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1. Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy

Author

Hoffmann, Emily, Schache, Daniel, Höltke, Carsten, Soltwisch, Jens, Niland, Stephan, Krähling, Tobias, Bergander, Klaus, Grewer, Martin, Geyer, Christiane, Groeneweg, Linda, Eble, Johannes A., Vogl, Thomas, Roth, Johannes, Heindel, Walter, Maus, Bastian, Helfen, Anne, Faber, Cornelius, Wildgruber, Moritz, Gerwing, Mirjam, and Hoerr, Verena

Published
2023
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6. Electrostatic anti-CD33-antibody–protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia

Author

Bäumer, Nicole, Scheller, Annika, Wittmann, Lisa, Faust, Andreas, Apel, Mara, Nimmagadda, Subbaiah Chary, Geyer, Christiane, Grunert, Katharina, Kellmann, Neele, Peipp, Matthias, Kailayangiri, Sareetha, Gutierrez Suburu, Matias Ezequiel, Strassert, Cristian A., Schenk, Mathias, Greune, Lilo, Rüter, Christian, Dersch, Petra, Hartmann, Wolfgang, Rossig, Claudia, Neri, Dario, Müller-Tidow, Carsten, Schwöppe, Christian, Schliemann, Christoph, Khandanpour, Cyrus, Lenz, Georg, Berdel, Wolfgang E., and Bäumer, Sebastian

Published
2022
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9. Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation

Author

Vogl, Thomas, Stratis, Athanasios, Wixler, Viktor, Voller, Tom, Thurainayagam, Sumita, Jorch, Selina K., Zenker, Stefanie, Dreiling, Alena, Chakraborty, Deblina, Frohling, Mareike, Paruzel, Peter, Wehmeyer, Corinna, Hermann, Sven, Papantonopoulou, Olympia, Geyer, Christiane, Loser, Karin, Schafers, Michael, Ludwig, Stephan, Stoll, Monika, Leanderson, Tomas, Schultze, Joachim L., Konig, Simone, Pap, Thomas, and Roth, Johannes

Subjects
Inflammation -- Development and progression -- Prevention, Cellular proteins -- Health aspects, Inflammation mediators -- Physiological aspects -- Health aspects, Phagocytes -- Physiological aspects, Health care industry
Abstract

Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation. Combining protease degradation, pull-down assays, mass spectrometry, and targeted mutations, we identified specific peptide sequences within the second calcium-binding EF- hands triggering TLR4/MD2-dependent inflammation. These binding sites are free when S100A8/S100A9 heterodimers are released at sites of inflammation. Subsequently, S100A8/S100A9 activities are locally restricted by calcium-induced [(S100A8/ S100A9).sub.2] tetramer formation hiding the TLR4/MD2-binding site within the tetramer interphase, thus preventing undesirable systemic effects. Loss of this autoinhibitory mechanism in vivo results in TNF-[alpha]-driven fatal inflammation, as shown by lack of tetramer formation in crossing [S100A9.sup.-/-] mice with 2 independent TNF-[alpha]-transgene mouse strains. Since S100A8/S100A9 is the most abundant DAMP in many inflammatory diseases, specifically blocking the TLR4-binding site of active S100 dimers may represent a promising approach for local suppression of inflammatory diseases, avoiding systemic side effects., Introduction The term 'sterile inflammation' describes inflammatory processes not triggered by microbial agents (1, 2), but rather induced by endogenous molecules released during tissue damage or cell stress (3). For [...]

Published
2018
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10. Profiling specific cell populations within the inflammatory tumor microenvironment by oscillating-gradient diffusion-weighted MRI

Author

Hoffmann, Emily, primary, Gerwing, Mirjam, additional, Niland, Stephan, additional, Niehoff, Rolf, additional, Masthoff, Max, additional, Geyer, Christiane, additional, Wachsmuth, Lydia, additional, Wilken, Enrica, additional, Höltke, Carsten, additional, Heindel, Walter L, additional, Hoerr, Verena, additional, Schinner, Regina, additional, Berger, Philipp, additional, Vogl, Thomas, additional, Eble, Johannes A, additional, Maus, Bastian, additional, Helfen, Anne, additional, Wildgruber, Moritz, additional, and Faber, Cornelius, additional

Published
2023
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12. Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer

Author

Gerwing, Mirjam, primary, Hoffmann, Emily, additional, Kronenberg, Katharina, additional, Hansen, Uwe, additional, Masthoff, Max, additional, Helfen, Anne, additional, Geyer, Christiane, additional, Wachsmuth, Lydia, additional, Höltke, Carsten, additional, Maus, Bastian, additional, Hoerr, Verena, additional, Krähling, Tobias, additional, Hiddeßen, Lena, additional, Heindel, Walter, additional, Karst, Uwe, additional, Kimm, Melanie A., additional, Schinner, Regina, additional, Eisenblätter, Michel, additional, Faber, Cornelius, additional, and Wildgruber, Moritz, additional

Published
2022
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13. Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer

Author

Gerwing, Mirjam, Hoffmann, Emily, Kronenberg, Katharina, Hansen, Uwe, Masthoff, Max, Helfen, Anne, Geyer, Christiane, Wachsmuth, Lydia, Höltke, Carsten, Maus, Bastian, Hoerr, Verena, Krähling, Tobias, Hiddeßen, Lena, Heindel, Walter, Karst, Uwe, Kimm, Melanie Alexandra, Schinner, Regina, Eisenblätter, Michel, Faber, Cornelius, and Wildgruber, Moritz

Subjects
610 Medicine and health
Abstract

Objective: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach. Methods: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy. Results: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher Ktrans values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower Ktrans values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90th percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models. Conclusions: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time., Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).

Published
2022
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15. Tumor‐Cell‐Specific Targeting of Ibrutinib: Introducing Electrostatic Antibody‐Inhibitor Conjugates (AiCs)

Author

Faust, Andreas, primary, Bäumer, Nicole, additional, Schlütermann, Alina, additional, Becht, Manuel, additional, Greune, Lilo, additional, Geyer, Christiane, additional, Rüter, Christian, additional, Margeta, Renato, additional, Wittmann, Lisa, additional, Dersch, Petra, additional, Lenz, Georg, additional, Berdel, Wolfgang E., additional, and Bäumer, Sebastian, additional

Published
2021
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18. Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis

Author

Stölting, Miriam, Geyer, Christiane, Helfen, Anne, Hahnenkamp, Anke, Usai, Marco V., Wardelmann, Eva, Kuhlmann, Michael Theodor, Wildgruber, Moritz, Höltke, Carsten, and Universitäts- und Landesbibliothek Münster

Subjects
endothelin receptor expression, 610 Medicine and health, endothelin system, molecular imaging, Article, atherosclerosis, ApoE-KnockOut, carotid endarterectomy, fluorescence imaging, lcsh:Biology (General), Medicine and health, ddc:610, lcsh:QH301-705.5
Abstract

Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the development of atherosclerosis. We aimed to reveal the expression levels of the endothelin-A receptor (ETAR) in the course of atherogenesis to reveal possible time frames for targeted imaging and interventions. We used the ApoE−/− mice model and human specimens and evaluated ETAR expression by quantitative rtPCR (qPCR), histology and fluorescence molecular imaging. We found a significant upregulation of ETAR after 22 weeks of high-fat diet in the aortae of ApoE−/− mice. With regard to translation to human disease, we applied the fluorescent probe to fresh explants of human carotid and femoral artery specimens. The findings were correlated with qPCR and histology. While ETAR is upregulated during the progression of early atherosclerosis in the ApoE−/− mouse model, we found that ETAR expression is substantially reduced in advanced human atherosclerotic plaques. Moreover, those expression changes were clearly depicted by fluorescence imaging using our in-house designed ETAR-Cy 5.5 probe confirming its specificity and potential use in future studies., Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).

Published
2020

20. ultraMEDIS – Ultra-Wideband Sensing in Medicine

Author

Hilger, Ingrid, primary, Dahlke, Katja, additional, Rimkus, Gabriella, additional, Geyer, Christiane, additional, Seifert, Frank, additional, Kosch, Olaf, additional, Thiel, Florian, additional, Hein, Matthias, additional, di Clemente, Francesco Scotto, additional, Schwarz, Ulrich, additional, Helbig, Marko, additional, and Sachs, Jurgen, additional

Published
2013
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21. Tumor‐Cell‐Specific Targeting of Ibrutinib: Introducing Electrostatic Antibody‐Inhibitor Conjugates (AiCs).

Author

Faust, Andreas, Bäumer, Nicole, Schlütermann, Alina, Becht, Manuel, Greune, Lilo, Geyer, Christiane, Rüter, Christian, Margeta, Renato, Wittmann, Lisa, Dersch, Petra, Lenz, Georg, Berdel, Wolfgang E., and Bäumer, Sebastian

Subjects
BRUTON tyrosine kinase, WALDENSTROM'S macroglobulinemia, MANTLE cell lymphoma, CD20 antigen, CHRONIC lymphocytic leukemia, PROTEIN-tyrosine kinases
Abstract

Ibrutinib is an inhibitor of Bruton's tyrosine kinase that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia and is connected with toxicities. To minimize its toxicities, we linked ibrutinib to a cell‐targeted, internalizing antibody. To this end, we synthesized a poly‐anionic derivate, ibrutinib‐Cy3.5, that retains full functionality. This anionic inhibitor is complexed by our anti‐CD20‐protamine targeting conjugate and free protamine, and thereby spontaneously assembles into an electrostatically stabilized vesicular nanocarrier. The complexation led to an accumulation of the drug driven by the CD20 antigen internalization to the intended cells and an amplification of its pharmacological effectivity. In vivo, we observed a significant enrichment of the drug in xenograft lymphoma tumors in immune‐compromised mice and a significantly better response to lower doses compared to the original drug. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Tumorzellspezifisches Targeting von Ibrutinib: Einführung von elektrostatischen Antikörper‐Inhibitor‐Konjugaten (AiCs).

Author

Faust, Andreas, Bäumer, Nicole, Schlütermann, Alina, Becht, Manuel, Greune, Lilo, Geyer, Christiane, Rüter, Christian, Margeta, Renato, Wittmann, Lisa, Dersch, Petra, Lenz, Georg, Berdel, Wolfgang E., and Bäumer, Sebastian

Abstract

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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25. Target-Specific Imaging of Cathepsin and S100A8/A9 Reflects Specific Features of Malignancy and Enables Estimation of Tumor Malignancy

Author

Helfen, Anne, primary, Große Hokamp, Nils, additional, Geyer, Christiane, additional, Heindel, Walter, additional, Bremer, Christoph, additional, Vogl, Thomas, additional, Höltke, Carsten, additional, Masthoff, Max, additional, Barczyk-Kahlert, Katarzyna, additional, Roth, Johannes, additional, Wildgruber, Moritz, additional, and Eisenblaetter, Michel, additional

Published
2019
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33. Optical In Vivo Imaging of the Alarmin S100A9 in Tumor Lesions Allows for Estimation of the Individual Malignant Potential by Evaluation of Tumor–Host Cell Interaction

Author

Becker, Anne, primary, Hokamp, Nils Große, additional, Zenker, Stefanie, additional, Flores-Borja, Fabian, additional, Barzcyk, Katarzyna, additional, Varga, Georg, additional, Roth, Johannes, additional, Geyer, Christiane, additional, Heindel, Walter, additional, Bremer, Christoph, additional, Vogl, Thomas, additional, and Eisenblaetter, Michel, additional

Published
2015
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34. Ultra-wideband (UWB) as imaging tool for diagnostic purposes

Author

Geyer, Christiane and Hilger, Ingrid

Abstract

Purpose Methods and Materials Results Conclusion, Purpose: The application spectrum of ultra-wideband (UWB) is currently growing [1]. For example, a number of studies demonstrate the use in the field of information and communication technologies (e.g. [2]), basically because of its ability to transfer large...

Published
2009
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35. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity

Author

Vogl, Thomas, primary, Eisenblätter, Michel, additional, Völler, Tom, additional, Zenker, Stefanie, additional, Hermann, Sven, additional, van Lent, Peter, additional, Faust, Andreas, additional, Geyer, Christiane, additional, Petersen, Beatrix, additional, Roebrock, Kirsten, additional, Schäfers, Michael, additional, Bremer, Christoph, additional, and Roth, Johannes, additional

Published
2014
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36. Effects of cell structure of gram-positive and gram-negative bacteria based on their dielectric properties.

Author

Dahlke, Katja, Geyer, Christiane, Dees, Stephan, Helbig, Marko, Sachs, Jurgen, Scotto di Clemente, Francesco, Hein, Matthias, Kaiser, Werner Alois, and Hilger, Ingrid

Abstract

Current procedures for the identification and characterization of microorganisms are based on complex and time-consuming protocols. Here, we hypothesize that the distinct cellular composition of microorganisms could be identified by dielectric spectroscopy. Gram-positive and Gram-negative bacterial strain permittivity measurement was performed using a network analyzer and a coaxial probe in the frequency range from 50 MHz to 300 MHz. All bacterial strains in suspension demonstrated correlation between cell count and permittivity values during the growth phase. When determining isolated cell pellets, a clear discrimination between Gram-positive and Gram-negative strains was possible in a frequency range between 50 MHz and 100 MHz. Our data clearly show that dielectric spectroscopy is able to obsess the growth kinetics and to identify the Gram-status of bacterial strains. In future this simple method could be used for biomedical diagnostics of infections. [ABSTRACT FROM PUBLISHER]

Published
2012

37. Tumor-Cell-Specific Targeting of Ibrutinib: Introducing Electrostatic Antibody-Inhibitor Conjugates (AiCs).

Author

Faust A, Bäumer N, Schlütermann A, Becht M, Greune L, Geyer C, Rüter C, Margeta R, Wittmann L, Dersch P, Lenz G, Berdel WE, and Bäumer S

Subjects
Adenine chemistry, Adenine pharmacology, Animals, Antibodies, Monoclonal chemistry, Antineoplastic Agents chemistry, Carbocyanines chemistry, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Humans, Lymphoma, Large B-Cell, Diffuse pathology, Mice, Neoplasms, Experimental drug therapy, Neoplasms, Experimental pathology, Piperidines chemistry, Protein Engineering, Protein Kinase Inhibitors chemistry, Static Electricity, Adenine analogs & derivatives, Antibodies, Monoclonal pharmacology, Antineoplastic Agents pharmacology, Carbocyanines pharmacology, Lymphoma, Large B-Cell, Diffuse drug therapy, Piperidines pharmacology, Protein Kinase Inhibitors pharmacology
Abstract

Ibrutinib is an inhibitor of Bruton's tyrosine kinase that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia and is connected with toxicities. To minimize its toxicities, we linked ibrutinib to a cell-targeted, internalizing antibody. To this end, we synthesized a poly-anionic derivate, ibrutinib-Cy3.5, that retains full functionality. This anionic inhibitor is complexed by our anti-CD20-protamine targeting conjugate and free protamine, and thereby spontaneously assembles into an electrostatically stabilized vesicular nanocarrier. The complexation led to an accumulation of the drug driven by the CD20 antigen internalization to the intended cells and an amplification of its pharmacological effectivity. In vivo, we observed a significant enrichment of the drug in xenograft lymphoma tumors in immune-compromised mice and a significantly better response to lower doses compared to the original drug., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Published
2022
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