Prostate Cancer Therapy with Annexin II Nanoparticles

膜联蛋白 II 纳米颗粒治疗前列腺癌

• 批准号: 6925691
• 负责人: JAMBOOR K. VISHWANATHA
• 金额: $ 12.21万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-08 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925691
• 关键词: angiogenesis; annexins; apoptosis; athymic mouse; biotechnology; cell line; cell migration; cell proliferation; disease /disorder model; flow cytometry; gene expression; gene therapy; mixed tissue /cell culture; molecular oncology; nanotechnology; neoplasm /cancer blood supply; neoplasm /cancer genetics; neoplastic cell; neoplastic growth; particle; phenotype; proliferating cell nuclear antigen; prostate neoplasms

DESCRIPTION (provided by applicant): Annexin II expression is lost during progression of prostate cancer from the prostate intraepithelial neoplasia (PIN) stage to cancer. Annexin II functions both at the cell surface and in the nucleus: At the cell surface, Annexin II organizes a proteolytic center proposed to regulate angiogenesis, tumor invasion and metastasis. Annexin II in the cell nucleus regulates cell proliferation and DNA synthesis. The long-term goal of our research program is to identify the key molecular events that lead to development and progression of prostate cancer, in order that improved detection methods and therapies to treat this disease can be developed. The objective of studies outlined in this application is to determine if replacement of the Annexin II gene results in inhibition of prostate cancer growth and angiogenesis. Our central hypothesis is that the nanoparticle-mediated sustained expression of Annexin II gene would lead to prolonged accumulation of Annexin II in the nucleus resulting in inhibition of cell proliferation and sustained cell surface Annexin II expression resulting anti-angiogenesis, collectively inhibiting prostate cancer growth. We propose the following specific aims: Aim 1: To determine the in vitro effect of nanoparticle-mediated Annexin II delivery on phenotypes associated with prostate cancer growth. The working hypothesis for this aim, based upon preliminary data, is that sustained nanoparticle- mediated nuclear accumulation of Annexin II results in inhibition of prostate cancer cell proliferation. Aim 2: To determine the effect of nanoparticle-mediated Annexin II delivery on growth and angiogenesis of prostate tumors in a mouse model system. The working hypothesis for this aim is that sustained delivery of the anti-angiogenic Annexin II to prostate tumors in mice leads to reduction in tumor number and volume, and prolongs animal survival. These studies are innovative in that we are proposing a new approach of Annexin ll-based therapy for prostate cancer. At the completion of this project, it is our expectation that we will have determined that the nanoparticle-mediated sustained Annexin II gene delivery would result in retardation of prostate growth and reduced tumor burden.

描述（由申请人提供）：膜联蛋白II表达在期间丢失 前列腺癌从前列腺上皮内肿瘤（PIN）阶段的进展到癌症。膜联蛋白II在细胞表面和细胞核中起作用：在细胞表面，膜联蛋白II组织一个蛋白水解中心，提出了调节血管生成，肿瘤侵袭和转移的蛋白水解中心。细胞核中的膜联蛋白II调节细胞增殖和DNA合成。我们的研究计划的长期目标是确定导致前列腺癌发展和进展的关键分子事件，以便可以开发出改进的检测方法和治疗该疾病的疗法。本应用中概述的研究的目的是确定替代膜联蛋白II基因是否导致抑制前列腺癌的生长和血管生成。我们的中心假设是，纳米颗粒介导的膜联蛋白II基因的持续表达将导致核中膜联蛋白II的延长积累，从而抑制细胞增殖和持续的细胞表面膜联蛋白II表达，从而导致抗血管生成，从而集体抑制前列腺癌的生长。我们提出以下具体目标： 目标1：确定纳米粒子介导的膜联蛋白II递送对与前列腺癌生长相关的表型的体外作用。基于初步数据的此目的的工作假设是，纳米颗粒介导的核对核积累的核核积累导致前列腺癌细胞增殖的抑制。 目标2：确定纳米颗粒介导的膜联蛋白II递送对小鼠模型系统中前列腺肿瘤生长和血管生成的影响。该目标的工作假设是，抗血管生成膜蛋白II持续递送到小鼠中的前列腺肿瘤会导致肿瘤数量和体积减少，并延长动物的存活率。 这些研究具有创新性，因为我们提出了一种基于LL LL的前列腺癌疗法的新方法。该项目完成后，我们期望我们将确定纳米颗粒介导的持续膜联蛋白II基因递送将导致前列腺生长的迟缓和减轻肿瘤负担。