Role of prostaglandin pathways in radiotherapy-induced mucositis.

Abstract

e20509 Background: Pathways associated with proinflammatory molecules are upregulated in oral mucositis. Lalla (Support Care Cancer 18:95, 2010) found an association between mucositis pain scores, tissue COX-1, and salivary prostaglandins in 4 patients receiving dose-dense chemotherapy. We investigated whether similar changes would be seen with radiotherapy (XRT)-induced mucositis. Methods: Patients receiving XRT including the oropharynx were evaluated at 4 time points, before XRT, midway through XRT, end of XRT, and 1 month after XRT. Subjective report of pain and objective mucositis scores were recorded. Patients also provided a 5-minute stimulated saliva specimen at each time point collected on ice with a protease inhibitor cocktail. Proteins were estimated using a Bradford assay. Prostaglandins were measured using ELISA assays. Results: 8 evaluable patients entered the study, including 7 male/1 female, median age 60 (range 48-66), primary site (oropharynx 1, unknown primary 1, base of tongue 3, tonsil 1, tongue 1, supraglottis 1), median XRT 7000 rads (range 6000-7200 rads), concomitant chemotherapy (cisplatin 7, none 1), histology (squamous 7, mucoepidermoid 1). Pain and mucositis scores increased during XRT and improved at 1 month after XRT. No increase in COX-2 levels was seen. Salivary PGD2, PGE2, and PGF2 increased from baseline with the greatest increase 1 month after XRT. There was a significant time effect for PGF2 (p=0.028) and marginal time effects for PGD2 (p=0.107) and PGE2 (p=0.069). Conclusions: Increased salivary prostaglandins are seen during and after XRT-induced oral mucositis, suggesting a role for proinflammatory mediators and providing a possible therapeutic target. Clinical trial information: NCT01252498. [Table: see text]

NF‐κB targeting for overcoming tumor resistance and normal tissues toxicity

“…Probably, prostaglandin E2 (PGE2) production, which is associated with ROS generation, is the most important product of COX-2 after exposure to radiation (Grunberg et al, 2013). The production of PGE2 is associated with oxidative DNA damage and genomic instability that may be prolonged for some days after exposure to radiation (Chai et al, 2012).…”

“…NF‐κB, via stimulation of COX‐2, regulates the release of prostaglandins in both irradiated and nonirradiated organs, through a phenomenon known as nontargeted effect (Chai et al, ). Probably, prostaglandin E2 (PGE2) production, which is associated with ROS generation, is the most important product of COX‐2 after exposure to radiation (Grunberg et al, ). The production of PGE2 is associated with oxidative DNA damage and genomic instability that may be prolonged for some days after exposure to radiation (Chai et al, ).…”

Regulation of inflammation by lipid mediators in oral diseases

“…Saliva levels of various LM are more widely used for studying oral diseases than for systemic diseases. For example, patients with radiotherapy‐caused oral mucositis displayed higher saliva levels of PGD 2 , PGE 2 , and PGF 2 (Grunberg et al , ). Similarly, a different study found elevated levels of LTA 4 hydrolase in oral mucositis patients (Jehmlich et al , ).…”