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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

基本信息

批准号：
8721197
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
项目类别：
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/8721197
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 in vivo imaging irradiation long bone mandible/maxilla orofacial osteogenic osteoprogenitor cell prevent regenerative senescence skeletal standard of care tissue regeneration

项目摘要

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，会导致面部毁容、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。我们之前的工作表明，根据胚胎起源部位，人骨间充质干细胞的成骨和骨再生特性具有骨骼部位依赖性，在此基础上，我们将阐明潜在的辐射诱导的细胞事件，这些事件会在辐射后调节颌骨愈合。我们假设辐射不同地调节颌骨破骨细胞-成骨细胞平衡以促进坏死。我们将确定差异辐射引起的缺氧如何加速颌部 ORN。了解骨间充质干细胞对辐射的反应对于开发可改善癌症幸存者生活质量的预防性疗法至关重要。