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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在过去的12个月里，我们已经取得了显着的进展，扩大了与ApcMIn/+小鼠的癌症恶病质有关的骨骼肌质量减轻的初步数据。我们与该项目相关的计划将集中在进一步的数据生成、新的赠款开发以及手稿的准备和提交上。1)我们将于2006年7月1日重新向NCI提交修订后的拨款，题为《ApcMIn/+小鼠中的恶病质：IL-6的作用》。虽然最初提交的材料没有打分，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，赠款的重点更加突出，共同投资机构的作用已经扩大，以提供更深层次的经验。该提案中的实验旨在机械地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。提案中的具体目标将使用体内功能测试、生化分析和形态检查来证明这一工作假说，即通过纤维型特定机制启动和促进肌肉萎缩的慢性炎症状态会增加循环中的IL-6。我们将在来年继续收集拨款建议中概述的实验的数据。2)其他项目：正在制定第二项拨款，研究IL-6对骨骼肌解偶联蛋白诱导的脂肪组织损失的调节。与实验室其他工作相关的另一个拨款想法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肌肥大。3)生产力：我们将完成两份与恶病质有关的手稿，目前正在编写中，将在2006-2007年期间提交和出版。第一篇手稿侧重于IL-6在ApcMin/+小鼠中的作用。我们还将提交另外两篇目前正在准备中的手稿，这两篇论文是科布雷资助的与ApcMin/+小鼠的锻炼、饮食和化学预防相关的研究。5)癌症与运动：2006年7月1日将提交美国癌症研究所拨款申请的修订本。上一次提交的申请距离资金额度只有1个百分点。这项建议将允许在ApcMin/+小鼠中继续进行由Cobre基金发起的运动、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.