Biomarkers, mechanisms and modulation of oxidative stress associated risk factors in carcinogenesis
致癌过程中氧化应激相关危险因素的生物标志物、机制和调节
基本信息
- 批准号:10704632
- 负责人:
- 金额:$ 42.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-14 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdverse eventAgingAlgorithmsAnimal ModelAnimalsAppointmentArchitectureBindingBinding SitesBiologicalBiological AssayBiological MarkersCCCTC-binding factorCaloric RestrictionCancer BiologyCancer PatientCarcinogen exposureCarcinogensCause of DeathCell Cycle RegulationCell LineCellsChIP-seqChromatinChronicCitiesClinicalClinical DataClonal ExpansionColorectalColorectal CancerColorectal NeoplasmsComputational BiologyComputational TechniqueDNA DamageDNA RepairDNA Sequence AlterationDataDedicationsDefectDeveloped CountriesDeveloping CountriesDevelopmentDietDiseaseEnergy IntakeEpidemiologyEpigenetic ProcessExerciseExposure toExtramural ActivitiesFacultyFastingFecesFundingFutureGenesGeneticGenomicsGrowthHigh School StudentHumanIncidenceIndividualInduced MutationInduction of ApoptosisInflammationInflammatoryInstitutionIntakeIntermittent fastingInternationalJointsJournalsLaboratoriesLeadLeadershipLife StyleLinkLocationMalignant NeoplasmsMalignant neoplasm of gastrointestinal tractMalignant neoplasm of prostateMathematicsMeatMediatingMedicineMentorsMentorshipMetabolicMolecularMolecular BiologyMolecular ComputationsMolecular EpidemiologyMutagenesisMutagensMutationNormal CellNormal tissue morphologyObesityOutcomeOxidative StressPatientsPatternPeer ReviewPelvisPeripheral Blood Mononuclear CellPersonal SatisfactionPhase I/II TrialPhysiciansPositioning AttributePostdoctoral FellowPredispositionProbabilityProcessPublicationsQuality of lifeRadiationRadiation OncologyRadiation therapyRandomizedReactive Oxygen SpeciesRectal CancerReportingResearchRisk FactorsSafetyScienceScientistSmokingSocietiesSomatic MutationTP53 geneTestingTherapeuticTherapeutic IndexTimeTissuesToxic effectTranslatingTreatment-related toxicityUltraviolet RaysUnhealthy DietUrineUrothelial CellWorkcancer cellcancer genomecancer initiationcancer riskcarcinogenesiscareercareer networkingchronic inflammatory diseaseclinical translationcohortcolon cancer patientscomputerized toolscytokinedietarydriver mutationepigenomicsexperiencegenome sequencingimprovedinduced pluripotent stem celllifestyle datalifestyle factorsmodifiable riskmultidisciplinarymultiple omicsnovelobesity geneticsphase 3 studypre-clinicalprimary endpointprofessorpromoterprospectiverepairedside effecttooltranscriptome sequencingtumortumorigenesiswhole genome
项目摘要
Abstract
Cancer is the second most common cause of death in developed nations, and incidence is rising among
developing nations. An estimated 70% of cancers are attributable to “modifiable” risk factors, including obesity,
chronic inflammatory diseases, and poor diet, all of which have been associated with increased oxidative
stress. These are not themselves “carcinogenetic”, but they are thought to act as “cancer promoters”,
increasing the probability of developing cancer. With advances in whole genome sequencing and development
of computational techniques to examine the cancer genome, we can now use mathematical profiling of somatic
mutational profiles (termed mutational signatures) to identify potential causes underlying a given tumor (e.g.,
smoking versus UV light). It remains unclear, however, if there is a mutational signature that is a biomarker of
cumulative lifetime exposure to reactive oxygen species (ROS)-mediated DNA damage and if this correlates
with cancer-associated lifestyle factors. Here, we will utilize cutting-edge multi-omic profiling and molecular
biology and computational tools to better understand the contribution/mechanism of oxidative stress as a
cancer promoter.
To examine the correlation of ROS mutational signature levels and inflammation-related cancer risk
factors, we will perform whole genome sequencing and mutational signature analysis of a large cohort of
colorectal tumors from patients with detailed, longitudinally collected lifestyle data (e.g., smoking, caloric
intake, red meat intake, exercise level, etc.) collected by the Molecular Epidemiology of Colorectal Cancer
study. We will also evaluate whether accumulation of ROS-generated mutations is biased toward CTCF
binding loci and whether chromosomal architecture is modified by exposure to carcinogens or cancer-
associated processes, thereby mediating unique “epigenomic signatures”. These aims will also provide data
that can be used in the development of two novel computational tools for the analysis of cancer driver
mutational signatures and epigenomic signatures of carcinogen exposure.
Finally, we will test the molecular and clinical benefit of intermittent fasting during daily radiation therapy
based on the hypothesis that lifestyle factors could modulate susceptibility to ROS mutagenesis. Patient-
reported quality of life and clinician-reported adverse events, as well as molecular assay for tissue-specific
levels of ROS-associated DNA damage, will allow us to assess whether intermittent fasting can reduce normal
tissue toxicity. Successful completion of the proposed research will provide a comprehensive examination of
the epidemiology and mechanism of ROS-mediated DNA damage in human cancers and demonstrate the
safety and potential efficacy of intermittent fasting as a clinically translatable and easily adaptable approach to
reducing both acute and chronic side effects associated with radiotherapy.
摘要
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.
推动基因组引导精准放射治疗的发展。
- DOI:10.3390/cancers15225314
- 发表时间:2023-11-07
- 期刊:
- 影响因子:5.2
- 作者:Tam, Andrew;Mercier, Benjamin D.;Thomas, Reeny M.;Tizpa, Eemon;Wong, Irene G.;Shi, Juncong;Garg, Rishabh;Hampel, Heather;Gray, Stacy W.;Williams, Terence;Bazan, Jose G.;Li, Yun R.
- 通讯作者:Li, Yun R.
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Yun Rose Li其他文献
Delayed definitive management of localized prostate cancer: what do we know?
局限性前列腺癌的延迟确定性治疗:我们知道什么?
- DOI:
10.1038/s41391-024-00876-2 - 发表时间:
2024-08-11 - 期刊:
- 影响因子:5.800
- 作者:
Osama Mohamad;Yun Rose Li;Felix Feng;Julian C. Hong;Anthony Wong;Zakaria El Kouzi;Mohamed Shelan;Thomas Zilli;Peter Carroll;Mack Roach - 通讯作者:
Mack Roach
Experience from an Early Exposure Education Program in Radiation Oncology for High School and Undergraduate Students.
高中生和本科生放射肿瘤学早期暴露教育计划的经验。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:3.3
- 作者:
Andrew Tam;C. Ladbury;Scott Glaser;Arya Amini;Yi;Yun Rose Li - 通讯作者:
Yun Rose Li
Grade 5 Radiation Necrosis After Whole-Brain Radiation Therapy.
全脑放射治疗后 5 级放射性坏死。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:3.3
- 作者:
Andrew Tam;Yun Rose Li;Terence Williams;Stephanie Yoon - 通讯作者:
Stephanie Yoon
2012: Impact of Metabolic Syndrome on Testosterone Recovery after Stopping Androgen Deprivation Therapy
2012年:代谢综合征对停止雄激素剥夺治疗后睾丸激素恢复的影响
- DOI:
10.1016/s0167-8140(24)02304-1 - 发表时间:
2024-05-01 - 期刊:
- 影响因子:5.300
- 作者:
Andrew Tam;Qianhua Feng;Colton Ladbury;Juncong Ashley Shi;Nicholas Correnti;Stephanie Zheng;Jeffrey Wong;Savita Dandapani;Scott Glaser;Tanya Dorff;Yun Rose Li - 通讯作者:
Yun Rose Li
Uncovering novel mutational signatures by emde novo/em extraction with SigProfilerExtractor
- DOI:
10.1016/j.xgen.2022.100179 - 发表时间:
2022-11-09 - 期刊:
- 影响因子:9.000
- 作者:
S.M. Ashiqul Islam;Marcos Díaz-Gay;Yang Wu;Mark Barnes;Raviteja Vangara;Erik N. Bergstrom;Yudou He;Mike Vella;Jingwei Wang;Jon W. Teague;Peter Clapham;Sarah Moody;Sergey Senkin;Yun Rose Li;Laura Riva;Tongwu Zhang;Andreas J. Gruber;Christopher D. Steele;Burçak Otlu;Azhar Khandekar;Ludmil B. Alexandrov - 通讯作者:
Ludmil B. Alexandrov
Yun Rose Li的其他文献
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{{ truncateString('Yun Rose Li', 18)}}的其他基金
Biomarkers, mechanisms and modulation of oxidative stress associated risk factors in carcinogenesis
致癌过程中氧化应激相关危险因素的生物标志物、机制和调节
- 批准号:
10481713 - 财政年份:2022
- 资助金额:
$ 42.26万 - 项目类别:
Examining the impact of the obesity-inflammation axis on cancer by genomic and transcriptomic profiling
通过基因组和转录组分析检查肥胖-炎症轴对癌症的影响
- 批准号:
9767517 - 财政年份:2018
- 资助金额:
$ 42.26万 - 项目类别:
Integrative Analysis of Genomic Risk Factors in Juvenile Idiopathic Arthritis
幼年特发性关节炎基因组危险因素的综合分析
- 批准号:
8717915 - 财政年份:2014
- 资助金额:
$ 42.26万 - 项目类别:
Integrative Analysis of Genomic Risk Factors in Juvenile Idiopathic Arthritis
幼年特发性关节炎基因组危险因素的综合分析
- 批准号:
8879958 - 财政年份:2014
- 资助金额:
$ 42.26万 - 项目类别:
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