Inhibition of ADP ribosylation prevents and cures helicobacter-induced gastric preneoplasia

Cancer Research
Isabella M TollerAnne Müller

Abstract

Gastric adenocarcinoma develops as a consequence of chronic inflammation of the stomach lining that is caused by persistent infection with the bacterium Helicobacter pylori. Gastric carcinogenesis progresses through a sequence of preneoplastic lesions that manifest histologically as atrophic gastritis, intestinal metaplasia, and dysplasia. We show here in several preclinical models of Helicobacter-induced atrophic gastritis, epithelial hyperplasia, and metaplasia that the inhibition of ADP ribosylation by the small-molecule inhibitor PJ34 not only prevents the formation of gastric cancer precursor lesions, but also efficiently reverses preexisting lesions. PJ34 exerts its chemopreventive and therapeutic effects by impairing Helicobacter-specific T-cell priming and T(H)1 polarization in the gut-draining mesenteric lymph nodes. The subsequent infiltration of pathogenic T cells into the gastric mucosa and the ensuing gastric T cell-driven immunopathology are prevented efficiently by PJ34. Our data indicate that PJ34 directly suppresses T-cell effector functions by blocking the IFN-gamma production of mesenteric lymph node T cells ex vivo. Upon exposure to PJ34, purified T cells failed to synthesize ADP-ribose polymers and to activ...Continue Reading

References

Oct 17, 1991·The New England Journal of Medicine·J ParsonnetR K Sibley
Sep 1, 1993·Zentralblatt Für Bakteriologie : International Journal of Medical Microbiology·A LeeY Li
Nov 20, 1998·Science·S SmithT de Lange
Sep 9, 1999·The Journal of Cell Biology·V A KickhoeferL H Rome
Aug 29, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·H B JijonK L Madsen
Mar 21, 2002·Nature Reviews. Cancer·Richard M Peek, Martin J Blaser
Jul 19, 2002·Biochemical Pharmacology·Emanuela MazzonSalvatore Cuzzocrea
Jan 16, 2004·Gastroenterology·Jia Qing HuangRichard H Hunt
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Salvatore Cuzzocrea
Nov 29, 2005·European Journal of Pharmacology·Rosanna Di PaolaSalvatore Cuzzocrea
Aug 16, 2006·The New England Journal of Medicine·Arlene H Sharpe, Abul K Abbas
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mustapha OumounaHamid Boulares
Jan 4, 2007·The Journal of Clinical Investigation·James G Fox, Timothy C Wang
Mar 22, 2007·European Journal of Pharmacology·Susana Sánchez-FidalgoCatalina Alarcón de la Lastra
Jul 25, 2008·Nature·Alberto MantovaniFrances Balkwill
May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ayca SayiAnne Müller
Jun 26, 2009·The New England Journal of Medicine·Peter C FongJohann S de Bono
Nov 27, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yvette Drew, Ruth Plummer

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Citations

Sep 8, 2011·Proceedings of the National Academy of Sciences of the United States of America·Isabella M TollerAnne Müller
Mar 16, 2011·Genome Biology and Evolution·Isabelle C ArnoldAnne Müller
Jan 22, 2014·International Immunopharmacology·Sheikh Fayaz AhmadSaleh A Bakheet
Sep 27, 2012·Neurochemical Research·Marina ScaliaVittoria Spina-Purrello
Jul 28, 2015·Expert Opinion on Therapeutic Targets·Michael O Hottiger
Nov 21, 2012·Gastroenterology·Corina A Schmid, Anne Müller
Jul 16, 2015·Cancer Biology & Therapy·Yonghe LiWei Zhang
Mar 16, 2013·Immunology·Maria Manuela RosadoClaudio Pioli
Jan 20, 2011·BJOG : an International Journal of Obstetrics and Gynaecology·A MukhopadhyayR J Edmondson
Oct 3, 2012·ACS Chemical Biology·Albert A AntolínJordi Mestres
Feb 19, 2017·British Journal of Pharmacology·Nathan A BergerCsaba Szabo
Aug 24, 2018·Current Opinion in Gastroenterology·David Y Graham, Winnie Y Zou
Feb 26, 2016·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Ioannis C KotsopoulosNicola J Curtin
Jan 25, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Friedrich A KunzeMichael O Hottiger
Mar 10, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Iris HitzlerAnne Müller
Apr 27, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Isabelle C ArnoldAnne Müller
Aug 21, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sung Hoon ChoMark Boothby

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Atrophic Gastritis

Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.