Prosaposin: A Novel Biomarker of Prostate Cancer Progression in African Americans
Prosaposin:非裔美国人前列腺癌进展的新型生物标志物
基本信息
- 批准号:8147010
- 负责人:
- 金额:$ 18.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-09-30 至 2011-07-02
- 项目状态:已结题
- 来源:
- 关键词:AffectAfrican AmericanAftercareAgeApoptoticBehaviorBenignBiologicalBiological AssayBiological MarkersCancer EtiologyCaucasiansCaucasoid RaceCell LineCell SurvivalCellsCessation of lifeCharacteristicsClinicalDataDevelopmentDiagnosisDiseaseDisease ProgressionEarly DiagnosisEnzyme-Linked Immunosorbent AssayExtracellular MatrixGlandGleason Grade for Prostate CancerHealth Services AccessibilityIn VitroIncidenceIndolentInvestigationLaboratoriesMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of prostateMetastatic Prostate CancerModelingMolecularNOD/SCID mouseNeoplasm MetastasisNude MiceOrganPC3 cell linePatientsPatternPeptide HydrolasesPhenotypePilot ProjectsPrimary NeoplasmPrognostic FactorProstateProteinsRNA InterferenceRadical ProstatectomyRisk FactorsSamplingScreening for Prostate CancerScreening procedureSerumSpecimenStagingStaining methodStainsTNMTestingTimeTissuesTumor MarkersUndifferentiatedXenograft procedurebasecancer cellcancer diagnosiscell motilityclinically significantfollow-upimplantationimprovedmRNA Expressionmenmigrationmortalitynoveloverexpressionprognosticprotein expressionpublic health relevanceracial differencesubcutaneoustissue resourcetumortumor growthtumor progressiontumor xenograft
项目摘要
DESCRIPTION (provided by applicant): Prostate cancer (PCa), the second leading cause of cancer-related death in US men, presents the greatest racial disparity of any malignant disease in African Americans, with a 1.6-1.9 times higher incidence rate and 2 - 3 times higher mortality rate than Caucasians. PCa in African Americans presents with more advanced clinical stages and aggressive tumors. PCa biomarkers are needed to improve early detection of clinically significant tumors and to distinguish indolent or slow growing tumors from more aggressive ones. In our search for tumor markers, we cloned prosaposin (PSAP) as a secreted protein and discovered its overexpression in metastatic PCa cells and tissues. Previously, we demonstrated that PSAP and/or its active molecular derivatives increase migration and invasion and up regulate matrix-degrading proteolytic enzymes expression in PCa cells. In Caucasians, serum-PSAP levels are increased in metastatic PCa when compared to primary PCa or normal prostate tissues. In addition, there was no difference in serum-PSAP levels between organ-confined and locally-invasive tumors. In contrast to Caucasians, our pilot study in African Americans shows that a) tissue expression of PSAP is significantly higher in undifferentiated tumors with Gleason grade 4/5 pattern than in the differentiated tumors with Gleason grade d 3 or benign glands (BPH) and b) serum-PSAP levels are higher in locally invasive (stage III/IV) tumors than in the organ-confined (stage I/II) tumors which positively correlates with disease progression. Based on these observations, we hypothesized that PSAP contributes to PCa progression and has the characteristics of a novel biomarker discriminating the aggressive tumors from non- aggressive ones in African American patients. To test our hypothesis, we propose the following Aims: 1) Define the clinical significance of serum-PSAP as a marker of PCa progression or aggressiveness in African Americans; 2) Determine the association between tissue expression of PSAP and clinical and histopathological predictors or prognosticators of PCa progression or aggressiveness in African Americans; and 3) Determine the association between PSAP and invasive and metastatic phenotypes in PSAP-over expressed or -silenced African American PCa cells. We will use immunohistochemical analysis and sandwich-ELISA assays to quantify PSAP expression levels in a large pool of tissue and serum samples and to determine their association with clinicohistopathological predictors or prognosticators of PCa aggressiveness and progression in African Americans. We will also test the effect of increased or decreased PSAP expression on tumor growth rate and spontaneous metastatic ability in subcutaneous and orthotopic tumor xenografts in African American- derived PCa cells. At the conclusion of this proposal, we will have defined the clinical and histopathological significance of PSAP as a biomarker of PCa progression and/or aggressiveness in African Americans that could be further utilized in clinical development.
PUBLIC HEALTH RELEVANCE: The incidences, mortality, and aggressiveness of prostate cancer (PCa) in African American (AA) men are higher than in Caucasians. To improve early detection of clinically significant tumors and to discriminate indolent or slow growing tumors from more aggressive ones, reliable prognostic factors or biomarkers are needed. An in-depth investigation of our preliminary discovery of a high expression of prosaposin (PSAP) levels in locally invasive and/or metastatic PCa cells, tissues, and serum samples from AA men would provide us with the clinical and histopathological values of this molecule as a biomarker for PCa screenings, diagnoses, or post-treatment follow up in AAs.
描述(由申请人提供):前列腺癌 (PCa) 是美国男性癌症相关死亡的第二大原因,是非裔美国人中所有恶性疾病中种族差异最大的,其发病率是非裔美国人的 1.6-1.9 倍,并且是非裔美国人的 2 倍。 - 死亡率比白人高3倍。非裔美国人的 PCa 呈现出更晚期的临床阶段和侵袭性肿瘤。需要 PCa 生物标志物来改善临床显着肿瘤的早期检测,并区分惰性或缓慢生长的肿瘤与更具侵袭性的肿瘤。在寻找肿瘤标志物的过程中,我们克隆了前列腺素 (PSAP) 作为一种分泌蛋白,并发现其在转移性 PCa 细胞和组织中过度表达。此前,我们证明 PSAP 和/或其活性分子衍生物可增加 PCa 细胞的迁移和侵袭,并上调基质降解蛋白水解酶的表达。在白种人中,与原发性前列腺癌或正常前列腺组织相比,转移性前列腺癌中的血清 PSAP 水平升高。此外,器官局限性肿瘤和局部侵袭性肿瘤之间的血清 PSAP 水平没有差异。与白种人相反,我们在非裔美国人中的初步研究表明,a) 格里森 4/5 级未分化肿瘤中 PSAP 的组织表达显着高于格里森 d 3 级或良性腺体 (BPH) 的分化肿瘤,b ) 局部侵袭性(III/IV 期)肿瘤的血清 PSAP 水平高于器官局限性(I/II 期)肿瘤,这与疾病进展呈正相关。基于这些观察,我们假设 PSAP 有助于 PCa 进展,并具有区分非洲裔美国患者侵袭性肿瘤和非侵袭性肿瘤的新型生物标志物的特征。为了检验我们的假设,我们提出以下目标:1)定义血清 PSAP 作为非裔美国人 PCa 进展或侵袭性标志物的临床意义; 2) 确定非裔美国人中 PSAP 的组织表达与 PCa 进展或侵袭性的临床和组织病理学预测因子或预后因子之间的关联; 3)确定PSAP与PSAP过度表达或沉默的非裔美国人PCa细胞中的侵袭性和转移性表型之间的关联。我们将使用免疫组织化学分析和夹心 ELISA 测定来量化大量组织和血清样本中的 PSAP 表达水平,并确定它们与非裔美国人中 PCa 侵袭性和进展的临床组织病理学预测因子或预后因子的关联。我们还将测试 PSAP 表达增加或减少对非洲裔美国人 PCa 细胞皮下和原位肿瘤异种移植物中肿瘤生长速率和自发转移能力的影响。在本提案结束时,我们将定义 PSAP 作为非裔美国人 PCa 进展和/或侵袭性的生物标志物的临床和组织病理学意义,可在临床开发中进一步利用。
公共卫生相关性:非洲裔美国 (AA) 男性前列腺癌 (PCa) 的发病率、死亡率和侵袭性高于白种人。为了改善临床上显着肿瘤的早期检测,并区分惰性或缓慢生长的肿瘤与更具侵袭性的肿瘤,需要可靠的预后因素或生物标志物。我们初步发现 AA 男性局部侵袭性和/或转移性 PCa 细胞、组织和血清样本中前列腺素 (PSAP) 水平高表达,对此进行深入研究将为我们提供该分子的临床和组织病理学价值:用于 PCa 筛查、诊断或 AA 治疗后随访的生物标志物。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SHAHRIAR KOOCHEKPOUR其他文献
SHAHRIAR KOOCHEKPOUR的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SHAHRIAR KOOCHEKPOUR', 18)}}的其他基金
Therapeutic Efficacy of Riluzole in Prostate Cancer
利鲁唑治疗前列腺癌的疗效
- 批准号:
8751365 - 财政年份:2014
- 资助金额:
$ 18.27万 - 项目类别:
Metabotropic Glutamate Receptor 1 in African American Prostate Cancer
非裔美国人前列腺癌中的代谢型谷氨酸受体 1
- 批准号:
8675361 - 财政年份:2014
- 资助金额:
$ 18.27万 - 项目类别:
Therapeutic Efficacy of Riluzole in Prostate Cancer
利鲁唑治疗前列腺癌的疗效
- 批准号:
8889227 - 财政年份:2014
- 资助金额:
$ 18.27万 - 项目类别:
Metabotropic Glutamate Receptor 1 in African American Prostate Cancer
非裔美国人前列腺癌中的代谢型谷氨酸受体 1
- 批准号:
8829801 - 财政年份:2014
- 资助金额:
$ 18.27万 - 项目类别:
PROSAPOSIN, A NOVEL INFLAMMATORY RESPONSE FACTOR FOR PROSTATE CANCER PROGRESSION
PROSAPOSIN,一种前列腺癌进展的新型炎症反应因子
- 批准号:
8360448 - 财政年份:2011
- 资助金额:
$ 18.27万 - 项目类别:
Prognostic value of AR mutation in primary African American prostate cancer
AR 突变在非裔美国人原发性前列腺癌中的预后价值
- 批准号:
8416144 - 财政年份:2010
- 资助金额:
$ 18.27万 - 项目类别:
Prognostic value of AR mutation in primary African American prostate cancer
AR 突变在非裔美国人原发性前列腺癌中的预后价值
- 批准号:
7989304 - 财政年份:2010
- 资助金额:
$ 18.27万 - 项目类别:
Prosaposin: A Novel Biomarker of Prostate Cancer Progression in African Americans
Prosaposin:非裔美国人前列腺癌进展的新型生物标志物
- 批准号:
8501024 - 财政年份:2010
- 资助金额:
$ 18.27万 - 项目类别:
Significance of an novel germline AR mutation in black men with prostate cancer
患有前列腺癌的黑人男性中一种新的种系 AR 突变的意义
- 批准号:
8367933 - 财政年份:2010
- 资助金额:
$ 18.27万 - 项目类别:
Prosaposin: A Novel Biomarker of Prostate Cancer Progression in African Americans
Prosaposin:非裔美国人前列腺癌进展的新型生物标志物
- 批准号:
8288659 - 财政年份:2010
- 资助金额:
$ 18.27万 - 项目类别:
相似海外基金
StuDy AimED at Increasing AlCohol AbsTinEnce (DEDICATE)
旨在提高酒精戒断率的研究(奉献)
- 批准号:
10577022 - 财政年份:2023
- 资助金额:
$ 18.27万 - 项目类别:
Germline Genetic Modifiers of Radiation Response
辐射反应的种系遗传修饰剂
- 批准号:
10741022 - 财政年份:2023
- 资助金额:
$ 18.27万 - 项目类别:
Project 3: Credentialing CDK 4/6 inhibitors used with radiation as an effective treatment strategy in locally advanced ER+ and TNBC
项目 3:认证 CDK 4/6 抑制剂与放射结合使用作为局部晚期 ER 和 TNBC 的有效治疗策略
- 批准号:
10554474 - 财政年份:2023
- 资助金额:
$ 18.27万 - 项目类别:
Long Term Effectiveness of Uterine Sparing Fibroid Treatments
保留子宫肌瘤治疗的长期有效性
- 批准号:
10656850 - 财政年份:2023
- 资助金额:
$ 18.27万 - 项目类别:
Using grassroots wellness coaching to enhance reach and sustainability of behavioral weight management
利用基层健康辅导来提高行为体重管理的影响力和可持续性
- 批准号:
10417877 - 财政年份:2022
- 资助金额:
$ 18.27万 - 项目类别: