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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：
10317398
负责人：
Dan Gabriel Duda
金额：
$ 37.81万
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/10317398
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治疗反应的理解将受益于容易获得的，病人- 概括人类肿瘤的生物学和解剖学的特定测定。为此，我们将制定体外将肿瘤外植体与工程化基质和脉管系统整合的方法学。与适当在培养条件下，自组装的血管网络发育，然后并入共培养的肿瘤中从老鼠或病人身上切除。该系统提供了代表性的细胞外基质，相关的基质细胞，和管腔化血管网络。该方法是直接的并且适合于高通量测定，使其成为体外药物筛选或指导患者特异性化疗的有吸引力的工具。使用通过这种方法，我们建议创建一个平台，用于最佳地维持来自胰腺癌患者的样本，导管腺癌（PDAC）在血管化肿瘤外植体（VTE）中离体用于生物学分析和药物测试我们将使用小鼠异种移植模型和外科手术来表征VTE并验证该系统。来自在MGH癌症中心治疗的PDAC患者的组织样品。完成后，该项目将建立一个强大的、高通量的、经过验证的平台，用于分析肿瘤生物学或药物测试，从而加速癌症研究和实现癌症的个性化治疗。