Using Mouse Endoscopy for Evaluating Colon Cancer
使用小鼠内窥镜评估结肠癌
基本信息
- 批准号:7533904
- 负责人:
- 金额:$ 35.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-08-01 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:A/J MouseAberrant crypt fociAddressAdenomatous PolypsArachidonic AcidsBiopsy SpecimenCancer EtiologyCessation of lifeChemopreventionChemopreventive AgentClinicClinicalClinical ChemopreventionClinical TrialsColonColon CarcinomaColonic AdenomaColorectal CancerDevelopmentDisease regressionDoseEarly DiagnosisEndoscopyEventFutureGenesGenomicsGenus ColaGoalsGrowthHumanImageIn SituIndividualInterventionLaboratoriesLesionMapsMethodologyMethodsModelingMolecularMolecular AnalysisMolecular ProfilingMolecular TargetMonitorMorbidity - disease rateMucous MembraneMusNumbersPathway interactionsPatientsPilot ProjectsPopulationPredictive ValuePremalignantPrevention strategyProteinsProteomicsProtocols documentationPublic HealthRateRelative (related person)ResistanceRiskScreening procedureSiteSulindacTestingTimeTissuesWeekadenomabasecancer preventioncancer riskcolon carcinogenesisdesignimprovedmortalitynovelresponsetumortumor progression
项目摘要
DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer deaths in the U.S. Screening high-risk individuals for the early detection of colon lesions is an important approach to improving treatment and survival. This application is intended to develop and refine a novel combined endoscopic and proteomic method for evaluating precancerous aberrant crypt foci (ACF) and adenomatous polyps. This methodology aims to establish molecular features that predict, and potentially confer, the efficacy of specific chemoprevention agents. We will use sulindac, currently being tested in an NCI multi-center pilot chemoprevention clinical trial (CPN), as a model chemopreventive agent to develop this methodology. Our proposed studies will address the following issues: (1) The efficacy of sulindac against ACF and adenomas will be tracked in situ using a novel endoscopic imaging/lesion mapping protocol in mice; (2) The proteomic and genomic features of adenomas that predict and/or confer their response to sulindac will be identified; (3) The predictive value of these molecular targets for sulindac efficacy will be evaluated in human colon tissues in a six-week sulindac pilot study. Our hypothesis is that the molecular features of early precancerous lesions and adenomas will predict and potentially confer the efficacy of chemoprevention. Ultimately we envision generating a molecular profile of colon lesions to serve as the basis for assessing risk, designing cancer- prevention strategies customized to the individual and identifying targets for the development of future chemopreventive agents. Although our proposed studies focus on the response to sulindac, this general strategy could be adapted to chemoprevention agents that function through different modes of action. A more comprehensive understanding of how the molecular profile of an individual's colon lesions relates to their response to specific chemopreventive agents could ultimately be used to develop safe and effective strategies that fully realize the promise of chemoprevention for reducing mortality and morbidity related to colon cancer. PUBLIC HEALTH RELEVANCE: We are developing an approach to view the events of colon carcinogenesis and chemoprevention in 'real-time'. It will be possible in principal to determine which subpopulations of early colon lesions develop into tumors, and whether chemoprevention agents suppress the rate of ACF formation, or promote their regression. Our approach is predicted to recapitulate potential clinical situations, in which protein markers can be used to identify individuals with 'high-risk' ACF or adenomas. In addition, a long-term goal of our approach is to customize chemoprevention in human populations based on expression of predictive proteins or genes uncovered in precancerous lesions. Although our proposed studies focus on the response to sulindac, this general strategy could be adapted to chemoprevention agents that function through different modes of action. A more comprehensive understanding of how the molecular profile of an individual's colon lesions relates to their response to specific chemopreventive agents could ultimately be used to develop safe and effective strategies that fully realize the promise of chemoprevention for reducing mortality and morbidity related to colon cancer.
描述(申请人提供):结直肠癌(CRC)是美国癌症死亡的第二大原因。筛查高危人群以早期发现结肠病变是提高治疗和生存率的重要途径。这项应用旨在开发和改进一种新的内窥镜和蛋白质组学相结合的方法来评估癌前异常隐窝病灶(ACF)和腺瘤性息肉。这一方法论旨在建立预测和潜在地赋予特定化学预防药效的分子特征。我们将使用目前正在NCI多中心化学预防临床试验(CPN)中测试的舒林酸作为模型化学预防药物来开发这一方法学。我们拟议的研究将涉及以下问题:(1)将使用一种新的内窥镜成像/病变映射协议在小鼠身上原位追踪舒林酸对ACF和腺瘤的疗效;(2)将确定预测和/或提供舒林酸疗效的腺瘤的蛋白质组和基因组特征;(3)将在一项为期六周的舒林酸先导研究中,在人类结肠组织中评估这些分子靶点对舒林酸疗效的预测价值。我们的假设是,早期癌前病变和腺瘤的分子特征将预测并潜在地赋予化学预防的效果。最终,我们设想生成结肠病变的分子图谱,作为评估风险、设计针对个人定制的癌症预防策略以及为未来化学预防药物的开发确定靶点的基础。虽然我们建议的研究重点放在舒林酸的反应上,但这一总体策略可以适用于通过不同作用模式发挥作用的化学预防药物。更全面地了解个人结肠病变的分子特征与他们对特定化学预防药物的反应之间的关系,最终可以用来开发安全有效的策略,充分实现化学预防降低与结肠癌相关的死亡率和发病率的前景。与公共健康相关:我们正在开发一种方法来实时查看结肠癌发生和化学预防的事件。原则上有可能确定早期结肠病变的哪些亚群发展为肿瘤,以及化学预防药物是抑制ACF的形成速度,还是促进其消退。我们的方法预计将概括潜在的临床情况,在这些情况下,蛋白质标记物可以用来识别患有‘高危’ACF或腺瘤的个体。此外,我们方法的长期目标是根据癌前病变中发现的预测蛋白或基因的表达来定制人类群体的化学预防。虽然我们建议的研究重点放在舒林酸的反应上,但这一总体策略可以适用于通过不同作用模式发挥作用的化学预防药物。更全面地了解个人结肠病变的分子特征与他们对特定化学预防药物的反应之间的关系,最终可以用来开发安全有效的策略,充分实现化学预防降低与结肠癌相关的死亡率和发病率的前景。
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 }}
Daniel William Rosenberg其他文献
Daniel William Rosenberg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('Daniel William Rosenberg', 18)}}的其他基金
(PQ1) Mechanisms for Early Onset Colorectal Cancer
(PQ1) 早发性结直肠癌的机制
- 批准号:
10178968 - 财政年份:2021
- 资助金额:
$ 35.45万 - 项目类别:
Are ACF Surrogate Markers for Chemoprevention?
ACF 替代标记物可用于化学预防吗?
- 批准号:
8278959 - 财政年份:2012
- 资助金额:
$ 35.45万 - 项目类别:
Are ACF Surrogate Markers for Chemoprevention?
ACF 替代标记物可用于化学预防吗?
- 批准号:
8637744 - 财政年份:2012
- 资助金额:
$ 35.45万 - 项目类别:
Are ACF Surrogate Markers for Chemoprevention?
ACF 替代标记物可用于化学预防吗?
- 批准号:
9040895 - 财政年份:2012
- 资助金额:
$ 35.45万 - 项目类别:
Are ACF Surrogate Markers for Chemoprevention?
ACF 替代标记物可用于化学预防吗?
- 批准号:
8474718 - 财政年份:2012
- 资助金额:
$ 35.45万 - 项目类别:
Using Mouse Endoscopy for Evaluating Colon Cancer
使用小鼠内窥镜评估结肠癌
- 批准号:
8080447 - 财政年份:2008
- 资助金额:
$ 35.45万 - 项目类别:
Using Mouse Endoscopy for Evaluating Colon Cancer
使用小鼠内窥镜评估结肠癌
- 批准号:
7835815 - 财政年份:2008
- 资助金额:
$ 35.45万 - 项目类别:
Using Mouse Endoscopy for Evaluating Colon Cancer
使用小鼠内窥镜评估结肠癌
- 批准号:
8267088 - 财政年份:2008
- 资助金额:
$ 35.45万 - 项目类别:
相似海外基金
UCI 07-70: INHIBITING EGF RECEPTOR SIGNALING IN ABERRANT CRYPT FOCI OF THE COLON
UCI 07-70:抑制结肠异常隐窝灶中的 EGF 受体信号传导
- 批准号:
8166931 - 财政年份:2009
- 资助金额:
$ 35.45万 - 项目类别:
Aberrant Crypt Foci as a Biomarker for Chemoprevention
异常隐窝病灶作为化学预防的生物标志物
- 批准号:
7035435 - 财政年份:2006
- 资助金额:
$ 35.45万 - 项目类别:
Aberrant Crypt Foci as a Biomarker for Chemoprevention
异常隐窝病灶作为化学预防的生物标志物
- 批准号:
7283263 - 财政年份:2006
- 资助金额:
$ 35.45万 - 项目类别:
Aberrant Crypt Foci as a Biomarker for Chemoprevention
异常隐窝病灶作为化学预防的生物标志物
- 批准号:
7494571 - 财政年份:2006
- 资助金额:
$ 35.45万 - 项目类别:
Aberrant Crypt Foci as a Biomarker for Chemoprevention
异常隐窝病灶作为化学预防的生物标志物
- 批准号:
7691251 - 财政年份:2006
- 资助金额:
$ 35.45万 - 项目类别:
Gene analysis of aberrant crypt foci in patients with ulcerative colitis
溃疡性结肠炎患者隐窝异常病灶基因分析
- 批准号:
13670536 - 财政年份:2001
- 资助金额:
$ 35.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Aberrant crypt foci, multistep process of colon carcinogenesis and ras farnesylation
异常隐窝病灶、结肠癌发生的多步过程和 ras 法尼基化
- 批准号:
194630-1997 - 财政年份:2000
- 资助金额:
$ 35.45万 - 项目类别:
Discovery Grants Program - Individual
Prevalence and Molecular Biological Feature of Human Aberrant Crypt Foci
人类异常隐窝病灶的患病率和分子生物学特征
- 批准号:
12671255 - 财政年份:2000
- 资助金额:
$ 35.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Aberrant crypt foci, multistep process of colon carcinogenesis and ras farnesylation
异常隐窝病灶、结肠癌发生的多步过程和 ras 法尼基化
- 批准号:
194630-1997 - 财政年份:1999
- 资助金额:
$ 35.45万 - 项目类别:
Discovery Grants Program - Individual
MOLECULAR CHARACTERIZATION OF ACF (ABERRANT CRYPT FOCI)
ACF(异常隐窝灶)的分子特征
- 批准号:
6405357 - 财政年份:1999
- 资助金额:
$ 35.45万 - 项目类别: