Novel therapeutic approaches to remediate radiotherapy-induced bone necrosis

修复放射治疗引起的骨坏死的新治疗方法

基本信息

  • 批准号:
    10912194
  • 负责人:
  • 金额:
    $ 20万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-15 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Oropharyngeal cancer (OPC) is the 9th most common cancer in the United States, and 26% of patients do not survive the first year after diagnosis due to cancer severity and treatment complications. African-Americans (AA) who develop OPC consistently demonstrate poorer survival than Caucasians. Assessments of the Surveillance, Epidemiology, and End Results (SEER) data have shown that 5-year relative survival of Caucasians with OPC is close to 57% while AA had a survival rate close to 33%. Post-cancer therapy complications account for majority of the racially disparate poor OPC survival outcomes. While radiotherapy for OPC improves survival, osteoradionecrosis (ORN) of the jaw and altered quality of life are unfortunate outcomes. Radiation promotes osteoblast and osteocyte apoptosis and induces G0G1 cell cycle arrest of jaw (orofacial) mesenchymal stem cells (OFMSCs) to deplete jaw osteoprogenitor cells. Lower levels of circulating progenitor cells in AA is an established contributor to health disparities. Coupled with high jaw susceptibility to ORN compared to other skeletal sites, the AA OPC patient has higher disadvantage of developing ORN complications and poor OPC survival outcomes. Understanding efficacy of OFMSC therapy for ORN in AA with lower circulating progenitor cells is vital for improving OPC outcomes. Injectable osteoanabolic drugs are attractive therapies for promoting bone healing in radio-damaged bone, but they are often unaffordable by AA from low socioeconomic group resulting in poor patient compliance. Penn Center for Innovation and Precision Dentistry has pioneered expression of protein drugs (PDs) in plant chloroplasts (lettuce leaves) for oral delivery that demonstrated bioavailability and efficacy to treat several diseases. Oral delivery of a novel aglycosylated IGF-1 with E-peptide bioencapsulated in plant cells restored bone healing with increased bone volume, density, and area in diabetic mouse model of bone fracture. Collectively, these suggest that enhancing osteogenesis with grafted OFMSCs and orally delivered IGF-1 are promising novel approaches to remediate jaw ORN, maximize therapeutic index of OPC radiotherapy and reduce racially disparate OPC outcomes. In Aim 1 will remediate jaw ORN in a rat model using grafted OFMSCs from two racial groups (AA vs. Caucasian) as rescue therapy. Aim 2 will evaluate efficacy of orally bioavailable IGF-1 and combined IGF-1/OFMSCs (AA vs. Caucasians) to mitigate jaw ORN. We predict that therapeutic applications of racially distinct OFMSCs and orally bioavailable IGF-1 will promote healing by protecting jaw bone cells from radiation-induced apoptosis. The outcome of this novel therapeutic models is expected to increase affordability and patient compliance, especially in the underprivileged and low socio- economic populations associated with majority of the poor OPC survival outcomes.
项目总结

项目成果

期刊论文数量(0)
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Sunday O Akintoye其他文献

Sunday O Akintoye的其他文献

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{{ truncateString('Sunday O Akintoye', 18)}}的其他基金

Biological Indicators of Racial Disparity in Ameloblastoma Recurrence
成釉细胞瘤复发的种族差异的生物学指标
  • 批准号:
    10347638
  • 财政年份:
    2021
  • 资助金额:
    $ 20万
  • 项目类别:
Biological Indicators of Racial Disparity in Ameloblastoma Recurrence
成釉细胞瘤复发的种族差异的生物学指标
  • 批准号:
    10540745
  • 财政年份:
    2021
  • 资助金额:
    $ 20万
  • 项目类别:
Dental outcomes in Fibrous Dysplasia/McCune Albright Syndrome
纤维性发育不良/麦库恩奥尔布赖特综合征的牙科结果
  • 批准号:
    8705613
  • 财政年份:
    2013
  • 资助金额:
    $ 20万
  • 项目类别:
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:
    8721197
  • 财政年份:
    2012
  • 资助金额:
    $ 20万
  • 项目类别:
Intracellular trafficking of Bisphosphonates in bone mesenchymal Stem Cells
骨髓间充质干细胞中双磷酸盐的细胞内运输
  • 批准号:
    8537887
  • 财政年份:
    2012
  • 资助金额:
    $ 20万
  • 项目类别:
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
  • 财政年份:
    2012
  • 资助金额:
    $ 20万
  • 项目类别:
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:
    8546712
  • 财政年份:
    2012
  • 资助金额:
    $ 20万
  • 项目类别:
Intracellular trafficking of Bisphosphonates in bone mesenchymal Stem Cells
骨髓间充质干细胞中双磷酸盐的细胞内运输
  • 批准号:
    8356486
  • 财政年份:
    2012
  • 资助金额:
    $ 20万
  • 项目类别:
Treatment of Osteoradionecrosis with Bone Marrow Stromal Cells
骨髓基质细胞治疗放射性骨坏死
  • 批准号:
    7668426
  • 财政年份:
    2006
  • 资助金额:
    $ 20万
  • 项目类别:
Treatment of Osteoradionecrosis with Bone Marrow Stromal Cells
骨髓基质细胞治疗放射性骨坏死
  • 批准号:
    7893103
  • 财政年份:
    2006
  • 资助金额:
    $ 20万
  • 项目类别:

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Drug Abuse and Crime Across the Life Course in an African American Population
非裔美国人一生中的药物滥用和犯罪
  • 批准号:
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  • 财政年份:
    2008
  • 资助金额:
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Drug Abuse and Crime Across the Life Course in an African American Population
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  • 批准号:
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非裔美国人一生中的药物滥用和犯罪
  • 批准号:
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  • 财政年份:
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Drug Abuse and Crime Across the Life Course in an African American Population
非裔美国人一生中的药物滥用和犯罪
  • 批准号:
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  • 财政年份:
    2008
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    $ 20万
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Molecular and Genetic Signatures of Perturbed Diabetic Pathways with Hepatitis C Virus infection and Co-morbidity Risks in African American Population
丙型肝炎病毒感染引起的糖尿病通路紊乱的分子和遗传特征以及非洲裔美国人的共病风险
  • 批准号:
    10132461
  • 财政年份:
    1997
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Molecular and Genetic Signatures of Perturbed Diabetic Pathways with Hepatitis C Virus infection and Co-morbidity Risks in African American Population
丙型肝炎病毒感染引起的糖尿病通路紊乱的分子和遗传特征以及非洲裔美国人的共病风险
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  • 财政年份:
    1997
  • 资助金额:
    $ 20万
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Molecular and Genetic Signatures of Perturbed Diabetic Pathways with Hepatitis C Virus infection and Co-morbidity Risks in African American Population
丙型肝炎病毒感染引起的糖尿病通路紊乱的分子和遗传特征以及非洲裔美国人的共病风险
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Molecular and Genetic Signatures of Perturbed Diabetic Pathways with Hepatitis C Virus infection and Co-morbidity Risks in African American Population
丙型肝炎病毒感染引起的糖尿病通路紊乱的分子和遗传特征以及非洲裔美国人的共病风险
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