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Saborowski A, Wolff K, Spielberg S, et al. Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer . Hepatol Commun. 2019;3(3):423-436doi: 10.1002/hep4.1312.
Saborowski, A., Wolff, K., Spielberg, S., Beer, B., Hartleben, B., Erlangga, Z., Becker, D., Dow, L. E., Marhenke, S., Woller, N., Unger, K., Schirmacher, P., Manns, M. P., Marquardt, J. U., Vogel, A., & Saborowski, M. (2019). Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer . Hepatology communications, 3(3), 423-436. https://doi.org/10.1002/hep4.1312
Saborowski, Anna, et al. "Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer ." Hepatology communications vol. 3,3 (2019): 423-436. doi: https://doi.org/10.1002/hep4.1312
Saborowski A, Wolff K, Spielberg S, Beer B, Hartleben B, Erlangga Z, Becker D, Dow LE, Marhenke S, Woller N, Unger K, Schirmacher P, Manns MP, Marquardt JU, Vogel A, Saborowski M. Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer . Hepatol Commun. 2019 Feb 05;3(3):423-436. doi: 10.1002/hep4.1312. eCollection 2019 Mar. PMID: 30859153; PMCID: PMC6396372.
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Hepatol Commun. 2019 Feb 05;3(3):423-436. doi: 10.1002/hep4.1312. eCollection 2019 Mar.

Murine Liver Organoids as a Genetically Flexible System to Study Liver Cancer .

Hepatology communications

Anna Saborowski, Katharina Wolff, Steffi Spielberg, Benedikt Beer, Björn Hartleben, Zulrahman Erlangga, Diana Becker, Lukas E Dow, Silke Marhenke, Norman Woller, Kristian Unger, Peter Schirmacher, Michael P Manns, Jens U Marquardt, Arndt Vogel, Michael Saborowski

Affiliations

  1. Department of Gastroenterology, Hepatology, and Endocrinology Hannover Medical School Hannover Germany.
  2. Institute of Pathology Hannover Medical School Hannover Germany.
  3. Department of Medicine I, Lichtenberg Research Group Johannes Gutenberg University Mainz Germany.
  4. Meyer Cancer Center, Division of Hematology & Medical Oncology, Department of Medicine Weill Cornell Medicine New York NY.
  5. Research Unit of Radiation Cytogenetics Helmholtz Zentrum München Neuherberg Germany.
  6. Institute of Pathology University Hospital Heidelberg Heidelberg Germany.

PMID: 30859153 PMCID: PMC6396372 DOI: 10.1002/hep4.1312

Abstract

The rising incidence of cholangiocarcinoma (CCA) coupled with a low 5-year survival rate that remains below 10% delineates the urgent need for more effective treatment strategies. Although several recent studies provided detailed information on the genetic landscape of this fatal malignancy, versatile model systems to functionally dissect the immediate clinical relevance of the identified genetic alterations are still missing. To enhance our understanding of CCA pathophysiology and facilitate rapid functional annotation of putative CCA driver and tumor maintenance genes, we developed a tractable murine CCA model by combining the cyclization recombination (Cre)-lox system, RNA interference, and clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology with liver organoids, followed by subsequent transplantation into immunocompetent, syngeneic mice. Histologically, resulting tumors displayed cytokeratin 19-positive ductal structures surrounded by a desmoplastic stroma-hallmark features of human CCAs. Despite their initial biliary phenotype

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