Models of EBV Cancer

EBV癌症模型

• 批准号: 10627695
• 负责人: Samantha Standish Soldan
• 金额: $ 30.54万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-11 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627695
• 关键词: ARID1A gene; Animal Cancer Model; Animal Model; Animals; Bacterial Artificial Chromosomes; Carcinoma; Cell Culture Techniques; Cell Line; Cells; Chemicals; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Collection; Development; Disease; Drug Combinations; Drug Screening; EBV-associated disease; Engraftment; Environment; Epigenetic Process; Epithelium; Epstein-Barr Virus Infections; Epstein-Barr Virus-Related Malignant Neoplasm; Exclusion; Fingerprint; Genes; Human; Human Herpesvirus 4; Human Resources; Immune; In Vitro; Infection; Infrastructure; Injections; Intervention; Knock-out; Label; Luciferases; Lymphoid Cell; Malignant Neoplasms; Metabolic; Metabolic Control; Methodology; Methods; Microsatellite Repeats; Mission; Modeling; Mus; Nasopharynx; Nasopharynx Carcinoma; Operative Surgical Procedures; Organ; Organoids; Pathogenesis; Pharmaceutical Preparations; Physiological; Pre-Clinical Model; Recombinants; Research Personnel; Research Project Grants; Research Support; Resources; Role; Services; Stomach; Stomach Carcinoma; System; TP53 gene; Technology; Terminal Repeat Sequences; Testing; The Wistar Institute; Therapeutic; Training Programs; Tropism; Universities; Variant; Viral; Virus; Work; Xenograft Model; Xenograft procedure; bioluminescence imaging; cancer risk; experimental study; gastric cancer cell; gastric organoids; genetic testing; genome integrity; humanized mouse; imaging study; in vivo; in vivo Model; malignant stomach neoplasm; member; mouse model; mutant; novel; patient derived xenograft model; pharmacologic; programs; recombinant virus; repository; research and development; response; tool; tumor microenvironment; tumorigenesis; ultrasound

CORE C – PROJECT SUMMARY The Preclinical Models of Epstein-Barr Virus (EBV) Cancer Core provides major resources to the three Program Project Investigators, including viral mutants and strains, EBV+ and EBV- nasopharyngeal carcinoma and gastric carcinoma cell lines; human gastric cancer organoid cultures; patient derived xenografts and other in vivo models of EBV-associated cancers; compound testing; and recombinant viruses. Core C has acquired a large repository of EBV+ and EBV- epithelial (gastric and nasopharyngeal) and lymphoid cell lines that have been fingerprinted and are routinely verified by microsatellite/short terminal repeat (STR) testing to exclude cross- contamination. In collaboration with Dr. Calvin Kuo (Stanford University), gastric cancer organoid cultures that are now continuously available through Core C at The Wistar Institute. Organoids are superior to standard cell culture because they recapitulate many features of the organs that they are derived from, including organ ultrastructure, and mimic the tumor microenvironment. These organoid cultures will provide important tools for studying viral and cellular determinants of Epstein-Barr virus-associated cancers (Project 1) and for drug screening (Projects 2 and 3). Importantly, these organoid cultures are genetically tractable and TP53 and ARID1A knockout organoid cultures are already available in Core C. In addition to cell culture models, Core C routinely performs studies using several murine models of EBV- associated cancers. Patient-derived xenografts that are exclusively maintained in vivo are available for all three Projects. Cell line-derived models of EBV associated gastric carcinoma and NPC have been adapted for bioluminescent imaging studies. These murine models will be used for compound testing (Projects 1-3) in collaboration with Core B. Finally, Core C will provide high-titer, recombinant EBV (Projects 1-3) using a bacterial artificial chromosome system to interrogate the specific contributions of EBV genes to the development of cancer.

核心C--项目摘要 EB病毒(EBV)癌症核心的临床前模型为三个项目提供了主要资源 项目调查人员，包括病毒突变体和毒株，EBV+和EBV-鼻咽癌和 胃癌细胞系；人胃癌器官培养；患者来源的异种移植和其他体内移植 EBV相关癌症模型；化合物测试；重组病毒。核心C已经收购了一家大型 EBV+和EBV-上皮(胃和鼻咽)和淋巴样细胞系的储存库 并常规通过微卫星/短末端重复(STR)测试进行验证，以排除交叉 污染。在与Calvin Kuo博士(斯坦福大学)的合作下，胃癌有机化合物培养 现已通过Wistar研究所的Core C持续提供。有机化合物优于标准细胞 文化，因为它们概括了它们起源的器官的许多特征，包括器官 超微结构，并模拟肿瘤微环境。这些有机培养物将为 研究EB病毒相关癌症的病毒和细胞决定因素(项目1)和药物 筛选(项目2和项目3)。重要的是，这些有机物培养物在遗传上是容易处理的，而且TP53和 ARID1A基因敲除的有机物培养物已经在Core C中可用。 除了细胞培养模型外，Core C还常规使用几种EBV-小鼠模型进行研究- 相关癌症。仅在体内维护的患者来源的异种移植物可用于所有三种 项目。EBV相关性胃癌和鼻咽癌细胞系衍生模型已被改编用于 生物发光成像研究。这些小鼠模型将用于化合物测试(项目1-3)。 与核心B合作。最后，核心C将提供高效价重组EBV(项目1-3)，使用 细菌人工染色体系统询问EBV基因对发育的特定贡献 癌症的威胁。