The pathobiology of mucositis

Sonis, Stephen T.

doi:10.1038/nrc1318

Cited by 1,126 publications

(1,046 citation statements)

References 48 publications

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“…In addition to apoptosis, our results also support a role for claudin-1 in aiding tissue regeneration, a newly identified function of claudin-1, as its overexpression coincides with the known time point of cellular regeneration in the epithelium of the jejunum and colon (72 h). [4][5][6] Unexpectedly however, this was accompanied by a decrease in protein expression in the colonic crypts and which may be attributable to the second wave of apoptosis, as the body resets homeostasis. 1 There is conflicting evidence regarding mRNA analysis of tight junction proteins following chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…3 CIGT development is a multifactorial process characterized by dynamic biochemical interactions between chemotherapeutic agents and cellular constituents of the mucosa. [4][5][6] Recent research has focused on the molecular mechanisms that underpin CIGT, highlighting roles for apoptosis, 1 the immune system, 7 the gut microbiome, 8 and matrix metalloproteinases (MMPs). 9 More recently, intestinal tight junctions were proposed to play important roles in the pathophysiology of CIGT.…”

Section: Introductionmentioning

confidence: 99%

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Irinotecan disrupts tight junction proteins within the gut

Wardill

Bowen

Al‐Dasooqi

et al. 2013

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Irinotecan disrupts tight junction proteins within the gut

Wardill

Bowen

Al‐Dasooqi

et al. 2013

Cancer Biology & Therapy

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“…The effect of anti‐inflammatory cytokines in reducing oral mucositis has been explored. However, although multiple preclinical studies suggested potential benefit, these benefits have not been verified in clinical studies 42.…”

Section: Molecular Basis Of Oral Mucosal Injurymentioning

confidence: 99%

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

et al. 2016

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In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state‐of‐the‐science regarding mTOR inhibitor‐associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2–78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR‐associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high‐dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop.

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“…OM is a toxicity of radiation and chemotherapy for HNC patients and is associated with pain, functional impairment, treatment interruptions and increased use of costly healthcare resources 8, 9, 10. Dental fillings are a known factor that can exacerbate mucosal toxicity since it generates unpredictable scattering of the radiation and compromises the accuracy of the dose calculation to the adjacent sites due to the imaging artifact that is produced by these fillings on CT scan 6, 7.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies3, 4, 5, 11, 12, 13 have proposed dose and volumetric guidelines to reduce OM by treatment planning intervention but none of them has specifically focused on the effect of dental fillings nor investigated whether it is feasible to optimize the IMRT plan based on such guidelines in vivo. We frequently observe OM on the lateral tongue in patients with dental fillings and this site is also known to be more sensitive to radiation/chemotherapy‐induced mucositis compared to areas of keratinized oral mucosa such as the dorsal tongue, hard palate, and gingiva 8. Therefore, we used OSL to measure lateral tongue dose to evaluate the dental filling effect to the adjacent oral mucosa and to see if it is feasible to modify IMRT plan based on the measured doses.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of optimizing intensity‐modulated radiation therapy plans based on measured mucosal dose adjacent to dental fillings and toxicity outcomes

Seol

Aggarwal

Eyben

et al. 2018

J Applied Clin Med Phys

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We prospectively investigated the feasibility of IMRT treatment plan optimization based on dosimeter measurements of lateral tongue mucosal dose adjacent to the dental fillings and evaluated dose‐toxicity relationship and factors affecting oral mucositis (OM) in head and neck cancer patients. Twenty‐nine head and neck cancer patients with metallic dental fillings who were scheduled to undergo fractionated external beam radiation therapy (RT) ± chemotherapy were enrolled. The lateral tongue dose was measured and if the calculated dose for the entire treatment was ≥35 Gy, a re‐plan was generated to reduce the lateral tongue mucosal dose. OM was graded weekly according to Common Terminology Criteria for Adverse Events version 4.0 and the patients completed the Oral Mucositis Weekly Questionnaire‐Head and Neck Cancer. The result showed that it was not feasible to optimize the IMRT plan based on measured tongue dose in most of the patients who needed re‐plan as re‐planning compromised the target coverage in 60% of these patients. The duration of grade (Gr) 2 OM was correlated with measured lateral tongue dose (P = 0.050). Concurrent cetuximab was significantly associated with faster onset of Gr2 OM than concurrent cisplatin (P = 0.006) and with longer duration of OM (P = 0.041) compared to concurrent cisplatin or IMRT‐alone. The pattern of reported pain over time was significantly different for each treatment type (RT and cetuximab, RT and cisplatin and RT‐alone) and depending on the dose level (P = 0.006). In conclusion, optimizing the IMRT plan based on measured lateral tongue dose was not feasible. Measured lateral tongue dose was significantly correlated with longer duration of OM ≥Gr2, and concurrent cetuximab was associated with earlier onset and longer duration of OM ≥Gr2.

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The pathobiology of mucositis

Cited by 1,126 publications

References 48 publications

Irinotecan disrupts tight junction proteins within the gut

Irinotecan disrupts tight junction proteins within the gut

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

Feasibility of optimizing intensity‐modulated radiation therapy plans based on measured mucosal dose adjacent to dental fillings and toxicity outcomes

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