Lymphagiogenesis and Lymphatic Metastasis in Prostate Cancer
前列腺癌的淋巴管生成和淋巴管转移
基本信息
- 批准号:8291327
- 负责人:
- 金额:$ 22.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-15 至 2013-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenovirus VectorAnimalsAntibodiesAreaBAY 54-9085Biological AssayBlood CirculationBlood VesselsBlood specimenCancer PatientClinicClinical ManagementClinical ResearchClinical TrialsComplexDevelopmentDiagnostic ImagingDiseaseDisease ProgressionDistalEvaluationExtracapsularFunctional ImagingFutureGleason Grade for Prostate CancerGrowthHandHumanImageImaging technologyImmune systemInstitutionInterventionInvestigationLifeLiverLungLymphangiogenesisLymphaticLymphatic MetastasisLymphatic vesselMalignant neoplasm of prostateMetastatic Prostate CancerModalityModelingMolecularMonitorMusNeoadjuvant TherapyNeoplasm MetastasisNodalOrganPalpablePathway interactionsPatientsPharmaceutical PreparationsPhasePhosphotransferasesPositive Lymph NodePositron-Emission TomographyPre-Clinical ModelProcessProstateProstatectomyProstatic NeoplasmsReceptor Protein-Tyrosine KinasesRecurrenceRecurrent diseaseReporter GenesReportingResearch PersonnelRouteSamplingSeminal VesiclesSentinel Lymph NodeSignal TransductionSiteSourceStagingSurrogate MarkersSystemTestingTherapeutic EffectTherapeutic InterventionTimeTissue MicroarrayTissue SampleTumor AngiogenesisUniversitiesUse EffectivenessVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3Vascular Endothelial Growth FactorsWashingtonWorkXenograft Modelangiogenesisantibody inhibitorautocrinebaseclinically relevantdensityhigh riskimaging modalityimprovedinhibitor/antagonistinterestkinase inhibitorlymph nodeslymphatic circulationmacrophagemetastatic processmolecular imagingmolecular markermortalityneoplastic cellnovelprognostic indicatorprogramsresearch studytumortumor progressionvector
项目摘要
Metastasis is the main cause of prostate cancer mortality. The support of prostate cancer SPORE
Developmental Program in the past two years has enabled us to investigate the contribution of
lymphangiogenesis to prostate cancer metastasis. We discovered that elevated pro-lymphangiogenic factor
(VEGF-C) in the prostate tumors induces the growth of lymphatic vessels, which in turn facilitates tumor cell
dissemination to regional lymph nodes. Moreover, the lymphatic dissemination process also greatly impacts
metastasis to distal organs, such as lung and liver. Hence, our current working hypothesis suggests that
lymphatic circulation is a preferred route of dissemination and that regional lymph nodes provide a reservoir
from which subsequent dissemination to distal sites occurs. This proposal will investigate this hypothesis
further. In particular, we will examine in detail the connection between lymphangiogenic pathways and
metastasis in prostate cancer patients, focusing our molecular and histological analyses on the patients with
node positive and recurrent disease. Using many relevant preclinical models developed at our institution,
our efforts will be directed towards addressing two areas of great need, i.e. therapeutic intervention and
diagnostic imaging of nodal metastasis. We will investigate therapeutic effects of blockading the
lymphangiogenic tyrosine kinase receptor by specific VEGFR3 antibody, and Sorafenib, a multi-kinase
inhibitor known to target both VEGFR3. Molecular imaging technologies will be applied to monitor the impact
of these interventions on the metastatic process. We will also evaluate the ability of a prostate-specific
imaging adenoviral vector to specifically detect nodal metastases in preclinical models. In addition, we will
develop and assess potential circulating surrogate markers for the lymphangiogenic pathways. The lack of
such markers has halted progress in anti-metastatic treatment. The prostate cancer SPORE program at
University of Washington is initiating a phase II neoadjuvant clinical trial of Sorafenib in patients with high-
risk localized prostate cancer. In a collaborative effort with this study, we will obtain blood and tissue
samples from the patients to analyze the molecular activity of Sorafenib against the VEGFR3 pathway and
tumor lymphangiogenesis axis. The myriad of approaches taken in this proposal is directed towards
improving the clinical management of metastasis stage of prostate cancer in the future.
转移是前列腺癌死亡的主要原因。前列腺癌孢子的支持
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 B AGUS其他文献
DAVID B AGUS的其他文献
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{{ truncateString('DAVID B AGUS', 18)}}的其他基金
(PQB6)An Integrative Computational and Bioengineered Tissue Model of Metastasis
(PQB6)转移的综合计算和生物工程组织模型
- 批准号:
8591092 - 财政年份:2013
- 资助金额:
$ 22.72万 - 项目类别:
(PQB6)An Integrative Computational and Bioengineered Tissue Model of Metastasis
(PQB6)转移的综合计算和生物工程组织模型
- 批准号:
8730584 - 财政年份:2013
- 资助金额:
$ 22.72万 - 项目类别:
Lymphagiogenesis and Lymphatic Metastasis in Prostate Cancer
前列腺癌的淋巴管生成和淋巴管转移
- 批准号:
7315068 - 财政年份:2007
- 资助金额:
$ 22.72万 - 项目类别:
Proteomic Predictors of Clinical Outcome of Targeted Therapies in Prostate Cancer
前列腺癌靶向治疗临床结果的蛋白质组预测因子
- 批准号:
7067896 - 财政年份:2005
- 资助金额:
$ 22.72万 - 项目类别:
Lymphagiogenesis and Lymphatic Metastasis in Prostate Cancer
前列腺癌的淋巴管生成和淋巴管转移
- 批准号:
7879464 - 财政年份:2002
- 资助金额:
$ 22.72万 - 项目类别:
Lymphagiogenesis and Lymphatic Metastasis in Prostate Cancer
前列腺癌的淋巴管生成和淋巴管转移
- 批准号:
7679544 - 财政年份:2002
- 资助金额:
$ 22.72万 - 项目类别:
Lymphagiogenesis and Lymphatic Metastasis in Prostate Cancer
前列腺癌的淋巴管生成和淋巴管转移
- 批准号:
8094356 - 财政年份:2002
- 资助金额:
$ 22.72万 - 项目类别:
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