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Low-grade intestina...
Low-grade intestinal inflammation two decades after pelvic radiotherapy.
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- Devarakonda, Sravani (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Thorsell, Annika, 1973 (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Proteomics,Core Facilities, Proteomics
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- Hedenström, Per (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Rezapour, Azar (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Heden, Lisen (author)
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Banerjee, Sanghita (author)
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- Johansson, Malin E V, 1971 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Birchenough, George M. H. (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine
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- Toft Morén, Amelie, 1994 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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Gustavsson, Karin (author)
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- Skokic, Viktor, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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Pettersson, Victor L (author)
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- Sjöberg, F. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Kalm, Marie, 1981 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Al Masri, Mohammad, 2001 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
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Ekh, Michaela (author)
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- Fagman, Henrik, 1975 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine
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Wolving, Mats (author)
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- Perkins, Rosie, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Morales, Rodrigo A (author)
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Castillo, Francisca (author)
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Villablanca, Eduardo J (author)
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- Yrlid, Ulf, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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- Bergmark, Karin, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Steineck, Gunnar, 1952 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Bull, Cecilia, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: EBioMedicine. - 2352-3964. ; 94
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- Neutrophil
- Pelvic radiation disease
- Pelvic radiotherapy
- Proctitis
- Proteomics
- Transcriptomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Devarakonda, Sra ...
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Thorsell, Annika ...
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Hedenström, Per
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Rezapour, Azar
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Heden, Lisen
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Banerjee, Sanghi ...
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show more...
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Johansson, Malin ...
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Birchenough, Geo ...
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Toft Morén, Amel ...
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Gustavsson, Kari ...
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Skokic, Viktor, ...
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Pettersson, Vict ...
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Sjöberg, F.
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Kalm, Marie, 198 ...
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Al Masri, Mohamm ...
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Ekh, Michaela
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Fagman, Henrik, ...
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Wolving, Mats
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Perkins, Rosie, ...
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Morales, Rodrigo ...
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Castillo, Franci ...
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Villablanca, Edu ...
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Yrlid, Ulf, 1971
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Bergmark, Karin, ...
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Steineck, Gunnar ...
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Bull, Cecilia, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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EBioMedicine
- By the university
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University of Gothenburg
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Karolinska Institutet