Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
基本信息
- 批准号:10312770
- 负责人:
- 金额:$ 67.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-12-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:8-hydroxyguanosineAccountingAdvanced Malignant NeoplasmAftercareAmericanAnimal ModelAntioxidantsAsianBiochemicalBloodCancer PatientCancer PrognosisCancer SurvivorChemopreventionChemopreventive AgentChineseClinicalCohort StudiesColorectal CancerDNADevelopmentDiagnosticEthnic groupEuropeanF2-IsoprostanesFollow-Up StudiesFree RadicalsHealthHumanIn VitroIntakeJointsLeadLinkLipid PeroxidationLongterm Follow-upMalignant NeoplasmsMeasurementMeasuresMolecularNatureOncogenicOncologistOutcomeOxidative StressParticipantPatient CarePatientsPhasePilot ProjectsPopulationPublishingRNARadiation therapyRandomized Clinical TrialsResearch PersonnelRiskRoleSample SizeSamplingScienceSupplementationSystemTarget PopulationsTimeUrineWomanWomen&aposs HealthWorkcancer cellcancer riskcancer survivalcarcinogenesiscell injurychemotherapycohortcolorectal cancer preventioncolorectal cancer riskcytotoxicdesigndiet and cancerepidemiology studyfollow-uphazardhealinginsightmale healthnoveloxidationoxidative damagesextheoriestranslational potentialtumortumorigenesis
项目摘要
SUMMARY
Conventional wisdom says that antioxidants should lower cancer risk by neutralizing cell-
damaging, cancer-causing oxidative stress. However, despite the compelling biochemical evidence that ties
oxidative damage to carcinogenesis for in vitro systems, almost all large randomized clinical trials have shown
that antioxidant supplementation provides no clear benefit and even increases cancer risk. These
disappointing and seemingly contradictory results have puzzled the public and researchers for decades. Even
more controversial is whether antioxidant supplementation is safe and effective for cancer survivors. An
estimated 15.5 million Americans in 2016 were cancer survivors, and up to 81% of them used antioxidant
supplements to promote healing. However, we do not understand whether and to what extent post-treatment
oxidative stress is associated with cancer prognosis. We recently conducted a molecular epidemiological study
of colorectal cancer (CRC). We found the first piece of evidence in humans that the association between
oxidative stress and CRC risk was bidirectional, with both beneficial and deleterious effects. Moreover, these
bidirectional effects were time-dependent. Specifically, in earlier phases of cancer development, high oxidative
stress was associated with increased risk of CRC, whereas in later phases, it was associated with decreased
risk. Correspondingly, we found that the association between antioxidant intake and CRC risk was also time-
dependent and varied by baseline oxidative stress. In the pilot study, we found that among patients with more
advanced cancer, their systemic levels of oxidative stress were actually lower. Furthermore, cancer patients
with higher post-treatment levels of oxidative stress had odds of living longer, after comprehensively adjusting
for clinical parameters. In this proposed study, we will conduct a large case-cohort study, building upon three
Asian and European cohorts to determine whether our novel findings—the time-dependent and bidirectional
effects of oxidative stress and antioxidants on CRC, first observed in Chinese women (discovery phase)—can
be replicated in both sexes and in different ethnic populations (replication phase). Comprehensive
assessments of oxidative stress in pre-diagnostic urine samples will be performed. We will also conduct a
follow-up study of CRC cases from whom both pre-diagnostic and post-treatment urine samples have been
collected. We will examine whether higher levels of systemic post-treatment oxidative stress are associated
with better CRC survival, while comprehensively accounting for pre-diagnostic oxidative stress and other
clinical parameters. We expect that this study, with its focus on the time-dependent and bidirectional
association between oxidative stress and CRC, will provide novel insights into the role of oxidative stress in
carcinogenesis, the first evidence linking oxidative stress and clinical outcomes of CRC, and much needed
information for identification of population subsets for chemoprevention. Thus, this study will have high
translational potential to lead to tailored strategies for CRC prevention and patient care.
总结
传统观点认为,抗氧化剂应该通过中和细胞来降低癌症风险-
破坏性的致癌氧化应激然而,尽管有令人信服的生化证据表明,
几乎所有的大型随机临床试验都表明,
补充抗氧化剂没有明显的益处,甚至会增加癌症风险。这些
几十年来,令人失望和看似矛盾的结果一直困扰着公众和研究人员。甚至
更有争议的是,抗氧化剂补充剂对癌症幸存者是否安全有效。一个
据估计,2016年有1550万美国人是癌症幸存者,其中高达81%使用抗氧化剂
补充剂,以促进愈合。然而,我们不知道是否以及在多大程度上后处理
氧化应激与癌症预后有关。我们最近进行了一项分子流行病学研究
结直肠癌(CRC)。我们在人类身上发现了第一个证据,
氧化应激和CRC风险是双向的,既有有益的影响,也有有害的影响。而且这些
双向效应具有时间依赖性。具体而言,在癌症发展的早期阶段,高氧化性
压力与CRC风险增加相关,而在后期阶段,压力与CRC风险降低相关。
风险相应地,我们发现抗氧化剂摄入量和CRC风险之间的关系也是时间-
依赖于和变化的基线氧化应激。在初步研究中,我们发现,
在晚期癌症中,他们的全身氧化应激水平实际上更低。此外,癌症患者
治疗后氧化应激水平较高的患者在综合调整后,
临床参数。在这项拟议的研究中,我们将进行一项大型病例队列研究,
亚洲和欧洲队列,以确定我们的新发现-时间依赖性和双向性
氧化应激和抗氧化剂对CRC的影响,首次在中国女性中观察到(发现阶段)-可以
在两性和不同种族人口中复制(复制阶段)。全面
将进行诊断前尿样中氧化应激的评估。我们亦会进行一项
对诊断前和治疗后尿液样本均已
收集。我们将研究是否更高水平的全身性治疗后氧化应激与
具有更好的CRC生存率,同时综合考虑诊断前氧化应激和其他
临床参数我们希望这项研究,其重点是时间依赖性和双向性
氧化应激和CRC之间的关联,将提供新的见解氧化应激的作用,
致癌作用,第一个证据连接氧化应激和CRC的临床结果,
用于鉴定用于化学预防的群体亚群的信息。因此,这项研究将具有很高的
翻译潜力,从而为CRC预防和患者护理提供量身定制的策略。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Qingxia Chen其他文献
Qingxia Chen的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Qingxia Chen', 18)}}的其他基金
DARSaW: Developing, Assessing, and Refining Synthetic Sampling Weights to Improve Generalizability of the All of Us Research Program Data
DARSaW:开发、评估和细化合成采样权重,以提高我们所有人研究计划数据的普遍性
- 批准号:
10796237 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
- 批准号:
10520027 - 财政年份:2019
- 资助金额:
$ 67.79万 - 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
- 批准号:
9887609 - 财政年份:2019
- 资助金额:
$ 67.79万 - 项目类别:
Time-dependent and bidirectional effect of oxidative stress - a missing piece of the free radical theory of cancer and its potential implications
氧化应激的时间依赖性和双向效应——癌症自由基理论的缺失部分及其潜在影响
- 批准号:
10063979 - 财政年份:2019
- 资助金额:
$ 67.79万 - 项目类别:
A New Approach to Correct Verification Bias Using Auxiliary Information
使用辅助信息纠正验证偏差的新方法
- 批准号:
8048932 - 财政年份:2010
- 资助金额:
$ 67.79万 - 项目类别:
A New Approach to Correct Verification Bias Using Auxiliary Information
使用辅助信息纠正验证偏差的新方法
- 批准号:
8207859 - 财政年份:2010
- 资助金额:
$ 67.79万 - 项目类别:
相似海外基金
Unraveling the Dynamics of International Accounting: Exploring the Impact of IFRS Adoption on Firms' Financial Reporting and Business Strategies
揭示国际会计的动态:探索采用 IFRS 对公司财务报告和业务战略的影响
- 批准号:
24K16488 - 财政年份:2024
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mighty Accounting - Accountancy Automation for 1-person limited companies.
Mighty Accounting - 1 人有限公司的会计自动化。
- 批准号:
10100360 - 财政年份:2024
- 资助金额:
$ 67.79万 - 项目类别:
Collaborative R&D
Accounting for the Fall of Silver? Western exchange banking practice, 1870-1910
白银下跌的原因是什么?
- 批准号:
24K04974 - 财政年份:2024
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A New Direction in Accounting Education for IT Human Resources
IT人力资源会计教育的新方向
- 批准号:
23K01686 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An empirical and theoretical study of the double-accounting system in 19th-century American and British public utility companies
19世纪美国和英国公用事业公司双重会计制度的实证和理论研究
- 批准号:
23K01692 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
An Empirical Analysis of the Value Effect: An Accounting Viewpoint
价值效应的实证分析:会计观点
- 批准号:
23K01695 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Accounting model for improving performance on the health and productivity management
提高健康和生产力管理绩效的会计模型
- 批准号:
23K01713 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
CPS: Medium: Making Every Drop Count: Accounting for Spatiotemporal Variability of Water Needs for Proactive Scheduling of Variable Rate Irrigation Systems
CPS:中:让每一滴水都发挥作用:考虑用水需求的时空变化,主动调度可变速率灌溉系统
- 批准号:
2312319 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Standard Grant
New Role of Not-for-Profit Entities and Their Accounting Standards to Be Unified
非营利实体的新角色及其会计准则将统一
- 批准号:
23K01715 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Improving Age- and Cause-Specific Under-Five Mortality Rates (ACSU5MR) by Systematically Accounting Measurement Errors to Inform Child Survival Decision Making in Low Income Countries
通过系统地核算测量误差来改善特定年龄和特定原因的五岁以下死亡率 (ACSU5MR),为低收入国家的儿童生存决策提供信息
- 批准号:
10585388 - 财政年份:2023
- 资助金额:
$ 67.79万 - 项目类别: