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
基本信息
- 批准号:10540745
- 负责人:
- 金额:$ 36.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-14 至 2026-11-30
- 项目状态:未结题
- 来源:
- 关键词:African American populationAmeloblastomaAutophagocytosisAutophagosomeBRAF geneBioenergeticsBiologicalBiological MarkersBlack PopulationsBlack raceCD34 geneCaucasiansCell LineCell SurvivalCellsCharacteristicsClinicalColorectal CancerComplexCysteine-Rich DomainCytoprotectionDNA Sequence AlterationDisparityDrosophila pros proteinENG geneEpitheliumGTF2H1 geneGrowthHead and Neck NeoplasmsHypoxiaHypoxia Inducible FactorIncidenceKnowledgeMAP Kinase GeneMediatingMesenchymalModelingMusMutationNeoplasm MetastasisNutrientOdontogenic TumorsOncogenesOncogenicOperative Surgical ProceduresOxidative StressPECAM1 genePathway interactionsPatientsPatternPhagocytosisPhenotypePhosphotransferasesPrevalencePrognostic MarkerPropertyProtein-Serine-Threonine KinasesProteinsProto-Oncogene Proteins B-rafRaceRecurrenceRecyclingResidual stateRunningSamplingSignal PathwayStressTestingTissuesTreatment outcomeTumor PromotionVariantangiogenesiscancer stem cellcohortcomparativedensitydisparity reductionin vivomigrationmortalityneoplasticneoplastic cellprognostic indicatorprognostic valueracial disparityracial diversityracial health disparityracial populationstem-like cellsurvival outcometherapy resistanttraffickingtumortumor microenvironment
项目摘要
Project Summary
Ameloblastoma accounts for 14% of all odontogenic tumors and African-Americans are five times more likely to
develop ameloblastoma compared to Caucasians. Despite radical surgery, 10% of ameloblastomas recur and
25% of recurrent ameloblastomas occur in the black racial group. The biological determinants of ameloblastoma
racial disparity are unclear and there are no specific biological markers to predict recurrence. Most
ameloblastomas display genetic mutations of BRAF that encodes the serine/threonine protein kinase B-Raf, an
activator of MAPK/ERK-signaling pathway. BRAF oncogenes induce the expression of key autophagic markers
that include LC3, p62 and BECLIN1. High expressions of p62, ATG7 and LC3 have been identified in all variants
of ameloblastoma and our in vivo mouse ameloblastoma tumor model displayed elevated LC3 and p62 levels.
These suggest ameloblastoma recurrence can be attributed to autophagic cell survival mechanisms of residual
invasive neoplastic odontogenic epithelium. Interplay of autophagic regulator BECNLIN1 with RUBICON [Run
domain Beclin-1-interacting and cysteine-rich domain-containing protein], a component of LC3-associated
phagocytosis (LAP) dysregulates autophagosomal maturation and endocytic trafficking to promote tumor
migration and invasiveness. Our hypothesis is that autophagy reactivates residual invasive odontogenic
epithelium by LAP-mediated entosis and recycling of bioenergetic cellular components. Our collaborative group
has a relatively large cohort of ameloblastoma tissues and have generated epithelial-derived (EP-AMCs) and
mesenchymal-derived (MS-AMCs) ameloblastoma cell lines from BRAF V600E+ multicystic/follicular
ameloblastomas. To elucidate biological mechanisms contributing to racial disparity in Black versus White racial
groups, we will determine prognostic biomarkers of ameloblastoma recurrence and assess how LC3-mediated
autophagic ‘cargo’ processing orchestrate recurrence disparity. In Aim 1 we will determine whether autophagic
proteins are pro-oncogenic adaptors associated with ameloblastoma racial disparity, aggressive phenotype and
propensity for recurrence. In Aim 2, we will assess whether residual invasive ameloblastic epithelium survive using
LAP-mediated entosis and recycling of bioenergetic cellular components. While ameloblastoma is relatively rare,
understanding the interplay of two converging cytoprotective pathways in ameloblastoma growth pattern and
recurrence has the potential to lead to new prognostic biomarkers and precision-guided therapies to alleviate
racial disparities in BRAF+ tumors like ameloblastoma.
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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- 批准号:
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- 资助金额:
$ 36.43万 - 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
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- 批准号:
8537887 - 财政年份:2012
- 资助金额:
$ 36.43万 - 项目类别:
Complications of Jaw Osteoradionecrosis in Cancer Management
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- 批准号:
8546712 - 财政年份:2012
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Complications of Jaw Osteoradionecrosis in Cancer Management
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8353798 - 财政年份:2012
- 资助金额:
$ 36.43万 - 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
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8356486 - 财政年份:2012
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$ 36.43万 - 项目类别:
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$ 36.43万 - 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:
7084879 - 财政年份:2006
- 资助金额:
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