Umfassendes mechanisches und EZM-Profil der krebsbefallenen Leber während der Tumorprogression und nach Behandlung mit neuen theranostischen XTEN-Fusionsproteinen
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Projektinhalt
Während der Tumorentwicklung ist das Remodelling der Extrazellulärmatrix (EZM) im entzündeten Umgebungsgewebe von großer Bedeutung für Tumorwachstum und Metastasierung. Matrix-Metalloproteinasen (MMP) sind Regulatoren solcher strukturellen Veränderungen, die die mechanischen Gewebeeigenschaften modifizieren, welche durch Elastographie untersucht werden können. In diesem Projekt werden wir vollständig E. coli-exprimierbare, theranostische XTEN-Fusionsproteine entwickeln, die durch in der Tumorumgebung überexprimierte MMP aktiviert werden und die Korrelation zwischen mechanischen Eigenschaften und der Zusammensetzung der EZM in der krebsbefallenen Leber eines Mausmodells während des Tumorwachstums und nach Behandlung mit den Fusionsproteinen untersuchen.
Unser Team
Projektleitung:
Prof. Dr. med. Eyk Schellenberger
Dr. rer. nat. Jing Guo
PD Dr. med. Lynn Jeanette Savic
Doktoranden (PhD) und Postdoktoranden (PostDoc):
Karolina Garczynska (Phd)
Dr. rer. nat. Akvile Häckel (Postdoc)
Publikationen
- Keller S, Borde T, Brangsch J, Reimann C, Kader A, Schulze D, Buchholz R, Kaufmann JO, Karst U, Schellenberger E, Hamm B, Makowski MR. Assessment of the hepatic tumor extracellular matrix using elastin-specific molecular magnetic resonance imaging in an experimental rabbit cancer model. Sci Rep. 2020 Nov 27;10(1):20785. doi: 10.1038/s41598-020-77624-8. PMID: 33247185; PMCID: PMC7695832.
- Marticorena Garcia SR, Althoff CE, Dürr M, Halleck F, Budde K, Grittner U, Burkhardt C, Jöhrens K, Braun J, Fischer T, Hamm B, Sack I, Guo J. Tomoelastography for Longitudinal Monitoring of Viscoelasticity Changes in the Liver and in Renal Allografts after Direct-Acting Antiviral Treatment in 15 Kidney Transplant Recipients with Chronic HCV Infection. J Clin Med. 2021 Feb 1;10(3):510. doi: 10.3390/jcm10030510. PMID: 33535495; PMCID: PMC7867050.
- Garczyńska K, Tzschätzsch H, Assili S, Kühl AA, Häckel A, Schellenberger E, Berndt N, Holzhütter HG, Braun J, Sack I, Guo J. Effect of Post-mortem Interval and Perfusion on the Biophysical Properties of ex vivo Liver Tissue Investigated Longitudinally by MRE and DWI. Front Physiol. 2021 Aug 3;12:696304. doi: 10.3389/fphys.2021.696304. PMID: 34413787; PMCID: PMC8369239.
- Garczyńska K, Tzschätzsch H, Kühl AA, Morr AS, Lilaj L, Häckel A, Schellenberger E, Berndt N, Holzhütter HG, Braun J, Sack I, Guo J. Changes in Liver Mechanical Properties and Water Diffusivity During Normal Pregnancy Are Driven by Cellular Hypertrophy. Front Physiol. 2020 Nov 23;11:605205. doi: 10.3389/fphys.2020.605205. PMID: 33329058; PMCID: PMC7719759.
- Wang S, Millward JM, Hanke-Vela L, Malla B, Pilch K, Gil-Infante A, Waiczies S, Mueller S, Boehm-Sturm P, Guo J, Sack I, Infante-Duarte C. MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis. Front Neurol. 2020 Jan 13;10:1382. doi: 10.3389/fneur.2019.01382. PMID: 31998225; PMCID: PMC6970413.
- Hu J, Guo J, Pei Y, Hu P, Li M, Sack I, Li W. Rectal Tumor Stiffness Quantified by In Vivo Tomoelastography and Collagen Content Estimated by Histopathology Predict Tumor Aggressiveness. Front Oncol. 2021 Aug 13;11:701336. doi: 10.3389/fonc.2021.701336. PMID: 34485136; PMCID: PMC8415020.
- Zhu L, Guo J, Jin Z, Xue H, Dai M, Zhang W, Sun Z, Xu J, Marticorena Garcia SR, Asbach P, Hamm B, Sack I. Distinguishing pancreatic cancer and autoimmune pancreatitis with in vivo tomoelastography. Eur Radiol. 2021 May;31(5):3366-3374. doi: 10.1007/s00330-020-07420-5. Epub 2020 Oct 30. PMID: 33125553.
- Grossmann M, Tzschätzsch H, Lang ST, Guo J, Bruns A, Dürr M, Hoyer BF, Grittner U, Lerchbaumer M, Nguyen Trong M, Schultz M, Hamm B, Braun J, Sack I, Marticorena Garcia SR. US Time-Harmonic Elastography for the Early Detection of Glomerulonephritis. Radiology. 2019 Sep;292(3):676-684. doi: 10.1148/radiol.2019182574. Epub 2019 Jul 9. PMID: 31287390.
- Marticorena Garcia SR, Zhu L, Gültekin E, Schmuck R, Burkhardt C, Bahra M, Geisel D, Shahryari M, Braun J, Hamm B, Jin ZY, Sack I, Guo J. Tomoelastography for Measurement of Tumor Volume Related to Tissue Stiffness in Pancreatic Ductal Adenocarcinomas. Invest Radiol. 2020 Dec;55(12):769-774. doi: 10.1097/RLI.0000000000000704. PMID: 32796197.
- Shahryari M, Tzschätzsch H, Guo J, Marticorena Garcia SR, Böning G, Fehrenbach U, Stencel L, Asbach P, Hamm B, Käs JA, Braun J, Denecke T, Sack I. Tomoelastography Distinguishes Noninvasively between Benign and Malignant Liver Lesions. Cancer Res. 2019 Nov 15;79(22):5704-5710. doi: 10.1158/0008-5472.CAN-19-2150. Epub 2019 Sep 24. PMID: 31551364.
- Asbach P, Ro SR, Aldoj N, Snellings J, Reiter R, Lenk J, Köhlitz T, Haas M, Guo J, Hamm B, Braun J, Sack I. In Vivo Quantification of Water Diffusion, Stiffness, and Tissue Fluidity in Benign Prostatic Hyperplasia and Prostate Cancer. Invest Radiol. 2020 Aug;55(8):524-530. doi: 10.1097/RLI.0000000000000685. PMID: 32496317.
- Lang ST, Guo J, Bruns A, Dürr M, Braun J, Hamm B, Sack I, Marticorena Garcia SR. Multiparametric Quantitative MRI for the Detection of IgA Nephropathy Using Tomoelastography, DWI, and BOLD Imaging. Invest Radiol. 2019 Oct;54(10):669-674. doi: 10.1097/RLI.0000000000000585. PMID: 31261295.
- Wang S, Hesse B, Roman M, Stier D, Castillo-Michel H, Cotte M, Suuronen JP, Lagrange A, Radbruch H, Paul F, Taupitz M, Schellenberger E, Sack I, Infante-Duarte C. Increased Retention of Gadolinium in the Inflamed Brain After Repeated Administration of Gadopentetate Dimeglumine: A Proof-of-Concept Study in Mice Combining ICP-MS and Micro- and Nano-SR-XRF. Invest Radiol. 2019 Oct;54(10):617-626. doi: 10.1097/RLI.0000000000000571. PMID: 31033673.
- Guo J, Bertalan G, Meierhofer D, Klein C, Schreyer S, Steiner B, Wang S, Vieira da Silva R, Infante-Duarte C, Koch S, Boehm-Sturm P, Braun J, Sack I. Brain maturation is associated with increasing tissue stiffness and decreasing tissue fluidity. Acta Biomater. 2019 Nov;99:433-442. doi: 10.1016/j.actbio.2019.08.036. Epub 2019 Aug 23. PMID: 31449927.
- Li M, Guo J, Hu P, Jiang H, Chen J, Hu J, Asbach P, Sack I, Li W. Tomoelastography Based on Multifrequency MR Elastography for Prostate Cancer Detection: Comparison with Multiparametric MRI. Radiology. 2021 May;299(2):362-370. doi: 10.1148/radiol.2021201852. Epub 2021 Mar 9. Erratum in: Radiology. 2021 May;299(2):E259. PMID: 33687285.
- Schrank F, Warmuth C, Görner S, Meyer T, Tzschätzsch H, Guo J, Uca YO, Elgeti T, Braun J, Sack I. Real-time MR elastography for viscoelasticity quantification in skeletal muscle during dynamic exercises. Magn Reson Med. 2020 Jul;84(1):103-114. doi: 10.1002/mrm.28095. Epub 2019 Nov 27. PMID: 31774210.
- Bertalan G, Klein C, Schreyer S, Steiner B, Kreft B, Tzschätzsch H, de Schellenberger AA, Nieminen-Kelhä M, Braun J, Guo J, Sack I. Biomechanical properties of the hypoxic and dying brain quantified by magnetic resonance elastography. Acta Biomater. 2020 Jan 1;101:395-402. doi: 10.1016/j.actbio.2019.11.011. Epub 2019 Nov 11. PMID: 31726251.
- Lilaj L, Fischer T, Guo J, Braun J, Sack I, Hirsch S. Separation of fluid and solid shear wave fields and quantification of coupling density by magnetic resonance poroelastography. Magn Reson Med. 2021 Mar;85(3):1655-1668. doi: 10.1002/mrm.28507. Epub 2020 Sep 9. PMID: 32902011.
- Bertalan G, Boehm-Sturm P, Schreyer S, Morr AS, Steiner B, Tzschätzsch H, Braun J, Guo J, Sack I. The influence of body temperature on tissue stiffness, blood perfusion, and water diffusion in the mouse brain. Acta Biomater. 2019 Sep 15;96:412-420. doi: 10.1016/j.actbio.2019.06.034. Epub 2019 Jun 25. PMID: 31247381.
- Hudert CA, Tzschätzsch H, Rudolph B, Loddenkemper C, Holzhütter HG, Kalveram L, Wiegand S, Braun J, Sack I, Guo J. How histopathologic changes in pediatric nonalcoholic fatty liver disease influence in vivo liver stiffness. Acta Biomater. 2021 Mar 15;123:178-186. doi: 10.1016/j.actbio.2021.01.019. Epub 2021 Jan 17. PMID: 33472102.
- Xie J, Haeckel A, Hauptmann R, Ray IP, Limberg C, Kulak N, Hamm B, Schellenberger E. Iron(III)-tCDTA derivatives as MRI contrast agents: Increased T1 relaxivities at higher magnetic field strength and pH sensing. Magn Reson Med. 2021 Jun;85(6):3370-3382. doi: 10.1002/mrm.28664. Epub 2021 Feb 4. PMID: 33538352.