Genes & Proteins of Urothelial-ECM Interaction
基因
基本信息
- 批准号:7595910
- 负责人:
- 金额:$ 29.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-01 至 2011-03-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAnimal ModelAntibodiesAntisense RNAApoptosisBacteriaBasal CellBioinformaticsBiologicalBiological AssayBiological MarkersBladderBladder DiseasesCandidate Disease GeneCell LineCellsChromatographyComplexDataDatabasesDevelopmentDiagnosisDifferentiation and GrowthDimensionsDiseaseDrug DesignEpithelial-Stromal CommunicationExtracellular MatrixGene ExpressionGene Expression ProfileGene ProteinsGenerationsGenesGenomicsGrowthHealthHumanImmunofluorescence ImmunologicImmunohistochemistryIn Situ HybridizationIndividualInformaticsInterstitial CystitisInvestigationLearningMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of urinary bladderMethodsModelingNIH Program AnnouncementsPathologicPathologyPathway interactionsPeptide Signal SequencesPhasePhysiologyPreparationPrincipal InvestigatorProcessPropertyProteinsProteomeProteomicsResearchRoleSignal TransductionSmall Interfering RNASystemTestingTimeTissuesTranscriptTransfectionTranslationsUrineUrothelial CellUrotheliumWorkbasecancer cellcell typedata miningexpression vectorfunctional genomicsgene discoveryin vivoinhibitor/antagonistinnovationinterestknock-downmalignant phenotypemeetingsnovelprogramsresponsetooltumorurologic
项目摘要
DESCRIPTION (provided by applicant): The urothelium lines the bladder and protects it from bacteria and toxic or carcinogenic substances in the urine by maintaining an impermeable barrier. Although this functions remarkably well, it fails in bladder cancer, interstitial cystitis, and possibly other diseases as well. Understanding how the urothelium grows and differentiates and carries out its function may provide important clues to the diagnosis and treatment of bladder diseases. Although urothelium can be cultured, most models fail to adequately model the interactions between the urothelium and the underlying stroma. Together the two form a complex and interacting system. This proposal describes studies to meet the requirements of a PAR to develop cell-selective tools, specifically item (8) identification of cell specific markers to aid studies of epithelial-stromal interactions in normal and malignant tissues and secondarily item (5) discovery of biomarkers that indicate health or mass of individual cell types and item (1) discovery of genes selective to individual cell types. Novel methods for growth of urothelium as an artificial tissue in 3-dimensions and for bladder cancers as artificial tumors on both normal and cancer-modified matrix provides a basis for discovering the genes and proteins involved in defining normal and malignant urothelium. In a first discovery phase, microarrays and a novel proteomics approach with 2-D chromatography will be combined with innovative bioinformatics approaches to identify candidate genes and proteins. A public database of gene expression and protein levels will be constructed. Candidate genes/proteins will be validated sequentially, first by data mining and informatics to identify plausible mechanisms and to compare with other expression data, then biochemically by immunohistochemistry or quantitative PCR. A limited number of the most interesting genes will be investigated in greater depth in a second phase of hypothesis testing. Expression will be forced in cell lines not expressing a gene or knocked down in those that do. The "deliverables" will be sets of genes and proteins subjected to several levels of verification for their role in aiding studies of epithelial-stromal interactions in normal and malignant tissues.
描述(申请人提供):尿路上皮覆盖膀胱,并通过保持不透水屏障来保护其免受细菌和尿液中有毒或致癌物质的侵害。虽然它的作用非常好,但它在膀胱癌、间质性膀胱炎,以及可能还有其他疾病上都失败了。了解尿路上皮是如何生长、分化和执行其功能的,可能会为膀胱疾病的诊断和治疗提供重要线索。虽然尿路上皮可以培养,但大多数模型不能充分模拟尿路上皮和基质之间的相互作用。两者共同构成了一个复杂的、相互作用的系统。这项建议描述了为满足PAR的要求而开展的研究,以开发细胞选择工具,具体地说,项目(8)确定细胞特异性标记物,以帮助研究正常组织和恶性肿瘤组织中的上皮-间质相互作用,其次是项目(5)发现指示单个细胞类型的健康或质量的生物标记物,以及项目(1)发现对单个细胞类型具有选择性的基因。尿路上皮作为人工组织的三维生长和膀胱癌作为人工肿瘤在正常和癌症修饰的基质上生长的新方法为发现与界定正常和恶性尿路上皮有关的基因和蛋白质提供了基础。在第一个发现阶段,微阵列和一种新的蛋白质组学方法与创新的生物信息学方法将结合在一起,以识别候选基因和蛋白质。将建立一个基因表达和蛋白质水平的公共数据库。候选基因/蛋白质将被顺序验证,首先通过数据挖掘和信息学来确定可信的机制并与其他表达数据进行比较,然后通过免疫组织化学或定量PCR进行生化验证。在假设检验的第二阶段,将对数量有限的最有趣的基因进行更深入的研究。在不表达基因的细胞系中,表达将被强迫,在表达基因的细胞系中,表达将被抑制。“可交付成果”将是一组基因和蛋白质,它们在帮助研究正常和恶性组织中的上皮-间质相互作用方面所起的作用,将接受多个水平的验证。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Intravesical chondroitin sulfate inhibits recruitment of inflammatory cells in an acute acid damage "leaky bladder" model of cystitis.
- DOI:10.1016/j.urology.2011.10.010
- 发表时间:2012-02
- 期刊:
- 影响因子:2.1
- 作者:Engles CD;Hauser PJ;Abdullah SN;Culkin DJ;Hurst RE
- 通讯作者:Hurst RE
From microarray to biology: an integrated experimental, statistical and in silico analysis of how the extracellular matrix modulates the phenotype of cancer cells.
- DOI:10.1186/1471-2105-9-s9-s4
- 发表时间:2008-08-12
- 期刊:
- 影响因子:3
- 作者:Dozmorov MG;Kyker KD;Hauser PJ;Saban R;Buethe DD;Dozmorov I;Centola MB;Culkin DJ;Hurst RE
- 通讯作者:Hurst RE
System level changes in gene expression in maturing bladder mucosa.
成熟膀胱粘膜基因表达的系统水平变化。
- DOI:10.1016/j.juro.2010.12.101
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Dozmorov,Mikhail;Stone2nd,Randolph;Clifford,JohnL;Sabichi,AnitaL;Engles,CDirk;Hauser,PaulJ;Culkin,DanielJ;Hurst,RobertE
- 通讯作者:Hurst,RobertE
Impaired Expression of Prostaglandin E2 (PGE2) Synthesis and Degradation Enzymes during Differentiation of Immortalized Urothelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome.
间质性膀胱炎/膀胱疼痛综合征患者永生化尿路上皮细胞分化过程中前列腺素 E2 (PGE2) 合成和降解酶的表达受损。
- DOI:10.1371/journal.pone.0129466
- 发表时间:2015
- 期刊:
- 影响因子:3.7
- 作者:Marentette,JohnO;Hurst,RobertE;McHowat,Jane
- 通讯作者:McHowat,Jane
Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.
- DOI:10.1016/j.juro.2015.01.090
- 发表时间:2015-08
- 期刊:
- 影响因子:0
- 作者:Hauser PJ;VanGordon SB;Seavey J;Sofinowski TM;Ramadan M;Abdullah S;Buffington CA;Hurst RE
- 通讯作者:Hurst RE
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ROBERT Evan HURST其他文献
ROBERT Evan HURST的其他文献
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{{ truncateString('ROBERT Evan HURST', 18)}}的其他基金
SuperGAGs for Intravesicular Treatment of Interstitial Cystitis
用于间质性膀胱炎膀胱内治疗的 SuperGAG
- 批准号:
10205046 - 财政年份:2018
- 资助金额:
$ 29.18万 - 项目类别:
The Role of Altered Permeability in Bladder Diseases
渗透性改变在膀胱疾病中的作用
- 批准号:
8447150 - 财政年份:2012
- 资助金额:
$ 29.18万 - 项目类别:
The Role of Altered Permeability in Bladder Diseases
渗透性改变在膀胱疾病中的作用
- 批准号:
8566182 - 财政年份:2012
- 资助金额:
$ 29.18万 - 项目类别:
The Role of Altered Permeability in Bladder Diseases
渗透性改变在膀胱疾病中的作用
- 批准号:
8549231 - 财政年份:2012
- 资助金额:
$ 29.18万 - 项目类别:
INGENUITY SOFTWARE FOR PATHWAY AND NETWORK ANALYSIS
用于路径和网络分析的独创性软件
- 批准号:
7960030 - 财政年份:2009
- 资助金额:
$ 29.18万 - 项目类别:
INGENUITY SOFTWARE FOR PATHWAY AND NETWORK ANALYSIS
用于路径和网络分析的独创性软件
- 批准号:
7725108 - 财政年份:2008
- 资助金额:
$ 29.18万 - 项目类别:
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