Pathology

病理

• 批准号: 6986013
• 负责人: Sherif S Farag
• 金额: $ 20.85万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986013
• 关键词: epigenetics; genes; leukemia; pathology; tissue resource /registry; tissues

Epigenetic silencing of critical genes through aberrant methylation appears to play a key role in tumor development. To advance our basic understanding of the epigenetic regulation of gene expression in cancer cells, and clinically test the hypothesis that remethylation of genes has therapeutic potential, we will investigate chronic lymphocytic leukemia (CLL) as a model in the projects presented in this program project proposal. However, the ability to meaningfully conduct basic studies and translate important findings to the clinical setting is greatly facilitated by the availability of an extensive repository of tissue samples, with accompanying pathologic and clinical data, procured from relevant patients CLL. This Core, the Pathology/Tissue Procurement Core, through the collaboration of the OSU Leukemia Tissue Bank (LTB), will serve this function in supporting the basic and clinical projects of this Program Project. The OSU leukemia tissue bank has a well-established infrastructure directly under our leadership. The Core will participate in the procurement of procurement of CLL cells and the molecular characterization of CLL cases for the Projects. All the essentials of effective tissue bank management, including the activities of tissue collection, quality control of specimens, tissue storage, procurement of initial and follow-up samples and their pathology and clinical information, data entry and database management, and patient consent and confidentiality are very well developed in this Core. In addition, this Core has the established capacity to process procured specimens for the preparation of pure cell populations (e.g., CLL cells though CD19 positive selection), cell lysates, nucleic acids and proteins in a uniform manner for ready distribution to investigators. Furthermore, the procedures for prioritizing and distributing tissue to a large base of investigators, within and outside our institution, are effectively in place. Against this background, we believe that this Core will function well in the support of the 5 projects proposed in this application, as well as future projects and collaborations. While funding currently exists for the infrastructure of OSU LTB, it is emphasized that there is no overlap in funding requested for this Core, as all of the new work proposed in this Program Project is not currently funded by NCI or other peer reviewed grants. The Specific Aims of this Core are, therefore, to: 1) provide central collection, processing and a state-of-the-art repository for samples collected from CLL patients treated at OSU, including protocols relevant to this Program Project; 2) provide materials from processed CLL samples for the support of Projects 1-5 of this Program Project proposal in a standardized manner, and 3) perform molecular characterization, including cytogenetic fluorescent in-situ hybridization (FISH) studies, lgVH and p53 mutational status, on all CLL cases used in the Projects to permit subsequent correlation with clinical and laboratory results.

通过异常甲基化导致的关键基因的表观遗传沉默似乎在肿瘤中发挥着关键作用 发展。增进我们对癌症基因表达表观遗传调控的基本了解 细胞，并临床测试基因再甲基化具有治疗潜力的假设，我们将 研究慢性淋巴细胞白血病（CLL）作为本计划项目中提出的项目的模型 提议。然而，有意义地进行基础研究并将重要发现转化为现实的能力 广泛的组织样本库的可用性极大地促进了临床环境， 随附的病理和临床数据来自相关 CLL 患者。这个核心， 病理学/组织采购核心，通过与 OSU 白血病组织库 (LTB) 的合作， 将在支持该计划项目的基础和临床项目中发挥这一作用。俄勒冈州立大学白血病 组织库拥有完善的基础设施，直接在我们的领导下。核心将参加 采购 CLL 细胞以及项目 CLL 病例的分子表征。全部 有效组织库管理的要点，包括组织采集活动、质量控制 标本的收集、组织储存、初始和后续样本的采购及其病理学和临床 信息、数据输入和数据库管理以及患者同意和保密都非常好 在此核心中开发。此外，该核心具有处理采购样本的既定能力 纯细胞群的制备（例如，通过 CD19 正选的 CLL 细胞）、细胞裂解物、核酸 酸和蛋白质以统一的方式分发给研究人员。此外，程序 优先考虑并将组织分配给我们机构内外的大量研究人员 有效到位。在此背景下，我们相信这个核心在支持下将会很好地发挥作用。 本申请中提出了 5 个项目，以及未来的项目和合作。目前资助的同时 存在 OSU LTB 的基础设施，需要强调的是，为此请求的资金不存在重叠 核心，因为该计划项目中提出的所有新工作目前均未获得 NCI 或其他同行的资助 审查了赠款。因此，该核心的具体目标是： 1) 提供集中收集、处理 以及一个最先进的存储库，用于存放从 OSU 治疗的 CLL 患者收集的样本，包括方案 与本计划项目相关； 2) 提供加工后的CLL样本材料以支持项目 本计划的 1-5 以标准化方式提出项目提案，以及 3) 进行分子表征， 包括细胞遗传学荧光原位杂交 (FISH) 研究、lgVH 和 p53 突变状态， 项目中使用的 CLL 病例可以与临床和实验室结果进行后续关联。