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Projectomschrijving

Ronde 2014 Internationaal (Innovative Systems Toxicology for Alternatives to Animal Testing): The liver is a central organ in cancer pathology. Apart from highly prevalent primary cancers (Hepatocellular carcinoma, HCC) the liver is one of the prime sites of metastasis of other cancers. Treatment of cancers requires a balanced combination of cytotoxic agents, which have maximal oncostatic effects on the tumor and limited toxicity to healthy liver tissue. Predicting therapy response is essential for a personalized medicine approach to cancer. However, conventional culture of primary cancer cells is problematic, requiring xenografts in a large number of mice. Here, we will use innovative culture technology to grow organoids obtained from liver tumor and healthy liver tissue and analyze the impact of known hepatotoxic and/or oncostatic compounds by employing a state-of-the art microfluidics system. By employing a system biology approach we identify key histological, biochemical, genomic and proteomic predictors of optimal on-target and off-target efficacy for personalized treatment of HCC.

Producten

Titel: Characterisation of patient-derived liver organoids for precision medicine in primary liver cancers
Auteur: Michael Koch
Titel: Liver cancer organoids as a drug screening model
Auteur: Ruby Lieshout
Titel: Towards personalized medicine for hepatocellular carcinoma (HCC)
Auteur: Luc van der Laan
Titel: Characterisation of patient-derived liver organoids for precision medicine in primary liver cancers
Auteur: Michael Koch, Ernst H. K. Stelzer, Francesco Pampaloni
Titel: Characterisation of patient-derived liver organoids for precision medicine in primary liver cancers
Auteur: Michael Koch,Ernst H. K. Stelzer, Francesco Pampaloni
Titel: Characterisation of patient-derived liver organoids for precision medicine in primary liver cancers
Auteur: Michael Koch,Susanna M. Lissek, Rebecca Lotz, Ernst H. K. Stelzer, Francesco Pampaloni
Titel: Liver Cancer organoids as a drug screening model
Auteur: Ruby Lieshout
Titel: Culture of tumor-derived organoids from cholangiocarcinoma for personalized medicine applications
Auteur: Marcia Gaspersz
Titel: Leverkanker organoiden: Een kweekmodel voor primaire leverkanker
Auteur: Ruby Lieshout
Titel: Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells
Auteur: Tüysüz, Nesrin, van Bloois, Louis, van den Brink, Stieneke, Begthel, Harry, Verstegen, Monique M. A., Cruz, Luis J., Hui, Lijian, van der Laan, Luc J. W., de Jonge, Jeroen, Vries, Robert, Braakman, Eric, Mastrobattista, Enrico, Cornelissen, Jan J., Clevers, Hans, ten Berge, Derk
Magazine: Nature Communications
Titel: Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma
Auteur: Vicent, Silvestre, Lieshout, Ruby, Saborowski, Anna, Verstegen, Monique M A, Raggi, Chiara, Recalcati, Stefania, Invernizzi, Pietro, van der Laan, Luc J W, Alvaro, Domenico, Calvisi, Diego F., Cardinale, Vincenzo
Magazine: Liver International
Titel: Ultra-thin fluorocarbon foils optimise multiscale imaging of three-dimensional native and optically cleared specimens
Auteur: Katharina Hötte, Michael Koch, Lotta Hof, Marcel Tuppi, Monique MA Verstegen, Luc JW van der Laan, Til Moreth, Ernst H. K. Stelzer, Francesco Pampaloni
Magazine: BioRxiv
Link: https://www.biorxiv.org/content/early/2019/02/12/533844.full.pdf
Titel: From organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix
Auteur: Jorke Willemse, Ruby Lieshout, Luc JW van der Laan & Monique MA Verstegen
Magazine: Best Practice and Research Clinical Gastroenterology
Titel: Tissue-specific mutation accumulation in human adult stem cells during life
Auteur: Blokzijl, Francis, de Ligt, Joep, Jager, Myrthe, Sasselli, Valentina, Roerink, Sophie, Sasaki, Nobuo, Huch, Meritxell, Boymans, Sander, Kuijk, Ewart, Prins, Pjotr, Nijman, Isaac J., Martincorena, Inigo, Mokry, Michal, Wiegerinck, Caroline L., Middendorp, Sabine, Sato, Toshiro, Schwank, Gerald, Nieuwenhuis, Edward E. S., Verstegen, Monique M. A., van der Laan, Luc J. W., de Jonge, Jeroen, IJzermans, Jan N. M., Vries, Robert G., van de Wetering, Marc, Stratton, Michael R., Clevers, Hans, Cuppen, E
Magazine: Nature
Titel: Liver regenerative medicine
Auteur: Luc van der Laan & Monique Verstegen

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Samenvatting van de aanvraag

The liver is a central organ in cancer pathology. Apart from highly prevalent primary cancers (Hepatocellular carcinoma, HCC) the liver is one of the prime sites of metastasis of other cancers. Treatment of cancers requires a balanced combination of cytotoxics,, which have maximal oncostatic effects on the tumor and limited toxicity to healthy liver tissue. Predicting therapy response is essential for a personalized medicine approach to cancer. However, conventional culture of primary cancer cells is problematic, requiring xenografts in a large number of mice. Here, we will use innovative culture technology to grow organoids obtained from liver tumor and healthy liver tissue and analyze the impact of known hepatotoxic and/or oncostatic compounds by employing a state-of-the art microfluidics system. By employing a system biology approach we identify key histological, biochemical, genomic and proteomic predictors of optimal on-target and off-target efficacy for personalized treatment of HCC.

Onderwerpen

Kenmerken

Projectnummer:
114027003
Looptijd: 100%
Looptijd: 100 %
2015
2019
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. ing. M.M.A. Verstegen
Verantwoordelijke organisatie:
Erasmus MC