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了证据表明胰岛素样生长因子与前列腺癌发生有关。一些前瞻性人群研究表明，IGF-I和胰岛素抵抗水平升高代表了随后的前列腺癌的新风险因素，并且在前列腺致癌动物模型中获得了与该结论一致的结果。但是，知识的重要差距仍然存在，该应用程序旨在在前列腺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普遍或高级别肿瘤的风险有关，尤其是前列腺癌的风险相关，（2）（2）研究法最终范围是否会影响这些血清分析的范围，（3）是否会影响这些血清的效果，（3）是否存在这些分析范围，（3）是否存在分析范围。前列腺癌风险，（3）研究这些分析物的浓度是否与凋亡率有关 或处于危险的正常前列腺细胞和/或肿瘤前列腺细胞的增殖速率。此外，有可能共同检查肥胖和IGF水平对风险的影响，并通过涉及IGF生理学和/或胰岛素抵抗的机制来解决以下假设。拟议的研究涉及将对用于PCPT参与者组装的广泛的血清和组织库进行实验室测量，并与PCPT结果数据一起分析这些数据。拟议的研究将提供与前列腺致癌有关的新基本科学信息，并且（1）与定义男性的定义有关，而原碱性为化学预防策略特别有价值，（2）有助于确定新颖的，潜在的可修改的危险因素对前列腺癌。修订后的项目解决了所有审阅者的关注，包括与核心C合作支持组织IGF信号研究的新的初步数据。