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Altered mRNA Expression due to Acute Mesenteric Ischaemia in a Porcine Model
Örebro University, School of Health and Medical Sciences.ORCID iD: 0000-0003-4879-528X
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2011 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 41, no 2, p. 281-287Article in journal (Refereed) Published
Abstract [en]

Introduction: Messenger RNA (mRNA) changes in the small intestine in response to acute mesenteric ischaemia (AMI) could offer novel diagnostic possibilities, but have not been described. The aim was to characterize the mRNA response to experimental AMI. Materials and methods: Twelve pigs underwent catheterisation of the superior mesenteric artery with injection of polivinylalcohol embolisation particles or sodium chloride. Laparotomy and intestinal tissue sampling were performed. Microarray analysis was performed using the GeneChip (R) whole porcine genome array. Results: Seven down-regulated cellular pathways were associated with protein, lipid and carbohydrate metabolism. Seventeen up-regulated pathways were associated with inflammatory and immunological activity, regulation of extracellular matrix and decreased cellular proliferation. Thrombospondin (THS), monocyte chemoattractant protein 1(MCP-1) and gap junction alpha 1(GJA-1) were consistently up-regulated in all embolised pigs. Genes encoding earlier proposed biomarkers for AMI were up-regulated, such as lactate dehydrogenase and creatine kinase, or down-regulated, such as intestinal fatty acid binding protein and glutathione S-transferase. Conclusion: This study describes the intestinal tissue response on a gene expression level to AMI. THS, MCP-1 and GJA-1 were consistently up-regulated by ischaemia, whereas earlier proposed biomarkers for AMI were not. Gene expression may not be directly linked to the use of the corresponding proteins as potential clinical biomarkers. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
2011. Vol. 41, no 2, p. 281-287
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-18783DOI: 10.1016/j.ejvs.2010.09.012ISI: 000288469000022PubMedID: 21095140Scopus ID: 2-s2.0-79651475389OAI: oai:DiVA.org:oru-18783DiVA, id: diva2:444531
Available from: 2011-09-29 Created: 2011-09-29 Last updated: 2019-03-29Bibliographically approved
In thesis
1. Clinical studies of RNA as a prognostic and diagnostic marker for disease
Open this publication in new window or tab >>Clinical studies of RNA as a prognostic and diagnostic marker for disease
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Technologies for RNA detection are evolving rapidly and gives an op-portunity for discovery of new markers for early detection of complex diseases. Today in clinical work we rely on signs and symptoms in com-bination with the measurement of protein levels for diagnosis. The quick turnaround time of mRNA synthesis may provide an earlier diagnostic signal than protein-based biomarkers assays, in acute dramatic condi-tions such as acute mesenteric ischemia (AMI), for early detection of cancer, as prognostic tool in cancer treatment and as an aid in difficult diagnosis of unknown origin.

The main goals of this thesis was to apply a whole genome approach to study different complex diseases to evaluate the applicability of RNA as a diagnostic or prognostic marker for disease, preferably from an easily accessible source such as peripheral blood. This was investigated in an animal model with induced AMI, a cohort of ovarian cancer patients and in a single-patient study of a girl with a severe inflammatory syn-drome.

Through this thesis we have gained insight into how gene expression is regulated in ischemic intestinal tissue.

We found that a peripheral blood test can distinguish between ovarian cancer patients with or without residual tumour mass after surgery with the help of expression analysis of six genes. We also found that gene expressions of three genes can predict overall survival in peripheral whole blood from ovarian cancer patients. And that gene expression profiles indeed can significantly distinguish between two groups of high and low risk ovarian cancer. In the single-patient study, we tried but failed to device a successful treatment before it was too late. Neverthe-less, the things we learned and the case studies that were published may serve as a diagnostic tool for clinicians facing similar syndromes.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. p. 57
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 168
Keywords
gene expression, ovarian cancer, hypercalprotectinaemia, hyperzincaemia, ischemia, biomarker
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-61626 (URN)978-91-7529-219-9 (ISBN)
Public defence
2017-12-15, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2018-01-13Bibliographically approved

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Isaksson, Helena S.Nilsson, Torbjörn K.

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