Department of Otolaryngology, Head and Neck Surgery, Stanford University, 801 Welch Road, Stanford, CA, 94305-5739, USA.
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Sci Rep. 2020 Oct 15;10(1):17327. doi: 10.1038/s41598-020-73875-7.
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 µm, p < 0.01), ventral tongue (30,793 vs 39,095 µm, *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.
口腔黏膜炎是指癌症患者在接受放疗(联合或不联合化疗)时出现的口腔黏膜损伤,它会显著影响生活质量。目前,人们迫切需要一种能够预防放疗(单独或联合化疗)引起的口腔黏膜炎的治疗方法。我们研究了局部给予肝素结合表皮生长因子样生长因子(HB-EGF)的疗效,HB-EGF 是一种强有力的口腔黏膜上皮增殖和迁移刺激物,可作为预防放射性口腔黏膜炎的潜在治疗方法。我们采用单次口腔腔照射(20 Gy)雌性 C57BL/6J 小鼠模型,评估了 HB-EGF 治疗(5 µl 10 µg/ml 溶液)的疗效。结果表明,与载体对照组相比,HB-EGF 治疗可显著增加舌部上皮厚度(舌背黏膜(42,106 µm 比 53,493 µm,p<0.01),舌腹黏膜(30,793 µm 比 39,095 µm,*p<0.05)),促进新上皮细胞分裂,并增加舌部和颊部口腔黏膜中桥粒的质量和数量。这些数据提供了概念验证,即局部给予 HB-EGF 具有开发为局部治疗药物的潜力,可用于减轻放疗后的口腔黏膜炎。