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Pancreatic Neoplasms: HELP
Articles by Kivanc Görgülü
Based on 4 articles published since 2010
(Why 4 articles?)
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Between 2010 and 2020, Kivanc Görgülü wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Pharmacotherapeutic Management of Pancreatic Ductal Adenocarcinoma: Current and Emerging Concepts. 2017

Ruess, Dietrich A / Görgülü, Kivanc / Wörmann, Sonja M / Algül, Hana. ·Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. dietrich.ruess@uniklinik-freiburg.de. · Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. · Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. hana.alguel@mri.tum.de. ·Drugs Aging · Pubmed #28349415.

ABSTRACT: Pancreatic ductal adenocarcinoma is a devastating malignancy, which is the result of late diagnosis, aggressive disease, and a lack of effective treatment options. Thus, pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related death by 2030. This review summarizes recent developments of oncological therapy in the palliative setting of metastatic pancreatic ductal adenocarcinoma. It further compiles novel targets and therapeutic approaches as well as promising treatment combinations, which are presently in preclinical evaluation, covering several aspects of the hallmarks of cancer. Finally, challenges to the implementation of an individualized therapy approach in the context of precision medicine are discussed.

2 Article Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice. 2019

Görgülü, Kivanc / Diakopoulos, Kalliope N / Ai, Jiaoyu / Schoeps, Benjamin / Kabacaoglu, Derya / Karpathaki, Angeliki-Faidra / Ciecielski, Katrin J / Kaya-Aksoy, Ezgi / Ruess, Dietrich A / Berninger, Alexandra / Kowalska, Marlena / Stevanovic, Marija / Wörmann, Sonja M / Wartmann, Thomas / Zhao, Yue / Halangk, Walter / Voronina, Svetlana / Tepikin, Alexey / Schlitter, Anna Melissa / Steiger, Katja / Artati, Anna / Adamski, Jerzy / Aichler, Michaela / Walch, Axel / Jastroch, Martin / Hartleben, Götz / Mantzoros, Christos S / Weichert, Wilko / Schmid, Roland M / Herzig, Stephan / Krüger, Achim / Sainz, Bruno / Lesina, Marina / Algül, Hana. ·Klinik und Poliklinik für Innere Medizin II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Institute of Molecular Immunology and Experimental Oncology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Klinik für Chirurgie Bereich Experimentelle Operative Medizin, Universitätsklinikum Magdeburg, Magdeburg, Germany. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Institute of Pathology, Technische Universität München, Munich, Germany and German Cancer Consortium, Munich, Germany. · Institute of Pathology, Technische Universität München, Munich, Germany and German Cancer Consortium, Munich, Germany; Comparative Experimental Pathology, Institute of Pathology, Technische Universität München, Munich, Germany. · Institute of Experimental Genetics, Genome Analysis Centre, Helmholtz Zentrum München, Neuherberg, Germany. · Institute of Experimental Genetics, Genome Analysis Centre, Helmholtz Zentrum München, Neuherberg, Germany; Institute for Diabetes and Cancer, German Center for Diabetes Research, Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany. · Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany. · Helmholtz Diabetes Center and German Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany. · Institute for Diabetes and Cancer, German Center for Diabetes Research, Neuherberg, Germany. · Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, Massachusetts. · Department of Biochemistry, School of Medicine, Autónoma University of Madrid, Madrid, Spain. · Klinik und Poliklinik für Innere Medizin II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: marina.lesina@tum.de. · Klinik und Poliklinik für Innere Medizin II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: hana.alguel@mri.tum.de. ·Gastroenterology · Pubmed #30296435.

ABSTRACT: BACKGROUND AND AIMS: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. METHODS: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5 RESULTS: A5 CONCLUSIONS: In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.

3 Article Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase. 2018

Ruess, Dietrich A / Heynen, Guus J / Ciecielski, Katrin J / Ai, Jiaoyu / Berninger, Alexandra / Kabacaoglu, Derya / Görgülü, Kivanc / Dantes, Zahra / Wörmann, Sonja M / Diakopoulos, Kalliope N / Karpathaki, Angeliki F / Kowalska, Marlena / Kaya-Aksoy, Ezgi / Song, Liang / van der Laan, Eveline A Zeeuw / López-Alberca, María P / Nazaré, Marc / Reichert, Maximilian / Saur, Dieter / Erkan, Mert M / Hopt, Ulrich T / Sainz, Bruno / Birchmeier, Walter / Schmid, Roland M / Lesina, Marina / Algül, Hana. ·Mildred-Scheel-Chair of Tumor Metabolism, Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany. · Cancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Society, Berlin, Germany. · Medicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany. · Koç University School of Medicine, Istanbul, Turkey. · Department of Biochemistry, Autónoma University of Madrid, School of Medicine, Instituto de Investigaciones Biomédicas "Alberto Sols", Madrid, Spain. · Mildred-Scheel-Chair of Tumor Metabolism, Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. hana.alguel@mri.tum.de. ·Nat Med · Pubmed #29808009.

ABSTRACT: The ubiquitously expressed non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, is involved in signal transduction downstream of multiple growth factor, cytokine and integrin receptors

4 Article Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated With Patient Survival. 2016

Wörmann, Sonja M / Song, Liang / Ai, Jiaoyu / Diakopoulos, Kalliope N / Kurkowski, Magdalena U / Görgülü, Kivanc / Ruess, Dietrich / Campbell, Andrew / Doglioni, Claudio / Jodrell, Duncan / Neesse, Albrecht / Demir, Ihsan E / Karpathaki, Angelica-Phaedra / Barenboim, Maxim / Hagemann, Thorsten / Rose-John, Stefan / Sansom, Owen / Schmid, Roland M / Protti, Maria P / Lesina, Marina / Algül, Hana. ·II Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Beatson Institute for Cancer Research, University of Glasgow, Glasgow, United Kingdom. · Pathology Unit, San Raffaele Scientific Institute, Ospedale San Raffaele, Milan, Italy. · Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom. · Department of Gastroenterology, Endocrinology and Metabolism, Philipps-University, Marburg, Germany. · Chirurgische Klinik und Poliklinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · II Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany. · Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, United Kingdom. · Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany. · Tumor Immunology Unit, San Raffaele Scientific Institute, Ospedale San Raffaele, Milan, Italy. · II Medizinische Klinik, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: hana.alguel@mri.tum.de. ·Gastroenterology · Pubmed #27003603.

ABSTRACT: BACKGROUND & AIMS: One treatment strategy for pancreatic ductal adenocarcinoma is to modify, rather than deplete, the tumor stroma. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is associated with progression of pancreatic and other solid tumors. We investigated whether loss of P53 function contributes to persistent activation of STAT3 and modification of the pancreatic tumor stroma in patients and mice. METHODS: Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice). Pancreata were collected and analyzed by immunohistochemistry, in situ hybridization, quantitative reverse-transcription polymerase chain reaction (qPCR), or immunoblot assays; fluorescence-activated cell sorting was performed to identify immune cells. We obtained frozen pancreatic tumor specimens from patients and measured levels of phosphorylated STAT3 and P53 by immunohistochemistry; protein levels were associated with survival using Kaplan-Meier analyses. We measured levels of STAT3, P53, ligands for gp130, interleukin 6, cytokines, sonic hedgehog signaling, STAT3 phosphorylation (activation), and accumulation of reactive oxygen species in primary pancreatic cells from mice. Mice with pancreatic tumors were given gemcitabine and a Janus kinase 2 (JAK2) inhibitor; tumor growth was monitored by 3-dimensional ultrasound. RESULTS: STAT3 was phosphorylated constitutively in pancreatic tumor cells from KC mice with loss or mutation of P53. Tumor cells of these mice accumulated reactive oxygen species and had lower activity of the phosphatase SHP2 and prolonged phosphorylation of JAK2 compared with tumors from KC mice with functional P53. These processes did not require the gp130 receptor. Genetic disruption of Stat3 in mice, or pharmacologic inhibitors of JAK2 or STAT3 activation, reduced fibrosis and the numbers of pancreatic stellate cells in the tumor stroma and altered the types of immune cells that infiltrated tumors. Mice given a combination of gemcitabine and a JAK2 inhibitor formed smaller tumors and survived longer than mice given control agents; the tumor stroma had fewer activated pancreatic stellate cells, lower levels of periostin, and alterations in collagen production and organization. Phosphorylation of STAT3 correlated with P53 mutation and features of infiltrating immune cells in human pancreatic tumors. Patients whose tumors had lower levels of phosphorylated STAT3 and functional P53 had significantly longer survival times than patients with high levels of phosphorylated STAT3 and P53 mutation. CONCLUSIONS: In pancreatic tumors of mice, loss of P53 function activates JAK2-STAT3 signaling, which promotes modification of the tumor stroma and tumor growth and resistance to gemcitabine. In human pancreatic tumors, STAT3 phosphorylation correlated with P53 mutation and patient survival time. Inhibitors of this pathway slow tumor growth and stroma formation, alter immune cell infiltration, and prolong survival of mice. Transcript profiling: ArrayExpress accession number: E-MTAB-3278.