Hannah R Wardill1, Richard M Logan2, Joanne M Bowen3, Ysabella Z A Van Sebille4, Rachel J Gibson5. 1. Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5005, Australia. hannah.wardill@adelaide.edu.au. 2. School of Dentistry, University of Adelaide, Adelaide, South Australia, Australia. richard.logan@adelaide.edu.au. 3. Discipline of Physiology, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. joanne.bowen@adelaide.edu.au. 4. Discipline of Physiology, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. ysabella.vansebille@adelaide.edu.au. 5. Discipline of Anatomy and Pathology, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, 5005, Australia. rachel.gibson@adelaide.edu.au.
Abstract
PURPOSE: Oral mucositis is one of the most common and debilitating side effects of chemotherapy treatment. Patients are often unable to eat and drink, which can lead to poor clinical outcomes and extensive resource utilisation. The primary aim of this study was to determine the molecular integrity of oral epithelial tight junctions in patients undergoing chemotherapy. The secondary aim was to correlate these changes with proinflammatory cytokines and matrix metalloproteinase profiles. METHODS: Patients (n = 23) were recruited from the Royal Adelaide Hospital between 2000 and 2003. Reach patient underwent two oral buccal mucosa biopsies (4 mm): one prior to chemotherapy treatment and a second one after chemotherapy treatment. Oral buccal mucosa biopsies were also taken from seven healthy volunteers with no history of cancer, chemo- or radiotherapy treatment or inflammatory disorders. Routine haematoxylin and eosin staining was performed to determine epithelial thickness. Immunohistochemical staining was performed for claudin-1, zonular occludens-1, occludin, interleukin-1β, tumour necrosis factor, interleukin-6, matrix metalloproteinase-2 and metalloproteinase-9. RESULTS: Patients receiving standard dose chemotherapy had significant epithelial atrophy. Elevations in all cytokines and matrix metalloproteinases were seen, with significant lamina propria staining for interleukin-6 and tumour necrosis factor. Matrix metalloproteinase-2 appeared most upregulated within the oral epithelium. These changes coincided with altered tight junction staining properties. Changes in the staining intensity and localisation were both noted, with clear cytoplasmic staining for zonular occludens-1 and claudin-1 in patients treated with chemotherapy. CONCLUSIONS: Chemotherapy causes defects in oral tight junctions, coupled with altered cytokine and matrix metalloproteinase profiles. Tight junction disruption in the epithelium may contribute to ulcer development or lead to poor tissue integrity, and the timing of these events may be a target for preventative treatment.
PURPOSE:Oral mucositis is one of the most common and debilitating side effects of chemotherapy treatment. Patients are often unable to eat and drink, which can lead to poor clinical outcomes and extensive resource utilisation. The primary aim of this study was to determine the molecular integrity of oral epithelial tight junctions in patients undergoing chemotherapy. The secondary aim was to correlate these changes with proinflammatory cytokines and matrix metalloproteinase profiles. METHODS:Patients (n = 23) were recruited from the Royal Adelaide Hospital between 2000 and 2003. Reach patient underwent two oral buccal mucosa biopsies (4 mm): one prior to chemotherapy treatment and a second one after chemotherapy treatment. Oral buccal mucosa biopsies were also taken from seven healthy volunteers with no history of cancer, chemo- or radiotherapy treatment or inflammatory disorders. Routine haematoxylin and eosin staining was performed to determine epithelial thickness. Immunohistochemical staining was performed for claudin-1, zonular occludens-1, occludin, interleukin-1β, tumour necrosis factor, interleukin-6, matrix metalloproteinase-2 and metalloproteinase-9. RESULTS:Patients receiving standard dose chemotherapy had significant epithelial atrophy. Elevations in all cytokines and matrix metalloproteinases were seen, with significant lamina propria staining for interleukin-6 and tumour necrosis factor. Matrix metalloproteinase-2 appeared most upregulated within the oral epithelium. These changes coincided with altered tight junction staining properties. Changes in the staining intensity and localisation were both noted, with clear cytoplasmic staining for zonular occludens-1 and claudin-1 in patients treated with chemotherapy. CONCLUSIONS: Chemotherapy causes defects in oral tight junctions, coupled with altered cytokine and matrix metalloproteinase profiles. Tight junction disruption in the epithelium may contribute to ulcer development or lead to poor tissue integrity, and the timing of these events may be a target for preventative treatment.
Authors: Noor Al-Dasooqi; Rachel J Gibson; Joanne M Bowen; Richard M Logan; Andrea M Stringer; Dorothy M Keefe Journal: Exp Biol Med (Maywood) Date: 2010-08-03
Authors: Noor Al-Dasooqi; Joanne M Bowen; Rachel J Gibson; Richard M Logan; Andrea M Stringer; Dorothy M Keefe Journal: Int J Exp Pathol Date: 2011-04-05 Impact factor: 1.925
Authors: Noor Al-Dasooqi; Stephen T Sonis; Joanne M Bowen; Emma Bateman; Nicole Blijlevens; Rachel J Gibson; Richard M Logan; Raj G Nair; Andrea M Stringer; Roger Yazbeck; Sharon Elad; Rajesh V Lalla Journal: Support Care Cancer Date: 2013-04-21 Impact factor: 3.603
Authors: Richard M Logan; Rachel J Gibson; Joanne M Bowen; Andrea M Stringer; Stephen T Sonis; Dorothy M K Keefe Journal: Cancer Chemother Pharmacol Date: 2007-08-17 Impact factor: 3.333
Authors: Romany L Stansborough; Emma H Bateman; Noor Al-Dasooqi; Joanne M Bowen; Dorothy M K Keefe; Ann S J Yeoh; Richard M Logan; Eric E K Yeoh; Andrea M Stringer; Rachel J Gibson Journal: Support Care Cancer Date: 2017-02-07 Impact factor: 3.603
Authors: Romany L Stansborough; Noor Al-Dasooqi; Emma H Bateman; Joanne M Bowen; Dorothy M K Keefe; Richard M Logan; Ann S J Yeoh; Eric E K Yeoh; Andrea M Stringer; Rachel J Gibson Journal: Support Care Cancer Date: 2018-05-12 Impact factor: 3.603
Authors: Hannah R Wardill; Rachel J Gibson; Ysabella Za Van Sebille; Kate R Secombe; Richard M Logan; Joanne M Bowen Journal: Exp Biol Med (Maywood) Date: 2016-03-31