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.

项目摘要/摘要：虚拟生物储存库（核心A）

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