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Author Dieter Saur

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Morphology Matters: A Critical Reappraisal of the Clinical Relevance of Morphologic Criteria From the 2019 WHO Classification in a Large Colorectal Cancer Cohort Comprising 1004 Cases.

Moritz Jesinghaus, Maxime Schmitt, Corinna Lang, Marianne Reiser, Alexander Scheiter, Björn Konukiewitz, Katja Steiger, Miguel Silva, Markus Tschurtschenthaler, Sebastian Lange, Sebastian Foersch, Karl F Becker, Dieter Saur, Helmut Friess, Kathrin Halfter, Jutta Engel, Melanie Boxberg, Nicole Pfarr, Dirk Wilhelm, Wilko Weichert,

The 2019 World Health Organization (WHO) classification of colorectal carcinoma (CRC) profoundly reclassified CRC subtypes and introduces tumor budding as a second major grading criterion, while condensing conventional grade into a 2-tiered system. So far it remains largely unexplored how these parameters interact with each other and whether they truly ... Read more >>

Am J Surg Pathol (The American journal of surgical pathology)
[2021, 45(7):969-978]

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Artificial intelligence in early drug discovery enabling precision medicine.

Fabio Boniolo, Emilio Dorigatti, Alexander J Ohnmacht, Dieter Saur, Benjamin Schubert, Michael P Menden,

<b>Introduction</b>: Precision medicine is the concept of treating diseases based on environmental factors, lifestyles, and molecular profiles of patients. This approach has been found to increase success rates of clinical trials and accelerate drug approvals. However, current precision medicine applications in early drug discovery use only a handful of molecular ... Read more >>

Expert Opin Drug Discov (Expert opinion on drug discovery)
[2021, :1-17]

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Metabolic Response of Pancreatic Carcinoma Cells under Treatment with Dichloroacetate.

Benedikt Feuerecker, Philipp Biechl, Christian Veltkamp, Dieter Saur, Wolfgang Eisenreich,

In modern oncology, the analysis and evaluation of treatment response are still challenging. Hence, we used a <sup>13</sup>C-guided approach to study the impacts of the small molecule dichloroacetate (DCA) upon the metabolic response of pancreatic cancer cells. Two different oncogenic PI3K-driven pancreatic cancer cell lines, 9580 and 10,158, respectively, were ... Read more >>

Metabolites (Metabolites)
[2021, 11(6):]

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Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Benoit Thibault, Fernanda Ramos-Delgado, Elvire Pons-Tostivint, Nicole Therville, Celia Cintas, Silvia Arcucci, Stephanie Cassant-Sourdy, Gabriela Reyes-Castellanos, Marie Tosolini, Amelie V Villard, Coralie Cayron, Romain Baer, Justine Bertrand-Michel, Delphine Pagan, Dina Ferreira Da Mota, Hongkai Yan, Chiara Falcomatà, Fabrice Muscari, Barbara Bournet, Jean-Pierre Delord, Ezra Aksoy, Alice Carrier, Pierre Cordelier, Dieter Saur, Celine Basset, Julie Guillermet-Guibert,

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC ... Read more >>

EMBO Mol Med (EMBO molecular medicine)
[2021, :e13502]

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Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment

Yanqing Huang, Carolina Garcia Garcia, Daniel Lin, Nicholas Nguyen, Tara Fujimoto, Jun Zhao, Jaewon Lee, Vincent Bernard, Meifang Yu, Abagail Delahoussaye, Jae Phan, Amit Deorukhkar, Jessica Molkentine, Natividad Fuentes, Madeleine Turner, Dieter Saur, Anirban Maitra, Cullen Taniguchi,

<h4>Background & Aims</h4> Pancreatic ductal adenocarcinoma (PDAC) has a hypoxic, immunosuppressive stroma, which contributes to its resistance to immune checkpoint blockade therapies. The hypoxia-inducible factors (HIFs) mediate the cellular response to hypoxia, but their role within the PDAC tumor microenvironment remains unknown. <h4>Methods</h4> We used a dual recombinase mouse model ... Read more >>

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Cannabidiol converts NFκB into a tumor suppressor in glioblastoma with defined antioxidative properties.

Marie N M Volmar, Jiying Cheng, Haitham Alenezi, Sven Richter, Alisha Haug, Zonera Hassan, Maria Goldberg, Yuping Li, Mengzhuo Hou, Christel Herold-Mende, Cecile L Maire, Katrin Lamszus, Charlotte Flüh, Janka Held-Feindt, Gaetano Gargiulo, Geoffrey J Topping, Franz Schilling, Dieter Saur, Günter Schneider, Michael Synowitz, Joel A Schick, Roland E Kälin, Rainer Glass,

<h4>Background</h4>The transcription factor NFκB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma; GBM). Precise therapeutic modulation of NFκB activity can suppress central oncogenic signalling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive.<h4>Methods</h4>In a pharmacogenomics study with a panel of transgenic glioma ... Read more >>

Neuro Oncol (Neuro-oncology)
[2021, :]

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Important role of Nfkb2 in the KrasG12D-driven carcinogenesis in the pancreas.

Zonera Hassan, Christian Schneeweis, Matthias Wirth, Sebastian Müller, Claudia Geismann, Thorsten Neuß, Katja Steiger, Oliver H Krämer, Roland M Schmid, Roland Rad, Alexander Arlt, Maximilian Reichert, Dieter Saur, Günter Schneider,

<h4>Background</h4>Oncogenic Kras initiates and drives carcinogenesis in the pancreas by complex signaling networks, including activation of the NFκB pathway. Although recent evidence has shown that oncogenic gains in Nfκb2 collaborate with Kras in the carcinogenesis, no data at the level of genetics for the contribution of Nfκb2 is available so ... Read more >>

Pancreatology (Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.])
[2021, :]

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A GATA6-centred gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer.

Bernhard Kloesch, Vivien Ionasz, Sumit Paliwal, Natascha Hruschka, Jaime Martinez de Villarreal, Rupert Öllinger, Sebastian Mueller, Hans Peter Dienes, Martin Schindl, Elisabeth S Gruber, Judith Stift, Dietmar Herndler-Brandstetter, Gwen A Lomberk, Barbara Seidler, Dieter Saur, Roland Rad, Raul A Urrutia, Francisco X Real, Paola Martinelli,

<h4>Objective</h4>Molecular taxonomy of tumours is the foundation of personalised medicine and is becoming of paramount importance for therapeutic purposes. Four transcriptomics-based classification systems of pancreatic ductal adenocarcinoma (PDAC) exist, which consistently identified a subtype of highly aggressive PDACs with basal-like features, including ΔNp63 expression and loss of the epithelial master ... Read more >>

Gut (Gut)
[2021, :]

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ExoBow: A transgenic strategy to study CD63 exosomes in vivo

Bárbara Adem, Nuno Bastos, Carolina Ruivo, Patrícia F. Vieira, Barbara Seidler, José C. Machado, Dieter Saur, Dawen Cai, Sonia Melo,

<h4>ABSTRACT</h4> Exosomes are described as central players in a myriad of biological processes. However, the available methodologies to study their function in complex biological systems in vivo are still very limited. The biodistribution of endogenously produced exosomes, the ability to trace their spontaneous flow in order to identify the cell ... Read more >>

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Porcine model elucidates function of p53 isoform in carcinogenesis and reveals novel circTP53 RNA.

Guanglin Niu, Isabel Hellmuth, Tatiana Flisikowska, Hubert Pausch, Beate Rieblinger, Alexander Carrapeiro, Benjamin Schade, Brigitte Böhm, Eva Kappe, Konrad Fischer, Bernhard Klinger, Katja Steiger, Reiner Burgkart, Jean-Christophe Bourdon, Dieter Saur, Alexander Kind, Angelika Schnieke, Krzysztof Flisikowski,

Recent years have seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries a Cre-removable transcriptional stop signal in intron 1, and an oncogenic mutation TP53<sup>R167H</sup> (orthologous to human TP53<sup>R175H</sup>) in exon 5. Pigs with ... Read more >>

Oncogene (Oncogene)
[2021, 40(10):1896-1908]

Cited: 2 times

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Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging.

Takahisa Maruno, Akihisa Fukuda, Norihiro Goto, Motoyuki Tsuda, Kozo Ikuta, Yukiko Hiramatsu, Satoshi Ogawa, Yuki Nakanishi, Yuichi Yamaga, Takuto Yoshioka, Kyoichi Takaori, Shinji Uemoto, Dieter Saur, Tsutomu Chiba, Hiroshi Seno,

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although rigorous efforts identified the presence of 'cancer stem cells (CSCs)' in PDAC and molecular markers for them, stem cell dynamics in vivo have not been clearly demonstrated. Here we focused on Doublecortin-like kinase 1 (Dclk1), known as a CSC marker of ... Read more >>

Elife (eLife)
[2021, 10:]

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Oscillating calcium signals in smooth muscle cells underlie the persistent basal tone of internal anal sphincter.

Ping Lu, Jun Chen, Chenghai Zhang, Dieter Saur, Christina E Baer, Lawrence M Lifshitz, Kevin E Fogarty, Ronghua ZhuGe,

A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and ... Read more >>

J Cell Physiol (Journal of cellular physiology)
[2021, 236(8):5937-5952]

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A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions.

Joshua J Yim, Stefan Harmsen, Krzysztof Flisikowski, Tatiana Flisikowska, Hong Namkoong, Megan Garland, Nynke S van den Berg, José G Vilches-Moure, Angelika Schnieke, Dieter Saur, Sarah Glasl, Dimitris Gorpas, Aida Habtezion, Vasilis Ntziachristos, Christopher H Contag, Sanjiv S Gambhir, Matthew Bogyo, Stephan Rogalla,

Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in high-risk patients. Here we demonstrate the utility and potential for clinical translation of a fluorescently labeled cathepsin-activated chemical probe to highlight gastrointestinal lesions. This probe stays ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(1):]

Cited: 1 time

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Low-cost single-point optoacoustic sensor for spectroscopic measurement of local vascular oxygenation.

Antonios Stylogiannis, Lucas Riobo, Ludwig Prade, Sarah Glasl, Sabine Klein, Giulia Lucidi, Martin Fuchs, Dieter Saur, Vasilis Ntziachristos,

Optical sensors developed for the assessment of oxygen in tissue microvasculature, such as those based on near-infrared spectroscopy, are limited in application by light scattering. Optoacoustic methods are insensitive to light scattering, and therefore, they can provide higher specificity and accuracy when quantifying local vascular oxygenation. However, currently, to the ... Read more >>

Opt Lett (Optics letters)
[2020, 45(24):6579-6582]

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Targeting the ubiquitin-proteasome system in a pancreatic cancer subtype with hyperactive MYC.

Katharina Lankes, Zonera Hassan, María Josefina Doffo, Christian Schneeweis, Svenja Lier, Rupert Öllinger, Roland Rad, Oliver H Krämer, Ulrich Keller, Dieter Saur, Maximilian Reichert, Günter Schneider, Matthias Wirth,

The myelocytomatosis oncogene (MYC) is an important driver in a subtype of pancreatic ductal adenocarcinoma (PDAC). However, MYC remains a challenging therapeutic target; therefore, identifying druggable synthetic lethal interactions in MYC-active PDAC may lead to novel precise therapies. First, to identify networks with hyperactive MYC, we profiled transcriptomes of established ... Read more >>

Mol Oncol (Molecular oncology)
[2020, 14(12):3048-3064]

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Mesenchymal Plasticity Regulated by Prrx1 Drives Aggressive Pancreatic Cancer Biology.

Karin Feldmann, Carlo Maurer, Katja Peschke, Steffen Teller, Kathleen Schuck, Katja Steiger, Thomas Engleitner, Rupert Öllinger, Alice Nomura, Nils Wirges, Aristeidis Papargyriou, Rim Sabrina Jahan Sarker, Raphela Aranie Ranjan, Zahra Dantes, Wilko Weichert, Anil K Rustgi, Roland M Schmid, Roland Rad, Günter Schneider, Dieter Saur, Maximilian Reichert,

<h4>Background & aims</h4>Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibroblast-rich desmoplastic stroma. Cancer-associated fibroblasts (CAFs) have been shown to display a high degree of interconvertible states including quiescent, inflammatory, and myofibroblastic phenotypes; however, the mechanisms by which this plasticity is achieved are poorly understood. Here, we aim to elucidate ... Read more >>

Gastroenterology (Gastroenterology)
[2021, 160(1):346-361.e24]

Cited: 3 times

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Linkage of genetic drivers and strain-specific germline variants confound mouse cancer genome analyses.

Sebastian Mueller, Sebastian Lange, Katharina A N Collins, Stefan Krebs, Helmut Blum, Günter Schneider, Lena Rad, Dieter Saur, Roland Rad,

Nat Commun (Nature communications)
[2020, 11(1):4474]

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Porcine model elucidates function of p53 isoform in carcinogenesis

Guanglin Niu, Isabel Hellmuth, Tatiana Flisikowska, Hubert Pausch, Beate Rieblinger, Alexander Carrapeiro, Benjamin Schade, Brigitte Böhm, Eva Kappe, Konrad Fischer, Bernhard Klinger, Katja Steiger, Reiner Burgkart, Jean-Christophe Bourdon, Dieter Saur, Alexander Kind, Angelika Schnieke, Krzysztof Flisikowski,

<h4>Background</h4> The pig has long been an important animal species for biomedical research. Recent years has also seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele which carries a Cre-removable transcriptional stop signal in intron 1, ... Read more >>

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In vivo functional screening for systems-level integrative cancer genomics.

Julia Weber, Christian J Braun, Dieter Saur, Roland Rad,

With the genetic portraits of all major human malignancies now available, we next face the challenge of characterizing the function of mutated genes, their downstream targets, interactions and molecular networks. Moreover, poorly understood at the functional level are also non-mutated but dysregulated genomes, epigenomes or transcriptomes. Breakthroughs in manipulative mouse ... Read more >>

Nat Rev Cancer (Nature reviews. Cancer)
[2020, 20(10):573-593]

Cited: 2 times

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Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.

Zahra Dantes, Hsi-Yu Yen, Nicole Pfarr, Christof Winter, Katja Steiger, Alexander Muckenhuber, Alexander Hennig, Sebastian Lange, Thomas Engleitner, Rupert Öllinger, Roman Maresch, Felix Orben, Irina Heid, Georgios Kaissis, Kuangyu Shi, Geoffrey Topping, Fabian Stögbauer, Matthias Wirth, Katja Peschke, Aristeidis Papargyriou, Massoud Rezaee-Oghazi, Karin Feldmann, Arlett Pg Schäfer, Raphela Ranjan, Clara Lubeseder-Martellato, Daniel E Stange, Thilo Welsch, Marc Martignoni, Güralp O Ceyhan, Helmut Friess, Alexander Herner, Lucia Liotta, Matthias Treiber, Guido von Figura, Mohamed Abdelhafez, Peter Klare, Christoph Schlag, Hana Algül, Jens Siveke, Rickmer Braren, Gregor Weirich, Wilko Weichert, Dieter Saur, Roland Rad, Roland M Schmid, Günter Schneider, Maximilian Reichert,

One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs ... Read more >>

JCI Insight (JCI insight)
[2020, 5(15):]

Cited: 3 times

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A GATA6-centered gene regulatory network involving HNFs and ΔNp63 controls plasticity and immune escape in pancreatic cancer

Bernhard Kloesch, Natascha Hruschka, Vivien Ionasz, Rupert Oellinger, Sebastian Mueller, Jaime Martinez de Villareal, Hans-Peter Dienes, Martin Schindl, Elisabeth Gruber, Judith Stift, Gwen Lomberk, Barbara Seidler, Dieter Saur, Roland Rad, Raul Urrutia, Francisco Real, Paola Martinelli,

<h4>Objective</h4> Molecular taxonomy of tumors is the foundation of personalized medicine and is becoming of paramount importance for therapeutic purposes. Four transcriptomics-based classification systems of pancreatic ductal adenocarcinoma (PDAC) exist, which consistently identified a subtype of highly aggressive PDACs with basal-like features, including ΔNp63 expression and loss of the epithelial ... Read more >>

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Blocking the road to de-differentiation: HNF1A/KDM6A complex safeguards epithelial integrity in pancreatic cancer.

Stefanie Bärthel, Günter Schneider, Dieter Saur,

Epithelial differentiation of normal and tumor cells is orchestrated by lineage-determining transcriptional regulatory networks that enforce cell identity. Recent research by Kalisz et al (2020) in the EMBO Journal elucidates the molecular mechanisms by which a transcriptional differentiation program governed by HNF1A and KDM6A maintains acinar differentiation and the epithelial identity ... Read more >>

EMBO J (The EMBO journal)
[2020, 39(9):e104759]

Cited: 1 time

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Analysis pipelines for cancer genome sequencing in mice.

Sebastian Lange, Thomas Engleitner, Sebastian Mueller, Roman Maresch, Maximilian Zwiebel, Laura González-Silva, Günter Schneider, Ruby Banerjee, Fengtang Yang, George S Vassiliou, Mathias J Friedrich, Dieter Saur, Ignacio Varela, Roland Rad,

Mouse models of human cancer have transformed our ability to link genetics, molecular mechanisms and phenotypes. Both reverse and forward genetics in mice are currently gaining momentum through advances in next-generation sequencing (NGS). Methodologies to analyze sequencing data were, however, developed for humans and hence do not account for species-specific ... Read more >>

Nat Protoc (Nature protocols)
[2020, 15(2):266-315]

Cited: 3 times

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SUMO pathway inhibition targets an aggressive pancreatic cancer subtype.

Alexander Biederstädt, Zonera Hassan, Christian Schneeweis, Markus Schick, Lara Schneider, Alexander Muckenhuber, Yingfen Hong, Gerrit Siegers, Lisa Nilsson, Matthias Wirth, Zahra Dantes, Katja Steiger, Kathrin Schunck, Steve Langston, H-P Lenhof, Andrea Coluccio, Felix Orben, Jolanta Slawska, Anna Scherger, Dieter Saur, Stefan Müller, Roland Rad, Wilko Weichert, Jonas Nilsson, Maximilian Reichert, Günter Schneider, Ulrich Keller,

<h4>Objective</h4>Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of ... Read more >>

Gut (Gut)
[2020, 69(8):1472-1482]

Cited: 7 times

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Personalizing KRAS-Mutant Allele-Specific Therapies.

Chiara Falcomatà, Günter Schneider, Dieter Saur,

KRAS G12R mutations occur almost exclusively in pancreatic ductal adenocarcinoma. The results of a study that reveals specific differences in KRAS downstream signaling and metabolic rewiring of pancreatic cancer cells harboring KRAS G12R mutations promise to improve our possibilities to better stratify patients for individualized therapies.See related article by Hobbs ... Read more >>

Cancer Discov (Cancer discovery)
[2020, 10(1):23-25]

Cited: 1 time

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