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Pancreatic Neoplasms: HELP
Articles by Silvia Ribback
Based on 7 articles published since 2009
(Why 7 articles?)
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Between 2009 and 2019, Silvia Ribback wrote the following 7 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma. 2018

Mahajan, Ujjwal Mukund / Langhoff, Eno / Goni, Elisabetta / Costello, Eithne / Greenhalf, William / Halloran, Christopher / Ormanns, Steffen / Kruger, Stephan / Boeck, Stefan / Ribback, Silvia / Beyer, Georg / Dombroswki, Frank / Weiss, Frank-Ulrich / Neoptolemos, John P / Werner, Jens / D'Haese, Jan G / Bazhin, Alexandr / Peterhansl, Julian / Pichlmeier, Svenja / Büchler, Markus W / Kleeff, Jörg / Ganeh, Paula / Sendler, Matthias / Palmer, Daniel H / Kohlmann, Thomas / Rad, Roland / Regel, Ivonne / Lerch, Markus M / Mayerle, Julia. ·Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany. · Department of Medicine III, University Hospital, LMU Munich, Germany. · Department of Pathology, University Medicine Greifswald, Greifswald, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther University Halle-Wittenberg, Halle, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. · Department of Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Center for Translational Cancer Research (TranslaTUM), Technische Universität München, Munich, Germany. · Department of Medicine II, University Hospital, LMU Munich, Germany; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany. Electronic address: julia.mayerle@med.uni-muenchen.de. ·Gastroenterology · Pubmed #30092175.

ABSTRACT: BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.

2 Article Perioperative, Spatiotemporally Coordinated Activation of T and NK Cells Prevents Recurrence of Pancreatic Cancer. 2018

Brooks, Jennifer / Fleischmann-Mundt, Bettina / Woller, Norman / Niemann, Julia / Ribback, Silvia / Peters, Kristin / Demir, Ihsan Ekin / Armbrecht, Nina / Ceyhan, Guralp O / Manns, Michael P / Wirth, Thomas C / Kubicka, Stefan / Bernhardt, Gunter / Smyth, Mark J / Calvisi, Diego F / Gürlevik, Engin / Kühnel, Florian. ·Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. · Institute of Pathology, University Medicine of Greifswald, Greifswald, Germany. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Cancer Center Reutlingen, District Hospital, Reutlingen, Germany. · Institute of Immunology, Hannover Medical School, Hannover, Germany. · QIMR Berghofer Medical Research Institute, Herston, Australia. · Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. kuehnel.florian@mh-hannover.de. ·Cancer Res · Pubmed #29180478.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and natural killier (NK) cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells. Local T-cell activation was confirmed by increased tumor infiltration with CD103

3 Article The Epidermal Growth Factor Receptor (EGFR) Inhibitor Gefitinib Reduces but Does Not Prevent Tumorigenesis in Chemical and Hormonal Induced Hepatocarcinogenesis Rat Models. 2016

Ribback, Silvia / Sailer, Verena / Böhning, Enrico / Günther, Julia / Merz, Jaqueline / Steinmüller, Frauke / Utpatel, Kirsten / Cigliano, Antonio / Peters, Kristin / Pilo, Maria G / Evert, Matthias / Calvisi, Diego F / Dombrowski, Frank. ·Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. silvia.ribback@uni-greifswald.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. verena.sailer@ukb.uni-bonn.de. · Englander Institut for Precision Medicine, Weill Cornell University of Medicine, New York, NY 10065, USA. verena.sailer@ukb.uni-bonn.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. e.boehning@yahoo.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. guenther.julia@hotmail.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. jacqueline.merz@gmx.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. f.steinmueller@diako-online.de. · Pathologisches Institut Diakonie-Krankenhaus, 27356 Rotenburg (Wümme), Germany. f.steinmueller@diako-online.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. kirsten.utpatel@klinik.uni-regensburg.de. · Institut für Pathologie, Universitätsklinikum Regensburg, 93053 Regensburg, Germany. kirsten.utpatel@klinik.uni-regensburg.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. a.cyglius@gmail.com. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. tp905@web.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. giuliapilo1983@gmail.com. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. matthias.evert@uni-greifswald.de. · Institut für Pathologie, Universitätsklinikum Regensburg, 93053 Regensburg, Germany. matthias.evert@uni-greifswald.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. dcalvisi@uni-greifswald.de. · Institut für Pathologie, Universitätsmedizin Greifswald, 17489 Greifswald, Germany. frank.dombrowski@uni-geifswald.de. ·Int J Mol Sci · Pubmed #27669229.

ABSTRACT: Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N-Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thyroid follicles in thyroidectomized (TTx) and ovarian fragments in ovariectomized (OTx) rats was conducted for the induction of foci of altered hepatocytes (FAH). Gefitinib was administered for two weeks (20 mg/kg) or three and nine months (10 mg/kg). In NNM-treated rats, Gefitinib administration decreased the amount of FAH when compared to controls. The amount of HCA and HCC was decreased, but development was not prevented. Upon all transplantation models, proliferative activity of FAH was lower after administration of Gefitinib in short-term experiments. Nevertheless, the burden of HCA and HCC was not changed in later stages. Thus, EGFR inhibition by Gefitinib diminishes chemical and hormonal also induced hepatocarcinogenesis in the initiation stage in the non-cirrhotic liver. However, progression to malignant hepatocellular tumors was not prevented, indicating only a limited relevance of the EGFR signaling cascade in later stages of hepatocarcinogenesis.

4 Article Administration of Gemcitabine After Pancreatic Tumor Resection in Mice Induces an Antitumor Immune Response Mediated by Natural Killer Cells. 2016

Gürlevik, Engin / Fleischmann-Mundt, Bettina / Brooks, Jennifer / Demir, Ihsan Ekin / Steiger, Katja / Ribback, Silvia / Yevsa, Tetyana / Woller, Norman / Kloos, Arnold / Ostroumov, Dmitrij / Armbrecht, Nina / Manns, Michael P / Dombrowski, Frank / Saborowski, Michael / Kleine, Moritz / Wirth, Thomas C / Oettle, Helmut / Ceyhan, Güralp O / Esposito, Irene / Calvisi, Diego F / Kubicka, Stefan / Kühnel, Florian. ·Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: guerlevik.engin@gmx.net. · Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Pathology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Pathology, University Medicine of Greifswald, Greifswald, Germany. · Department of Surgery, Hannover Medical School, Hannover, Germany. · Charité University Medicine Berlin, Berlin, Germany. · Institute of Pathology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; Institute of Pathology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. · Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; Cancer Center Reutlingen, District Hospital, Reutlingen, Germany. · Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: kuehnel.florian@mh-hannover.de. ·Gastroenterology · Pubmed #27210037.

ABSTRACT: BACKGROUND & AIMS: Even after potentially curative R0 resection, patients with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis owing to high rates of local recurrence and metastasis to distant organs. However, we have no suitable transgenic animal models for surgical interventions. METHODS: To induce formation of pancreatic tumor foci, we electroporated oncogenic plasmids into pancreata of LSL-KrasG12D × p53fl/fl mice; mutant Kras was expressed in p53fl/fl mice using a sleeping beauty transposon. We co-delivered a transposon encoding a constitutively active form of Akt2 (myrAkt2). Carcinogenesis and histopathologic features of tumors were examined. Metastasis was monitored by bioluminescence imaging. Tumors were resected and mice were given gemcitabine, and tumor recurrence patterns and survival were determined. Immune cells were collected from resection sites and analyzed by flow cytometry and in depletion experiments. RESULTS: After electroporation of oncogenic plasmids, mice developed a single pancreatic tumor nodule with histopathologic features of human PDAC. Pancreatic tumors that expressed myrAkt2 infiltrated the surrounding pancreatic tissue and neurons and became widely metastatic, reflecting the aggressive clinical features of PDAC in patients. Despite early tumor resection, mice died from locally recurring and distant tumors, but adjuvant administration of gemcitabine after tumor resection prolonged survival. In mice given adjuvant gemcitabine or vehicle, gemcitabine significantly inhibited local recurrence of tumors, but not metastasis to distant organs, similar to observations in clinical trials. Gemcitabine inhibited accumulation of CD11b+Gr1intF4/80int myeloid-derived suppressor cells at the resection margin and increased the number of natural killer (NK) cells at this location. NK cells but not T cells were required for gemcitabine-mediated antitumor responses. CONCLUSIONS: Gemcitabine administration after resection of pancreatic tumors in mice activates NK cell-mediated antitumor responses and inhibits local recurrence of tumors, consistent with observations from patients with PDAC. Transgenic mice with resectable pancreatic tumors might be promising tools to study adjuvant therapy strategies for patients.

5 Article Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer. 2016

Mahajan, Ujjwal M / Teller, Steffen / Sendler, Matthias / Palankar, Raghavendra / van den Brandt, Cindy / Schwaiger, Theresa / Kühn, Jens-Peter / Ribback, Silvia / Glöckl, Gunnar / Evert, Matthias / Weitschies, Werner / Hosten, Norbert / Dombrowski, Frank / Delcea, Mihaela / Weiss, Frank-Ulrich / Lerch, Markus M / Mayerle, Julia. ·Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany. · ZIK HIKE-Center for Innovation Competence Humoral Immune Reactions in Cardiovascular Diseases, Greifswald, Germany. · Department of Radiology and Neuroradiology, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. · Institute of Pathology, University Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany. · Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany. ·Gut · Pubmed #27196585.

ABSTRACT: OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and is projected to be the second leading cause of cancer-related death by 2030. Despite extensive knowledge and insights into biological properties and genetic aberrations of PDAC, therapeutic options remain temporary and ineffective. One plausible explanation for the futile response to therapy is an insufficient and non-specific delivery of anticancer drugs to the tumour site. DESIGN: Superparamagnetic iron oxide nanoparticles (SPIONs) coupled with siRNA directed against the cell cycle-specific serine-threonine-kinase, Polo-like kinase-1 (siPLK1-StAv-SPIONs), could serve a dual purpose for delivery of siPLK1 to the tumour and for non-invasive assessment of efficiency of delivery in vivo by imaging the tumour response. siPLK1-StAv-SPIONs were designed and synthesised as theranostics to function via a membrane translocation peptide with added advantage of driving endosomal escape for mediating transportation to the cytoplasm (myristoylated polyarginine peptides) as well as a tumour-selective peptide (EPPT1) to increase intracellular delivery and tumour specificity, respectively. RESULTS: A syngeneic orthotopic as well as an endogenous cancer model was treated biweekly with siPLK1-StAv-SPIONs and tumour growth was monitored by small animal MRI. In vitro and in vivo experiments using a syngeneic orthotopic PDAC model as well as the endogenous LSL-Kras CONCLUSIONS: Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC.

6 Article Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma. 2013

Tschaharganeh, Darjus Felix / Chen, Xin / Latzko, Philipp / Malz, Mona / Gaida, Matthias Martin / Felix, Klaus / Ladu, Sara / Singer, Stephan / Pinna, Federico / Gretz, Norbert / Sticht, Carsten / Tomasi, Maria Lauda / Delogu, Salvatore / Evert, Matthias / Fan, Biao / Ribback, Silvia / Jiang, Lijie / Brozzetti, Stefania / Bergmann, Frank / Dombrowski, Frank / Schirmacher, Peter / Calvisi, Diego Francesco / Breuhahn, Kai. ·Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. ·Gastroenterology · Pubmed #23419361.

ABSTRACT: BACKGROUND & AIMS: Cancer cells often lose contact inhibition to undergo anchorage-independent proliferation and become resistant to apoptosis by inactivating the Hippo signaling pathway, resulting in activation of the transcriptional co-activator yes-associated protein (YAP). However, the oncogenic mechanisms of YAP activity are unclear. METHODS: By using cross-species analysis of expression data, the Notch ligand Jagged-1 (Jag-1) was identified as a downstream target of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells. We analyzed the functions of YAP in HCC cells via overexpression and RNA silencing experiments. We used transgenic mice that overexpressed a constitutively activated form of YAP (YAP(S127A)), and measured protein levels in HCC, colorectal and pancreatic tumor samples from patients. RESULTS: Human HCC cell lines and mouse hepatocytes that overexpress YAP(S127A) up-regulated Jag-1, leading to activation of the Notch pathway and increased proliferation. Induction of Jag-1, activation of Notch, and cell proliferation required binding of YAP to its transcriptional partner TEA domain family member 4 (TEAD4); TEAD4 binding required the Mst1/2 but not β-catenin signaling. Levels of YAP correlated with Jag-1 expression and Notch signaling in human tumor samples and correlated with shorter survival times of patients with HCC or colorectal cancer. CONCLUSIONS: The transcriptional regulator YAP up-regulates Jag-1 to activate Notch signaling in HCC cells and mouse hepatocytes. YAP-dependent activity of Jag-1 and Notch correlate in human HCC and colorectal tumor samples with patient survival times, suggesting the use of YAP and Notch inhibitors as therapeutics for gastrointestinal cancer. Transcript profiling: microarray information was deposited at the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jxepvsumwosqkve&acc=GSE35004).

7 Article V-AKT murine thymoma viral oncogene homolog/mammalian target of rapamycin activation induces a module of metabolic changes contributing to growth in insulin-induced hepatocarcinogenesis. 2012

Evert, Matthias / Calvisi, Diego F / Evert, Katja / De Murtas, Valentina / Gasparetti, Gioia / Mattu, Sandra / Destefanis, Giulia / Ladu, Sara / Zimmermann, Antje / Delogu, Salvatore / Thiel, Sara / Thiele, Andrea / Ribback, Silvia / Dombrowski, Frank. ·Institut für Pathologie, Ernst-Moritz-Arndt-Universität, Greifswald, Germany. ·Hepatology · Pubmed #22271091.

ABSTRACT: CONCLUSIONS: The present results indicate that activation of the AKT/mTOR cascade by unconstrained insulin signaling induces a defined module of metabolic alterations in hepatocytes contributing to aberrant cell growth. Thus, inhibition of AKT/mTOR and related metabolic changes might represent a novel preventive and therapeutic approach to effectively inhibit insulin-induced hepatocarcinogenesis.