ArticleSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2018
Matrix metalloproteinase expression is altered in the small and large intestine following fractionated radiation in vivo.
Article in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Matrix metalloproteinase-driven epithelial-mesenchymal transition: implications in health and disease.Journal of translational medicine · 2025Review
- Repurposing FDA-approved drugs as inhibitors of therapy-induced invadopodia activity in glioblastoma cells.Molecular and cellular biochemistry · 2023Article
- Immunomodulation by radiotherapy in tumour control and normal tissue toxicity.Nature reviews. Immunology · 2022Review
- Combined Radiochemotherapy: Metalloproteinases Revisited.Frontiers in oncology · 2021Review
- Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study.Journal of cellular and molecular medicine · 2020Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeRadiotherapy-induced gut toxicity (RIGT) is associated with significant diarrhoea, pain and rectal bleeding. Matrix metalloproteinases (MMPs) have been reported to be involved in chemotherapy-induced gut toxicity and RIGT following single-dose irradiation in vivo. We therefore proposed MMPs would be involved in the pathobiology of RIGT following fractionated irradiation.
methodsDark Agouti rats were treated with fractionated radiation (3 × 2.5 Gy/week for 6 weeks). Rats were killed at 3, 6 and 15 weeks to represent acute and chronic toxicities. Sections of jejunum and colon were immunostained for MMP-1, MMP-2, MMP-9 and MMP-14. Relative mRNA expression in jejunum and colon was quantified by RT-PCR for MMP-1, MMP-2, MMP-9 and MMP-14. Western blotting was also conducted on jejunum and colon tissue collected at week 6 to determine protein levels of pro- and active MMP-2.
resultsMMP-2 total protein levels, determined by western blotting, significantly increased in both the jejunum (p = 0.0359) and the colon (p = 0.0134) 6 weeks into the fractionated radiation schedule. MMP-1, MMP-2, and MMP-14 mRNA expression significantly increased in the jejunum. MMP-2 mRNA expression was also significantly increased in the colon. Immunostaining of MMP-2 was observed to be increased in both crypt enterocytes and the lamina propria.
conclusionsMMP-2 plays a role in the pathobiology of gastrointestinal toxicities following fractionated irradiation. Whilst MMP-1 and MMP-14 mRNA expression was increased, this occurred only in the jejunum, suggesting MMPs are differentially involved in RIGT depending on the intestinal region. Further studies are needed to elucidate the role these mediators play in the development and potentiation of RIGT.
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