Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
권호 표지

The Effect of Recombinant Human Epidermal Growth Factor on Cisplatin and Radiotherapy Induced Oral Mucositis in Mice

마우스에서 Cisplatin과 방사선조사로 유발된 구내염에 대한 재조합 표피성장인자의 효과

  • Na, Jae-Boem (Departments of Diagnostic Radiology, Gyeongsang National University School of Medicine) ;
  • Kim, Hye-Jung (Departments of Pharmacology, Gyeongsang National University School of Medicine) ;
  • Chai, Gyu-Young (Departments of Radiation Oncology, Gyeongsang National University School of Medicine) ;
  • Lee, Sang-Wook (Department of Radiation Oncology, University of Ulsan College of Medicine) ;
  • Lee, Kang-Kyoo ( Department of Radiation Oncology, Wonkwang University College of Medicine) ;
  • Chang, Ki-Churl (Departments of Pharmacology, Gyeongsang National University School of Medicine) ;
  • Choi, Byung-Ock (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Jang, Hong-Seok (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Jeong, Bea-Keon (Departments of Radiation Oncology, Gyeongsang National University School of Medicine) ;
  • Kang, Ki-Mun (Departments of Radiation Oncology, Gyeongsang National University School of Medicine)
  • 나재범 (경상대학교 의학전문대학원 영상의학교실) ;
  • 김혜정 (경상대학교 의학전문대학원 약리학교실) ;
  • 채규영 (경상대학교 의학전문대학원 방사선종양학교실, 경상대학교 건강과학연구원) ;
  • 이상욱 (울산대학교 의과대학 방사선종양학교실) ;
  • 이강규 (원광대학교 의과대학 방사선종양학교실) ;
  • 장기철 (경상대학교 의학전문대학원 약리학교실) ;
  • 최병옥 (가톨릭대학교 의과대학 방사선종양학교실) ;
  • 장홍석 (가톨릭대학교 의과대학 방사선종양학교실) ;
  • 정배권 (경상대학교 의학전문대학원 방사선종양학교실, 경상대학교 건강과학연구원) ;
  • 강기문 (경상대학교 의학전문대학원 방사선종양학교실, 경상대학교 건강과학연구원)
  • Published : 2007.12.30

Abstract

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

Keywords

File

Download PDF

References

  1. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the newborn animal. J Biol Chem 1962;237:1555-1562
  2. Cohen S, Carpenter G. Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci USA 1975;72:1317-1321 https://doi.org/10.1073/pnas.72.4.1317
  3. Steidler NE, Reade PC. Histomorphological effects of epidermal growth factor on skin and oral mucosa in neonatal mice. Arch Oral Biol 1980;25:37-43 https://doi.org/10.1016/0003-9969(80)90153-3
  4. Cohen S. The epidermal growth factor (EGF). Cancer 1983; 51:1787-1791 https://doi.org/10.1002/1097-0142(19830515)51:10<1787::AID-CNCR2820511004>3.0.CO;2-A
  5. Waterfield MD. Epidermal growth factor and related molecules. Lancet 1989;1:1243-1246
  6. Weaver LT, Gonnella PA, Israel EJ, Walker WA. Uptake and transport of epidermal growth factor by the small intestinal epithelium of the fetal rat. Gastroenterology 1990;98: 828-837 https://doi.org/10.1016/0016-5085(90)90004-K
  7. Carpenter G. Epidermal growth factor is a major growthpromoting agent in human milk. Science 1980;210:198-199 https://doi.org/10.1126/science.6968093
  8. Jung KI, Kim SH, Moon SY, et al. Effects of recombinant epidermal growth factor on experimental radiation-induced oral mucositis in rats. J Korean Soc Ther Radiol Oncol 2006;24: 67-76
  9. Bensadoun RJ, Magne N, Marcy PY, Demard F. Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: new trends in pathophysiology, prevention and treatment. Eur Arch Otorhinolaryngol 2001;258:481- 487 https://doi.org/10.1007/s004050100368
  10. Rose-Ped AM, Bellm LA, Epstein JB, et al. Complications of radiation therapy for head and neck cancers. The patient's perspective. Cancer Nurs 2002;25:461-467 https://doi.org/10.1097/00002820-200212000-00010
  11. Ruescher TJ, Sodeifi A, Scrivani SJ, et al. The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 1998;82:2275-2281 https://doi.org/10.1002/(SICI)1097-0142(19980601)82:11<2275::AID-CNCR25>3.0.CO;2-Q
  12. Rapoport AP, Miller Watelet LF, Linder T, et al. Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants. J Clin Oncol 1999;17:2446-2453 https://doi.org/10.1200/JCO.1999.17.8.2446
  13. Armstrong TS. Stomatitis in the bone marrow transplant patient. An overview and proposed oral care protocol. Cancer Nurs 1994;17:403-410
  14. Plevova P. Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: a review. Oral Oncol 1999;35:453-470 https://doi.org/10.1016/S1368-8375(99)00033-0
  15. Worthington HV, Clarkson JE. Prevention of oral mucositis and oral candidiasis for patients with cancer treated with chemotherapy: cochrane systematic review. J Dent Educ 2002; 66:903-911
  16. Antonadou D, Pepelassi M, Synodinou M, Puglisi M, Throuvalas N. Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2002;52: 739-747 https://doi.org/10.1016/S0360-3016(01)02683-9
  17. Castagna L, Benhamou E, Pedraza E, et al. Prevention of mucositis in bone marrow transplantation: a double blind randomised controlled trial of sucralfate. Ann Oncol 2001;12: 953-955 https://doi.org/10.1023/A:1011119721267
  18. Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-14 https://doi.org/10.1002/(SICI)1097-0142(19981001)83:7<1433::AID-CNCR22>3.0.CO;2-4
  19. Dazzi C, Cariello A, Giovanis P, et al. Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Ann Oncol 2003;14: 559-563 https://doi.org/10.1093/annonc/mdg177
  20. Guo H, Seixas-Silva JA Jr, Epperly MW, et al. Prevention of radiation-induced oral cavity mucositis by plasmid/ liposome delivery of the human manganese superoxide dismutase (SOD2) transgene. Radiat Res 2003;159:361-370 https://doi.org/10.1667/0033-7587(2003)159[0361:PORIOC]2.0.CO;2
  21. Borges L, Rex KL, Chen JN, et al. A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis. Int J Radiat Oncol Biol Phys. 2006;66:254-262 https://doi.org/10.1016/j.ijrobp.2006.05.025
  22. Saadeh CE. Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment. Pharmacotherapy 2005;25:540-554 https://doi.org/10.1592/phco.25.4.540.61035
  23. Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004;100:2026-2046 https://doi.org/10.1002/cncr.20163
  24. Nanney LB, Magid M, Stoscheck CM, King LE Jr. Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages. J Invest Dermatol 1984;83:385-393 https://doi.org/10.1111/1523-1747.ep12264708
  25. Brown GL, Curtsinger L 3rd, Brightwell JR, et al. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med 1986;163:1319-1324 https://doi.org/10.1084/jem.163.5.1319
  26. Brown GL, Nanney LB, Griffen J, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med 1989;321:76-79 https://doi.org/10.1056/NEJM198907133210203
  27. Brown GL, Curtsinger L, Jurkiewicz MJ, Nahai F, Schultz G. Stimulation of healing of chronic wounds by epidermal growth factor. Plast Reconstr Surg 1991;88:189-194 https://doi.org/10.1097/00006534-199108000-00001
  28. Chao JC, Liu KY, Chen SH, Fang CL, Tsao CW. Effect of oral epidermal growth factor on mucosal healing in rats with duodenal ulcer. World J Gastroenterol 2003;9:2261-2265 https://doi.org/10.3748/wjg.v9.i10.2261
  29. Saibishkumar EP, Patel FD, Ghoshal S, et al. Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: a retrospective analysis. Int J Radiat Oncol Biol Phys 2005;63:828-833 https://doi.org/10.1016/j.ijrobp.2005.04.002
  30. LoRusso P, Pazdur R, Redman BG, Kinzie J, Vaitkevicius V. Low-dose continuous infusion 5-fluorouracil and cisplatin: phase II evaluation in advanced colorectal carcinoma. Am J Clin Oncol 1989;12:486-490 https://doi.org/10.1097/00000421-198912000-00005
  31. Lee SW, Jung KI, Kim YW, et al. Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats. Int J Radiat Oncol Biol Phys 2007;67:1172-1178 https://doi.org/10.1016/j.ijrobp.2006.10.038