Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Marc Peeters
Based on 17 articles published since 2010
(Why 17 articles?)
||||

Between 2010 and 2020, M. Peeters wrote the following 17 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. 2012

Van Laethem, J-L / Verslype, C / Iovanna, J L / Michl, P / Conroy, T / Louvet, C / Hammel, P / Mitry, E / Ducreux, M / Maraculla, T / Uhl, W / Van Tienhoven, G / Bachet, J B / Maréchal, R / Hendlisz, A / Bali, M / Demetter, P / Ulrich, F / Aust, D / Luttges, J / Peeters, M / Mauer, M / Roth, A / Neoptolemos, J P / Lutz, M / Anonymous1151075. ·Gastrointestinal Cancer Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. jl.vanlaethem@erasme.ulb.ac.be ·Ann Oncol · Pubmed #21810728.

ABSTRACT: Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

2 Review Unmet Needs in Functional and Nonfunctional Pancreatic Neuroendocrine Neoplasms. 2019

Jensen, Robert T / Bodei, Lisa / Capdevila, Jaume / Couvelard, Anne / Falconi, Massimo / Glasberg, Simona / Kloppel, Günter / Lamberts, Steven / Peeters, Marc / Rindi, Guido / Rinke, Anja / Rothmund, Mathias / Sundin, Anders / Welin, Staffan / Fazio, Nicola / Anonymous1371017 / Anonymous1381017. ·Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USArobertj@bdg10.niddk.nih.gov. · Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Medical Oncology, Vall d'Hebron University Hospital, Vall Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain. · Service de Pathologie, Hôpital Bichat, Paris, France. · Chirurgia del Pancreas, Università Vita e Salute, San Raffaele Hospital IRCCS, Milan, Italy. · Neuroendocrine Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. · Institute of Pathology, Technische Universität München, Munich, Germany. · Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Oncology, Antwerp University Hospital, Edegem, Belgium. · Institute of Anatomic Pathology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. · Department of Gastroenterology, UKGM Marburg and Philipps University, Marburg, Germany. · Department of Surgery, Philipps University, Marburg, Germany. · Department of Radiology, Institute of Surgical Sciences, Uppsala University, Uppsala, Sweden. · Endocrine Oncology Unit, Department of Medical Sciences, University Hospital, Uppsala, Sweden. · Gastrointestinal and Neuroendocrine Oncology Unit, European Institute of Oncology (IEO), Milan, Italy. ·Neuroendocrinology · Pubmed #30282083.

ABSTRACT: Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.

3 Review Molecular profiling of pancreatic neuroendocrine tumors (pNETS) and the clinical potential. 2018

Camilli, Massimiliano / Papadimitriou, Konstantinos / Nogueira, Amanda / Incorvaia, Lorena / Galvano, Antonio / D'Antonio, Federica / Ferri, Jose / Santini, Daniele / Silvestris, Nicola / Russo, Antonio / Peeters, Marc / Rolfo, Christian. ·a Department of Oncology , University Campus Biomedico of Rome , Rome , Italy. · b Oncology Department , Antwerp University Hospital , Edegem , Belgium. · c Phase I-Early Clinical Trials Unit, Oncology Department , Antwerp University Hospital & Center for Oncological Research (CORE) , Antwerp , Belgium. · d Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy. · e Medical Oncology Department , Oncological institute Giovanni Paolo II , Bari , Italy. ·Expert Rev Gastroenterol Hepatol · Pubmed #29629846.

ABSTRACT: INTRODUCTION: Pancreatic neuroendocrine tumors (pNETs) represent a small part of pancreatic neoplasms, and the knowledge about their indolent clinical course remains a subject of investigation. They occur sporadically or as part of familial cancer syndromes and are classified by WHO in 3 categories. There is ongoing research to understand their molecular profiling and leading mutations. Areas covered: The aim of this review is to clarify the overall aspects of tumorigenesis, to expose the latest developments in understanding the course of the disease and the possible therapeutic implications of these. The review also discusses functional and non-functional pNETs and associated inherited syndromes as well as pNET molecular profiling and its possible guidance in the use of targeted therapy. Expert commentary: In the next decade, a more extensive application of new technologies will help improve quality of life and survival, individualizing treatment protocols and identifying which therapeutic strategy is more suitable for each kind of NET.

4 Clinical Trial Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer. 2017

Van Laethem, Jean-Luc / Riess, Hanno / Jassem, Jacek / Haas, Michael / Martens, Uwe M / Weekes, Colin / Peeters, Marc / Ross, Paul / Bridgewater, John / Melichar, Bohuslav / Cascinu, Stefano / Saramak, Piotr / Michl, Patrick / Van Brummelen, David / Zaniboni, Alberto / Schmiegel, Wollf / Dueland, Svein / Giurescu, Marius / Garosi, Vittorio L / Roth, Katrin / Schulz, Anke / Seidel, Henrik / Rajagopalan, Prabhu / Teufel, Michael / Childs, Barrett H. ·Department of Gastroenterology, Erasme University Hospital, CP 572/10, route de Lennik 808, 1070, Brussels, Belgium. JL.VanLaethem@erasme.ulb.ac.be. · Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charity Hospital, Virchow-Klinikum Campus, Augustenburger Platz 1, 13353, Berlin, Germany. · Department of Oncology and Radiotherapy, Medical University of Gdansk, M. Skłodowskiej-Curie 3a Street, Gdansk, 80-210, Poland. · Department of Hematology and Oncology, University of Munich Medical Center, Marchioninistraße 15, 81366, Munich, Germany. · Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, Am Gesundbrunnen 20-26, 74078, Heilbronn, Germany. · Division of Medical Oncology, University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA. · Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium. · Department of Medical Oncology, Guy's & St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. · Department of Oncology, UCL Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK. · Department of Oncology, Palacky University Medical School and University Hospital Olomouc, Křížkovského 8, 771 47, Olomouc, Czech Republic. · Department of Medical Oncology, A.O.U. United Hospitals, Polytechnic University of Marche, Piazza Roma, 22, Ancona, Italy. · Department of Oncological Gastroenterology, Maria Skłodowska-Curie Memorial Cancer Center, ul. W.K. Roentgena 5, 02-781, Warsaw, Poland. · Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital of Giessen and Marburg, Baldingerstraße, 35043, Marburg, Germany. · Universitätsklinikum Halle - University Hospital Halle (Saale), Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany. · Department of Radiotherapy, UZ Brussels, Avenue du Laerbeek 101, 1090, Brussels, Belgium. · Department of Medical Oncology, Poliambulanza Foundation Hospital Institute, Via Bissolati, 57, Brescia, Italy. · Department of Gastroenterology and Hepatology, Medical University Hospital Bochum, Alexandrinenstraße 1, Bochum, 44791, Germany. · Department of Oncology, Oslo University Radium Hospital, Trondheimsveien 235, Bjerke, 0514, Oslo, Norway. · Bayer Pharma AG, Müllerstraße 178, 13353, Berlin, Germany. · Bayer S.p.A., Viale Certosa 126-130, 20156, Milan, Italy. · Bayer HealthCare Pharmaceuticals, Inc., 100 Bayer Blvd, Whippany, NJ, 07981, USA. ·Target Oncol · Pubmed #27975152.

ABSTRACT: BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA. RESULTS: Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m CONCLUSION: Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation.

5 Clinical Trial A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. 2015

Fuchs, C S / Azevedo, S / Okusaka, T / Van Laethem, J-L / Lipton, L R / Riess, H / Szczylik, C / Moore, M J / Peeters, M / Bodoky, G / Ikeda, M / Melichar, B / Nemecek, R / Ohkawa, S / Świeboda-Sadlej, A / Tjulandin, S A / Van Cutsem, E / Loberg, R / Haddad, V / Gansert, J L / Bach, B A / Carrato, A. ·Department of Medical Oncology/Solid Tumor Oncology, Dana-Farber Cancer Institute, Boston, USA charles_fuchs@dfci.harvard.edu. · Oncology Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium. · Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia. · Department of Hematology, Oncology, and Tumor Immunology, Charité University, Berlin, Germany. · Department of Oncology, Military Institute of Health Services, Warsaw, Poland. · Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. · Department of Oncology, Antwerp University Hospital, Edegum, Belgium. · Department of Oncology, St László Hospital, Budapest, Hungary. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc. · Department of Oncology, Masaryk University Medical School and Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Haematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland. · Department of Clinical Pharmacology and Chemotherapy, Russian Cancer Research Center, Moscow, Russia. · Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. · Medical Sciences, Amgen Inc., Thousand Oaks, USA. · Global Biostatistical Science, Amgen Ltd, Cambridge, UK. · Global Development, Thousand Oaks. · Development Oncology Therapeutics, Amgen Inc., Thousand Oaks, USA. · Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain. ·Ann Oncol · Pubmed #25609246.

ABSTRACT: BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

6 Clinical Trial Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. 2010

Van Laethem, Jean-Luc / Hammel, Pascal / Mornex, Françoise / Azria, David / Van Tienhoven, Geertjan / Vergauwe, Philippe / Peeters, Marc / Polus, Marc / Praet, Michel / Mauer, Murielle / Collette, Laurence / Budach, Volker / Lutz, Manfred / Van Cutsem, Eric / Haustermans, Karin. ·Department of Gastroenterology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. JL.Vanlaethem@erasme.ulb.ac.be ·J Clin Oncol · Pubmed #20837948.

ABSTRACT: PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. PATIENTS AND METHODS: Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). RESULTS: Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3-related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%). CONCLUSION: Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.

7 Article Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells. 2019

Van Loenhout, Jinthe / Flieswasser, Tal / Freire Boullosa, Laurie / De Waele, Jorrit / Van Audenaerde, Jonas / Marcq, Elly / Jacobs, Julie / Lin, Abraham / Lion, Eva / Dewitte, Heleen / Peeters, Marc / Dewilde, Sylvia / Lardon, Filip / Bogaerts, Annemie / Deben, Christophe / Smits, Evelien. ·Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. jinthe.vanloenhout@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. tal.flieswasser@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. Laurie.freireboullosa@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. jorrit.dewaele@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. jonas.vanaudenaerde@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. elly.marcq@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. julie.jacobs@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. abraham.lin@uantwerpen.be. · Plasma, Laser Ablation and Surface Modelling Group, University of Antwerp, 2610 Wilrijk, Belgium. abraham.lin@uantwerpen.be. · Laboratory of Experimental Hematology, University of Antwerp, 2610 Wilrijk, Belgium. eva.lion@uantwerpen.be. · Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, 9000 Ghent, Belgium. heleen.dewitte@ugent.be. · Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, 1090 Jette, Belgium. heleen.dewitte@ugent.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. marc.peeters@uza.be. · Department of Oncology, Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital, 2650 Edegem, Belgium. marc.peeters@uza.be. · Proteinchemistry, proteomics and epigenetic signaling group, University of Antwerp, 2610 Wilrijk, Belgium. sylvia.dewilde@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. filip.lardon@uantwerpen.be. · Plasma, Laser Ablation and Surface Modelling Group, University of Antwerp, 2610 Wilrijk, Belgium. annemie.bogaerts@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. christophe.deben@uantwerpen.be. · Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium. evelien.smits@uza.be. ·Cancers (Basel) · Pubmed #31635070.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs). Recently, physical cold atmospheric plasma consisting of reactive oxygen and nitrogen species has emerged as a novel treatment option for cancer. In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In contrast, pPBS induced no ICD in PSC. In general, pPBS treatment of PCCs and PSCs created a more immunostimulatory secretion profile (higher TNF-α and IFN-γ, lower TGF-β) in coculture with DC. Altogether, these data show that plasma treatment via pPBS has the potential to induce ICD in PCCs and to reduce the immunosuppressive tumor microenvironment created by PSCs. Therefore, these data provide a strong experimental basis for further in vivo validation, which might potentially open the way for more successful combination strategies with immunotherapy for PDAC.

8 Article Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms. 2019

Vandamme, T / Beyens, M / Boons, G / Schepers, A / Kamp, K / Biermann, K / Pauwels, P / De Herder, W W / Hofland, L J / Peeters, M / Van Camp, G / Op de Beeck, K. ·Center of Oncological Research (CORE), University of Antwerp, Antwerp, Belgium. · Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. · Center of Medical Genetics, University of Antwerp, Antwerp, Belgium. · Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Pathology, University of Antwerp, Antwerp, Belgium. ·Endocr Relat Cancer · Pubmed #30021865.

ABSTRACT: Mutations in DAXX/ATRX, MEN1 and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel. Novel amplicon-based algorithms were used to identify both single nucleotide variants (SNVs) and insertion-deletions (indels) present in >10% of reads (high abundance) and in <10% of reads (low abundance). Found variants were validated by Sanger sequencing. Sequencing resulted in 416,711,794 reads with an average target base coverage of 2663 ± 1476. Across all samples, 32 high-abundance somatic, 3 germline and 30 low-abundance mutations were withheld after filtering and validation. Overall, 92% of high-abundance and 84% of low-abundance mutations were predicted to be protein damaging. Frequently, mutated genes were MEN1, DAXX, ATRX, TSC2, PI3K/Akt/mTOR and MAPK-ERK pathway-related genes. Additionally, recurrent alterations on the same genomic position, so-called hotspot mutations, were found in DAXX, PTCH2 and CYFIP2. This first ultra-deep sequencing study highlighted genetic intra-tumor heterogeneity in pNEN, by the presence of low-abundance mutations. The importance of the ATRX/DAXX pathway was confirmed by the first-ever pNEN-specific protein-damaging hotspot mutation in DAXX. In this study, both novel genes, including the pro-apoptotic CYFIP2 gene and hedgehog signaling PTCH2, and novel pathways, such as the MAPK-ERK pathway, were implicated in pNEN.

9 Article Natural killer cells and their therapeutic role in pancreatic cancer: A systematic review. 2018

Van Audenaerde, Jonas R M / Roeyen, Geert / Darcy, Phillip K / Kershaw, Michael H / Peeters, M / Smits, Evelien L J. ·Center for Oncological Research, University of Antwerp, Antwerp, Belgium; Cancer Immunotherapy and Immune Innovation Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia. Electronic address: jonas.vanaudenaerde@uantwerp.be. · Dept of Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Antwerp, Belgium. · Cancer Immunotherapy and Immune Innovation Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia. · Center for Oncological Research, University of Antwerp, Antwerp, Belgium; Dept of Oncology and Multidisciplinary Oncological Centre Antwerp, Antwerp University Hospital, Antwerp, Belgium. · Center for Oncological Research, University of Antwerp, Antwerp, Belgium; Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium. ·Pharmacol Ther · Pubmed #29660367.

ABSTRACT: Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and immunotherapeutic approaches did not live up to their expectations. Therefore, other horizons have to be explored. Natural Killer (NK) cells are gaining more and more interest as a highly attractive target for cancer immunotherapies, both as pharmaceutical target and for cell therapies. In this systematic review we summarise the pathophysiological adaptions of NK cells in pancreatic cancer and highlight possible (future) therapeutic NK cell-related targets. Furthermore, an extensive overview of recent therapeutic approaches with an effect on NK cells is given, including cytokine-based, viro- and bacteriotherapy and cell therapy. We also discuss ongoing clinical trials that might influence NK cells. In conclusion, although several issues regarding NK cells in pancreatic cancer remain unsolved and need further investigation, extensive evidence is already provided that support NK cell oriented approaches in pancreatic cancer.

10 Article Interleukin-15 stimulates natural killer cell-mediated killing of both human pancreatic cancer and stellate cells. 2017

Van Audenaerde, Jonas R M / De Waele, Jorrit / Marcq, Elly / Van Loenhout, Jinthe / Lion, Eva / Van den Bergh, Johan M J / Jesenofsky, Ralf / Masamune, Atsushi / Roeyen, Geert / Pauwels, Patrick / Lardon, Filip / Peeters, Marc / Smits, Evelien L J. ·Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. · Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. · Department of Medicine II, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Antwerp, Belgium. · Department of Pathology, Antwerp University Hospital, Antwerp, Belgium. · Department of Oncology, Multidisciplinary Oncological Centre Antwerp, Antwerp University Hospital, Antwerp, Belgium. ·Oncotarget · Pubmed #28915646.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the 4

11 Article Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors. 2016

Vandamme, Timon / Beyens, Matthias / de Beeck, Ken Op / Dogan, Fadime / van Koetsveld, Peter M / Pauwels, Patrick / Mortier, Geert / Vangestel, Christel / de Herder, Wouter / Van Camp, Guy / Peeters, Marc / Hofland, Leo J. ·Center of Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. · Section of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015GD Rotterdam, The Netherlands. · Center of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. · Department of Pathology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. · Department of Molecular Imaging, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. ·Br J Cancer · Pubmed #26978006.

ABSTRACT: BACKGROUND: The mTOR-inhibitor everolimus improves progression-free survival in advanced pancreatic neuroendocrine tumours (PNETs). However, adaptive resistance to mTOR inhibition is described. METHODS: QGP-1 and BON-1, two human PNET cell lines, were cultured with increasing concentrations of everolimus up to 22 weeks to reach a dose of 1 μM everolimus, respectively, 1000-fold and 250-fold initial IC50. Using total DNA content as a measure of cell number, growth inhibitory dose-response curves of everolimus were determined at the end of resistance induction and over time after everolimus withdrawal. Response to ATP-competitive mTOR inhibitors OSI-027 and AZD2014, and PI3K-mTOR inhibitor NVP-BEZ235 was studied. Gene expression of 10 PI3K-Akt-mTOR pathway-related genes was evaluated using quantitative real-time PCR (RT-qPCR). RESULTS: Long-term everolimus-treated BON-1/R and QGP-1/R showed a significant reduction in everolimus sensitivity. During a drug holiday, gradual return of everolimus sensitivity in BON-1/R and QGP-1/R led to complete reversal of resistance after 10-12 weeks. Treatment with AZD2014, OSI-027 and NVP-BEZ235 had an inhibitory effect on cell proliferation in both sensitive and resistant cell lines. Gene expression in BON-1/R revealed downregulation of MTOR, RICTOR, RAPTOR, AKT and HIF1A, whereas 4EBP1 was upregulated. In QGP-1/R, a downregulation of HIF1A and an upregulation of ERK2 were observed. CONCLUSIONS: Long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1.

12 Article Whole-exome characterization of pancreatic neuroendocrine tumor cell lines BON-1 and QGP-1. 2015

Vandamme, Timon / Peeters, Marc / Dogan, Fadime / Pauwels, Patrick / Van Assche, Elvire / Beyens, Matthias / Mortier, Geert / Vandeweyer, Geert / de Herder, Wouter / Van Camp, Guy / Hofland, Leo J / Op de Beeck, Ken. ·Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium timon.vandamme@uantwerp.be. · Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. · Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium Department of OncologyUniversity of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, BelgiumSection of EndocrinologyDepartment of Internal Medicine, Erasmus Medical Center, Dr. Molenwaterplein 50, 3015GE Rotterdam, The NetherlandsCenter of Medical GeneticsDepartment of PathologyUniversity of Antwerp and Antwerp University Hospital, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. ·J Mol Endocrinol · Pubmed #25612765.

ABSTRACT: The human BON-1 and QGP-1 cell lines are two frequently used models in pancreatic neuroendocrine tumor (PNET) research. Data on the whole-exome genetic constitution of these cell lines is largely lacking. This study presents, to our knowledge, the first whole-exome profile of the BON-1 and QGP-1 cell lines. Cell line identity was confirmed by short tandem repeat profiling. Using GTG-banding and a CytoSNP-12v2 Beadchip array, cell line ploidy and chromosomal alterations were determined in BON-1 and QGP-1. The exomes of both cell lines were sequenced on Ilumina's HiSeq next-generation sequencing (NGS) platform. Single-nucleotide variants (SNVs) and insertions and deletions (indels) were detected using the Genome Analysis ToolKit. SNVs were validated by Sanger sequencing. Ploidy of BON-1 and QGP-1 was 3 and 4 respectively, with long stretches of loss of heterozygosity across multiple chromosomes, which is associated with aggressive tumor behavior. In BON-1, 57 frameshift indels and 1725 possible protein-altering SNVs were identified in the NGS data. In the QGP-1 cell line, 56 frameshift indels and 1095 SNVs were identified. ATRX, a PNET-associated gene, was mutated in both cell lines, while mutation of TSC2 was detected in BON-1. A mutation in NRAS was detected in BON-1, while KRAS was mutated in QGP-1, implicating aberrations in the RAS pathway in both cell lines. Homozygous mutations in TP53 with possible loss of function were identified in both cell lines. Various MUC genes, implicated in cell signaling, lubrication and chemical barriers, which are frequently expressed in PNET tissue samples, showed homozygous protein-altering SNVs in the BON-1 and QGP-1 cell lines.

13 Article Assessment of neovascular permeability in a pancreatic tumor model using dynamic contrast-enhanced (DCE) MRI with contrast agents of different molecular weights. 2011

Delrue, Louke J / Casneuf, Veerle / Van Damme, Nancy / Blanckaert, Peter / Peeters, Marc / Ceelen, Wim P / Duyck, Philippe C O. ·Department of Radiology, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. Louke.Delrue@uzgent.be ·MAGMA · Pubmed #21567161.

ABSTRACT: OBJECT: We evaluated the relationship of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters and contrast agents with different molecular weights (MW) in a pancreatic tumor mouse model. MATERIALS AND METHODS: Panc02 tumors were induced in mice at the hind leg. DCE-MRI was performed using Gadolinium (Gd)-based contrast agents with different MW: Gd-DOTA (0.5 kDa), P846 (3.5 kDa), and P792 (6.47 kDa). Quantitative vascular parameters (AUC, K(trans), V(e), and V(p)) were calculated according to a modified Tofts two-compartment model. Values for all contrast groups were compared for tumor and control (muscle) tissues. RESULTS: Values for K(trans) and V(e) were significantly higher in tumor tissue than in muscle tissue. When comparing contrast agents, lowest absolute K(trans) values were observed using P792. The relative increase in K(trans) in tumor tissue compared with normal tissue was highest after the use of P792. In both tumor and normal tissues, K(trans) decreased with increasing molecular weight of the contrast agent used. CONCLUSION: It was demonstrated that values for the different DCE-MRI vascular (permeability) parameters are highly dependent on the contrast agent used. Due to their potential to better differentiate tumor from muscle tissue, higher molecular weight contrast agents show promise when evaluating tumors using DCE-MRI.

14 Article Noninvasive monitoring of therapy-induced microvascular changes in a pancreatic cancer model using dynamic contrast-enhanced magnetic resonance imaging with P846, a new low-diffusible gadolinium-based contrast agent. 2011

Casneuf, Veerle F / Delrue, Louke / Van Damme, Nancy / Demetter, Pieter / Robert, Philippe / Corot, Claire / Duyck, Philippe / Ceelen, Wim / Boterberg, Tom / Peeters, Marc. ·Department of Gastroenterology, Ghent University Hospital, De Pintelaan, Gent, Belgium. Veerle.Casneuf@UGent.be ·Radiat Res · Pubmed #21175342.

ABSTRACT: A predictive technique in the management of patients with cancer could improve the therapeutic index by allowing better individualization of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique that can provide anatomical and physiological information on the tumor and its microenvironment. We studied the effect of chemotherapy (gemcitabine), anti-angiogenesis therapy (sunitinib) and radiotherapy on the kinetics of DCE-MRI parameters in a preclinical model of pancreatic cancer using P846, a new low-diffusible contrast agent. Mice underwent DCE-MRI before treatment (MRI1), after 1 week of treatment (MRI2), and after 1 additional week (MRI3). Combined treatment with radiotherapy and sunitinib had a synergistic effect on tumor growth. In radiotherapy/sunitinib-treated mice, a decrease in K(trans) at MRI2 predicted its superior antivascular and antitumor effect at an early time. An increased K(trans) at MRI2, as seen in gemcitabine- and gemcitabine/sunitinib-treated mice, reflects increased permeability for P846 and might predict a smaller therapeutic effect at this early time. This study shows that the kinetics of DCE-MRI parameters depends on the contrast agent used. P846 appears to be a promising low-diffusible agent to monitor therapeutic effects in this preclinical cancer model, but further studies are needed to compare its behavior with Gd-DTPA and macromolecular-weight contrast agents. Sunitinib as a radiosensitizer is promising for future clinical trials in human pancreatic cancer.

15 Article Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. 2010

Maréchal, Raphaël / Mackey, John R / Lai, Raymond / Demetter, Pieter / Peeters, Marc / Polus, Marc / Cass, Carol E / Salmon, Isabelle / Devière, Jacques / Van Laethem, Jean-Luc. ·Department of Gastroenterology and Hepato-Pancreatology, Free University of Brussels, Brussels, Belgium. rmarecha@ulb.ac.be ·Cancer · Pubmed #20669326.

ABSTRACT: BACKGROUND: Gemcitabine (2',2'-difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine-based chemoradiation regimen. METHODS: Forty-five patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based-therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK-positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values. RESULTS: The median follow-up was 19.95 months (95% confident interval [CI], 3.3-107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P = .001; OS: HR, 3.2; 95% CI,1.44-7.13; P = .004). CONCLUSIONS: dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection.

16 Article The low-molecular-weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model. 2010

Debergh, I / Van Damme, N / Pattyn, P / Peeters, M / Ceelen, W P. ·Department of Surgery, University Hospital, De Pintelaan 185, Ghent, Belgium. ·Br J Cancer · Pubmed #20125158.

ABSTRACT: BACKGROUND: Recently, low-molecular-weight heparins (LMWHs) were found to confer a survival advantage in cancer patients. The mechanism underlying this observation is unclear, but may involve inhibition of tumour angiogenesis. We aimed to examine the effects of nadroparin on tumour angiogenesis using a dorsal skinfold window chamber model in the Syrian hamster. METHODS: AMel-3 and HAP-T1 tumours were grown in donor animals and fragments implanted in the window chambers. Animals (N=46) were treated with 200 IU of nadroparin or saline for 10 days. Repeated intravital fluorescence microscopy was performed to calculate functional microcirculatory parameters: number (N) and length (L) of microvessels, vascular area fraction (AF), and red blood cell velocity (V). Microvessel density (MVD), fractal dimension, and pericyte coverage were assessed histologically. RESULTS: Active angiogenesis was observed in control animals, resulting in a significant increase in N, L, and AF. In nadroparin-treated animals, however, N and L did not increase whereas AF decreased significantly. Both groups showed an initial increase in V, but nadroparin treatment resulted in an earlier decrease in red blood cell velocity over time. Compared with control animals, nadroparin-treated animals showed a significantly lower MVD and fractal dimension but significantly higher pericyte coverage index (PCI). CONCLUSIONS: Taken together, these results suggest that the LMWH nadroparin inhibits tumour angiogenesis and results in microvessel normalisation.

17 Minor Serum neuron-specific enolase level is an independent predictor of overall survival in patients with gastroenteropancreatic neuroendocrine tumors. 2016

van Adrichem, R C S / Kamp, K / Vandamme, T / Peeters, M / Feelders, R A / de Herder, W W. ·Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands. · Department of Oncology, University of Antwerp, Antwerp, Belgium. · Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, Rotterdam, The Netherlands w.w.deherder@erasmusmc.nl. ·Ann Oncol · Pubmed #26712902.

ABSTRACT: -- No abstract --