Molecular Mechanisms of Initiation of Benign Prostatic Hyperplasia
Molecular Mechanisms of Initiation of Benign Prostatic Hyperplasia
批准号:
9201326
负责人:
Li Xin
金额:
$35.66万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2018-06-30
关键词:
AcuteAddressAdultAgeAgingAndrogen ReceptorAndrogensAttenuatedAutoimmune ResponsesBenign Prostatic HypertrophyBiological AssayCell LineageCellsClinicClinicalColony-Stimulating Factor OverexpressionCombined Modality TherapyCytokeratin 8DiseaseDisease ProgressionDoxazosinElectron MicroscopyEpithelialEpithelial Cell ProliferationEpithelial CellsEtiologyFibrosisFinasterideGoalsHistologicHomeostasisHumanImmuneImmune responseImpairmentInfiltrationInflammationInflammatoryInterleukin-1KnowledgeLeftLifeMacrophage Colony-Stimulating FactorMediatingModelingMolecularMosaicismMusNatural regenerationNon-MalignantPathway interactionsPharmacologyPhenotypeProstateProstaticProteinsPublishingReceptor SignalingRisk ReductionSignal TransductionSpecimenStem cellsStromal CellsStructureTamoxifenTight JunctionsTissuesTransgenic MiceUrinary RetentionWorkadrenergic blockbaseclinical riskdensitygenetic approachimprovedin vivolower urinary tract symptomsmacrophagemenmouse modelnoveloverexpressionpublic health relevancereceptor expressionreceptor functiontargeted treatmenttherapeutic target
中文摘要
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英文摘要
DESCRIPTION (provided by applicant): Benign prostatic hyperplasia is a progressive condition in the aging men characterized by the enlargement of the periurethral regions of prostate gland due to nonmalignant proliferations in both the prostate epithelial and stromal compartments. An estimated 50% of men have histologic evidence of BPH by age 50 years and 75% by age 80 years. BPH is often accompanied by lower urinary tract symptoms (LUTS). BPH is rarely fatal, but may cause serious life-threatening complications such as acute urinary retention if left untreated. Androgen targeted therapies such as finasteride are clinically employed for the treatment of BPH. However, the MTOPS study shows that even combination therapy using finasteride and doxazosin only leads to a 66% reduction of risk for clinical progression of LUTS/BPH, suggesting the existence of unrecognized mechanisms that promote disease progression. The goal of this application is to investigate novel molecular mechanisms that contribute to BPH initiation and progression. This application is based on our novel preliminary observation that attenuating the androgen receptor signaling in prostate epithelial cells induces an inflammatory microenvironment. We hypothesize that this prostatic inflammatory microenvironment contributes to progression of BPH. Through the three Aims in this application, we seek to generate novel mouse models for human BPH, use mouse models to determine the contribution of immune cells to prostate epithelial cell proliferation, and identiy novel key signaling mediated by the inflammatory prostatic microenvironment that is capable of promoting epithelial cell proliferation.
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专著(0)
科研奖励(0)
会议论文
Support for the 2023 Society of Basic Urological Diseases annual meeting
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批准号:10748948
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项目类别:
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资助金额:$1.5万
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财政年份:2023
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负责人:Li Xin
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依托单位:
Stromal Foxf2 suppresses prostate cancer progression
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批准号:10461677
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项目类别:
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资助金额:$49.36万
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财政年份:2022
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负责人:Li Xin
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依托单位:
Stromal Foxf2 suppresses prostate cancer progression
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批准号:10643864
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项目类别:
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资助金额:$46.5万
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财政年份:2022
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负责人:Li Xin
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依托单位:
Reprogramming of Prostate Stromal Cells by Prostate Inflammation
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批准号:9098081
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项目类别:
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资助金额:$22.23万
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财政年份:2016
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负责人:Li Xin
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依托单位:
Molecular mechanisms of initiation of benign prostatic hyperplasia
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批准号:10398260
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项目类别:
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资助金额:$57.77万
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财政年份:2016
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负责人:Li Xin
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依托单位:
Reprogramming of Prostate Stromal Cells by Prostate Inflammation
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批准号:9247932
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项目类别:
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资助金额:$18.52万
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财政年份:2016
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负责人:Li Xin
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依托单位:
Molecular mechanisms of initiation of benign prostatic hyperplasia
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批准号:10625982
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项目类别:
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资助金额:$57.77万
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财政年份:2016
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负责人:Li Xin
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依托单位:
Molecular mechanisms of initiation of benign prostatic hyperplasia
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批准号:9883608
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项目类别:
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资助金额:$60.22万
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财政年份:2016
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负责人:Li Xin
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依托单位:
The Notch Signaling in Prostate Homeostasis and Carcinogenesis
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批准号:8958462
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项目类别:
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资助金额:$36.26万
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财政年份:2015
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负责人:Li Xin
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依托单位:
The Notch Signaling in Prostate Homeostasis and Carcinogenesis
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批准号:9107395
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项目类别:
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资助金额:$36.26万
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财政年份:2015
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负责人:Li Xin
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依托单位:
The Prostate Epithelial Cell Lineage Hierarchy
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批准号:8245407
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项目类别:
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资助金额:$34.04万
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财政年份:2011
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负责人:Li Xin
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依托单位:
The Prostate Epithelial Cell Lineage Hierarchy
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批准号:8339460
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项目类别:
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资助金额:$34.04万
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财政年份:2011
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负责人:Li Xin
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依托单位:
The Prostate Epithelial Cell Lineage Hierarchy
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批准号:8725648
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项目类别:
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资助金额:$34.04万
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财政年份:2011
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负责人:Li Xin
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依托单位:
The Prostate Epithelial Cell Lineage Hierarchy
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批准号:8537919
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项目类别:
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资助金额:$32.85万
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财政年份:2011
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:8244661
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项目类别:
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资助金额:$5.65万
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财政年份:2007
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:7221466
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项目类别:
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资助金额:$8.72万
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财政年份:2007
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:7917091
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项目类别:
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资助金额:$24.9万
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财政年份:2007
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:8120409
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项目类别:
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资助金额:$23.45万
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财政年份:2007
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:7324066
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项目类别:
-
资助金额:$8.92万
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财政年份:2007
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负责人:Li Xin
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依托单位:
Characterization of prostatic stem cells and prostate cancer-initiating cells
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批准号:7925733
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项目类别:
-
资助金额:$24.9万
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财政年份:2007
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负责人:Li Xin
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依托单位:
海外基金