Validated Modeling and Culture of Salivary Cancers

唾液腺癌的验证模型和培养

基本信息

批准号：
8445079
负责人：
WENDELL G YARBROUGH
金额：
$ 20.76万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8445079
关键词：
Adenocarcinoma Adenoid Cystic Carcinoma Adenoidal structure Animal Model Cancer Cell Growth Carcinoma Ex Pleomorphic Adenoma Cell Culture Techniques Cell Line Cells Characteristics Classification Collection Consent Data Defect Development Dissociation Ductal Carcinoma Environment Epithelial Excision Fibrous capsule of kidney Gene Expression Gene Expression Profiling Goals Growth Head and Neck Cancer Head and neck structure Histology Human Hypoxia Image Immunohistochemistry Implant Incidence Infection Institutional Review Boards Knowledge Laboratories Left Luciferases Malignant Epithelial Cell Malignant Neoplasms Measures Methods Microsatellite Repeats Modeling Molecular Molecular Profiling Morphology Mucoepidermoid Carcinoma Mus Mutation Names Nerve Operative Surgical Procedures Parents Parotid Gland Pathogenesis Patients Primary Neoplasm Promega Protocols documentation Radiation Rattus Relative (related person)Research Infrastructure Resources Salivary Salivary Gland Carcinoma Salivary Gland Neoplasms Short Tandem Repeat Source Specific qualifier value System Tissues Tumor Cell Line Tumor Tissue Tumor-Associated Process United States Validation World Health Organization Xenograft Model Xenograft procedure cancer cell cancer type cytotoxic effective therapy experience improved in vivo insight oncology preclinical study public health relevance repository subcutaneous success tumor tumor growth tumor initiation tumor microenvironment tumor xenograft

项目摘要

DESCRIPTION (provided by applicant): Salivary cancers are a devastating group of malignancies treated almost exclusively by surgical excision with or without radiation. The low incidences, multiple histologies, lack of molecular details and inadequate infrastructure for collecting these tumors have each contributed to the relative paucity of treatment options. We suggest that the largest impediment blocking understanding of salivary cancers and advancement of therapy has been the lack or scarcity of validated xenograft models or cell lines for study. Without freely available xenografts or cell lines mechanistic or pre-clinical studies ar not possible. Here, we propose to create mouse xenograft models of human salivary cancers of multiple histologies. We have xenografted multiple salivary types including: adenoid cystic, adenocarcinoma not otherwise specified, polymorphous low grade adenocarcinoma, carcinoma ex-pleomorphic adenoma, and salivary ductal carcinoma. We also propose to create cell lines from multiple histological types of salivary cancer using primary tumors or murine xenografted tumors as starting material. For development of cell lines, we continue to optimize our culture environment with adjustment of tumor dissociation protocols, media, plate coatings, and culture hypoxia. By making these adjustments, we have increased our success of early cell culture derived from multiple salivary cancer types, and we currently have active early passages of cells derived from adenocarcinoma not otherwise specified, polymorphous low grade adenocarcinoma, and carcinoma ex-pleomorphic adenoma. Once xenografts and cell lines are created, they will be validated by comparison of morphology (xenografts) and gene expression (xenografts and cell cultures). We have the infrastructure for collection of salivary cancers from surgical resections and have developed expertise in processing of the tumors for short-term culture and murine xenograft modeling. We will leverage these resources to create and validate murine xenograft models and cell lines for salivary cancers. These validated cell lines and xenografted tumors will be critical to advance molecular understanding of salivary cancers and will be needed for advancement of therapy.

描述（由申请人提供）：唾液癌是一群毁灭性的恶性肿瘤，几乎完全通过手术切除或没有辐射治疗。低发病率，多种组织学，缺乏分子细节以及用于收集这些肿瘤的基础设施不足，都导致治疗选择的相对缺乏。我们建议，阻碍对唾液癌的理解和治疗进展的最大障碍是缺乏或缺乏经过验证的异种移植模型或细胞系进行研究。没有免费的异种移植物或细胞系机械或临床前研究。在这里，我们建议创建多种组织学人类唾液癌的小鼠异种移植模型。我们已经有多种唾液类型的类型，包括：腺样囊肿，未指定的腺癌，多态低级腺癌，癌前胸膜腺瘤和唾液导管癌。我们还建议使用原发性肿瘤或鼠类异种移植肿瘤作为起始材料从多种组织学类型的唾液癌中产生细胞系。为了开发细胞系，我们继续通过调整肿瘤解离方案，培养基，板涂层和培养缺氧来优化我们的培养环境。通过进行这些调整，我们提高了从多种唾液癌类型的早期细胞培养的成功，目前，我们目前具有源自另外指定的腺癌衍生的细胞的活跃早期传递，多态低级腺癌和癌癌前肾上腺瘤。一旦创建异种移植和细胞系，将通过比较形态学（异种移植）和基因表达（异种移植物和细胞培养物）进行验证。我们拥有从外科手术切除术收集唾液癌的基础设施，并在处理短期培养和鼠内异种移植物建模的肿瘤方面开发了专业知识。我们将利用这些资源来创建和验证唾液癌的鼠内异种移植模型和细胞系。这些经过验证的细胞系和异种移植肿瘤对于提高对唾液癌的分子理解至关重要，并且需要进行治疗的发展。