Prostatitis and Prostate Cancer Development

前列腺炎和前列腺癌的发展

基本信息

批准号：
8677581
负责人：
Lawrence Fong
金额：
$ 40.16万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
https://reporter.nih.gov/project-details/8677581
关键词：
Acute Prostatitis Adenocarcinoma Affect Animal Model Antibody Formation Antigens Atypia Autoantibodies Autoantigens Autoimmune Diseases Autoimmunity Biological Markers Biopsy Cessation of life Chronic Chronic Prostatitis Clinical Colorectal Data Development Disease Epitopes Etiology Foundations Frequencies Genetic Genetic Engineering Genetically Engineered Mouse Human Immune Immune Tolerance Immune response Immune system Immunologics Inflammation Inflammatory Knockout Mice Large T Antigen LoxP-flanked allele Lung Malignant Neoplasms Malignant neoplasm of prostate Modeling Mus Nature PTEN gene Pancreas Papillary Patients Pelvic Pain Prostate Prostatic Prostatic Intraepithelial Neoplasias Proteins Role Self Tolerance Seminal Vesicles Simian virus 40 Stomach T cell response Testing Thyroid Gland Tissues To autoantigen Transgenic Mice Wild Type Mouse Work autoreactivity chronic pelvic pain disease diagnosis insight men mouse model novel novel strategies prostate cancer model prostate cancer prevention prostatitis recombinase tumor tumor progression

Acute Prostatitis Adenocarcinoma Affect Animal Model Antibody Formation Antigens Atypia Autoantibodies Autoantigens Autoimmune Diseases Autoimmunity Biological Markers Biopsy Cessation of life Chronic Chronic Prostatitis Clinical Colorectal Data Development Disease Epitopes Etiology Foundations Frequencies Genetic Genetic Engineering Genetically Engineered Mouse Human Immune Immune Tolerance Immune response Immune system Immunologics Inflammation Inflammatory Knockout Mice Large T Antigen LoxP-flanked allele Lung Malignant Neoplasms Malignant neoplasm of prostate Modeling Mus Nature PTEN gene Pancreas Papillary Patients Pelvic Pain Prostate Prostatic Prostatic Intraepithelial Neoplasias Proteins Role Self Tolerance Seminal Vesicles Simian virus 40 Stomach T cell response Testing Thyroid Gland Tissues To autoantigen Transgenic Mice Wild Type Mouse Work autoreactivity chronic pelvic pain disease diagnosis insight men mouse model novel novel strategies prostate cancer model prostate cancer prevention prostatitis recombinase tumor tumor progression

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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.

描述（由申请人提供）：前列腺炎和前列腺癌是男性极为常见的疾病，但是这两种疾病之间的关系尚不清楚。虽然急性前列腺炎本质上是传染性的，但慢性前列腺炎和慢性骨盆疼痛综合征（CP/CPPS）的病因尚不清楚。通过研究缺乏免疫耐受性并发展自发前列腺炎的AIRE缺陷小鼠，我们已经确定了一种新型的前列腺自身抗原。此外，我们发现，前列腺腺体炎症的CP/CPP患者对类似的人蛋白塞木凝素（SG）具有免疫反应。这些结果为支持自身免疫性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，我们可能能够检测到有症状或无症状男性的前列腺炎症。动物模型以及临床观察结果表明，慢性炎症可以增强发育或某些肿瘤。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）对人类对前列腺自身抗原SG的免疫反应与人类前列腺癌之间是否存在关联； 2）慢性炎症是否可以增强小鼠模型中前列腺癌的发展。在特定目标1中，我们将确定对SG的免疫反应是否与接受前列腺活检的男性中的炎症和/或前列腺癌有关。在特定目标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。该提案将为慢性炎症和前列腺癌发展的作用提供洞察力。此外，这些结果可以通过治疗慢性前列腺炎来为预防前列腺癌的理由提供理由。