Vascularized tumor explants for drug testing

用于药物测试的血管化肿瘤外植体

基本信息

批准号：
10424580
负责人：
Dan Gabriel Duda
金额：
$ 37.05万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10424580
关键词：
Address Adjuvant Adjuvant Therapy Aftercare Anatomy Apoptosis Biological Biological Assay Biology Blood Vessels Cancer Biology Cancer Center Cell Proliferation Cells Chemoresistance Clinical Collagen Diagnosis Disease Drug Screening Drug usage Engineering Excision Extracellular Matrix Fibroblasts Fibronectins Fluorouracil Growth Harvest Histologic Human Hyaluronan Immunodeficient Mouse Implant In Vitro Investigational Therapies Leucovorin Localized Disease Maintenance Malignant Neoplasms Methodology Mus Neoplasm Metastasis Neoplasms in Vascular Tissue Oncologist Operative Surgical Procedures Oxygen Pancreatic Ductal Adenocarcinoma Pathway interactions Patient Transfer Patients Perioperative Pharmaceutical Preparations Population Postoperative Period Primary Neoplasm Probability Protocols documentation Regimen Resected Rest Sampling Scientist Specimen Stromal Cells System Technology Testing Time Tissue Sample Tissues Tumor Biology Tumor Tissue Tumor-associated macrophages Xenograft Model Xenograft procedure anticancer research base case-by-case basis chemotherapy clinically relevant cytotoxic density drug testing effective therapy experimental study gemcitabine high throughput screening improved in vivo irinotecan novel strategies oxaliplatin pancreatic ductal adenocarcinoma cell personalized cancer therapy predictive tools preservation prevent prospective response second harmonic generation imaging single-cell RNA sequencing standard care standard of care success tool treatment duration treatment planning treatment response tumor tumor growth tumor progression vascular bed

项目摘要

Project Abstract Our understanding of cancer progression or response to therapies would benefit from easily accessible, patient- specific assays that recapitulate the biology and anatomy of human tumors. To this end, we will develop methodology for integrating tumor explants with engineered stroma and vasculature in vitro. With appropriate culture conditions, a self-assembled vascular network develops and then incorporates into co-cultured tumors excised from mice or patients. The system provides a representative extracellular matrix, associated stromal cells, and a lumenized vessel network. The methodology is straightforward and amenable to high throughput assays, making it an attractive tool for in vitro drug screening or for the guidance of patient-specific chemotherapies. Using this approach, we propose to create a platform for optimally maintaining samples from patients with pancreatic ductal adenocarcinoma (PDAC) ex vivo in vascularized tumor explants (VTEs) for the purpose of biological analysis and drug testing. We will characterize the VTEs and validate the system using mouse xenograft models and surgical tissue samples from PDAC patients treated at the MGH Cancer Center. When complete, this project will establish a robust, high throughput, and validated platform for analyzing tumor biology or drug testing, thus accelerating cancer research and enabling personalize therapy for cancer.

项目摘要我们对癌症进展或对疗法反应的理解将受益于易于访问，患者 - 概括了人类肿瘤的生物学和解剖结构的特定测定。为此，我们将发展在体外将肿瘤外植体与工程基质和脉管系统相结合的方法。适当培养条件，自组装的血管网络发展，然后纳入共培养肿瘤从小鼠或患者中切除。该系统提供了代表性的细胞外基质，相关的基质细胞，和一个亮船网络。该方法很简单，可以接受高通量测定法，使其成为体外药物筛查或指导患者特异性化学疗法的有吸引力的工具。使用这种方法，我们建议创建一个平台，以最佳地维护胰腺患者的样品血管化肿瘤外植体（VTE）的导管腺癌（PDAC）出于生物分析的目的和药物测试。我们将使用鼠标异种移植模型和外科手术来表征VTE并验证系统来自MGH癌症中心治疗的PDAC患者的组织样品。完成后，该项目将建立一个可靠，高通量和经过验证的平台，用于分析肿瘤生物学或药物测试，从而加速癌症研究并实现个性化癌症治疗。