COBRE: USC: EXERCISE AND POLYPOSIS IN THE APCMIN/+ MOUSE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去的12个月里，我们在ApcMIn/+小鼠的骨骼肌质量损失与癌症恶病质相关的初步数据上取得了重大进展。我们与这个项目相关的计划将集中在进一步的数据生成、新的拨款开发和稿件准备和提交上。1)我们将于2006年7月1日向NCI重新提交题为“ApcMIn/+小鼠中的恶病质：IL-6的作用”的修订后的拨款。虽然最初的提交没有得分，但审查是积极的，表明有很大的潜力。已经收集了更多的试点数据，赠款更加集中，共同项目负责人的作用已经扩大，以提供更深入的经验。本实验旨在从机制上扩展我们的初步数据，证明IL-6对ApcMin/+小鼠恶病质的调节潜力。该提案的具体目标将使用体内功能测试，生化分析和形态学检查来证明慢性炎症状态升高循环IL-6通过纤维类型的特定机制启动和促进肌肉萎缩的工作假设。在接下来的一年里，我们将继续为拨款提案中概述的实验收集数据。2)其他项目：第二笔拨款正在制定中，将研究IL-6对骨骼肌中解偶联蛋白诱导脂肪组织损失的调节。另一项与实验室其他工作相关的研究是雄激素受体在肌肉萎缩过程中的作用。一篇博士论文和南加州大学医学院的合作者也在研究恶病质小鼠的心脏肥厚。3)生产力：我们将完成2篇与恶病质相关的手稿，目前正在准备中，将在2006-2007年期间提交和发表。第一篇论文的重点是IL-6在ApcMin/+小鼠中的作用。我们还将提交另外2篇正在准备中的论文，它们是COBRE资助的关于ApcMin/+小鼠的运动、饮食和化学预防的研究。5)癌症和运动：美国癌症研究协会拨款申请的修订版将于2006年7月1日提交。上一次提交的文件比供资线差1点。该提案将允许继续在COBRE资助的ApcMin/+小鼠中进行运动，饮食和化学预防研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have made significant progress over the past 12 months expanding on preliminary data related to skeletal muscle mass loss with cancer cachexia in the ApcMIn/+ mouse. Our plans related to this project will focus on further data generation, new grant development, and manuscript preparation and submission. 1) We will resubmit the revised grant titled ¿Cachexia in ApcMIn/+ mice: the role of IL-6¿ to the NCI on July 1 2006. Although the initial submission was not scored, the reviews were positive and indicated strong potential. Additional pilot data have been collected, the grant is better focused, and the roles of co-PIs have been broadened to provide deeper experience. The experiments in the proposal are designed to mechanistically extend our preliminary data demonstrating the potential for IL-6 regulation of cachexia in the ApcMin/+ mouse. The specific aims in the proposal will use both in vivo functional tests, biochemical analysis, and morphological examination to prove the working hypothesis that a chronically inflamed state that elevates circulating IL-6 both initiates and promotes muscle wasting by fiber-type specific mechanisms. We will continue to collect data over the next year on experiments outlined in the grant proposal. 2) Other projects: A second grant is being formulated that would examine IL-6 regulation of adipose tissue loss due to the induction of uncoupling proteins in skeletal muscle. An additional grant idea related to other work in the lab is the role of the androgen receptor in the process of muscle wasting. The cardiac hypertrophy in the cachectic mouse is also being examined by a Doctoral Dissertation and with collaborators at the USC Medical School. 3) Productivity: We will finish 2 cachexia-related manuscripts that are currently in preparation and will be pushed towards submission and publication during 2006-2007. The first manuscript is focused on the role of IL-6 in ApcMin/+ mice. We will also be submitting 2 additional manuscripts currently in preparation that were COBRE- funded studies related to exercise, diet and chemoprevention in the ApcMin/+ mouse. 5) Cancer and exercise: A revision of the American Institute for Cancer Research grant submission will be submitted July 1 2006. The previous submission was 1 point from the funding line. This proposal will allow for continuation of the exercise, diet and chemoprevention studies in the ApcMin/+ mouse that were intitiated by COBRE funding.