This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. When isolating liver cells, some pathways are activated, e. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell—derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun. Since this time, there have been a number of advances in the understanding of hepatocyte functions, cell signaling, and mechanisms in liver toxicity, as well as culture techniques such as 3D cultures and co-culture with non-parenchymal cells NPCs. More recently, great advances have also been made in the generation of hepatocyte alternative models from iPS cells, embryonic stem cells, etc.
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For more than two decades, colorectal cancer has served as the paradigm for the cooperative activity of oncogenes and tumor suppressor genes in cancer initiation and progression. The depth of molecular characterization for this disease is unparalleled, with specific mutations correlated to each histologic stage of progression from normal colon to malignant colorectal cancer. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. This book explores the past, present, and future of colorectal cancer genetics, with particular emphasis on how knowledge of the molecular pathogenesis of the disease leads to the development of novel therapeutic strategies.
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Search Google Map. David C. Burr grad student , Heiner Deubel post-doc , Paul M. Bays post-doc , David Alais grad student. Witter research assistant , Ayumu Tashiro grad student. Jean Livet grad student , Hillel Adesnik post-doc. Kevin T. Larkin grad student , Thomas Borkovec post-doc. Johan Wessberg post-doc , Uta Sailer collaborator. Nicephorus Blemmydes grad student , Theodorus Exapterigus grad student.
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