Peripheral Blood Molecular Staging of Breast Cancer
Peripheral Blood Molecular Staging of Breast Cancer
批准号:
7669268
负责人:
William E. Gillanders
金额:
$23.49万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-09-12 至 2011-07-31
关键词:
AddressAgeAmericanBenignBiological AssayBlood specimenBreast Cancer CellBreast DiseasesCancer PatientCaucasoid RaceCharacteristicsClinicalCohort StudiesDensity Gradient CentrifugationDetectionDevelopmentDiagnosticDiseaseDouble-Blind MethodGene ExpressionGenesIndividualMalignant NeoplasmsMedicalMedicineModalityMolecularMolecular BiologyMolecular GeneticsMonitorNucleotidesOutcomePatientsProcessProtocols documentationRaceResearchResearch PersonnelReverse Transcriptase Polymerase Chain ReactionSaintsSamplingSouth CarolinaSpecimenStagingSystemic TherapyTFF1 geneTechniquesTechnologyTest ResultTimeTreatment ProtocolsUniversitiesValidationWashingtonWomanbasecandidate markerclinically relevantcohortcostdesignexperiencehealthy volunteermalignant breast neoplasmmimeticsmolecular markerneoplastic cellnew technologynoveloutcome forecastoverexpressionperipheral bloodprognosticprogramsprospectiveresponse
中文摘要
描述(由申请人提供):乳腺癌仍然是美国女性中最常见的癌症,约占女性新发癌症病例的30%。目前乳腺癌的分期方式是侵入性的,昂贵的,缺乏敏感性,限制了临床医生为个体患者量身定制治疗的能力。乳腺癌中过度表达基因的鉴定与分子生物学的最新进展相结合,为建立更敏感、更特异、更具有潜在成本效益的乳腺癌分期方法提供了机会。最近开发的两项新技术显著增强了检测外周血中乳腺癌相关基因过表达的能力:一种新型多孔屏障密度梯度离心技术和实时RT-PCR。本研究的假设是,实时RT-PCR检测乳腺癌患者外周血中的乳腺癌细胞与临床预后相关。在具体目标1,目标1中,我们将建立定义阳性分子检测结果的标准。为了建立严格的标志物阳性阈值,我们将从一组没有恶性肿瘤证据的健康志愿者中获取外周血样本。我们将在这些标本中确定候选分子标记物的背景表达。我们还将确定候选标记物的背景表达是否独立于基线患者特征,包括年龄(bbb50 vs =50)、种族(白人vs非白人)和乳腺良性疾病的存在(存在vs不存在)。在目标2中,我们将设计并验证内部阳性对照基因片段模拟物,作为分子分析的额外对照。在Specific Aim 2中,我们将在圣路易斯华盛顿大学和南卡罗来纳医科大学的一项涉及92名受试者的双盲前瞻性队列研究中定义循环乳腺癌细胞分子检测的临床相关性。主要假设是,与没有外周血中乳腺癌分子证据的IV期乳腺癌患者相比,IV期乳腺癌患者开始新的全身治疗方案将经历1年无进展期和总生存率的减少。次要目标将讨论治疗开始后乳腺癌细胞分子检测的意义。
英文摘要
DESCRIPTION (provided by applicant): Breast cancer remains the most common cancer among American women, representing an estimated 30% of all new cancer cases in women. The current staging modalities for breast cancer are invasive, expensive, and lack sensitivity, limiting the ability of clinicians to tailor therapies to individual patients. The identification of genes overexpressed in breast cancer combined with recent advances in molecular biology provide the opportunity to establish more sensitive, specific, and potentially cost-effective ways of staging breast cancer. Two new technologies have recently been developed that significantly enhance the ability to detect breast cancer-associated gene overexpression in the peripheral blood: a novel porous barrier density gradient centrifugation technique, and real-time RT-PCR. The hypothesis of the proposed research is that realtime RT-PCR detection of breast cancer cells in the peripheral blood of breast cancer patients is associated with clinical outcome. In Specific Aim 1, Objective 1 we will establish criteria for defining positive molecular test results. To establish rigorous threshold values for marker positivity, we will obtain peripheral blood samples from a cohort of healthy volunteer subjects with no evidence of malignancy. We will determine the background expression of candidate molecular markers in these specimens. We will also determine if the background expression of candidate markers is independent of baseline patient characteristics including age (>50 versus =50), race (White versus Not White) and the presence of benign breast disease (Present versus Absent). In Objective 2, we will design and validate internal positive control gene fragment mimetics to be used as an additional control for the molecular assays. In Specific Aim 2, we will define the clinical relevance of molecular detection of circulating breast cancer cells in a double-blinded prospective cohort study involving 92 subjects at Washington University in Saint Louis and the Medical University of South Carolina. The primary hypothesis is that Stage IV breast cancer patients initiating a new regimen of systemic therapy with molecular evidence of breast cancer in the peripheral blood will experience a decreased 1-year progression-free and overall survival compared to Stage IV breast cancer patients with no molecular evidence of breast cancer in the peripheral blood. Secondary objectives will address the significance of molecular detection of breast cancer cells after the initiation of therapy.
Advances in molecular genetics have brought a revolution to medicine; the successful development of a molecular assay for the detection of breast cancer cells in the peripheral blood of breast cancer patients is likely to do the same for those unfortunate women afflicted with this disease.
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Career Enhancement Program
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批准号:10904040
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Targeting Neoantigens in Triple Negative Breast Cancer
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批准号:10675496
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资助金额:$62.51万
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批准号:10461044
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批准号:10242184
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资助金额:$98.88万
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财政年份:2018
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负责人:William E. Gillanders
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依托单位:
Peripheral Blood Molecular Staging of Breast Cancer
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批准号:7923851
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项目类别:
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资助金额:$23.48万
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财政年份:2006
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负责人:William E. Gillanders
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依托单位:
Peripheral Blood Molecular Staging of Breast Cancer
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批准号:7285941
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资助金额:$21.06万
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财政年份:2006
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负责人:William E. Gillanders
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依托单位:
Peripheral Blood Molecular Staging of Breast Cancer
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批准号:7480253
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项目类别:
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资助金额:$23.49万
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财政年份:2006
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负责人:William E. Gillanders
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依托单位:
Peripheral Blood Molecular Staging of Breast Cancer
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批准号:7049661
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项目类别:
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资助金额:$23.51万
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财政年份:2006
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负责人:William E. Gillanders
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依托单位:
SCT PROBES FOR PATHOGEN IMMUNITY
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批准号:8604663
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项目类别:
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资助金额:$37.62万
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财政年份:2004
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:6772515
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项目类别:
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资助金额:$11.23万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:6904588
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项目类别:
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资助金额:$13.49万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:7013407
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项目类别:
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资助金额:$2.27万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:6546270
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项目类别:
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资助金额:$13.49万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:6659002
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项目类别:
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资助金额:$13.49万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
Molecular detection of breast cancer in peripheral blood
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批准号:7075333
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项目类别:
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资助金额:$13.49万
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财政年份:2002
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负责人:William E. Gillanders
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依托单位:
PEPTIDE MEDIATED IMMUNOTHERAPY IN TRANSPLANTATION
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批准号:2058892
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资助金额:$3.12万
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财政年份:1995
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负责人:William E. Gillanders
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依托单位:
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