Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer

Wardill, Hannah R.; Logan, Richard M.; Bowen, Joanne M.; Sebille, Ysabella Z.A. Van; Gibson, Rachel J.

doi:10.1007/s00520-015-2964-6

Cited by 16 publications

(8 citation statements)

References 37 publications

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“…This protective effect on the keratinocyte barrier integrity is probably related to the ability of TFs to inhibit P. gingivalis gingipains . Additionally, black tea TFs could reduce the expression of epithelial cell‐derived MMPs, which could also be involved in the damage of the barrier integrity, as previously reported .…”

Section: Discussionsupporting

confidence: 63%

Black tea theaflavins attenuate Porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti‐inflammatory activity

Lagha

Grenier

2016

J of Periodontal Research

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Section: Discussionsupporting

confidence: 63%

Black tea theaflavins attenuate Porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti‐inflammatory activity

Lagha

Grenier

2016

J of Periodontal Research

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“…Furthermore, DS exerts functions in extracellular matrix assembly, fibroblast activity and wound repair processes [19, 29–31]. Therefore, DS treatment could effectively modify various radiation-induced or -altered cellular or cell-matrix interactions [32–34]. To date, clinical applications of DS are scarce, although several preclinical and clinical studies revealed an array of potential indications.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis

et al. 2018

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PurposeOral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model.MethodsIrradiation was either applied alone or in combination with daily DS treatment (4 mg/kg, subcutaneously) over varying time intervals. Irradiation comprised single dose irradiation with graded doses to the lower tongue surface or daily fractionated irradiation of the whole tongue. Fractionation protocols (5 × 3 Gy/week) over one (days 0–4) or two weeks (days 0–4, 7–11) were terminated by an additional local single dose irradiation to a defined treatment field on the lower tongue surface to induce the mucosal radiation response. The additional single dose irradiation (top-up) on day 7 (after one week of fractionation) or day 14 (after 2 weeks of fractionation) comprised graded doses in order to generate full dose–effect curves. Ulceration of the epithelium of the lower tongue, corresponding to confluent mucositis, was analysed as clinically relevant endpoint. Additionally, the time course parameters, latent time and ulcer duration were analysed.ResultsDS treatment significantly reduced the incidence of ulcerations. DS application over longer time intervals resulted in a more pronounced reduction of ulcer frequency, increased latent times and reduced ulcer duration.ConclusionDS has a significant mucositis-ameliorating activity with pronounced effects on mucositis frequency as well as on time course parameters.

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“…Despite this, they are highly plastic structures vulnerable to post‐transcriptional and ‐translational modification by a variety of pathological cues . Tight junction disruption has been identified following treatment with a number of chemotherapeutic agents, both preclinically and clinically . To date, many studies have shown architectural abnormalities, and functional alteration, of key tight junction proteins such as claudin‐1, ZO‐1 and occludin.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Tight junction disruption has been identified following treatment with a number of chemotherapeutic agents, both preclinically 35,36 and clinically. [37][38][39] To date, many studies have shown architectural abnormalities, and functional alteration, of key tight junction proteins such as claudin-1, ZO-1 and occludin. As such, the current study focused on these three proteins, despite the numerous other proteins present within the junctional complex.…”

Section: Cancer Therapy and Preventionmentioning

confidence: 99%

Dacomitinib‐induced diarrhea: Targeting chloride secretion with crofelemer

Sebille

Gibson

Wardill

et al. 2017

Intl Journal of Cancer

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Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea, which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an antisecretory agent may be an effective intervention. T84 monolayers were treated with 1 µM dacomitinib and 10 µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n = 48) were treated with 7.5 mg/kg dacomitinib and/or 25 mg/kg crofelemer via oral gavage for 21 days. Crofelemer significantly worsened dacomitinib-induced diarrhea (p = 0.0003), and did not attenuate weight loss (p < 0.0001). Sections of the ileum and colon were mounted into Ussing chambers, and secretory processes analyzed. This indicated that crofelemer lost its anti-secretory action in the presence of dacomitinib in this model. Mass spectrometry revealed that crofelemer did not change serum concentration of dacomitinib. Serum FITC dextran levels indicated that crofelemer was unable to attenuate dacomitinib-induced barrier dysfunction. Tight junction proteins were visualized with immunofluorescence. Qualitative analysis showed dacomitinib induced proteolysis of ZO-1 and occludin, and internalization of claudin-1, which was not attenuated by crofelemer. Detailed histopathological analysis showed that crofelemer was unable to attenuate dacomitinib-induced ileal damage. Crofelemer worsened dacomitinib-induced diarrhea, suggesting that antisecretory drug therapy may be ineffective in this setting.

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Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer

Abstract: Tight junction defects are seen in the buccal mucosa of patients receiving standard dose chemotherapy for cancer

Cited by 16 publications

References 37 publications

Black tea theaflavins attenuate Porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti‐inflammatory activity

Black tea theaflavins attenuate Porphyromonas gingivalis virulence properties, modulate gingival keratinocyte tight junction integrity and exert anti‐inflammatory activity

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis

Dacomitinib‐induced diarrhea: Targeting chloride secretion with crofelemer

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