Grant R21CA202751

Surfactant lipids and associated proteins in radiation-induced mucositis

One of the most common and insidious side effects of cancer radiation therapy is oral mucositis, which occurs in as many as 30-70% of patients treated for head and neck tumors. Symptoms of oral mucositis include mouth pain and ulceration, infection, appetite loss, inability to eat, and occasional mortality. There is no clear understanding of the pathogenesis of radiation-induced mucositis and the treatment options are limited and generally not effective. Thus, there is a great need for an efficacious treatment to prevent and/or attenuate oral mucositis in patients undergoing radio-therapy for head and neck cancer. Based upon the PI laboratory's experience demonstrating the protective role of surface-active phospholipids (SAPL), and specifically phosphatidylcholine (PC) to protect the stomach and lower gut from injury and inflammation, we have proposed in this R21 grant pre-clinical experiments and in a pilot clinical study on head and neck cancer patients undergoing radio-therapy to investigate the role of SAPLs and their associated proteins (SPs) in radiation-induced mucositis. We will also investigate the potential role of soy PC to treat/prevent this condition either on its own or when complexed with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen as could be administered as a mouthwash. In proposed in vitro and in vivo experiments, the PI and his Co-Investigators Drs. Joseph Alcorn at UTHSCH and Katherine Mason at MDACC will investigate the presence of SAPLs and SPs in the salivary glands and saliva of rodents under control conditions and before and after radiation exposure to simulate the condition in the clinic. The PI will also use a gingival cell culture system to assess the potential protective role of PC alone and PC that has been pre-associated with, ibuprofen, based upon his experience with PC-NSAIDs, in animal studies and clinical trials to induce significantly fewer gastroduodenal ulcer than the unmodified NSAID. We will also assess the presence of SAPLs in the saliva of patients with head and neck cancer before, during and after radiation treatment with our clinical colleagues Drs. Rosenthal and Chambers at MDACC, and then compare these values collected by Dr. Yasmeen Haddad at the UTHSCH School of Dentistry to those of the saliva of cancer-free control subjects, that have been matched in age, gender and ethnicity to the above cancer patients. This project may lead to both an increased understanding of the role of SAPLs and SPs in the pathogenesis or oral mucositis, and the development of an effective and economical novel PC-based therapy to relieve this painful inflammatory condition in the vulnerable cancer patient population.