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
- 来源:
- 关键词:African AmericanAfrican American populationAlgorithmsAmericanApoptosisAreaBiological AvailabilityBiological ModelsBlack PopulationsBone MatrixBone RegenerationBone necrosisCancer PatientCaucasiansCell Cycle ArrestCellsChloroplastsCoupledDataDentistryDepositionDiabetic mouseDiagnosisDisadvantagedDiseaseFractureGoalsHistologicHumanImmunologicsInduction of ApoptosisInjectableInsulin-Like Growth Factor IJawLettuce - dietaryMalignant NeoplasmsMandibleMesenchymal Stem CellsModelingMolecularOralOsteoblastsOsteocytesOsteogenesisOsteoradionecrosisOutcomePatientsPeptidesPharmaceutical PreparationsPlantsPopulationPositron-Emission TomographyPredispositionQuality of lifeRaceRadiationRadiation therapyRadioRattusReportingSEER ProgramSeveritiesSiteSurvival RateSystemTestingTherapeuticTherapeutic IndexTransplantationUnited StatesX-Ray Computed Tomographybonebone cellbone healingcancer radiation therapycancer therapycomorbiditycompliance behaviordensityefficacy evaluationfunctional disabilityhealinghealth disparityhigh riskimprovedimproved outcomeinnovationinsightirradiationlow socioeconomic statusmalignant oropharynx neoplasmmicroCTmouse modelnovelnovel strategiesnovel therapeutic interventionnovel therapeuticsorofacialosteogenicosteoprogenitor cellpreclinical efficacypreventprotein expressionracial disparityracial populationremediationskeletalsocioeconomicsstem cellssurvival outcomesurvivorshiptranslational applications
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)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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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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