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Mechanisms of radiation-induced craniofacial bone growth inhibition and possibilities of cytoprotection |
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Defense | Thèse de privat-docent : Univ. Genève, 2012 | |
Abstract | Malignancies are frequently located in the head and neck region in children; their management usually requires radiotherapy, which has severe consequences on the growth of the craniofacial skeleton. The purpose of this work is to investigate the effects of radiation in the growing craniofacial skeleton in a rabbit model in vivo and in vitro and the possibilities of growth preservation using the cytoprotective drug Amifostine. The effects of radiation were studied in a single-dose radiation model, then in a more clinically-relevant fractionated-dose radiation model. Both radiation administration modes produced significant bone growth impairment. Administration of Amifostine prior to radiation significantly preserved craniofacial growth; this did not appeared to be related to vascularity as we did not demonstrated histomorphometric vessel changes or long-lasting changes in blood flow. Amifostine- treated animals had increased osteoblast counts, and improved bone turn-over compared to unprotected animals. In vitro, Amifostine enhanced the number of surviving cells after irradiation. This work suggests that radioprotection offers a viable pathway for the prevention of radiation-induced craniofacial bone growth inhibition and ensuing deformities. | |
Keywords | Amifostine — Amifostine/*pharmacology — Amifostine/pharmacology/*therapeutic use — Animals — Bone Development — Bone Development/*drug effects/*radiation effects — Cells, Cultured — Cephalometry — Craniofacial bone growth — Cytoprotection — Dose Fractionation — Facial Bone/growth and development — Facial Bone/radiation effects — Facial Bones/drug effects/*growth & development/*radiation effects — Growth/radiation effects — Head and Neck Neoplasms/radiotherapy — Hemodynamics/*radiation effects — Histology — Histopathology — Male — Mandible/radiography — Models, Animal — Orbit — Orbit/drug effects/radiation effects — Orbit/growth & development/radiation effects/radiography — Osteoblasts/drug effects/radiation effects — Periosteum/cytology/drug effects/radiation effects — Rabbits — Rabbits/radiation effects — Radiation — Radiation Injuries, Experimental/*physiopathology — Radiation protection — Radiation Protection/drug effects — Radiation-protective agents — Radiation-Protective Agents/*pharmacology — Radiation-Protective Agents/pharmacology/*therapeutic use — Radiation — Radiation Injuries — Radiation/adverse effects — Random Allocation — Skull/growth & development/radiation effects — Skull/growth and development — Tomography, X-Ray Computed — Zygoma — Zygoma/drug effects/radiation effects — Zygoma/growth & development/radiation effects/radiography | |
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Citation (ISO format) | LA SCALA, Giorgio. Mechanisms of radiation-induced craniofacial bone growth inhibition and possibilities of cytoprotection. Université de Genève. Thèse de privat-docent, 2012. doi: 10.13097/archive-ouverte/unige:21690 https://archive-ouverte.unige.ch/unige:21690 |