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: 10607403
• 负责人: FRANK D. MCKEON
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-11 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10607403
• 关键词: Adenocarcinoma; Advanced Malignant Neoplasm; Affect; American; Barrett Esophagus; Barrett' s Adenocarcinoma; Biology; Cancer Biology; Cell model; Cells; Cessation of life; Chemicals; Chemoresistance; Chronic; Clone Cells; Cloning; Communities; Data; Data Set; Databases; Diagnosis; Disease; Disease Progression; Dysplasia; Epithelial; Esophageal Adenocarcinoma; Esophagus; 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; Technology; Therapeutic; Visit; adult stem cell; biobank; cancer stem cell; carcinogenesis; data acquisition; density; drug discovery; epigenomics; experimental study; functional genomics; genetic pedigree; indexing; new technology; regenerative; response; stem cell technology; stem cells; targeted treatment; tumor; tumor heterogeneity; tumorigenesis; virtual

Project Summary/Abstract: Virtual Biorespository (Core A) 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.

项目概要/摘要：虚拟生物资源库（核心A） 在癌症生物学中缺乏可靠的、患者特异性的模型一直是癌症治疗的长期障碍。 了解异质性、进展、转移和化疗耐药性。的最新进展 用于克隆驻留在正常再生上皮中的成体干细胞的技术已经被改进， 从巴雷特食管克隆干细胞拟议中的中心的调查人员现在已经扩大了这一点， 在初步研究中，这项技术用于克隆发育异常的巴雷特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中的关键问题的影响，包括 肿瘤发生的精确步骤，从前驱病变，功能和基因组肿瘤内 异质性及其对化疗耐药性的影响，最后是干细胞的性质和靶向性 和坦率的腺癌，是潜在的变革。具有潜在变革性的是 利用这些干细胞的再生和克隆性质来扩展我们的知识， 以并行方式处理离散案件。在目标1中，我们将产生高密度的干细胞克隆阵列 对应于早期腺癌患者的四个粘膜切除术的拓扑采样。 目标2将从晚期食管腺癌病例中产生大量的癌症干细胞库。 AIM 3将生成一个交互式数据库，该数据库将来自 粘膜切除术以及与癌症干细胞文库分析相关的那些。我们预计 这种数据集的虚拟数据库将极大地增强具有相同库的下游研究， 离散克隆，因为每个克隆都将带有这样的链接数据集，这些数据集将通过正在进行的 未来的研究由中心内的研究人员和整个社区。

项目成果

The Cellular Origin of Barrett's Esophagus and Its Stem Cells.

• DOI: 10.1007/978-3-030-11096-3_5
• 发表时间: 2019
• 期刊: Advances in experimental medicine and biology
• 作者: W. Xian;M. Duleba;Yanting Zhang;Yusuke Yamamoto;K. Ho;C. Crum;F. McKeon

An Efficient Method for Cloning Gastrointestinal Stem Cells From Patients via Endoscopic Biopsies.

通过内窥镜活检克隆患者胃肠干细胞的有效方法。

• DOI: 10.1053/j.gastro.2018.08.062
• 发表时间: 2019
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Duleba,Marcin;Qi,Yutao;Mahalingam,Rajasekaran;Liew,Audrey-Ann;Neupane,Rahul;Flynn,Kevin;Rinaldi,Fabrizio;Vincent,Matthew;Crum,ChristopherP;Ho,KhekYu;Hou,JasonK;Hyams,JeffreyS;Sylvester,FranciscoA;McKeon,Frank;Xian,Wa
• 通讯作者: Xian,Wa

Biobanking Organoids or Ground-State Stem Cells?

生物样本库类器官还是基态干细胞？

• DOI: 10.3390/jcm7120555
• 发表时间: 2018
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Xian,Wa;Duleba,Marcin;Yamamoto,Yusuke;Vincent,Matthew;McKeon,Frank
• 通讯作者: McKeon,Frank