Hormonal Induction Mouse Models of Prostate Cancer
前列腺癌激素诱导小鼠模型
基本信息
- 批准号:7895865
- 负责人:
- 金额:$ 7.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-01 至 2012-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAndrogensAnimal ModelAnimalsAntioxidantsApplications GrantsBackBreedingCell ProliferationChemopreventionChemopreventive AgentChronicClinicalDependenceDevelopmentDisease ProgressionDoseEndocrineEpigallocatechin GallateEstradiolEstrogensEtiologyEvaluationExposure toFeasibility StudiesFibrous capsule of kidneyFrequenciesFundingFutureGene Knock-Out ModelGene ProteinsGenesGlandGoalsGrantHandHormonalHormonesHumanImplantIncidenceInjection of therapeutic agentKnock-outLaboratoriesLarge T AntigenLeadLearningLesionMaintenanceMalignant NeoplasmsMalignant neoplasm of prostateMethylnitrosoureaModelingMouse StrainsMusNIH Program AnnouncementsNKX3-1 geneNude MiceOutcomeOxidative StressPTEN genePlayPre-Clinical ModelPrevention ResearchPrincipal InvestigatorProcessProstateProstate Cancer Progress Review GroupProstate carcinomaProstaticProstatic Intraepithelial NeoplasiasProstatic NeoplasmsRattusRecombinantsReportingResearchRoleSeleniumSequential TreatmentSilasticSimian virus 40StagingTestingTestosteroneTimeTissuesTransgenic MiceTranslatingTumor PromotersUncertaintyVitamin EWorkalitretinoinanticancer researchcancer chemopreventioncancer preventioncarcinogenesiscostdehydroepiandrosteroneefficacy testinginnovationinterestlycopenemouse modelneoplasticnovelpre-clinicalprobasinprogramspromoterprostate carcinogenesisresearch studyresponsesexsoy protein isolatesteroid hormonesubcutaneoustumor
项目摘要
DESCRIPTION (provided by applicant):
This proposal is in response to PA-08-055, "Cancer Prevention Research Small Grant Program (R03)", proposing pilot-feasibility studies that address the development of innovative animal models to mimic the human [prostate] cancer process in order to expedite research in cancer prevention. Animal models of prostate carcinogenesis are essential in the development of chemopreventive agents. Only two models have been used to screen agents in a systematic fashion, the MNU (methylnitrosourea) plus testosterone rat model and the C3(1)-probasin-SV40-large T antigen transgenic mouse model, but neither model is ideal. There is clearly a need for additional models, particularly mouse models that recapitulate the various stages of human prostate cancer development and involve androgen action as human prostate carcinogenesis does. Mouse models have several major advantages over rat models, including their lower cost, the much smaller amounts of chemoprevention agents they require, and the potential to have shorter latent periods than those in rat models that typically require 12-13 months of treatment. These three issues have seriously impaired chemoprevention efficacy testing in animal models of prostate cancer. We propose here to test the hypothesis that two different experimental strategies for induction of prostate cancer that have been demonstrated to work in rats can be successfully applied to mice. These strategies include one model that has been used most extensively in preclinical chemoprevention efficacy testing, namely the MNU (methylnitrosourea) plus testosterone rat model. The other rat model, which entirely depends on steroid hormone action and involves oxidative stress mechanisms, is the so-called NBL (or Noble) rat model involving combined exposure to estradiol and testosterone. We propose to translate the steroid hormone prostate cancer induction approaches of the NBL and MNU plus testosterone rat models to mice. If successfully yielding a hormonally-induced prostate carcinogenesis mouse model, this will pave the way for R01-type and other grant applications applying this model (1) to identify efficacious prostate cancer chemoprevention agents and (2) to tests specific mechanistic hypotheses genetically modified mice treated with steroid hormones. The specific aims of the project are to determine whether prostate carcinomas and/or lesions comparable to human prostatic intraepithelial neoplasia (PIN) can be induced in mice by (1) MNU plus testosterone and (2) estradiol plus testosterone. The mouse models arising from this project may be well suited for the evaluation of chemopreventive activity of new candidate agents including antioxidants. Both approaches may also lead to development of new mouse models of prostate carcinogenesis for mechanistic research.
描述(由申请人提供):
这项建议是对PA-08-055“癌症预防研究小额资助计划(R03)”的响应,该计划提出了试验性可行性研究,旨在开发模拟人类[前列腺癌]癌症过程的创新动物模型,以加快癌症预防研究。前列腺癌的动物模型在化学预防药物的开发中是必不可少的。只有两种模型被用于系统地筛选药物,即MNU(甲基亚硝胺)+睾酮大鼠模型和C3(1)-PROPOWER-SV40-大T抗原转基因小鼠模型,但这两种模型都不是理想的。显然需要更多的模型,特别是小鼠模型,这些模型概括了人类前列腺癌发展的不同阶段,并涉及雄激素的作用,就像人类前列腺癌的发生一样。与大鼠模型相比,小鼠模型有几个主要优势,包括它们的成本更低,所需的化学预防药量要少得多,而且与通常需要12-13个月治疗的大鼠模型相比,潜伏期可能更短。这三个问题严重影响了前列腺癌动物模型的化学预防效果测试。我们在这里提出的假设是,两种不同的诱导前列腺癌的实验策略已经被证明在大鼠身上有效,可以成功地应用于小鼠。这些策略包括一种在临床前化学预防有效性测试中使用最广泛的模型,即MNU(甲基亚硝脲)+睾酮大鼠模型。另一种完全依赖类固醇激素作用并涉及氧化应激机制的大鼠模型,即所谓的NBL(或Noble)大鼠模型,涉及雌二醇和睾酮的联合暴露。我们建议将NBL和MNU+睾酮大鼠模型的类固醇激素前列腺癌诱导方法移植到小鼠身上。如果成功地产生了激素诱导的前列腺癌小鼠模型,这将为应用该模型的R01型和其他赠款应用铺平道路:(1)确定有效的前列腺癌化学预防药物;(2)测试使用类固醇激素治疗的特定机制假说的转基因小鼠。该项目的具体目标是确定(1)MNU+睾酮和(2)雌二醇+睾酮能否诱发前列腺癌和/或类似于人类前列腺上皮内瘤变(PIN)的病变。该项目建立的小鼠模型可能非常适合于评估包括抗氧化剂在内的新候选制剂的化学预防活性。这两种方法也可能导致新的前列腺癌小鼠模型的发展,用于机理研究。
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 }}
MAARTEN C BOSLAND其他文献
MAARTEN C BOSLAND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('MAARTEN C BOSLAND', 18)}}的其他基金
Effects of SOD2 genotype, oxidative stress, ER??, and genistein on prostate cance
SOD2 基因型、氧化应激、ER?? 和金雀异黄酮对前列腺癌的影响
- 批准号:
8236933 - 财政年份:2011
- 资助金额:
$ 7.85万 - 项目类别:
Effects of SOD2 genotype, oxidative stress, ER??, and genistein on prostate cance
SOD2 基因型、氧化应激、ER?? 和金雀异黄酮对前列腺癌的影响
- 批准号:
8115621 - 财政年份:2011
- 资助金额:
$ 7.85万 - 项目类别:
Preventive Activity of Black Raspberries against Prostate Cancer
黑树莓对前列腺癌的预防活性
- 批准号:
8101295 - 财政年份:2010
- 资助金额:
$ 7.85万 - 项目类别:
Preventive Activity of Black Raspberries against Prostate Cancer
黑树莓对前列腺癌的预防活性
- 批准号:
7963473 - 财政年份:2010
- 资助金额:
$ 7.85万 - 项目类别:
Hormonal Induction Mouse Models of Prostate Cancer
前列腺癌激素诱导小鼠模型
- 批准号:
7661989 - 财政年份:2009
- 资助金额:
$ 7.85万 - 项目类别:
CLINICAL TRIAL: PROSTATE CANCER CHEMOPREVENTION TRIAL
临床试验:前列腺癌化学预防试验
- 批准号:
7718384 - 财政年份:2008
- 资助金额:
$ 7.85万 - 项目类别:
ADJUVANT TRIAL WITH SOY AFTER RADICAL PROSTATECTOMY
根治性前列腺切除术后大豆辅助试验
- 批准号:
7093292 - 财政年份:2006
- 资助金额:
$ 7.85万 - 项目类别:
ADJUVANT TRIAL WITH SOY AFTER RADICAL PROSTATECTOMY
根治性前列腺切除术后大豆辅助试验
- 批准号:
7919428 - 财政年份:2006
- 资助金额:
$ 7.85万 - 项目类别:
ADJUVANT TRIAL WITH SOY AFTER RADICAL PROSTATECTOMY
根治性前列腺切除术后大豆辅助试验
- 批准号:
7487098 - 财政年份:2006
- 资助金额:
$ 7.85万 - 项目类别:
相似海外基金
Abnormalities in androgens and ovarian markers in reproductive-age racially and ethnically diverse women in a prospective longitudinal cohort
前瞻性纵向队列中不同种族和民族的育龄女性雄激素和卵巢标志物的异常
- 批准号:
10930196 - 财政年份:2023
- 资助金额:
$ 7.85万 - 项目类别:
Nonalcoholic Fatty Liver Disease (NAFLD) in Polycystic Ovary Syndrome: The Role of Androgens on Liver Injury and NAFLD Progression
多囊卵巢综合征中的非酒精性脂肪肝 (NAFLD):雄激素在肝损伤和 NAFLD 进展中的作用
- 批准号:
10735807 - 财政年份:2023
- 资助金额:
$ 7.85万 - 项目类别:
Elucidation of the mechanisms by which cells recognize and respond to different levels of androgens
阐明细胞识别和响应不同水平雄激素的机制
- 批准号:
10418461 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Sexual Differentiation of the Brain and Behaviour: Central and Peripheral Targets of Androgens
大脑和行为的性别分化:雄激素的中枢和外周目标
- 批准号:
RGPIN-2019-04999 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Discovery Grants Program - Individual
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10570208 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10355174 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10688086 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Use of novel 11-oxygenated androgens to improve diagnostic accuracy and therapeutics in polycystic ovary syndrome
使用新型 11-含氧雄激素提高多囊卵巢综合征的诊断准确性和治疗效果
- 批准号:
10431620 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Defining the impact of androgens on uterine immune cell function during endometrial tissue repair
确定子宫内膜组织修复过程中雄激素对子宫免疫细胞功能的影响
- 批准号:
2744296 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别:
Studentship
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10525097 - 财政年份:2022
- 资助金额:
$ 7.85万 - 项目类别: