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  • Devarakonda, SravaniGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology (author)

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/330322
  • https://gup.ub.gu.se/publication/330322URI
  • https://doi.org/10.1016/j.ebiom.2023.104691DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:153402727URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).

Subject headings and genre

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  • Thorsell, Annika,1973Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics(Swepub:gu)xdannm (author)
  • Hedenström, PerGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xhperi (author)
  • Rezapour, AzarKarolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xrezaz (author)
  • Heden, Lisen (author)
  • Banerjee, Sanghita (author)
  • Johansson, Malin E V,1971Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xjomal (author)
  • Birchenough, George M. H.Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine(Swepub:gu)xbirge (author)
  • Toft Morén, Amelie,1994Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xtofam (author)
  • Gustavsson, Karin (author)
  • Skokic, Viktor,1982Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xskovi (author)
  • Pettersson, Victor L (author)
  • Sjöberg, F.Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology (author)
  • Kalm, Marie,1981Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xkalma (author)
  • Al Masri, Mohammad,2001Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience(Swepub:gu)xalmas (author)
  • Ekh, Michaela (author)
  • Fagman, Henrik,1975Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine(Swepub:gu)xfagmh (author)
  • Wolving, Mats (author)
  • Perkins, Rosie,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xperro (author)
  • Morales, Rodrigo A (author)
  • Castillo, Francisca (author)
  • Villablanca, Eduardo J (author)
  • Yrlid, Ulf,1971Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology(Swepub:gu)xyrlul (author)
  • Bergmark, Karin,1962Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xbkari (author)
  • Steineck, Gunnar,1952Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xstegu (author)
  • Bull, Cecilia,1977Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology(Swepub:gu)xbulce (author)
  • Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för onkologi (creator_code:org_t)

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  • In:EBioMedicine942352-3964

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