دورية أكاديمية
High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.
العنوان: | High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival. |
---|---|
المؤلفون: | Björner K; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden., Chen WN; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden., Gannavarapu VR; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden., Axling F; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Gulyas M; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Halim MA; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden., Webb DL; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden., Hellström PM; Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden. |
المصدر: | Upsala journal of medical sciences [Ups J Med Sci] 2024 Jan 02; Vol. 28. Date of Electronic Publication: 2024 Jan 02 (Print Publication: 2023). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Upsala Medical Society Country of Publication: Sweden NLM ID: 0332203 Publication Model: eCollection Cited Medium: Internet ISSN: 2000-1967 (Electronic) Linking ISSN: 03009734 NLM ISO Abbreviation: Ups J Med Sci Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2021- : Uppsala, Sweden : Upsala Medical Society Original Publication: Uppsala : Stockholm : Upsala Medical Society ; distributed by Almqvist & Wiksell |
مواضيع طبية MeSH: | Colitis-Associated Neoplasms* , Inflammatory Bowel Diseases*/complications , Neoplasms*, Humans ; Interleukin-1beta ; Nitric Oxide Synthase Type II ; RNA, Messenger |
مستخلص: | Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown. Aim: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC. Methods: Immunohistochemistry was performed on tissue sections as follows: CAC ( n = 59); sporadic CRC (sCRC) ( n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) ( n = 22); paracancerous IBD (pIBD) ( n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases. Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS ( P < 0.01) and IL-1β ( P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa ( P < 0.001), whereas IL-1β was higher ( P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases. Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward. Competing Interests: The authors declare no conflict of interest. (© 2023 The Author(s). Published by Upsala Medical Society.) |
References: | Lancet. 2020 Jan 11;395(10218):123-131. (PMID: 31929014) Aliment Pharmacol Ther. 2017 May;45(9):1179-1192. (PMID: 28261835) Hum Vaccin Immunother. 2017 May 4;13(5):1105-1108. (PMID: 28121247) Exp Cell Res. 2012 Nov 15;318(19):2520-30. (PMID: 22884582) Biochem Soc Trans. 2010 Apr;38(2):327-30. (PMID: 20298177) Front Immunol. 2019 Jun 07;10:1266. (PMID: 31231388) Exp Cell Res. 2012 Oct 1;318(16):2116-27. (PMID: 22683859) J Crohns Colitis. 2014 Sep;8(9):1088-96. (PMID: 24630486) Mucosal Immunol. 2017 Nov;10(6):1504-1517. (PMID: 28198364) Eur J Cancer. 2006 Apr;42(6):751-9. (PMID: 16530403) Scand J Gastroenterol. 2003 Jan;38(1):66-72. (PMID: 12608467) Carcinogenesis. 2007 May;28(5):1122-30. (PMID: 17116728) Gastroenterology. 2007 Oct;133(4):1099-105; quiz 1340-1. (PMID: 17919486) N Engl J Med. 1990 Nov 1;323(18):1228-33. (PMID: 2215606) Biochem Pharmacol. 2020 Jun;176:113899. (PMID: 32145264) Inflamm Bowel Dis. 2013 Mar;19(3):599-613. (PMID: 23388544) Scand J Gastroenterol. 2002 Aug;37(8):944-8. (PMID: 12229970) Gut. 2001 Apr;48(4):526-35. (PMID: 11247898) Int J Cancer. 2014 Jan 1;134(1):189-96. (PMID: 23797639) World J Gastroenterol. 2006 Jun 7;12(21):3386-92. (PMID: 16733856) Annu Rev Physiol. 2017 Feb 10;79:541-566. (PMID: 27813830) Mech Ageing Dev. 2018 Mar;170:22-29. (PMID: 28739375) Dis Markers. 2008;25(1):1-16. (PMID: 18776587) Dig Liver Dis. 2022 Sep;54(9):1162-1167. (PMID: 35842365) Am J Gastroenterol. 2007 Apr;102(4):829-36. (PMID: 17222314) Life Sci. 1995;56(23-24):2201-7. (PMID: 7776850) Cell. 2018 Apr 5;173(2):400-416.e11. (PMID: 29625055) Oncol Rep. 2020 Mar;43(3):908-918. (PMID: 32020215) J Crohns Colitis. 2014 Mar;8(3):215-22. (PMID: 24035547) Gut. 1994 May;35(5):651-5. (PMID: 8200559) J Crohns Colitis. 2013 Oct;7(9):e351-7. (PMID: 23491313) Nature. 2002 Dec 19-26;420(6917):860-7. (PMID: 12490959) Gastroenterology. 2004 May;126(6):1518-32. (PMID: 15168364) Cell Commun Signal. 2020 Apr 7;18(1):59. (PMID: 32264958) Immunol Res. 2018 Dec;66(6):800-805. (PMID: 30694514) Nat Genet. 2013 Oct;45(10):1113-20. (PMID: 24071849) Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):415-20. (PMID: 17255260) J Cell Physiol. 2000 Mar;182(3):311-22. (PMID: 10653597) Gut. 1998 Feb;42(2):214-9. (PMID: 9536946) Dig Liver Dis. 2017 Apr;49(4):326-330. (PMID: 28089111) J Natl Cancer Inst. 2014 Feb;106(2):djt444. (PMID: 24491303) Biochem J. 2006 Mar 1;394(Pt 2):e3-5. (PMID: 16479620) J Clin Pathol. 1998 Oct;51(10):750-3. (PMID: 10023337) Biosci Rep. 2021 Apr 30;41(4):. (PMID: 33821998) Cancers (Basel). 2011 Apr 26;3(2):2160-8. (PMID: 24212801) J Clin Immunol. 1996 May;16(3):144-50. (PMID: 8734357) Vaccines (Basel). 2021 Jan 27;9(2):. (PMID: 33513777) J Immunol. 2003 Dec 15;171(12):6448-56. (PMID: 14662844) Free Radic Res. 1996 May;24(5):369-80. (PMID: 8733941) |
فهرسة مساهمة: | Keywords: Colorectal cancer; Interleukin-1β; colitis-associated colorectal cancer; inducible nitric oxide synthase; inflammatory bowel disease; tumor biology |
المشرفين على المادة: | 0 (Interleukin-1beta) EC 1.14.13.39 (Nitric Oxide Synthase Type II) 0 (RNA, Messenger) EC 1.14.13.39 (NOS2 protein, human) 0 (IL1B protein, human) |
تواريخ الأحداث: | Date Created: 20240108 Date Completed: 20240112 Latest Revision: 20240112 |
رمز التحديث: | 20240112 |
مُعرف محوري في PubMed: | PMC10770641 |
DOI: | 10.48101/ujms.v128.10241 |
PMID: | 38187473 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2000-1967 |
---|---|
DOI: | 10.48101/ujms.v128.10241 |