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Role of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a pilot study

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dc.contributor.authorLalla, R.
dc.contributor.authorPilbeam, C.
dc.contributor.authorWalsh, S.
dc.contributor.authorSonis, S.
dc.contributor.authorKeefe, D.
dc.contributor.authorPeterson, D.
dc.date.issued2010
dc.descriptionLink to a related website: http://europepmc.org/articles/pmc3034109?pdf=render, Open Access via Unpaywall
dc.description.abstractGoals: Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis. Materials and methods: We collected blood, saliva, and oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day −10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of oral mucositis was determined using the Oral Mucositis Index. Severity of pain due to oral mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Main results: Mean mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Conclusions: Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced mucositis.
dc.description.statementofresponsibilityRajesh V. Lalla, Carol C. Pilbeam, Stephen J. Walsh, Stephen T. Sonis, Dorothy M. K. Keefe and Douglas E. Peterson
dc.identifier.citationSupportive Care in Cancer, 2010; 18(1):95-103
dc.identifier.doi10.1007/s00520-009-0635-1
dc.identifier.issn0941-4355
dc.identifier.issn1433-7339
dc.identifier.orcidKeefe, D. [0000-0001-9377-431X]
dc.identifier.urihttp://hdl.handle.net/2440/54908
dc.language.isoen
dc.publisherSpringer-Verlag
dc.rightsCopyright 2009 Springer-Verlag
dc.source.urihttps://doi.org/10.1007/s00520-009-0635-1
dc.subjectMucositis
dc.subjectChemotherapy
dc.subjectHematopoetic stem cell transplant
dc.subjectCyclooxygenase
dc.subjectProstaglandin
dc.titleRole of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a pilot study
dc.typeJournal article
pubs.publication-statusPublished

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