Prostatitis and Prostate Cancer Development
前列腺炎和前列腺癌的发展
基本信息
- 批准号:8258692
- 负责人:
- 金额:$ 41.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2017-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acute ProstatitisAdenocarcinomaAffectAllelesAnimal ModelAntibody FormationAntigensAtypiaAutoantibodiesAutoantigensAutoimmune DiseasesAutoimmunityBiological MarkersBiopsyCessation of lifeChronicChronic ProstatitisClinicalColorectalDataDevelopmentDiseaseEngineeringEpitopesEtiologyFoundationsFrequenciesGeneticGenetically Engineered MouseHumanImmuneImmune ToleranceImmune responseImmune systemImmunologicsInflammationInflammatoryKnockout MiceLarge T AntigenLungMalignant NeoplasmsMalignant neoplasm of prostateModelingMusNaturePTEN genePancreasPapillaryPatientsPelvic PainProstateProstaticProstatic Intraepithelial NeoplasiasProteinsRoleSelf ToleranceSeminal VesiclesSimian virus 40StomachT cell responseTestingThyroid GlandTissuesTo autoantigenTransgenic MiceWild Type MouseWorkautoreactivitychronic pelvic paindisease diagnosisinsightmenmouse modelnovelnovel strategiesprostate cancer preventionprostatitisrecombinasetumortumor progression
项目摘要
DESCRIPTION (provided by applicant): Prostatitis and prostate cancer are extremely common diseases in men, but the relationship between these two diseases is unknown. While acute prostatitis is thought to be infectious in nature, the etiology of chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) and asymptomatic inflammatory prostatitis remains unclear. By studying Aire-deficient mice that have defective immune tolerance and develop spontaneous prostatitis, we have identified a novel prostate autoantigen. Moreover, we have found that CP/CPPS patients with biopsy-proven inflammation in their prostate glands possess immune responses to the analogous human protein, semenogelin (Sg). These results provide new evidence to support autoimmunity as a potential cause for chronic prostatitis. Moreover, by assessing for immune responses to Sg, we may be able to detect prostate inflammation in symptomatic or asymptomatic men. Animal models as well as clinical observations demonstrate that chronic inflammation can enhance the development or certain tumors. We hypothesize that chronic prostatitis contributes to prostate cancer development. The overall objectives of this proposal are to examine: 1) whether there is an association between an immune responses to the prostate autoantigen Sg and prostate cancer in humans; and 2) whether chronic inflammation can enhance the development of prostate cancer in mouse models. In specific aim 1, we will determine whether immune responses to Sg are associated with the presence of inflammation and/or prostate cancer in men undergoing prostate biopsy. In the specific aim 2, we will determine whether chronic prostatitis can alter the development of tumors in mouse models of prostate cancer. This proposal will provide insight in the role of chronic inflammation and prostate cancer development. Moreover, these results could provide a rationale for prostate cancer prevention by treating chronic prostatitis.
PUBLIC HEALTH RELEVANCE: Chronic inflammation is thought to contribute to the development of many different malignancies, but the role of inflammation in prostate cancer is unknown. Prostate cancer is the most common non-skin cancer in men. Chronic prostatitis is also an extremely common problem in men. By using a mouse model with a genetic deficiency that predisposes these mice to autoimmune disease, we have identified a protein target for the immune system that we believe to be important in chronic prostatitis in humans. We propose to assess for immune responses to this protein in men who are undergoing prostate biopsies. We will evaluate whether immune responses to this protein are associated with prostate inflammation and prostate cancer on biopsy. We will also determine whether prostatitis can accelerate the development of tumors in mice that are genetically engineered to develop spontaneous prostate cancer. In doing so, we may understand how autoimmunity can contribute to prostate cancer. Moreover, this work could provide the foundation for developing an approach to prostate cancer prevention.
描述(申请人提供):前列腺炎和前列腺癌是男性中极为常见的疾病,但这两种疾病之间的关系尚不清楚。虽然急性前列腺炎被认为是传染性的,慢性前列腺炎和慢性盆腔疼痛综合征(CP/CPPS)和无症状炎症性前列腺炎的病因仍不清楚。通过研究具有免疫耐受缺陷并发生自发性前列腺炎的Aire缺陷小鼠,我们鉴定了一种新的前列腺自身抗原。此外,我们发现,CP/CPPS患者的前列腺活检证实炎症具有免疫反应,类似的人类蛋白质,精液凝固蛋白(Sg)。这些结果为支持自身免疫作为慢性前列腺炎的潜在原因提供了新的证据。此外,通过评估对Sg的免疫反应,我们可能能够检测有症状或无症状男性的前列腺炎症。动物模型和临床观察表明,慢性炎症可促进某些肿瘤的发展。我们假设慢性前列腺炎有助于前列腺癌的发展。该提案的总体目标是检查:1)对前列腺自身抗原Sg的免疫应答与人类前列腺癌之间是否存在关联;以及2)慢性炎症是否可以增强小鼠模型中前列腺癌的发展。在具体目标1中,我们将确定对Sg的免疫应答是否与接受前列腺活检的男性中炎症和/或前列腺癌的存在相关。在具体目标2中,我们将确定慢性前列腺炎是否可以改变前列腺癌小鼠模型中肿瘤的发展。这项提案将提供洞察慢性炎症和前列腺癌发展的作用。此外,这些结果可以为通过治疗慢性前列腺炎来预防前列腺癌提供理论基础。
公共卫生相关性:慢性炎症被认为有助于许多不同恶性肿瘤的发展,但炎症在前列腺癌中的作用尚不清楚。前列腺癌是男性最常见的非皮肤癌。慢性前列腺炎也是一个非常常见的问题,在男性。通过使用具有遗传缺陷的小鼠模型,使这些小鼠易患自身免疫性疾病,我们已经确定了免疫系统的蛋白质靶点,我们认为这在人类慢性前列腺炎中很重要。我们建议在接受前列腺活检的男性中评估对这种蛋白质的免疫反应。我们将评估对这种蛋白质的免疫反应是否与前列腺炎症和前列腺癌活检相关。我们还将确定前列腺炎是否会加速基因工程小鼠自发性前列腺癌的肿瘤发展。通过这样做,我们可以了解自身免疫如何导致前列腺癌。此外,这项工作可以为开发预防前列腺癌的方法提供基础。
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)
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Lawrence Fong其他文献
Lawrence Fong的其他文献
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