IGF-1Axis and Insulin Resistance in PCPT

PCPT 中的 IGF-1 轴和胰岛素抵抗

• 批准号: 7102930
• 负责人: SCOTT M LIPPMAN
• 金额: $ 2万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102930
• 关键词: binding proteins; biopsy; cancer prevention; cancer risk; carcinogenesis; chemoprevention; clinical trials; finasteride; genetic polymorphism; growth factor receptors; human data; immunocytochemistry; insulin sensitivity /resistance; insulinlike growth factor; leptin; obesity; prostate neoplasms; receptor expression; western blottings

DESCRIPTION (provided by applicant): Recent laboratory and epidemiologic research has provided evidence that insulin-like growth factors are involved in prostate carcinogenesis. Several prospective population studies suggest that elevated levels of IGF-I and insulin resistance represent novel risk factors for subsequent prostate cancer, and results consistent with this conclusion have been obtained in animal models of prostate carcinogenesis. However, important gaps in knowledge remain, and this application seeks to address these in the context of the unique opportunities provided by the Prostate Cancer Prevention Trial. Research will be undertaken to (1) test whether baseline serum concentrations of serum analytes related to IGF physiology and/or insulin resistance and/or related genetic polymorphisms are associated with risk of prostate cancer in general or high-grade tumors in particular, (2) investigate whether finasteride affects these serum analytes, (3) determine if there are interactions between baseline levels of these serum analytes and the effect of finasteride on prostate cancer risk, and (3) investigate whether concentrations of these analytes are related to apoptosis rate or proliferation rate of at-risk normal prostate cells and/or neoplastic prostate cells. In addition, it will be possible to examine jointly the effects of obesity and IGF levels on risk, and to address the hypothesis that certain dietary risk factors or protective factors for prostate cancer act through mechanisms that involve IGF physiology and/or insulin resistance. The proposed studies involve laboratory measurements to be performed on the extensive serum and tissue banks assembled for PCPT participants, and analysis of these data in conjunction with the PCPT outcome data. The proposed research will provide new basic science information related to prostate carcinogenesis, and also may (1) be relevant to definition of subgroups of men for whom finasteride is particularly valuable as a chemoprevention strategy, (2) aid in defining novel, potentially modifiable risk factors for prostate cancer. The revised Project addresses all reviewer concerns, including that for new preliminary data supporting the tissue IGF signaling studies in collaboration with Core C.

描述（由申请人提供）：最近的实验室和流行病学研究提供的证据表明，胰岛素样生长因子参与前列腺癌的发生。几项前瞻性人群研究表明，IGF-I水平升高和胰岛素抵抗是随后前列腺癌的新风险因素，并且在前列腺癌发生的动物模型中获得了与此结论一致的结果。然而，重要的知识差距仍然存在，本申请试图在前列腺癌预防试验提供的独特机会的背景下解决这些问题。将进行研究以（1）测试与IGF生理学和/或胰岛素抵抗和/或相关遗传多态性相关的血清分析物的基线血清浓度是否与一般前列腺癌或特别是高级别肿瘤的风险相关，（2）调查芬鲁肽是否影响这些血清分析物，（3）确定这些血清分析物的基线水平与非那肽对前列腺癌风险的影响之间是否存在相互作用，以及（3）研究这些分析物的浓度是否与细胞凋亡率相关 或高危正常前列腺细胞和/或肿瘤前列腺细胞的增殖率。此外，将有可能共同研究肥胖和IGF水平对风险的影响，并解决某些饮食风险因素或前列腺癌的保护因素通过涉及IGF生理学和/或胰岛素抵抗的机制起作用的假设。拟议的研究涉及对为PCPT参与者收集的大量血清和组织库进行实验室测量，并结合PCPT结果数据分析这些数据。拟议的研究将提供与前列腺癌发生相关的新的基础科学信息，并且还可能（1）与定义男性亚组相关，对这些男性亚组而言，芬普胺作为一种化学预防策略特别有价值，（2）有助于定义新的，潜在的可改变的前列腺癌风险因素。修订后的项目解决了所有评审员关注的问题，包括与核心C合作支持组织IGF信号研究的新初步数据。