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Pancreatic Neoplasms: HELP
Articles by Fabrice Viol
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Fabrice Viol wrote the following 3 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Metastasis of pancreatic cancer: An uninflamed liver micromilieu controls cell growth and cancer stem cell properties by oxidative phosphorylation in pancreatic ductal epithelial cells. 2019

Fabian, Alexander / Stegner, Simon / Miarka, Lauritz / Zimmermann, Johannes / Lenk, Lennart / Rahn, Sascha / Buttlar, Jann / Viol, Fabrice / Knaack, Hendrike / Esser, Daniela / Schäuble, Sascha / Großmann, Peter / Marinos, Georgios / Häsler, Robert / Mikulits, Wolfgang / Saur, Dieter / Kaleta, Christoph / Schäfer, Heiner / Sebens, Susanne. ·Group Inflammatory Carcinogenesis, Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein (UKSH) Campus Kiel, Arnold-Heller-Str. 3, Building 17, 24105, Kiel, Germany. · Group Medical Systems Biology, Institute for Experimental Medicine, Michaelisstr. 5, Building 17, 24105, Kiel, Germany. · Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Schwanenweg 20, 24105, Kiel, Germany. · Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Beutenbergstraße 11A, 07745, Jena, Germany. · Group Molecular Cell Biology, Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany. · Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. · II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Group Inflammatory Carcinogenesis, Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein (UKSH) Campus Kiel, Arnold-Heller-Str. 3, Building 17, 24105, Kiel, Germany. Electronic address: susanne.sebens@email.uni-kiel.de. ·Cancer Lett · Pubmed #30930235.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed when liver metastases already emerged. We recently demonstrated that hepatic stromal cells determine the dormancy status along with cancer stem cell (CSC) properties of pancreatic ductal epithelial cells (PDECs) during metastasis. This study investigated the influence of the hepatic microenvironment - and its inflammatory status - on metabolic alterations and how these impact cell growth and CSC-characteristics of PDECs. Coculture with hepatic stellate cells (HSCs), simulating a physiological liver stroma, but not with hepatic myofibroblasts (HMFs) representing liver inflammation promoted expression of Succinate Dehydrogenase subunit B (SDHB) and an oxidative metabolism along with a quiescent phenotype in PDECs. SiRNA-mediated SDHB knockdown increased cell growth and CSC-properties. Moreover, liver micrometastases of tumor bearing KPC mice strongly expressed SDHB while expression of the CSC-marker Nestin was exclusively found in macrometastases. Consistently, RNA-sequencing and in silico modeling revealed significantly altered metabolic fluxes and enhanced SDH activity predominantly in premalignant PDECs in the presence of HSC compared to HMF. Overall, these data emphasize that the hepatic microenvironment determines the metabolism of disseminated PDECs thereby controlling cell growth and CSC-properties during liver metastasis.

2 Article Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. 2018

Rahn, Sascha / Zimmermann, Vivien / Viol, Fabrice / Knaack, Hendrike / Stemmer, Kerstin / Peters, Lena / Lenk, Lennart / Ungefroren, Hendrik / Saur, Dieter / Schäfer, Heiner / Helm, Ole / Sebens, Susanne. ·Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU) and University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany. · Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany. · Department of General Surgery and Thoracic Surgery, UKSH Campus Kiel, Germany; First Department of Medicine, UKSH Campus Lübeck, Lübeck, Germany. · II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU) and University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany. Electronic address: susanne.sebens@email.uni-kiel.de. ·Cancer Lett · Pubmed #29222037.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation. While hyperglycemia (25 mM d-glucose) did not impact the mesenchymal phenotype of Panc1 cells, CSC-properties were aggravated exemplified by increased Nanog expression and Nanog-dependent formation of holo- and meroclones. In H6c7-kras cells, high glucose increased secretion of Transforming-Growth-Factor-beta1 (TGF-β1) as well as TGF-β1 signaling, and in a TGF-β1-dependent manner reduced E-cadherin expression, increased Nestin expression and number of meroclones. Finally, reduced E-cadherin expression was detected in pancreatic ducts of hyperglycemic but not normoglycemic mice. These data suggest that hyperglycemia promotes the acquisition of mesenchymal and CSC-properties in PDEC by activating TGF-β signaling and might explain how T2DM facilitates pancreatic tumorigenesis.

3 Article The hepatic microenvironment essentially determines tumor cell dormancy and metastatic outgrowth of pancreatic ductal adenocarcinoma. 2017

Lenk, Lennart / Pein, Maren / Will, Olga / Gomez, Beatriz / Viol, Fabrice / Hauser, Charlotte / Egberts, Jan-Hendrik / Gundlach, Jan-Paul / Helm, Ole / Tiwari, Sanjay / Weiskirchen, Ralf / Rose-John, Stefan / Röcken, Christoph / Mikulits, Wolfgang / Wenzel, Patrick / Schneider, Günter / Saur, Dieter / Schäfer, Heiner / Sebens, Susanne. ·Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU) and University Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany. · Cell Biology and Tumor Biology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. · Molecular Imaging North Competence Center, Clinic of Radiology and Neuroradiology, CAU and UKSH Campus Kiel, Kiel, Germany. · Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH Campus Kiel, Kiel, Germany. · Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH Aachen University, Aachen, Germany. · Department of Biochemistry, CAU, Kiel, Germany. · Institute of Pathology, UKSH Campus Kiel, Kiel, Germany. · Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. · II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. ·Oncoimmunology · Pubmed #29296518.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed when liver metastases already emerged. This study elucidated the impact of hepatic stromal cells on growth behavior of premalignant and malignant pancreatic ductal epithelial cells (PDECs). Liver sections of tumor-bearing KPC mice comprised micrometastases displaying low proliferation located in an unobtrusive hepatic microenvironment whereas macrometastases containing more proliferating cells were surrounded by hepatic myofibroblasts (HMFs). In an age-related syngeneic PDAC mouse model livers with signs of age-related inflammation exhibited significantly more proliferating disseminated tumor cells (DTCs) and micrometastases despite comparable primary tumor growth and DTC numbers. Hepatic stellate cells (HSC), representing a physiologic liver stroma, promoted an IL-8 mediated quiescence-associated phenotype (QAP) of PDECs in coculture. QAP included flattened cell morphology, Ki67-negativity and reduced proliferation, elevated senescence-associated β galactosidase activity and diminished p-Erk/p-p38-ratio. In contrast, proliferation of PDECs was enhanced by VEGF in the presence of HMF. Switching the micromilieu from HSC to HMF or blocking VEGF reversed QAP in PDECs. This study demonstrates how HSCs induce and maintain a reversible QAP in disseminated PDAC cells, while inflammatory HMFs foster QAP reversal and metastatic outgrowth. Overall, the importance of the hepatic microenvironment in induction and reversal of dormancy during PDAC metastasis is emphasized.