Early Targets in Progression of Barrett's Esophagus to Esophageal Adenocarcinoma
巴雷特食管进展为食管腺癌的早期目标
基本信息
- 批准号:9277831
- 负责人:
- 金额:$ 108.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-21 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAdenocarcinomaAdvisory CommitteesAppearanceBarrett EsophagusBindingBiochemistryBudgetsCandidate Disease GeneCell surfaceCellsCenter for Translational Science ActivitiesClinicalClinical DataClinical ResearchCommunicationContractsDNADNA Sequence AlterationDNA copy numberDana-Farber Cancer InstituteDataDatabasesDetectionDeveloped CountriesDeveloping CountriesDimerizationDiseaseEndoscopesEndoscopyEsophagealEsophageal AdenocarcinomaEsophagogastric JunctionEsophagusExcisionFiberFormalinFoundationsFreezingGene ExpressionGene Expression ProfilingGene TargetingGenesGenomicsGoalsGrantHumanImageImmunohistochemistryIncidenceIndividualInstitutionInvestigational New Drug ApplicationLabelLesionLigandsLightLongitudinal cohortMalignant NeoplasmsMalignant neoplasm of esophagusMedicalMethodologyMichiganMissionMolecular ProfilingMolecular TargetMutationNeoplasmsOperative Surgical ProceduresOutcomeParaffin EmbeddingPatient RecruitmentsPatientsPeptidesPerformancePharmacology and ToxicologyPilot ProjectsPlasmaPremalignantPreventive measureProcessProtocols documentationResearchResearch PersonnelResearch Project GrantsResourcesReverse Transcriptase Polymerase Chain ReactionRiskRisk stratificationScreening for cancerSensitivity and SpecificitySerumSpatial DistributionSpecimenSurvival RateTelomeraseTestingTherapeutic InterventionTimeTissue MicroarrayTissuesTranslational ResearchUniversitiesUpdateVariantWashingtonbiobankclinical translationcohortdimerflexibilitygastroesophageal junction adenocarcinomagenomic toolshuman subjectimaging agentimaging modalityimprovedin vivoinnovationmonomernoveloverexpressionpatient registryprogramssample collectionspectrographsynergismtranscriptome sequencingtumor heterogeneityvirtual
项目摘要
- Project Summary/Abstract
Recently, the incidence of esophageal (EAC) and gastro-esophageal junction (GEJAC) adenocarcinoma
has increased dramatically, and have a poor 5-year survival rate of less than 15%. When detected early, these
patients can have a good clinical outcome following surgery. These observations underscore the importance
of early cancer detection. Patients with Barrett's esophagus (BE) are known to be at increased risk.
Our overarching goal is to advance new methods of imaging to visualize the effects of spatial distribution
of genetic alterations in BE by using novel imaging methods to evaluate tumor heterogeneity on the
progression toward EAC. We propose a multi-institutional, trans-disciplinary, translational Research Center in
the Barrett's Esophagus Translational Research Network (BETRNet). Our mission is to build on our expertise
in genomic characterization, peptide biochemistry, and clinical translation to achieve our ultimate goal to
perform early cancer detection at an early stage where therapeutic intervention can be most effective. We will
identify a complementary panel of genes that are overexpressed on the cell surface and will be used to
develop and validate new peptide imaging agents. The targets chosen will address 3 important clinical needs:
1) Real-time endoscopic identification of pre-malignant lesions and early stage cancer to guide endoscopic
resection; 2) Risk stratification of BE patients for timing of endoscopic surveillance; and 3) Detection of gastro-
esophageal junction adenocarcinomas in patients without endoscopic appearance of BE.
We will use state-of-the-art genomic tools to to identify early overexpressed gene targets that arise in
progression of BE to EAC by providing comprehensive analyses of gene expression alterations, DNA copy
number variation, and genetic mutations. We will select candidate genes that are expressed on the cell
surface where they can be endoscopically imaged in vivo. We will rigorously validate the panel of candidate
targets with quantitative RT-PCR and immunohistochemistry on tissue microarrays using an independent
cohort of human esophagus specimens. We will use these targets to first identify and validate monomer
peptides that are highly specific. We will then arrange monomer peptides in a dimer configuration to produce
multivalent ligand target interactions to improve binding performance and allow for early targets to be detected
at low levels of expression. We will use a flexible fiber multi-spectral endoscope that can pass through the
working channel of a standard medical endoscope to detect multiple targets at the same time.
Successful completion of these aims will provide an integrated multi-spectral imaging methodology to
longitudinally visualize overexpressed molecular targets that drive progression of Barrett's esophagus to
esophageal adenocarcinoma. This innovative approach can serve as the foundation for validated preventive
measures to improve patient management.
- 项目总结/摘要
近年来,食管(EAC)和胃食管连接部(GEJAC)腺癌的发病率
急剧增加,5年生存率低于15%。如果及早发现,
患者在手术后可具有良好的临床结果。这些观察强调了
早期癌症检测。已知Barrett食管(BE)患者的风险增加。
我们的首要目标是推进新的成像方法,以可视化空间分布的影响
通过使用新的成像方法来评估BE中的遗传改变,
向EAC迈进。我们建议建立一个多机构,跨学科,翻译研究中心,
Barrett食管转化研究网络(BETRNet)我们的使命是以我们的专业知识为基础
在基因组表征,肽生物化学和临床翻译,以实现我们的最终目标,
在治疗干预最有效的早期阶段进行早期癌症检测。我们将
鉴定在细胞表面过表达的互补基因组,并将用于
开发和验证新的肽显像剂。选择的目标将满足3个重要的临床需求:
1)实时内镜识别癌前病变和早期癌症,以指导内镜检查
切除术; 2)BE患者内镜监测时机的风险分层;以及3)胃-
内镜下无BE表现的食管连接部腺癌患者。
我们将使用最先进的基因组工具来鉴定在细胞中出现的早期过表达基因靶点。
通过提供基因表达改变、DNA拷贝、
数量变异和基因突变。我们将选择在细胞上表达的候选基因
它们可以在体内进行内窥镜成像的表面。我们将严格验证候选人小组
用定量RT-PCR和免疫组织化学在组织微阵列上检测靶点,
人食管样本队列。我们将使用这些目标首先识别和验证单体
高度特异性的肽。然后,我们将以二聚体构型排列单体肽,
多价配体靶相互作用,以改善结合性能并允许检测早期靶
低水平的表达。我们将使用一个灵活的光纤多光谱内窥镜,可以通过
标准医疗内窥镜的工作通道,以同时检测多个目标。
这些目标的成功实现将提供一种综合的多光谱成像方法,
纵向可视化过表达的分子靶点,这些分子靶点驱动巴雷特食管的进展,
食管腺癌这种创新的方法可以作为有效的预防性治疗的基础。
改善病人管理。
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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DAVID George BEER其他文献
DAVID George BEER的其他文献
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{{ truncateString('DAVID George BEER', 18)}}的其他基金
RNF128 Regulation of TP53 in Barrett's Progression
RNF128 对 Barrett 进展中 TP53 的调节
- 批准号:
10219176 - 财政年份:2017
- 资助金额:
$ 108.42万 - 项目类别:
Biomedical Computing and Informatics Strategies for Precision Medicine
精准医学的生物医学计算和信息学策略
- 批准号:
9366045 - 财政年份:2017
- 资助金额:
$ 108.42万 - 项目类别:
RNF128 Regulation of TP53 in Barrett's Progression
RNF128 对 Barrett 进展中 TP53 的调节
- 批准号:
9976469 - 财政年份:2017
- 资助金额:
$ 108.42万 - 项目类别:
Multi-Spectral Targeted Imaging for Early Detection of Cancer in Barrett's Esopha
多光谱靶向成像用于巴雷特食管癌症的早期检测
- 批准号:
8724430 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Identification and Characterization of Gene Fusions in Lung Adenocarcinoma
肺腺癌基因融合的鉴定和表征
- 批准号:
8018735 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Identification and Characterization of Gene Fusions in Lung Adenocarcinoma
肺腺癌基因融合的鉴定和表征
- 批准号:
8249361 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Multi-Spectral Targeted Imaging for Early Detection of Cancer in Barrett's Esopha
多光谱靶向成像用于巴雷特食管癌症的早期检测
- 批准号:
8919278 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Project 1: Identification and Validation of Panel of Early Cell Surface Gene Targets
项目 1:早期细胞表面基因靶标组的鉴定和验证
- 批准号:
10155438 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Identification and Characterization of Gene Fusions in Lung Adenocarcinoma
肺腺癌基因融合的鉴定和表征
- 批准号:
8445146 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
Multi-Spectral Targeted Imaging for Early Detection of Cancer in Barrett's Esopha
多光谱靶向成像用于巴雷特食管癌症的早期检测
- 批准号:
8209767 - 财政年份:2011
- 资助金额:
$ 108.42万 - 项目类别:
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