Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Mar Iglesias
Based on 8 articles published since 2010
(Why 8 articles?)
||||

Between 2010 and 2020, Mar Iglesias wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. 2019

Gasull, Magda / Pumarega, José / Kiviranta, Hannu / Rantakokko, Panu / Raaschou-Nielsen, Ole / Bergdahl, Ingvar A / Sandanger, Torkjel Manning / Goñi, Fernando / Cirera, Lluís / Donat-Vargas, Carolina / Alguacil, Juan / Iglesias, Mar / Tjønneland, Anne / Overvad, Kim / Mancini, Francesca Romana / Boutron-Ruault, Marie-Christine / Severi, Gianluca / Johnson, Theron / Kühn, Tilman / Trichopoulou, Antonia / Karakatsani, Anna / Peppa, Eleni / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Verschuren, Monique / Vermeulen, Roel / Rylander, Charlotta / Nøst, Therese Haugdahl / Rodríguez-Barranco, Miguel / Molinuevo, Amaia / Chirlaque, María-Dolores / Ardanaz, Eva / Sund, Malin / Key, Tim / Ye, Weimin / Jenab, Mazda / Michaud, Dominique / Matullo, Giuseppe / Canzian, Federico / Kaaks, Rudolf / Nieters, Alexandra / Nöthlings, Ute / Jeurnink, Suzanne / Chajes, Veronique / Matejcic, Marco / Gunter, Marc / Aune, Dagfinn / Riboli, Elio / Agudo, Antoni / Gonzalez, Carlos Alberto / Weiderpass, Elisabete / Bueno-de-Mesquita, Bas / Duell, Eric J / Vineis, Paolo / Porta, Miquel. ·Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · National Institute for Health and Welfare, Department of Health Security, Kuopio, Finland. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Biobank Research, Umeå University, Umeå, Sweden; Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. · Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain. · Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Universidad de Huelva, Huelva, Spain. · Department of Pathology, Hospital del Mar (PSMar), Barcelona, Spain. · Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. · CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain. · Hellenic Health Foundation, Athens, Greece. · Hellenic Health Foundation, Athens, Greece; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. · Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy. · Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. · Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Murcia, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Biobank Research, Umeå University, Umeå, Sweden; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden. · Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM/HuGeF, Torino, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Center for Chronic Immunodeficiency, Molecular Epidemiology, University Medical Center Freiburg, Freiburg, Germany. · Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany. · Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. · Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain. · Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: mporta@imim.es. ·Environ Res · Pubmed #30529143.

ABSTRACT: BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

2 Article Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches. 2019

Gomez-Rubio, Paulina / Piñero, Janet / Molina-Montes, Esther / Gutiérrez-Sacristán, Alba / Marquez, Mirari / Rava, Marta / Michalski, Christoph W / Farré, Antoni / Molero, Xavier / Löhr, Matthias / Perea, José / Greenhalf, William / O'Rorke, Michael / Tardón, Adonina / Gress, Thomas / Barberá, Victor M / Crnogorac-Jurcevic, Tatjana / Muñoz-Bellvís, Luís / Domínguez-Muñoz, Enrique / Balsells, Joaquim / Costello, Eithne / Yu, Jingru / Iglesias, Mar / Ilzarbe, Lucas / Kleeff, Jörg / Kong, Bo / Mora, Josefina / Murray, Liam / O'Driscoll, Damian / Poves, Ignasi / Lawlor, Rita T / Ye, Weimin / Hidalgo, Manuel / Scarpa, Aldo / Sharp, Linda / Carrato, Alfredo / Real, Francisco X / Furlong, Laura I / Malats, Núria / Anonymous2240962. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain. · Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain. · Department of Surgery, Technical University of Munich, Munich, Germany. · Department of Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. · Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain. · Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden. · Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain. · Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom. · Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. · Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain. · Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany. · Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain. · Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. · General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain. · Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany. · Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland. · ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden. · Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. · Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom. · Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · PanGenEU Study Investigators (Additional file 1: Annex S1). ·Int J Cancer · Pubmed #30229903.

ABSTRACT: Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

3 Article Increased plasma levels of galectin-1 in pancreatic cancer: potential use as biomarker. 2018

Martinez-Bosch, Neus / Barranco, Luis E / Orozco, Carlos A / Moreno, Mireia / Visa, Laura / Iglesias, Mar / Oldfield, Lucy / Neoptolemos, John P / Greenhalf, William / Earl, Julie / Carrato, Alfredo / Costello, Eithne / Navarro, Pilar. ·Cancer Research Program, IMIM, Hospital del Mar Medical Research Institute, Unidad Asociade CSIC, Barcelona, Spain. · Department of Gastroenterology, Universidad Autonoma de Barcelona, Hospital del Mar, Barcelona, Spain. · Department of Medical Oncology, Hospital del Mar, Barcelona, Spain. · Department of Pathology, Universidad Autonoma de Barcelona, Hospital del Mar, CIBERONC, Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Department of General Surgery, University of Heidelberg, Heidelberg, Germany. · Department of Medical Oncology, Ramon y Cajal University Hospital, CIBERONC, IRYCIS, Alcala University, Madrid, Spain. · Institute of Biomedical Research of Barcelona (IIBB-CSIC), Barcelona, Spain. ·Oncotarget · Pubmed #30250644.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) is the most frequent type of pancreatic cancer and one of the deadliest diseases overall. New biomarkers are urgently needed to allow early diagnosis, one of the only factors that currently improves prognosis. Here we analyzed whether the detection of circulating galectin-1 (Gal-1), a soluble carbohydrate-binding protein overexpressed in PDA tissue samples, can be used as a biomarker for PDA. Gal-1 levels were determined by ELISA in plasma from healthy controls and patients diagnosed with PDA, using three independent cohorts. Patients with chronic pancreatitis (CP) were also included in the study to analyze the potential of Gal-1 to discriminate between cancer and inflammatory process. Plasma Gal-1 levels were significantly increased in patients with PDA as compared to controls in all three cohorts. Gal-1 sensitivity and specificity values were similar to that of the CA19-9 biomarker (the only FDA-approved blood test biomarker for PDA), and the combination of Gal-1 and CA19-9 significantly improved their individual discriminatory powers. Moreover, high levels of Gal-1 were associated with lower survival in patients with non-resected tumors. Collectively, our data indicate a strong potential of using circulating Gal-1 levels as a biomarker for detection and prognostics of patients with PDA.

4 Article Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk. 2018

Orozco, Carlos A / Martinez-Bosch, Neus / Guerrero, Pedro E / Vinaixa, Judith / Dalotto-Moreno, Tomás / Iglesias, Mar / Moreno, Mireia / Djurec, Magdolna / Poirier, Françoise / Gabius, Hans-Joachim / Fernandez-Zapico, Martin E / Hwang, Rosa F / Guerra, Carmen / Rabinovich, Gabriel A / Navarro, Pilar. ·Cancer Research Program, Hospital del Mar Medical Research Institute, 08003 Barcelona, Spain. · Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina. · Department of Pathology, Autonomous University of Barcelona, 08005 Barcelona, Spain. · Centro de Investigación Biomédica en Red de Cáncer, Hospital del Mar, 08005 Barcelona, Spain. · Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas, 28029 Madrid, Spain. · Jacques Monod Institute, Paris Diderot University, UMR CNRS 7592, 75205 Paris Cedex 013, France. · Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, D-80539 Munich, Germany. · Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN 55905. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77230. · Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina; gabyrabi@gmail.com pnavarro@imim.es. · Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428 Buenos Aires, Argentina. · Cancer Research Program, Hospital del Mar Medical Research Institute, 08003 Barcelona, Spain; gabyrabi@gmail.com pnavarro@imim.es. · Institute of Biomedical Research of Barcelona-Consejo Superior de Investigaciones Cientificas, 080036 Barcelona, Spain. ·Proc Natl Acad Sci U S A · Pubmed #29615514.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a

5 Article The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. 2016

Martínez-Bosch, Neus / Guerrero, Pedro Enrique / Moreno, Mireia / José, Anabel / Iglesias, Mar / Munné-Collado, Jessica / Anta, Héctor / Gibert, Joan / Orozco, Carlos Alberto / Vinaixa, Judith / Fillat, Cristina / Viñals, Francesc / Navarro, Pilar. ·Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. · Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain. · Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. · Pathology Service, Hospital del Mar, Barcelona, Spain. · Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain. · Catalan Institute of Oncology-IDIBELL, Barcelona University, Barcelona, Spain. ·Oncotarget · Pubmed #27374084.

ABSTRACT: Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment.

6 Article Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer. 2014

Martínez-Bosch, Neus / Iglesias, Mar / Munné-Collado, Jessica / Martínez-Cáceres, Carlos / Moreno, Mireia / Guerra, Carmen / Yélamos, Jose / Navarro, Pilar. ·Cancer Research Programme, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. ·J Pathol · Pubmed #24889936.

ABSTRACT: Pancreatic cancer has a dismal prognosis and is currently the fourth leading cause of cancer-related death in developed countries. The inhibition of poly(ADP-ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP-ribosy)lation in response to DNA damage, has emerged as a promising treatment for several tumour types. Here we aimed to elucidate the involvement of Parp-1 in pancreatic tumour progression. We assessed Parp-1 protein expression in normal, preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc-driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar cells in normal and cancer tissues. In contrast, ductal cells expressed very low or undetectable levels of this protein, both in a normal and in a tumour context. The Parp-1 expression pattern was similar in human and mouse samples, thereby validating the use of animal models for further studies. To determine the in vivo effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss of Parp-1 resulted in increased tumour necrosis and decreased proliferation, apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally, molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3-MMP7 axis and is also involved in transcriptional up-regulation of the MDM2, VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1 depletion point to a novel role for this protein in pancreatic carcinogenesis and shed light into the clinical use of Parp-1 inhibitors.

7 Article Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and Hedgehog signaling activation. 2014

Martínez-Bosch, Neus / Fernández-Barrena, Maite G / Moreno, Mireia / Ortiz-Zapater, Elena / Munné-Collado, Jessica / Iglesias, Mar / André, Sabine / Gabius, Hans-Joachim / Hwang, Rosa F / Poirier, Françoise / Navas, Carolina / Guerra, Carmen / Fernández-Zapico, Martin E / Navarro, Pilar. ·Authors' Affiliations: Cancer Research Program and. · Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, Minnesota; · Authors' Affiliations: Cancer Research Program and Department of Pathology, IMIM (Hospital del Mar Medical Research Institute), Barcelona; · Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität, München, Germany; and. · Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; · Institute Jacques Monod, CNRS UMR7592, Université Paris Diderot, Paris, France. · Experimental Oncology Group, CNIO, Madrid, Spain; · Authors' Affiliations: Cancer Research Program and pnavarro@imim.es. ·Cancer Res · Pubmed #24812270.

ABSTRACT: Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy.

8 Article Key contribution of CPEB4-mediated translational control to cancer progression. 2011

Ortiz-Zapater, Elena / Pineda, David / Martínez-Bosch, Neus / Fernández-Miranda, Gonzalo / Iglesias, Mar / Alameda, Francesc / Moreno, Mireia / Eliscovich, Carolina / Eyras, Eduardo / Real, Francisco X / Méndez, Raúl / Navarro, Pilar. ·Cancer Research Programme, Hospital del Mar Research Institute (IMIM), Barcelona, Spain. ·Nat Med · Pubmed #22138752.

ABSTRACT: Malignant transformation, invasion and angiogenesis rely on the coordinated reprogramming of gene expression in the cells from which the tumor originated. Although deregulated gene expression has been extensively studied at genomic and epigenetic scales, the contribution of the regulation of mRNA-specific translation to this reprogramming is not well understood. Here we show that cytoplasmic polyadenylation element binding protein 4 (CPEB4), an RNA binding protein that mediates meiotic mRNA cytoplasmic polyadenylation and translation, is overexpressed in pancreatic ductal adenocarcinomas and glioblastomas, where it supports tumor growth, vascularization and invasion. We also show that, in pancreatic tumors, the pro-oncogenic functions of CPEB4 originate in the translational activation of mRNAs that are silenced in normal tissue, including the mRNA of tissue plasminogen activator, a key contributor to pancreatic ductal adenocarcinoma malignancy. Taken together, our results document a key role for post-transcriptional gene regulation in tumor development and describe a detailed mechanism for gene expression reprogramming underlying malignant tumor progression.