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31 results on '"Kraetzschmar, Joern"'

4. Differential inhibition of inducible T cell cytokine secretion by potent iron chelators

Author

Leung, Stewart, Holbrook, April, King, Beverly, Lu, Hong-Tao, Evans, Vincent, Miyamoto, Neil, Mallari, Cornell, Harvey, Susan, Davey, Dave, Ho, Elena, Li, Wei-Wei, Parkinson, John, Horuk, Richard, Jaroch, Stefan, Berger, Markus, Skuballa, Werner, West, Christopher, Pulk, Rebecca, Phillips, Gary, Bryant, Judi, Subramanyam, Babu, Schaefer, Caralee, Salamon, Hugh, Lyons, Eric, Schilling, Daniela, Seidel, Henrik, Kraetzschmar, Joern, Snider, Michael, and Perez, Daniel

Subjects
T cells -- Receptors, Cytokines -- Research, Antigen receptors, T cell -- Research, Biomolecules -- Research, Biological sciences, Research
Abstract

Effector functions and proliferation of Thelper (Th) cells are influenced by cytokines in the environment. Th1 cells respond to a synergistic effect of interleukin-12 (IL-12) and interleukin-18 (IL-18) to secrete [...]

Published
2005

7. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

Author

Nagelschmitz,Johannes, Blunck,Martin, Kraetzschmar,Joern, Ludwig,Mathias, Wensing,Georg, Hohlfeld,T, Nagelschmitz,Johannes, Blunck,Martin, Kraetzschmar,Joern, Ludwig,Mathias, Wensing,Georg, and Hohlfeld,T

Abstract

J Nagelschmitz,1 M Blunck,1 J Kraetzschmar,1 M Ludwig,1 G Wensing,1 T Hohlfeld2 1Bayer HealthCare AG, Clinical Pharmacology, Wuppertal, Germany; 2Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany Background: The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Methods: Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results: A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion: This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than o

Published
2014

10. Phase I Dose Escalation Study of Telatinib, a Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor 2 and 3, Platelet-Derived Growth Factor Receptor β, and c-Kit, in Patients With Advanced or Metastatic Solid Tumors

Author

Eskens, Ferry A.L.M., primary, Steeghs, Neeltje, additional, Verweij, Jaap, additional, Bloem, Johan L., additional, Christensen, Olaf, additional, van Doorn, Leni, additional, Ouwerkerk, Jan, additional, de Jonge, Maja J.A., additional, Nortier, Johan W.R., additional, Kraetzschmar, Joern, additional, Rajagopalan, Prabhu, additional, and Gelderblom, Hans, additional

Published
2009
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11. Differential Inhibition of Inducible T Cell Cytokine Secretion by Potent Iron Chelators

Author

Leung, Stewart, primary, Holbrook, April, additional, King, Beverly, additional, Lu, Hong-Tao, additional, Evans, Vincent, additional, Miyamoto, Neil, additional, Mallari, Cornell, additional, Harvey, Susan, additional, Davey, Dave, additional, Ho, Elena, additional, Li, Wei-Wei, additional, Parkinson, John, additional, Horuk, Richard, additional, Jaroch, Stefan, additional, Berger, Markus, additional, Skuballa, Werner, additional, West, Christopher, additional, Pulk, Rebecca, additional, Phillips, Gary, additional, Bryant, Judi, additional, Subramanyam, Babu, additional, Schaefer, Caralee, additional, Salamon, Hugh, additional, Lyons, Eric, additional, Schilling, Daniela, additional, Seidel, Henrik, additional, Kraetzschmar, Joern, additional, Snider, Michael, additional, and Perez, Daniel, additional

Published
2005
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12. Identification of Genes Regulated by the Antiprogestin, Onapristone, in Breast Cancer Cells using Microarray Analysis.

Author

Li, Jonathan J., Li, Sara A., Llombart-Bosch, Antonio, Crook, Simon J., Brook, J. David, Sommer, Anette, Kraetzschmar, Joern, and Robertson, John F. R.

Abstract

Progesterone receptor (PR) antagonists are a potential new therapeutic strategy for the treatment of patients with invasive breast cancer (BC). One such progesterone antagonist is Onapristone. Onapristone has been reported to have strong anti-progestational and anti-tumor activity. A tumor remission rate of approximately 66% was found in a phase II clinical trial of Onapristone as a first-line endocrine therapy in post-menopausal patients with primary BC. However, during this trial, a minority of the patients developed abnormal liver function test results. As a consequence, the further therapeutic use off this drug has stop. Although the mechanism of action of Onapristone has been suggested by animal model experiments, the genes regulated by the drug in the breast are not known. In the present study, the BC cell line T47D was treated with Onapristone and examined with Affymetrix microarrays and real-time RT-PCR to identify genes which were differentially expressed. Cells were treated with Onapristone either alone or in the presence of progesterone, and microarray analysis carried out upon the RNA extracted from the cells. The expression of a selection of up- or down-regulated genes observed was further investigated using real-time RT-PCR. In addition, the expression of these genes was investigated in the PR− cell line, MDA-MB-231 treated with Onapristone, to ensure that any changes in gene expression observed, were due to Onapristone effects via the PR. [ABSTRACT FROM AUTHOR]

Published
2005
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31. Phase I dose escalation study of telatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 3, platelet-derived growth factor receptor beta, and c-Kit, in patients with advanced or metastatic solid tumors.

Author

Eskens FA, Steeghs N, Verweij J, Bloem JL, Christensen O, van Doorn L, Ouwerkerk J, de Jonge MJ, Nortier JW, Kraetzschmar J, Rajagopalan P, and Gelderblom H

Subjects
Administration, Oral, Adolescent, Adult, Aged, Angiogenesis Inhibitors adverse effects, Angiogenesis Inhibitors pharmacokinetics, Biomarkers, Tumor blood, Contrast Media, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Magnetic Resonance Imaging, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Metastasis, Neoplasms blood supply, Neoplasms enzymology, Neoplasms pathology, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors pharmacokinetics, Pyridazines adverse effects, Pyridazines pharmacokinetics, Pyridines adverse effects, Pyridines pharmacokinetics, Time Factors, Treatment Outcome, Vascular Endothelial Growth Factor A blood, Vascular Endothelial Growth Factor Receptor-2 blood, Young Adult, Angiogenesis Inhibitors administration & dosage, Neoplasms drug therapy, Protein Kinase Inhibitors administration & dosage, Proto-Oncogene Proteins c-kit drug effects, Pyridazines administration & dosage, Pyridines administration & dosage, Receptor, Platelet-Derived Growth Factor beta antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Vascular Endothelial Growth Factor Receptor-3 antagonists & inhibitors
Abstract

Purpose: Telatinib (BAY 57-9352) is an orally available tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -2, VEGFR-3, platelet-derived growth factor receptor-beta, and c-Kit. This phase I dose escalation study was conducted to evaluate the safety and tolerability of telatinib, with additional pharmacokinetic, pharmacodynamic, and efficacy assessments., Patients and Methods: Patients with solid tumors refractory to standard therapies or with no standard therapy available were enrolled. Doses of continuously administered telatinib were escalated from 20 mg once daily to 1,500 mg twice daily., Results: Fifty-three patients were enrolled. Most frequently observed drug-related adverse events were nausea (26.4%; grade >or= 3, 0%) and hypertension (20.8%; grade 3, 11.3%; grade 4, 0%). Two dose-limiting toxicities were observed: one poorly controlled hypertension (600 mg twice daily), and one grade 2 weight loss, anorexia, and fatigue (1,500 mg twice daily). A formal maximum-tolerated dose was not reached. Telatinib was rapidly absorbed, with median time to peak concentration (t(max)) lower than 3 hours after dose. A nearly dose-proportional increase in exposure was observed with substantial variability. Telatinib half-life averaged 5.5 hours. Biomarker analyses showed dose-dependent increase in VEGF levels and decrease in plasma soluble VEGFR-2 levels, with a plateau at 900 mg twice daily. A decrease in tumor blood flow (K(trans) and IAUC(60)) was observed with dynamic contrast-enhanced magnetic resonance imaging. Best tumor response was stable disease, observed in 50.9% of patients., Conclusion: Telatinib was safe and well tolerated up to 1,500 mg twice daily. Based on pharmacodynamic and pharmacokinetic end points, telatinib 900 mg twice daily is the recommended dose for subsequent phase II studies.

Published
2009
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