, and Henri Richard
- Subjects
Vascular Endothelial Growth Factor A ,Swine ,Endothelial Growth Factors ,Biochemistry ,Neovascularization ,Mice ,chemistry.chemical_compound ,Neuropilin 1 ,Tumor Cells, Cultured ,RNA, Neoplasm ,Phosphorylation ,Lymphokines ,Neovascularization, Pathologic ,Gene Expression Regulation, Leukemic ,Reverse Transcriptase Polymerase Chain Reaction ,Vascular Endothelial Growth Factors ,Myeloid leukemia ,U937 Cells ,Hematology ,Neoplasm Proteins ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Leukemia ,medicine.anatomical_structure ,Leukemia, Myeloid ,Acute Disease ,Disease Progression ,Intercellular Signaling Peptides and Proteins ,medicine.symptom ,Recombinant Fusion Proteins ,Immunology ,Transfection ,In vivo ,medicine ,Animals ,Humans ,RNA, Messenger ,Leukemia, Experimental ,business.industry ,Genetic Therapy ,Cell Biology ,medicine.disease ,Vascular Endothelial Growth Factor Receptor-2 ,Neuropilin-1 ,Solubility ,chemistry ,Cancer research ,Endothelium, Vascular ,Bone marrow ,business ,Protein Processing, Post-Translational - Abstract
Recent findings implied that the progression of hematologic malignancies, like that of solid tumors, is dependent on neovascularization. Recent studies on patients with acute myeloid leukemia (AML) showed increased levels of leukocyte-associated vascular endothelial growth factor (VEGF) and neovascularization of the bone marrow. Murine (32D, M1) and human (HEL, U937, and UKE-1) leukemic cell lines and freshly isolated leukemic cells were analyzed for the expression of VEGF and VEGF receptor mRNA. The expression of VEGF and VEGF receptors KDR and neuropilin-1 (NRP-1) was detected in these cells. In a murine chloroma model, delivery of VEGF165using microencapsulation technology resulted in enhanced tumor growth and vascularization, whereas treatment with a VEGF antagonist soluble NRP-1 (sNRP-1) inhibited tumor angiogenesis and growth. In a systemic leukemia model, survival of mice injected with adenovirus (Ad) encoding for Fc-sNRP-1 (sNRP-1 dimer) was significantly prolonged as compared with mice injected with Ad-LacZ. Further analyses showed a reduction in circulating leukemic cells and infiltration of liver and spleen as well as bone marrow neovascularization and cellularity. Taken together, these results demonstrate that angiogenic factors such as VEGF promote AML progression in vivo. The use of VEGF antagonists as an antiangiogenesis approach offers a potential treatment for AML. Finally, our novel in vivo drug delivery model may be useful for testing the activities of other peptide antiangiogenic factors.
- Published
- 2002
37. [Untitled]
- Author
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Anthony Atala, Shay Soker, Gunter Schuch, and Oliver Kisker
- Subjects
Cancer Research ,medicine.medical_specialty ,Physiology ,Angiogenesis ,Clinical Biochemistry ,Basic fibroblast growth factor ,Biology ,medicine.disease ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Vascular endothelial growth factor A ,Endocrinology ,chemistry ,Tumor progression ,Pancreatic tumor ,Internal medicine ,Thrombospondin 1 ,medicine ,Cancer research ,Endostatin - Abstract
There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo. In this study, we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo. The human pancreatic cancer cell line Hs-776T (HS-W) produces slow-growing tumors in SCID mice. Cells of a variant form (HS-R) of Hs-776T produced faster-growing tumors compared to HS-W. Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2, but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R. Cell proliferation was similar in both tumor types in vivo, whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells (EC). Subsequently, VEGF was over-expressed in Hs-776T cells (HS-VF), resulting in rapidly growing tumors and lowering tumor and EC apoptosis. Collectively, our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors.
- Published
- 2002
38. Synergistic cytotoxic activity of treosulfan and gemcitabine in pancreatic cancer cell lines
- Author
-
Emilia, Nitsch, Sormeh, Mina, Ingo, Brammer, Andrea, Pace, Gunter, Schuch, Carsten, Bokemeyer, Axel, Zander, Nicolaus, Kröger, and Francis, Ayuk
- Subjects
Pancreatic Neoplasms ,Dose-Response Relationship, Drug ,Cell Line, Tumor ,Humans ,Antineoplastic Agents ,Drug Synergism ,Fluorouracil ,Busulfan ,Deoxycytidine ,Drug Antagonism ,Gemcitabine ,Cell Proliferation - Abstract
Treatment for advanced pancreatic cancer is still very unsatisfactory. Treosulfan is an alkylating agent used for conventional, as well as high-dose chemotherapy regimens, whereby plasma concentrations over 500 μg/ml can be achieved. We investigated the effects of treosulfan on pancreatic cancer cell lines.Using Panc-1, MIA PaCa-2 and Capan-2 cell lines, we investigated the in vitro cytotoxicity of treosulfan-alone and in combination with gemcitabine, 5-fluorouracil or irradiation.Treosulfan was potently cytotoxic against all pancreatic cancer cell lines at all concentrations (1-100 μg/ml). Combination of treosulfan and gemcitabine revealed strong synergistic effects independent of the sequence of drug administration. Similarly, synergism was observed with irradiation. Combination of treosulfan and 5-fluorouracil revealed antagonism.Treosulfan effectively kills pancreatic carcinoma cells in vitro and has synergistic activity in combination with gemcitabine and irradiation. These results warrant further investigation of treosulfan in the treatment of pancreatic cancer.
- Published
- 2014
39. List of Contributors
- Author
-
Russell C. Addis, Piero Anversa, Judith Arcidiacono, Anthony Atala, Joyce Axelman, Ashok Batra, Helen M. Blau, Susan Bonner-Weir, Mairi Brittan, Hal E. Broxmeyer, Mara Cananzi, Constance Cepko, Tao Cheng, Susana M. Chuva de Sousa Lopes, Gregory O. Clark, Maegen Colehour, Paolo de Coppi, Giulio Cossu, George Q. Daley, Jiyoung M. Dang, Natalie Direkze, Yuval Dor, Gregory R. Dressler, Charles N. Durfor, Ewa C.S. Ellis, Martin Evans, Donna M. Fekete, Donald Fink, Elaine Fuchs, Margaret T. Fuller, Richard L. Gardner, Zulma Gazit, Dan Gazit, John D. Gearhart, Victor M. Goldberg, Rodolfo Gonzalez, Deborah Lavoie Grayeski, Ronald M. Green, Markus Grompe, Stephen L. Hilbert, Marko E. Horb, Jerry I. Huang, Jaimie Imitola, D. Leanne Jones, Jan Kajstura, David S. Kaplan, Pritinder Kaur, Kathleen C. Kent, Candace L. Kerr, Ali Khademhosseini, Nadav Kimelman, Irina Klimanskaya, Jennifer N. Kraszewski, Mark A. LaBarge, Robert Langer, Robert Lanza, Ellen Lazarus, Jean Pyo Lee, Mark H. Lee, Annarosa Leri, Shulamit Levenberg, S. Robert Levine, John W. Littlefield, Richard McFarland, Jill McMahon, Douglas A. Melton, Mary Tyler Moore, Franz-Josef Mueller, Christine L. Mummery, Bernardo Nadal-Ginard, Hitoshi Niwa, Keisuke Okita, Jitka Ourednik, Vaclav Ourednik, Kook I. Park, Ethan S. Patterson, Gadi Pelled, Christopher S. Potten, Sean Preston, Philip R. Roelandt, Valerie D. Roobrouck, Nadia Rosenthal, Janet Rossant, Maurilio Sampaolesi, Maria Paola Santini, David T. Scadden, Holger Schlüter, Gunter Schuch, Michael J. Shamblott, Dima Sheyn, Richard L. Sidman, Evan Y. Snyder, Shay Soker, Stephen C. Strom, Lorenz Studer, M. Azim Surani, Francesco Saverio Tedesco, Yang D. Teng, David Tosh, Alan Trounson, Tudorita Tumbar, Edward Upjohn, George Varigos, Catherine M. Verfaillie, Zhan Wang, Gordon C. Weir, Kevin J. Whittlesey, J. Koudy Williams, James W. Wilson, Celia Witten, Nicholas A. Wright, Shinya Yamanaka, and Jung U. Yoo
- Published
- 2014
40. In vitro differentiation of endothelial cells from AC133-positive progenitor cells
- Author
-
Dieter K. Hossfeld, Christoph Wagener, Gunter Schuch, Nerbil Kilic, Thorsten Mende, Klaus Pantel, Udo Schumacher, Süleyman Ergün, Philippe Schafhausen, Ursula M. Gehling, Birgit Schäfer, Katrin Kluge, Walter Fiedler, and Marcus Otte
- Subjects
Pathology ,medicine.medical_specialty ,Endothelium ,Immunology ,CD34 ,Antigens, CD34 ,Biology ,Biochemistry ,Mice ,Vasculogenesis ,medicine ,Animals ,Humans ,Progenitor cell ,Cells, Cultured ,Interleukin 3 ,Cell Differentiation ,Cell Biology ,Hematology ,Flow Cytometry ,Hematopoietic Stem Cells ,Immunohistochemistry ,Hematopoietic Stem Cell Mobilization ,Cell biology ,Endothelial stem cell ,medicine.anatomical_structure ,Hemangioblast ,Endothelium, Vascular ,Stem cell - Abstract
Recent findings support the hypothesis that the CD34+-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133+ cells from granulocyte colony-stimulating factor–mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133+ progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulexeuropaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133+-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.
- Published
- 2000
41. Subject Index Vol. 32, 2009
- Author
-
Susanne Albrecht, Michael Zünd, Nikolaus de Gregorio, Yongzhi Zhuang, Bernd Klaeser, Ludwig G. Strauss, Thomas Hany, Eckart Laack, Nina Gottschalk, Peter Brauchli, Egbert Nitzsche, Spiros Christodoulou, Axel Sauerwald, Rolf Kreienberg, Dieter Köberle, Matthias Wolfgarten, Gisela Walgenbach-Bruenagel, Zhengyan Yu, Gunter Schuch, Christine Wulff, Flora Zagouri, Claudia Rogers, Niels Murawski, Thorleif Etgen, Corinne Cescato-Wenger, Lucas Widmer, Karl T.M. Schneider, Jingxuan Wang, Eva Wardelmann, Michael Pfreundschuh, Michael Safioleas, Sabine Balmer-Majno, Wolfgang Schmitt, Hanne Stensheim, George H. Sakorafas, Thomas Kubin, Aristotle Bamias, Antonia Dimitrakopoulou-Strauss, Roger von Moos, Martin Pölcher, Christian Rudlowski, Ina Thöm, Georg Weidenhöfer, Dieter K. Hossfeld, Tobias Höller, Volker R. Jacobs, Clemens Caspar, Thomas Ruhstaller, Christos Lappas, Birte Andritzky, Stephanie Pildner von Steinburg, Walther Kuhn, Ruediger Hein, Bernhard C. Pestalozzi, Wenjie Ma, Maria Papaefthimiou, Isabell Witzel, Thorsten Fischer, Qingyuan Zhang, Shu Zhao, Michael Braun, Meletios-Athanasios Dimopoulos, Jan C. Schuller, Shi Jin, Reinhard Büttner, Athanasios N. Chalazonitis, Nikolaos Antoniou, Manuel Debald, and Carsten Bokemeyer
- Subjects
Cancer Research ,Index (economics) ,Oncology ,Statistics ,Subject (documents) ,Hematology ,General Medicine ,Mathematics - Published
- 2009
42. Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia
- Author
-
Stockschläder M, H Bartels, H Renges, B Rüssmann, R. Kuse, N Kröger, W Krüger, G Wacker-Backhaus, N. Fuchs, M Dürken, Hartmut Kabisch, A R Zander, Rudolf Erttmann, S Hegewisch-Becker, Stefan S. Bielack, M de Wit, Gunter Schuch, and D Braumann
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Allogeneic transplantation ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Transplantation, Autologous ,Gastroenterology ,Disease-Free Survival ,Recurrence ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,Acute lymphocytic leukemia ,medicine ,Humans ,Transplantation, Homologous ,Autologous transplantation ,Child ,Antineoplastic Agents, Alkylating ,Bone Marrow Transplantation ,Etoposide ,Transplantation ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Total body irradiation ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Surgery ,Child, Preschool ,Female ,business ,Whole-Body Irradiation ,Busulfan ,medicine.drug - Abstract
We investigated an intensified conditioning regimen including fractionated total body irradiation (12 Gy), etoposide (30–45 mg/kg) and cyclophosphamide (120 mg/kg), followed by autologous (n = 5), allo-related (n = 13) or allo-unrelated (n = 6) bone marrow (n = 22) or peripheral stem cell (n = 2) transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. One patient received busulfan (16 mg/kg) instead of TBI. Nineteen patients were transplanted in 1CR, two in 2CR, one in 1PR and two in relapse. Major toxicity was mucositis grade II according to the Bearman scale in all patients. The treatment-related mortality was 25%, mainly due to infection or GVHD after allogeneic transplantation. After a median follow-up of 45 months (range 2–93), nine patients (37.5%) remain alive in CR. Nine patients (37.5%) relapsed and eight (33.3%) of these subsequently died. After autologous transplantation, four of five patients (80%) relapsed and died. Late relapse was seen after allogeneic, as well as autologous transplantation, at 33 and 59 months, respectively. The Kaplan–Meier estimate of leukemia-free survival for all patients is 38% at 3 years (95% CI: 18–58%) and 35% at 5 years (95% CI: 15–55%). For allogeneic transplants in first CR (n = 15) the estimate of disease-free survival was 46% at 3 years (95% CI: 19–73%) and 34% at 5 years (95% CI: 17–51%). Patients aged below 30 years had a better estimated overall survival at 3 years (61% vs 11%, P
- Published
- 1998
43. Long-Term Survival after Second-Line Therapy with Docetaxel and Carboplatin and Monthly Pamidronic Acid in a Woman with Metastatic Non-Small Cell Lung Cancer
- Author
-
Michael Goern, Gunter Schuch, Ina Thoem, Eckart Laack, Stephan Brandl, Birte Andritzky, and Carsten Bokemeyer
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Pamidronate ,Docetaxel ,Carboplatin ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Longitudinal Studies ,Lung cancer ,Second-line therapy ,Chemotherapy ,Diphosphonates ,business.industry ,Pamidronic acid ,Hematology ,Bisphosphonate ,medicine.disease ,respiratory tract diseases ,Treatment Outcome ,chemistry ,Lymphatic Metastasis ,Female ,Taxoids ,Non small cell ,business ,medicine.drug - Abstract
In patients with metastatic non-small cell lung cancer (NSCLC), second-line chemotherapy induces response rates of less than 20% and median survival times between 5 and 8 months.In the case described here, a patient with metastatic NSCLC responded with complete remission of the primary tumor and the involved lymph nodes as well as partial remission of bone metastases to a second-line chemotherapy with docetaxel and carboplatin. Since April 2003 (33 months), no tumor progression has been observed. Until present, the patient received monthly infusions of pamidronic acid.Our case report indicates that in certain patients with metastatic NSCLC who did not respond to first-line regimens, second-line chemotherapy can induce outstanding tumor response and significantly improve survival. It also indicates that the role of bisphosphonates in the treatment of NSCLC should be further investigated in large clinical trials.
- Published
- 2006
44. Difficult Diagnostic Cases
- Author
-
Georgia Schilling, Paul Scigalla, Maike de Wit, E. Laack, Jan Höltje, Walter Fiedler, Gunter Schuch, Mark Jacobs, and Dieter K. Hossfeld
- Subjects
Central nervous system disease ,Cancer Research ,Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Vascular disease ,Eye disease ,medicine ,Von Hippel–Lindau disease ,business ,medicine.disease - Published
- 2005
45. Contributors
- Author
-
Piero Anversa, Judith Arcidiacono, Anthony Atala, Yann Barrandon, Ashok Batra, Daniel Becker, Nicole M. Bergmann, Paolo Bianco, Helen M. Blau, Susan Bonner-Weir, Mairi Brittan, Hal E. Broxmeyer, Mara Cananzi, Arnold I. Caplan, Constance Cepko, Maegen Colehour, Giulio Cossu, George Q. Daley, Jiyoung M. Dang, Ayelet Dar, Brian R. Davis, Paolo de Coppi, Natalie Direkze, Juan Domínguez-Bendala, Yuval Dor, Gregory R. Dressler, Charles N. Durfor, Rita B. Effros, Ewa C.S. Ellis, Margaret A. Farley, Donna M. Fekete, Qiang Feng, Donald Fink, Elaine Fuchs, Dan Gazit, Zulma Gazit, Sharon Gerecht, Victor M. Goldberg, Rodolfo Gonzalez, François Gorostidi, Elizabeth Gould, Nicolas Grasset, Deborah Lavoie Grayeski, Ronald M. Green, Markus Grompe, Joshua M. Hare, Konstantinos E. Hatzistergos, Kevin E. Healy, Stephen L. Hilbert, Jerry I. Huang, James Huettner, Jaimie Imitola, Elizabeth F. Irwin, Joseph Itskovitz-Eldor, Josephine Johnston, Jan Kajstura, David S. Kaplan, Adam J. Katz, Pritinder Kaur, Erin A. Kimbrel, Nadav Kimelman, Chris Kintner, Naoko Koyano-Nakagawa, Tilo Kunath, Mark A. LaBarge, Robert Lanza, Stéphanie Lathion, Ellen Lazarus, Jean Pyo Lee, Mark H. Lee, Annarosa Leri, S. Robert Levine, Feng Li, Shi-Jiang Lu, John W. McDonald, Richard McFarland, Melissa K. McHale, Douglas A. Melton, Alexander F. Mericli, Christian Mirescu, Malcolm A.S. Moore, Mary Tyler Moore, Franz-Josef Mueller, Bernardo Nadal-Ginard, Jitka Ourednik, Vaclav Ourednik, Kook I. Park, Gadi Pelled, Antonello Pileggi, Jacob F. Pollock, Christopher S. Potten, Sean Preston, Nicole L. Prokopishyn, Camillo Ricordi, Pamela Gehron Robey, Ariane Rochat, Philip R. Roelandt, Valerie D. Roobrouck, Nadia Rosenthal, Janet Rossant, Maurilio Sampaolesi, Maria Paola Santini, David V. Schaffer, Holger Schlüter, Gunter Schuch, Sarah Selem, Dima Sheyn, Richard L. Sidman, Daniel Skuk, Evan Y. Snyder, Shay Soker, Stephen C. Strom, Lorenz Studer, Francesco Saverio Tedesco, Yang D. Teng, Jacques P. Tremblay, Tudorita Tumbar, Edward Upjohn, George Varigos, Catherine M. Verfaillie, Zhan Wang, Gordon C. Weir, Jennifer L. West, Kevin J. Whittlesey, J. Koudy Williams, J.W. Wilson, Celia Witten, Nicholas A. Wright, and Jung U. Yoo
- Published
- 2013
46. Combination therapy targeting integrins reduces glioblastoma tumor growth through antiangiogenic and direct antitumor activity and leads to activation of the pro-proliferative prolactin pathway
- Author
-
Carsten Bokemeyer, Walter Fiedler, Jessica Hauschild, Eva Maria Murga Penas, Marianne Klokow, Jasmin Wellbrock, Leticia Oliveira-Ferrer, Gunter Schuch, and Udo Bartsch
- Subjects
Collagen Type IV ,medicine.medical_specialty ,Cancer Research ,Integrins ,Tumstatin ,Angiogenesis ,Cell Survival ,Receptors, Prolactin ,Sus scrofa ,Angiogenesis Inhibitors ,Apoptosis ,Mice, SCID ,Biology ,Autoantigens ,Prolactin signaling pathway ,Mice ,Endostatin ,Internal medicine ,Glioma ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Autocrine signalling ,Cell Proliferation ,Cell growth ,Brain Neoplasms ,Prolactin receptor ,Research ,Gliobastoma ,medicine.disease ,Xenograft Model Antitumor Assays ,Endostatins ,Endocrinology ,Oncology ,Cancer research ,Molecular Medicine ,Glioblastoma ,Signal Transduction - Abstract
Background Tumors may develop resistance to specific angiogenic inhibitors via activation of alternative pathways. Therefore, multiple angiogenic pathways should be targeted to achieve significant angiogenic blockade. In this study we investigated the effects of a combined application of the angiogenic inhibitors endostatin and tumstatin in a model of human glioblastoma multiforme. Results Inhibitors released by stably transfected porcine aortic endothelial cells (PAE) showed anti-angiogenic activity in proliferation and wound-healing assays with endothelial cells (EC). Interestingly, combination of endostatin and tumstatin (ES + Tum) also reduced proliferation of glioma cells and additionally induced morphological changes and apoptosis in vitro. Microencapsulated PAE-cells producing these inhibitors were applied for local therapy in a subcutaneous glioblastoma model. When endostatin or tumstatin were applied separately, in vivo tumor growth was inhibited by 58% and 50%, respectively. Combined application of ES + Tum, in comparison, resulted in a significantly more pronounced inhibition of tumor growth (83%). cDNA microarrays of tumors treated with ES + Tum revealed an up-regulation of prolactin receptor (PRLR). ES + Tum-induced up-regulation of PRLR in glioma cells was also found in in vitro. Moreover, exogenous PRLR overexpression in vitro led to up-regulation of its ligand prolactin and increased proliferation suggesting a functional autocrine growth loop in these cells. Conclusion Our data indicate that integrin-targeting factors endostatin and tumstatin act additively by inhibiting glioblastoma growth via reduction of vessel density but also directly by affecting proliferation and viability of tumor cells. Treatment with the ES + Tum-combination activates the PRLR pro-proliferative pathway in glioblastoma. Future work will show whether the prolactin signaling pathway represents an additional target to improve therapeutic strategies in this entity.
- Published
- 2012
47. Scale-up von Destillationskolonnen
- Author
-
Ulrich Eiden, Dieter Wolf, Gunter Schuch, and Rudolf Kaiser
- Subjects
Engineering ,business.industry ,General Chemical Engineering ,General Chemistry ,Column (database) ,Industrial and Manufacturing Engineering ,law.invention ,Experimental testing ,law ,Economic constraints ,Mass transfer ,SCALE-UP ,Fluid dynamics ,business ,Process engineering ,Distillation ,Simulation - Abstract
Scale-up of Distillation Columns. In spite of remarkable advances in the development of computer programs for calculations on distillation columns, it is frequently still impossible to design them without experimental testing. Economic constraints demand use of miniaturised test plant, thus enhancing the importance of laboratory measurements. A system is presented for scale-up of separation which required information from laboratory experiments, includes data from reference columns, and takes account of models of fluid dynamics and mass transfer. The special feature of this approach lies in the free choise of internals, both in the laboratory and in the designed column.
- Published
- 1995
48. Die Krebsindustrie — Es rollt eine Kostenlawine auf uns zu
- Author
-
Gunter Schuch
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business - Published
- 2015
49. Transport of ebselen in plasma and its transfer to binding sites in the hepatocyte
- Author
-
Helmut Sies, Theodorus P.M. Akerboom, Gunter Wagner, and Gunter Schuch
- Subjects
Azoles ,Male ,Serum albumin ,Plasma protein binding ,Isoindoles ,Biochemistry ,Mice ,chemistry.chemical_compound ,Organoselenium Compounds ,Animals ,Carbon Radioisotopes ,Sulfhydryl Compounds ,Rats, Wistar ,Bovine serum albumin ,Cells, Cultured ,Pharmacology ,Binding Sites ,biology ,Chemistry ,Ebselen ,Albumin ,Serum Albumin, Bovine ,Glutathione ,Ascorbic acid ,Rats ,Perfusion ,Liver ,Covalent bond ,biology.protein ,Oxidation-Reduction ,Subcellular Fractions - Abstract
In vivo transport in plasma and in vitro transfer of ebselen to binding sites in the hepatocyte were studied. More than 90% of intravenously administered ebselen in mouse plasma is bound by selenium-sulfur bonds to reactive thiols in serum albumin. In in vitro experiments the uptake of [14C]-ebselen from a complex prepared with bovine serum albumin (BSA) was determined in isolated perfused rat liver. Radioactive ebselen metabolites were excreted into bile. In isolated hepatocytes, radioactivity was bound to all subcellular organelles. Ebselen is transferred from the BSA complex to membrane-associated proteins after reductive cleavage of the Se-S bond effected by endogenous protein thiols. In contrast, when proteins were separated by dialysis membranes, ebselen transfer from its BSA complex occurred only in the presence of externally added reductants. Among the physiological reductants tested, ebselen release from the BSA complex was highest with glutathione (75%) and lowest with ascorbic acid (less than 10%). Quantitative release of ebselen from its BSA complex was only achieved by the combined action of reductant, notably 2-mercaptoethanol, and guanidine thiocyanate, suggesting that ebselen interacts with proteins by covalent Se-S bonds as well as by ionic charge interactions.
- Published
- 1994
50. Interaction of ebselen with glutathione S-transferase and papain in vitro
- Author
-
Helmut Sies, Takeshi Nikawa, Gunter Schuch, and Gunter Wagner
- Subjects
Azoles ,Male ,Stereochemistry ,In Vitro Techniques ,Isoindoles ,Biochemistry ,Substrate Specificity ,chemistry.chemical_compound ,Organoselenium Compounds ,Papain ,Animals ,Sulfhydryl Compounds ,Rats, Wistar ,Glutathione Transferase ,Pharmacology ,chemistry.chemical_classification ,biology ,Ebselen ,Glutathione ,Cysteine protease ,Rats ,Isoenzymes ,Enzyme ,Glutathione S-transferase ,chemistry ,Ethylmaleimide ,Thiol ,biology.protein ,Spectrophotometry, Ultraviolet ,Cysteine - Abstract
The interaction of ebselen(2-phenyl-1,2-benzisoselenazol-3(2H)-one) with rat liver cytosolic glutathione S-transferases (GSTs) and the plant cysteine protease, papain, was studied as cysteine residues are important for the activity of these enzymes. The capacity of GST 1-2 and 3-4 for ebselen binding is similar (1.5 mol ebselen/mol GST isozyme), while GST 2-2 and GST 7-7 bind 0.3 and more than 2.0 mol ebselen/mol GST isozyme, respectively. Ebselen does not bind to N-ethylmaleimide-treated GST, and its binding to GST is prevented by 5 mM thiols. Ebselen irreversibly inactivates the different GST isozymes with a second order rate constant ranging from 20 to 2250 M-1 sec-1 for the different subunits. GST inhibition by ebselen is partially restored by 5 mM thiols. Ebselen binds to untreated papain and to cysteine-treated papain at a ratio of about 0.1 and 0.75 mol ebselen/mol papain, respectively. Ebselen does not bind to N-ethylmaleimide-treated papain, and its binding to papain is interfered with by added thiols. Papain is inactivated by ebselen with a second order rate constant of 1800 M-1 sec-1 in the absence of thiols. However, in the presence of GSH, 2-mercaptoethanol or sodium borohydride, ebselen exerts an activating effect on papain. The binding of ebselen by a seleno-sulfide bond to cysteine residues of GSTs and papain leads to their inactivation.
- Published
- 1994
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