Patient-Matched Stem Cells of the Barrett's-Dysplasia-Adenocarcinoma Sequence

Barretts-不典型增生-腺癌序列的患者匹配干细胞

• 批准号: 9761508
• 负责人: FRANK D. MCKEON
• 金额: $ 17.46万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761508
• 关键词: Adenocarcinoma; Barrett Esophagus; Barrett' s Adenocarcinoma; Biology; Cancer Biology; Cell model; Cells; Cessation of life; Chemicals; Chronic; Clone Cells; Cloning; Communities; Data; Data Set; Databases; Diagnosis; Disease; Disease Progression; Dysplasia; Epithelium; Esophageal; Esophageal Adenocarcinoma; Excision; Future; Gene Expression; Genomics; Goals; Heterogeneity; Individual; Knowledge; Lesion; Libraries; Link; Modeling; Molecular Genetics; Mucous Membrane; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Preventive therapy; Property; Regimen; Research; Research Personnel; Resected; Resistance; Resources; Sampling; Source; Stem cells; Technology; Therapeutic; Visit; adult stem cell; biobank; cancer stem cell; carcinogenesis; chemotherapy; data acquisition; density; drug discovery; epigenomics; experimental study; functional genomics; genetic pedigree; indexing; regenerative; response; stem cell technology; tumor; tumor heterogeneity; tumorigenesis; virtual

The absence of reliable, patient-specific models in cancer biology has been a chronic impediment to understanding heterogeneity, progression, metastasis, and chemotherapy resistance. Recent advances in technologies for cloning adult stem cells resident in normal, regenerative epithelia have been adapted to cloning stem cells from Barrett's esophagus. Investigators in the proposed Center have now extended this technology, in preliminary studies, to cloning the stem cells of dysplastic Barrett's and adenocarcinoma itself. The impact of this technology for resolving key questions in Barrett's and cancer biology in general, including the precise steps in tumorigenesis from precursor lesions, the functional and genomic intra-tumor heterogeneity and its impact on chemotherapy resistance, and lastly the nature and targetability of stem cells of precursor lesions and frank adenocarcinoma, is potentially transformative. As potentially transformative is a biorepository that exploits the regenerative and clonal nature of these stem cells to extend our knowledge of discrete cases in parallel fashion. In Aim 1, we will generate high-density arrays of stem cell clones corresponding to a topological sampling across four mucosal resections of patients with early adenocarcinoma. Aim 2 will generate large libraries of cancer stem cells from advanced cases of esophageal adenocarcinoma. Aim 3 will generate an interactive database that links datasets from both the arrays of clones derived from mucosal resections as well as those associated with analyses of the cancer stem cell libraries. We anticipate that such a virtual database of datasets would greatly augment downstream studies with the same libraries and discrete clones as each would come with such linked datasets that would be further extended by ongoing and future studies by investigators within the Center and across the community.

癌症生物学中缺乏可靠的，患者特异性的模型一直是慢性障碍 了解异质性，进展，转移和化学疗法抗性。最近的进步 克隆成年干细胞的克隆技术居住在正常，再生上皮菌中已适应 从巴雷特的食道来克隆干细胞。拟议中心的调查人员现已扩展了这一点 在初步研究中，技术来克隆发育不良的Barrett和腺癌本身的干细胞。 这项技术对解决巴雷特和癌症生物学的关键问题的影响，包括 前体病变（功能性和基因组内）肿瘤发生的精确步骤 异质性及其对化学疗法抗性的影响，最后是干细胞的性质和目标性 前体病变和坦率的腺癌具有可能性的变化。因为潜在的变革是 利用这些干细胞的再生性和克隆性质的生物座位，以扩展我们对 平行方式离散案例。在AIM 1中，我们将生成高密度的干细胞克隆 对应于早期腺癌患者的四个粘膜切除术进行拓扑采样。 AIM 2将产生大量的食管腺癌病例的癌症干细胞。 AIM 3将生成一个交互式数据库，该数据库链接来自两个来自来自的克隆阵列的数据集 粘膜切除术以及与癌症干细胞库分析相关的粘膜切除术。我们期待 这样的数据集的虚拟数据库将大大增加与同一库的下游研究 离散克隆，每个都将带有此类链接数据集，这些数据集将通过持续和 中心和整个社区的研究人员的未来研究。