Person: Real Arribas, Francisco
Loading...
First Name
Francisco
Last Name
Real Arribas
Institution
CNIO
Centrre
CNIC Organization
CNIO Organization
Institute
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Publication Reply to 'Mosaic loss of chromosome Y in leukocytes matters'.(Nature Publishing Group, 2019-01) Zhou, Weiyin; Machiela, Mitchell J; Freedman, Neal D; Rothman, Nathaniel; Malats, Nuria; Dagnall, Casey; Caporaso, Neil; Teras, Lauren T; Gaudet, Mia M; Gapstur, Susan M; Stevens, Victoria L; Jacobs, Kevin B; Sampson, Joshua; Albanes, Demetrius; Weinstein, Stephanie; Virtamo, Jarmo; Berndt, Sonja; Hoover, Robert N; Black, Amanda; Silverman, Debra; Figueroa, Jonine; Garcia-Closas, Montserrat; Real Arribas, Francisco; Earl, Julie; Marenne, Gaelle; Rodriguez-Santiago, Benjamin; Karagas, Margaret; Johnson, Alison; Schwenn, Molly; Wu, Xifeng; Gu, Jian; Ye, Yuanqing; Hutchinson, Amy; Tucker, Margaret; Perez-Jurado, Luis A; Dean, Michael; Yeager, Meredith; Chanock, Stephen J; United States Department of Health and Human ServicesPublication Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.(Nature Publishing Group, 2018-02-22) Cobo, Isidoro; Martinelli, Paola; Flández, Marta; Bakiri, Latifa; Zhang, Mingfeng; Carrillo-de-Santa-Pau, Enrique; Jia, Jinping; Sánchez-Arévalo Lobo, Víctor J; Megías, Diego; Felipe, Irene; Del Pozo, Natalia; Millán, Irene; Thommesen, Liv; Bruland, Torunn; Olson, Sara H; Smith, Jill; Schoonjans, Kristina; Bamlet, William R; Petersen, Gloria M; Malats, Núria; Amundadottir, Laufey T; Wagner, Erwin F; Real Arribas, Francisco; Ministerio de Economía y Competitividad (España); European Union (EU); Worldwide Cancer Research; Instituto de Salud Carlos III; United States Department of Health and Human Services; Unión Europea. European Cooperation in Science and Technology (COST); European Science Foundation (ESF); Department of Technology, Norwegian University of Science and Technology; Asociación Española Contra el CáncerChronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation. The orphan nuclear receptor NR5A2 participates in a wide variety of processes, including cholesterol and glucose metabolism in the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid production, pancreatic development and acinar differentiation. In genome-wide association studies, single nucleotide polymorphisms in the vicinity of NR5A2 have previously been associated with the risk of pancreatic adenocarcinoma. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration and cooperates with mutant Kras in tumour progression. Here, using a global transcriptomic analysis, we describe an epithelial-cell-autonomous basal pre-inflammatory state in the pancreas of Nr5a2+/- mice that is reminiscent of the early stages of pancreatitis-induced inflammation and is conserved in histologically normal human pancreases with reduced expression of NR5A2 mRNA. In Nr5a2+/-mice, NR5A2 undergoes a marked transcriptional switch, relocating from differentiation-specific to inflammatory genes and thereby promoting gene transcription that is dependent on the AP-1 transcription factor. Pancreatic deletion of Jun rescues the pre-inflammatory phenotype, as well as binding of NR5A2 to inflammatory gene promoters and the defective regenerative response to damage. These findings support the notion that, in the pancreas, the transcriptional networks involved in differentiation-specific functions also suppress inflammatory programmes. Under conditions of genetic or environmental constraint, these networks can be subverted to foster inflammation.Publication CD8+ Cytotoxic Immune Infiltrate in Non-Muscle Invasive Bladder Cancer: A Standardized Methodology to Study Association with Clinico-Pathological Features and Prognosis.(IOS Press, 2019-08-16) Masson-Lecomte, Alexandra; Maillé, Pascale; Pineda, Silvia; Soyeux, Pascale; Sagrera, Ana; Rava, Marta; de Maturana, Evangelina Lopez; Márquez, Mirari; Tardón, Adonina; Carrato, Alfredo; Kogevinas, Manolis; de la Taille, Alexandre; Hartmann, Arndt; Malats, Nuria; Real Arribas, Francisco; Allory, Yves; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; NIH - National Cancer Institute (NCI) (Estados Unidos); European Association of UrologyBACKGROUND Major interest lies in the evaluation of immune infiltrate in bladder cancer. CD8+ cytotoxic lymphocytes are key effectors of adaptive immune response. OBJECTIVES The aims of the study were to set up a standardized methodology for CD8+ lymphocytes estimation in NMIBC and investigate how intra-tumoral heterogeneity influences CD8+ immune infiltrate. METHODS We considered 995 NMIBC included in the Spanish Bladder Cancer (SBC)/EPICURO Study. Duplicate 0.6mm TMA spots and paired full sections (FS) for 50 selected cases were double stained with anti-pan cytokeratin antibody and anti-CD8 antibody. Slides were digitalized and CD8+ cells were automatically counted after tissue recognition (tumor vs stroma). Spatial heterogeneity was assessed and a resampling strategy was applied to estimate the proper number of 0.6mm TMA spots providing an adequate CD8+ cell estimate. Association between CD8+ count and expression of urothelial differentiation markers was estimated. Cox regression models were performed to assess association between CD8+ cell count and risk of recurrence and progression. RESULTS Microscopic examination of full sections showed spatial heterogeneity for CD8+ infiltrates. Simulation analyses demonstrated that 5 TMA regions provided a correct sampling of tumor and stromal compartments in Ta while 2 and 6 TMA regions were necessary in T1, respectively. CD8+ cells infiltration was associated with stage, regardless of the histological compartment analyzed (median CD8+ /mm2 were 25/mm2 and 129/mm2 in tumor and stroma respectively in Ta and 111/mm2 and 344/mm2 in T1; p-value = 0.006). CD8+ infiltration in tumor compartment was significantly associated with low FGFR3 expression. CD8+/mm2 count in the tumor compartment was not associated with prognosis. CONCLUSION Differences identified between Ta and T1 tumours supported the hypothesis that rigorous efforts should be placed in proper study design. These results provide a new framework to investigate microenvironment complexity in bladder cancer.Publication Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk.(American Association for Cancer Research (AACR), 2020-09-15) Yuan, Fangcheng; Hung, Rayjean J; Walsh, Naomi; Zhang, Han; Platz, Elizabeth A; Wheeler, William; Song, Lei; Arslan, Alan A; Beane Freeman, Laura E; Bracci, Paige; Canzian, Federico; Du, Mengmeng; Gallinger, Steven; Giles, Graham G; Goodman, Phyllis J; Kooperberg, Charles; Le Marchand, Loic; Neale, Rachel E; Rosendahl, Jonas; Scelo, Ghislaine; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Zheng, Wei; Albanes, Demetrius; Amiano, Pilar; Andreotti, Gabriella; Babic, Ana; Bamlet, William R; Berndt, Sonja I; Brennan, Paul; Bueno-de-Mesquita, Bas; Buring, Julie E; Campbell, Peter T; Chanock, Stephen J; Fuchs, Charles S; Gaziano, J Michael; Goggins, Michael G; Hackert, Thilo; Hartge, Patricia; Hassan, Manal M; Holly, Elizabeth A; Hoover, Robert N; Katzke, Verena; Kirsten, Holger; Kurtz, Robert C; Lee, I-Min; Malats, Nuria; Milne, Roger L; Murphy, Neil; Ng, Kimmie; Oberg, Ann L; Porta, Miquel; Rabe, Kari G; Real Arribas, Francisco; Rothman, Nathaniel; Sesso, Howard D; Silverman, Debra T; Thompson, Ian M; Wactawski-Wende, Jean; Wang, Xiaoliang; Wentzensen, Nicolas; Wilkens, Lynne R; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Shi, Jianxin; Duell, Eric J; Amundadottir, Laufey T; Li, Donghui; Petersen, Gloria M; Wolpin, Brian M; Risch, Harvey A; Yu, Kai; Klein, Alison P; Stolzenberg-Solomon, Rachael; NIH - National Cancer Institute (NCI) (Estados Unidos)Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.Publication The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver.(Springer, 2020-08) Hruschka, Natascha; Kalisz, Mark; Subijana, Maria; Graña-Castro, Osvaldo; Del Cano-Ochoa, Francisco; Brunet, Laia Paré; Chernukhin, Igor; Sagrera, Ana; De Reynies, Aurelien; Kloesch, Bernhard; Chin, Suet-Feung; Burgués, Octavio; Andreu, David; Bermejo, Begoña; Cejalvo, Juan Miguel; Sutton, Joe; Caldas, Carlos; Ramón-Maiques, Santiago; Carroll, Jason S; Prat, Aleix; Real Arribas, Francisco; Martinelli, Paola; Ministerio de Ciencia, Innovación y Universidades (España); Institute of Cancer Research of the Medical University Vienna; FWF Austrian Science FundAs the catalog of oncogenic driver mutations is expanding, it becomes clear that alterations in a given gene might have different functions and should not be lumped into one class. The transcription factor GATA3 is a paradigm of this. We investigated the functions of the most common GATA3 mutation (X308_Splice) and five additional mutations, which converge into a neoprotein that we called "neoGATA3," associated with excellent prognosis in patients. Analysis of available molecular data from >3000 breast cancer patients revealed a dysregulation of the ER-dependent transcriptional response in tumors carrying neoGATA3-generating mutations. Mechanistic studies in vitro showed that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone receptors, without fully abrogating them. ChIP-Seq analysis indicated that ER binding is reduced in neoGATA3-expressing cells, especially at distal regions, suggesting that neoGATA3 interferes with the fine tuning of ER-dependent gene expression. This has opposite outputs in distinct hormonal context, having pro- or anti-proliferative effects, depending on the estrogen/progesterone ratio. Our data call for functional analyses of putative cancer drivers to guide clinical application.