Locally administered heparin-binding epidermal growth factor-like growth factor reduces radiation-induced oral mucositis in mice. 2020

Jing Chen, and Laurent A Bekale, and Kelly M Khomtchouk, and Anping Xia, and Zhixin Cao, and Shoucheng Ning, and Susan J Knox, and Peter L Santa Maria
Department of Otolaryngology, Head and Neck Surgery, Stanford University, 801 Welch Road, Stanford, CA, 94305-5739, USA.

Oral mucositis refers to lesions of the oral mucosa observed in patients with cancer being treated with radiation with or without chemotherapy, and can significantly affect quality of life. There is a large unmet medical need to prevent oral mucositis that can occur with radiation either alone or in combination with chemotherapy. We investigated the efficacy of locally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent epithelial proliferation and migration stimulator of the oral mucosa as a potential therapy to prevent radiation induced oral mucositis. Using a single dose (20 Gy) of radiation to the oral cavity of female C57BL/6 J mice, we evaluated the efficacy of HB-EGF treatment (5 µl of 10 µg/ml) solution. The results show that HB-EGF delivered post radiation, significantly increased the area of epithelial thickness on the tongue (dorsal tongue (42,106 vs 53,493 µm2, p < 0.01), ventral tongue (30,793 vs 39,095 µm2, *p < 0.05)) compared to vehicle control, enhanced new epithelial cell division, and increased the quality and quantity of desmosomes in the oral mucosa measured in the tongue and buccal mucosa. This data provides the proof of concept that local administration of HB-EGF has the potential to be developed as a topical treatment to mitigate oral mucositis following radiation.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011878 Radiotherapy The use of IONIZING RADIATION to treat malignant NEOPLASMS and some benign conditions. Radiotherapy, Targeted,Targeted Radiotherapy,Radiation Therapy,Radiation Therapy, Targeted,Radiation Treatment,Targeted Radiation Therapy,Radiation Therapies,Radiation Therapies, Targeted,Radiation Treatments,Radiotherapies,Radiotherapies, Targeted,Targeted Radiation Therapies,Targeted Radiotherapies,Therapies, Radiation,Therapies, Targeted Radiation,Therapy, Radiation,Therapy, Targeted Radiation,Treatment, Radiation
D000287 Administration, Topical The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example. Drug Administration, Topical,Administration, Topical Drug,Topical Administration,Topical Drug Administration,Administrations, Topical,Administrations, Topical Drug,Drug Administrations, Topical,Topical Administrations,Topical Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013280 Stomatitis INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP. Oral Mucositis,Mucositis, Oral,Oromucositis,Mucositides, Oral,Oral Mucositides,Oromucositides,Stomatitides
D014059 Tongue A muscular organ in the mouth that is covered with pink tissue called mucosa, tiny bumps called papillae, and thousands of taste buds. The tongue is anchored to the mouth and is vital for chewing, swallowing, and for speech. Tongues
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D066257 Heparin-binding EGF-like Growth Factor An EGF family member that is expressed in a variety of hematopoietic, endothelial, vascular smooth muscle, and epithelial cells. It is synthesized as a transmembrane protein which is cleaved by proteases to produce the secreted form of the protein which has specificity for the EGF RECEPTOR and the ERBB-4 RECEPTOR. The membrane-bound form of the protein has been identified as the receptor which binds to and allows DIPHTHERIA TOXIN to enter cells. Heparin-binding EGF-like Growth-Factor,Diphtheria Toxin Receptor,Diphtheria Toxin Receptors,HB-EGF,HB-EGF Precursor,Heparin-binding Epidermal Growth Factor-like Growth Factor Precursor Protein,Receptor, Diphtheria Toxin,SF HB-EGF,Short Form HB-EGF,HB EGF,HB EGF Precursor,HB-EGF, Short Form,Heparin binding EGF like Growth Factor,Heparin binding Epidermal Growth Factor like Growth Factor Precursor Protein,Receptors, Diphtheria Toxin,SF HB EGF,Short Form HB EGF,Toxin Receptor, Diphtheria,Toxin Receptors, Diphtheria

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