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Pancreatic Neoplasms: HELP
Articles by Margaret E. Torrence
Based on 4 articles published since 2010
(Why 4 articles?)
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Between 2010 and 2020, Margaret E. Torrence wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. 2017

Olivares, Orianne / Mayers, Jared R / Gouirand, Victoire / Torrence, Margaret E / Gicquel, Tristan / Borge, Laurence / Lac, Sophie / Roques, Julie / Lavaut, Marie-Noëlle / Berthezène, Patrice / Rubis, Marion / Secq, Veronique / Garcia, Stéphane / Moutardier, Vincent / Lombardo, Dominique / Iovanna, Juan Lucio / Tomasini, Richard / Guillaumond, Fabienne / Vander Heiden, Matthew G / Vasseur, Sophie. ·Centre de Recherche en Cancérologie de Marseille (CRCM), Unité 1068, Institut National de la Santé et de la Recherche Médicale, Marseille F-13009, France. · Institut Paoli-Calmettes (IPC), Marseille F-13009, France. · Unité Mixte de Recherche (UMR 7258), Centre National de la Recherche Scientifique (CNRS), Marseille F-13009, France. · Université Aix-Marseille, Marseille F-13284, France. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK. · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. · Aix Marseille Univ, INSERM, CRO2, Marseille F-13005, France. · Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ·Nat Commun · Pubmed #28685754.

ABSTRACT: Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited. We show PDAC cells are able to take up collagen fragments, which can promote PDAC cell survival under nutrient limited conditions, and that collagen-derived proline contributes to PDAC cell metabolism. Finally, we show that proline oxidase (PRODH1) is required for PDAC cell proliferation in vitro and in vivo. Collectively, our results indicate that PDAC extracellular matrix represents a nutrient reservoir for tumour cells highlighting the metabolic flexibility of this cancer.

2 Article Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. 2016

Mayers, Jared R / Torrence, Margaret E / Danai, Laura V / Papagiannakopoulos, Thales / Davidson, Shawn M / Bauer, Matthew R / Lau, Allison N / Ji, Brian W / Dixit, Purushottam D / Hosios, Aaron M / Muir, Alexander / Chin, Christopher R / Freinkman, Elizaveta / Jacks, Tyler / Wolpin, Brian M / Vitkup, Dennis / Vander Heiden, Matthew G. ·Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. These authors contributed equally to this work. · Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Center for Computational Biology and Bioinformatics and Department of Systems Biology, Columbia University, New York, NY 10027, USA. · Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA. Broad Institute, Seven Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Dana-Farber Cancer Institute, Boston, MA 02115, USA. · Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Broad Institute, Seven Cambridge Center, Cambridge, MA 02142, USA. Dana-Farber Cancer Institute, Boston, MA 02115, USA. mvh@mit.edu. ·Science · Pubmed #27609895.

ABSTRACT: Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in expression levels of BCAA catabolic enzymes in both mice and humans. Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumor formation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements.

3 Article Circulating Metabolites and Survival Among Patients With Pancreatic Cancer. 2016

Yuan, Chen / Clish, Clary B / Wu, Chen / Mayers, Jared R / Kraft, Peter / Townsend, Mary K / Zhang, Mingfeng / Tworoger, Shelley S / Bao, Ying / Qian, Zhi Rong / Rubinson, Douglas A / Ng, Kimmie / Giovannucci, Edward L / Ogino, Shuji / Stampfer, Meir J / Gaziano, John Michael / Ma, Jing / Sesso, Howard D / Anderson, Garnet L / Cochrane, Barbara B / Manson, JoAnn E / Torrence, Margaret E / Kimmelman, Alec C / Amundadottir, Laufey T / Vander Heiden, Matthew G / Fuchs, Charles S / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (CY, ZRQ, DAR, KN, SO, MGVH, CSF, BMW) · Broad Institute of MIT and Harvard University, Cambridge, MA (CBC, MGVH) · Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China (CW) · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA (JRM, MET, MGVH) · Department of Epidemiology (PK, SST, ELG, SO, MJS, JM, HDS, JEM), Department of Biostatistics (PK), and Department of Nutrition (ELG, MJS), Harvard School of Public Health, Boston, MA · Department of Pathology (SO), and Channing Division of Network Medicine (MKT, SST, YB, ELG, MJS, JM, JEM, CSF) and Division of Preventive Medicine (JMG, HDS, JEM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MZ, LTA) · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (JMG) · Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA) · University of Washington School of Nursing, Seattle, WA (BBC) · Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (ACK). ·J Natl Cancer Inst · Pubmed #26755275.

ABSTRACT: BACKGROUND: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. RESULTS: Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. CONCLUSIONS: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.

4 Article Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. 2014

Mayers, Jared R / Wu, Chen / Clish, Clary B / Kraft, Peter / Torrence, Margaret E / Fiske, Brian P / Yuan, Chen / Bao, Ying / Townsend, Mary K / Tworoger, Shelley S / Davidson, Shawn M / Papagiannakopoulos, Thales / Yang, Annan / Dayton, Talya L / Ogino, Shuji / Stampfer, Meir J / Giovannucci, Edward L / Qian, Zhi Rong / Rubinson, Douglas A / Ma, Jing / Sesso, Howard D / Gaziano, John Michael / Cochrane, Barbara B / Liu, Simin / Wactawski-Wende, Jean / Manson, JoAnn E / Pollak, Michael N / Kimmelman, Alec C / Souza, Amanda / Pierce, Kerry / Wang, Thomas J / Gerszten, Robert E / Fuchs, Charles S / Vander Heiden, Matthew G / Wolpin, Brian M. ·Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. · Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Broad Institute of MIT and Harvard University, Cambridge, MA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana- Farber Cancer Institute, Boston, MA 02215. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Department of Nutrition, Harvard School of Public Health, Boston, MA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System. · University of Washington School of Nursing, Seattle, WA. · Departments of Epidemiology and Medicine, Brown University, Providence, RI. · Department of Social and Preventive Medicine, University at Buffalo, SUNY, Buffalo, NY. · Departments of Oncology and Medicine, McGill University, Montreal, QC, Canada. · Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN. · Cardiology Division, Massachusetts General Hospital, and Harvard Medical School, Boston, MA. · Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. ·Nat Med · Pubmed #25261994.

ABSTRACT: Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.