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Pancreatic Neoplasms: HELP
Articles by Irina Heid
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, I. Heid wrote the following 7 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Apparent Diffusion Coefficient (ADC) predicts therapy response in pancreatic ductal adenocarcinoma. 2017

Trajkovic-Arsic, M / Heid, I / Steiger, K / Gupta, A / Fingerle, A / Wörner, C / Teichmann, N / Sengkwawoh-Lueong, S / Wenzel, P / Beer, A J / Esposito, I / Braren, R / Siveke, J T. ·Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Nuclear Medicine, University Hospital of Ulm, Ulm, Germany. · Institute of Pathology, University Clinic Duesseldorf, Heinrich-Heine University, Duesseldorf, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. rbraren@tum.de. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. j.siveke@dkfz.de. · German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center (DKFZ), Heidelberg, Germany. j.siveke@dkfz.de. · 2. Medizinische Klinik, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. j.siveke@dkfz.de. ·Sci Rep · Pubmed #29213099.

ABSTRACT: Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.

2 Article Oncogenic KRas-induced Increase in Fluid-phase Endocytosis is Dependent on N-WASP and is Required for the Formation of Pancreatic Preneoplastic Lesions. 2017

Lubeseder-Martellato, Clara / Alexandrow, Katharina / Hidalgo-Sastre, Ana / Heid, Irina / Boos, Sophie Luise / Briel, Thomas / Schmid, Roland M / Siveke, Jens T. ·Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany. Electronic address: clara.lubeseder-martellato@tum.de. · Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany. · Institute of Radiology, Klinikum Rechts der Isar, Technical University of Munich, Germany. · Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Clinic and Polyclinic for Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center, DKFZ, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner Site Essen, West German Cancer Center, University Hospital Essen, Germany. Electronic address: j.siveke@dkfz.de. ·EBioMedicine · Pubmed #28057438.

ABSTRACT: Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas

3 Article Co-clinical Assessment of Tumor Cellularity in Pancreatic Cancer. 2017

Heid, Irina / Steiger, Katja / Trajkovic-Arsic, Marija / Settles, Marcus / Eßwein, Manuela R / Erkan, Mert / Kleeff, Jörg / Jäger, Carsten / Friess, Helmut / Haller, Bernhard / Steingötter, Andreas / Schmid, Roland M / Schwaiger, Markus / Rummeny, Ernst J / Esposito, Irene / Siveke, Jens T / Braren, Rickmer F. ·Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Germany. · Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Germany. · 2nd Medical Department, Klinikum rechts der Isar, Technische Universität München, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), partner site Essen, University Hospital Essen, Essen, Germany. · Department of Surgery, Koc University School of Medicine, Istanbul, Turkey. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Germany. · Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technische Universität München, Germany. · Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland. · Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Germany. · Institute of Pathology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany. rbraren@tum.de j.siveke@dkfz-heidelberg.de Irene.Esposito@med.uni-duesseldorf.de. · 2nd Medical Department, Klinikum rechts der Isar, Technische Universität München, Germany. rbraren@tum.de j.siveke@dkfz-heidelberg.de Irene.Esposito@med.uni-duesseldorf.de. · Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Germany. rbraren@tum.de j.siveke@dkfz-heidelberg.de Irene.Esposito@med.uni-duesseldorf.de. ·Clin Cancer Res · Pubmed #27663591.

ABSTRACT:

4 Article Membranous CD24 drives the epithelial phenotype of pancreatic cancer. 2016

Lubeseder-Martellato, Clara / Hidalgo-Sastre, Ana / Hartmann, Carolin / Alexandrow, Katharina / Kamyabi-Moghaddam, Zahra / Sipos, Bence / Wirth, Matthias / Neff, Florian / Reichert, Maximilian / Heid, Irina / Schneider, Günter / Braren, Rickmer / Schmid, Roland M / Siveke, Jens T. ·II. Medizinische Klinik und Poliklinik, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Current address: Klinik für Anaesthesiologie, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Institute of Pathology, University Tübingen, Tübingen, Germany. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Institute of Radiology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany. · Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. ·Oncotarget · Pubmed #27203385.

ABSTRACT: Surface CD24 has previously been described, together with CD44 and ESA, for the characterization of putative cancer stem cells in pancreatic ductal adenocarcinoma (PDAC), the most fatal of all solid tumors. CD24 has a variety of biological functions including the regulation of invasiveness and cell proliferation, depending on the tumor entity and subcellular localization. Genetically engineered mouse models (GEMM) expressing oncogenic KrasG12D recapitulate the human disease and develop PDAC. In this study we investigate the function of CD24 using GEMM of endogenous PDAC and a model of cerulein-induced acute pancreatitis. We found that (i) CD24 expression was upregulated in murine and human PDAC and during acute pancreatitis (ii) CD24 was expressed exclusively in differentiated PDAC, whereas CD24 absence was associated with undifferentiated tumors and (iii) membranous CD24 expression determines tumor subpopulations with an epithelial phenotype in grafted models. In addition, we show that CD24 protein is stabilized in response to WNT activation and that overexpression of CD24 in pancreatic cancer cells upregulated β-catenin expression augmenting an epithelial, non-metastatic signature. Our results support a positive feedback model according to which (i) WNT activation and subsequent β-catenin dephosphorylation stabilize CD24 protein expression, and (ii) sustained CD24 expression upregulates β-catenin expression. Eventually, membranous CD24 augments the epithelial phenotype of pancreatic tumors. Thus we link the WNT/β-catenin pathway with the regulation of CD24 in the context of PDAC differentiation.

5 Article Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice. 2016

Maresch, Roman / Mueller, Sebastian / Veltkamp, Christian / Öllinger, Rupert / Friedrich, Mathias / Heid, Irina / Steiger, Katja / Weber, Julia / Engleitner, Thomas / Barenboim, Maxim / Klein, Sabine / Louzada, Sandra / Banerjee, Ruby / Strong, Alexander / Stauber, Teresa / Gross, Nina / Geumann, Ulf / Lange, Sebastian / Ringelhan, Marc / Varela, Ignacio / Unger, Kristian / Yang, Fengtang / Schmid, Roland M / Vassiliou, George S / Braren, Rickmer / Schneider, Günter / Heikenwalder, Mathias / Bradley, Allan / Saur, Dieter / Rad, Roland. ·Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. · Institute of Radiology, Klinikum rechts der Isar, Technischen Universität München, 81675 Munich, Germany. · Department of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany. · Institute of Virology, Technische Universität München/Helmholtz Zentrum München, 81675 Munich, Germany. · Instituto de Biomedicina y Biotecnología de Cantabria, 39011 Santander, Spain. · Helmholtz Zentrum München, Research Unit Radiation Cytogenetics, 85764 Neuherberg, Germany. · Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ·Nat Commun · Pubmed #26916719.

ABSTRACT: Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery of CRISPR/Cas9 to the pancreas of adult mice, allowing simultaneous editing of multiple gene sets in individual cells. We use the method to induce pancreatic cancer and exploit CRISPR/Cas9 mutational signatures for phylogenetic tracking of metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as combinatorial gene-network analysis, in vivo synthetic lethality screening and chromosome engineering. Negative-selection screening in the pancreas using multiplexed-CRISPR/Cas9 confirms the vulnerability of pancreatic cells to Brca2-inactivation in a Kras-mutant context. We also demonstrate modelling of chromosomal deletions and targeted somatic engineering of inter-chromosomal translocations, offering multifaceted opportunities to study complex structural variation, a hallmark of pancreatic cancer. The low-frequency mosaic pattern of transfection-based CRISPR/Cas9 delivery faithfully recapitulates the stochastic nature of human tumorigenesis, supporting wide applicability for biological/preclinical research.

6 Article Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. 2015

Mazur, Pawel K / Herner, Alexander / Mello, Stephano S / Wirth, Matthias / Hausmann, Simone / Sánchez-Rivera, Francisco J / Lofgren, Shane M / Kuschma, Timo / Hahn, Stephan A / Vangala, Deepak / Trajkovic-Arsic, Marija / Gupta, Aayush / Heid, Irina / Noël, Peter B / Braren, Rickmer / Erkan, Mert / Kleeff, Jörg / Sipos, Bence / Sayles, Leanne C / Heikenwalder, Mathias / Heßmann, Elisabeth / Ellenrieder, Volker / Esposito, Irene / Jacks, Tyler / Bradner, James E / Khatri, Purvesh / Sweet-Cordero, E Alejandro / Attardi, Laura D / Schmid, Roland M / Schneider, Guenter / Sage, Julien / Siveke, Jens T. ·Department of Pediatrics, Stanford University School of Medicine, California, USA. · Department of Genetics, Stanford University School of Medicine, California, USA. · Second Department of Internal Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Radiation Oncology, Stanford University School of Medicine, California, USA. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · David H. Koch Institute for Integrative Cancer Research, Department of Biology, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · Department of Medicine, Stanford University School of Medicine, California, USA. · Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, California, USA. · Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, Bochum, Germany. · Ruhr-University Bochum, Medical Clinic, Knappschaftskrankenhaus, Bochum, Germany. · Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Pathology, University of Tübingen, Tübingen, Germany. · Institute of Virology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Division of Chronic Inflammation and Cancer, German Cancer Research center (DKFZ) Heidelberg, Germany. · Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen, Germany. · Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. · German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Nat Med · Pubmed #26390243.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9-based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy-induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors.

7 Article Early requirement of Rac1 in a mouse model of pancreatic cancer. 2011

Heid, Irina / Lubeseder-Martellato, Clara / Sipos, Bence / Mazur, Pawel K / Lesina, Marina / Schmid, Roland M / Siveke, Jens T. ·II. Medizinische Klinik Klinikum rechts der Isar, Technische Universität München, Munich, Germany. ·Gastroenterology · Pubmed #21684285.

ABSTRACT: BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease without effective chemopreventive or therapeutic approaches. Although the role of oncogenic Kras in initiating development of PDAC is well established, downstream targets of aberrant Ras signaling are poorly understood. Acinar-ductal metaplasia (ADM) appears to be an important prerequisite for development of pancreatic intraepithelial neoplasia (PanIN), a common precursor to PDAC. RAS-related C3 botulinum substrate 1 (Rac1), which controls actin reorganization, can be activated by Ras, is up-regulated in several human cancers, and is required for cerulein-induced morphologic changes in acini. We investigated effects of loss of Rac1 in Kras-induced pancreatic carcinogenesis in mice. METHODS: Using a Cre/lox approach, we deleted Rac1 from pancreatic progenitor cells in different mouse models of PDAC and in mice with cerulein-induced acute pancreatitis. Acinar epithelial explants of mutant mice were used to investigate the role of Rac1 in vitro. RESULTS: Rac1 expression increased in mouse and human pancreatic tumors, particularly in the stroma. Deletion of Rac1 in Kras(G12D)-induced PDAC in mice reduced formation of ADM, PanIN, and tumors and significantly prolonged survival. Pancreatic epithelial metaplasia was accompanied by apical-basolateral redistribution of F-actin, along with basal expression of Rac1. Acinar epithelial explants that lacked Rac1 or that were incubated with inhibitors of actin polymerization had a reduced ability to undergo ADM in 3-dimensional cultures. CONCLUSIONS: In mice, Rac1 is required for early metaplastic changes and neoplasia-associated actin rearrangements in development of pancreatic cancer. Rac1 might be developed as a diagnostic marker or therapeutic target for PDAC.