Complications of Jaw Osteoradionecrosis in Cancer Management

颌骨放射性骨坏死在癌症治疗中的并发症

• 批准号: 8353798
• 负责人: Sunday O Akintoye
• 金额: $ 19.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353798
• 关键词: Animal Model; Animals; Biochemistry; Blood Vessels; Bone Injury; Bone Marrow; Bone Regeneration; Bone remodeling; Cancer Survivor; Cell Cycle Arrest; Cellular biology; Combined Modality Therapy; Complication; Data; Development; Equilibrium; Event; Face; Genetic; Goals; Head and Neck Cancer; Healed; Human; Hyperbaric Oxygen; Hypoxia; Hypoxia Inducible Factor; Imaging technology; Immunohistochemistry; In Vitro; Incidence; Jaw; Life; Life Expectancy; Malignant Neoplasms; Mandible; Mesenchymal Stem Cells; Mesoderm; Methods; Modeling; Molecular; Morbidity - disease rate; Multimodal Imaging; Necrosis; Neural Crest; Osteoblasts; Osteoclasts; Osteogenesis; Osteoradionecrosis; Outcome; Pathogenesis; Population; Positron-Emission Tomography; Predisposition; Preventive; Process; Property; Quality of life; Radiation; Radiation Tolerance; Radiation therapy; Rattus; Recovery; Role; Scientist; Signal Transduction; Site; Staining method; Stains; Stem cells; Survival Rate; System; Tooth Loss; Work; bone; bone cell; bone healing; cancer cell; cancer radiation therapy; cancer therapy; career development; healing; hypoxia inducible factor 1; improved; in vivo; irradiation; long bone; mandible/maxilla; orofacial; osteogenic; osteoprogenitor cell; prevent; regenerative; senescence; skeletal; standard of care; tissue regeneration

DESCRIPTION (provided by applicant): Osteoradionecrosis (ORN) is major complication of cancer therapy that causes facial disfigurement, tooth loss, significant morbidity, debility and diminished quality of life. Factors that make the jaw highly susceptible to ORN are still unclear. Guided by our previous work demonstrating that osteogenesis and bone regenerative properties of human bone mesenchymal stem cells are skeletal site-dependent according to embryological site of origin, we will elucidate underlying radiation-induced cellular events that dysregulate jaw bone healing after irradiation. We hypothesize that radiation disparately regulate jaw osteoclast-osteoblast balance to promote necrosis. We will determine how differential radiation-induced hypoxia accelerates jaw ORN. Understanding the responsiveness of bone mesenchymal stem cells to irradiation is critical to development of preventive therapies that will improve quality o life of cancer survivors.

描述（由申请人提供）：放射性骨坏死（ORN）是癌症治疗的主要并发症，可导致面部毁容、牙齿脱落、严重发病、虚弱和生活质量下降。导致下颌高度易受ORN影响的因素尚不清楚。我们以前的工作表明，人骨髓间充质干细胞的成骨和骨再生特性是骨骼部位依赖性的胚胎学起源的网站的指导下，我们将阐明潜在的辐射诱导的细胞事件，失调照射后颌骨愈合。我们推测，放射线间接调节颌骨破骨细胞-成骨细胞平衡，促进坏死。我们将确定差异辐射诱导的缺氧如何加速颌骨ORN。了解骨髓间充质干细胞对辐射的反应性对于开发预防性治疗是至关重要的，这将改善癌症幸存者的生活质量。