Engineering of bacterial probiotics for the detection and treatment of hepatocellular carcinoma

用于检测和治疗肝细胞癌的细菌益生菌工程

基本信息

批准号：
9891034
负责人：
ZAKARY SINGER
金额：
$ 6.93万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9891034
关键词：
Address Affect Antibodies BALB/c Nude Mouse Bacteria Biological Models Cancer Etiology Cells Cessation of life Chronic Cirrhosis Colorectal Communities Cytolysis DNA Sequence Alteration Detection Diagnosis Disease Engineered Probiotics Engineering Escherichia coli Extracellular Space FGFR4 gene Fibroblast Growth Factor Fibroblasts Fibrosis Fluorouracil Gastrointestinal Diseases Growth Hepatitis B Hepatitis C Hepatitis C Therapy Human Human body Immune response Immunologic Surveillance Impairment In Vitro Inflammatory Intracellular Space Invaded Malignant - descriptor Malignant Neoplasms Malignant neoplasm of liver Metabolic Metastatic Neoplasm to the Liver Microscopy Modeling Mus Mutation Necrosis Nutrient Oral Administration Pathologic Pathway interactions Patients Population Growth Prevalence Primary carcinoma of the liver cells Probiotics Production Proteins Radiation Reactive Oxygen Species Recurrence Role Route Safety Sampling Signal Pathway Solid Neoplasm T-Lymphocyte Testing Therapeutic Time Tissues Toxin Treatment Efficacy Vascular Endothelial Growth Factors Vascularization Viral Physiology Viral Proteins Virus Diseases Xenograft procedure beneficial microorganism cancer cell chemotherapy curative treatments cytotoxic extracellular humanized mouse in vivo in vivo optical imaging liver inflammation microbiome research mouse model multimodality novel novel diagnostics novel therapeutics oxidative damage recruit small hairpin RNA subcutaneous synthetic biology therapeutic evaluation therapeutic target three dimensional cell culture time use tool tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Liver cancer, the second leading cause of cancer-related death globally, is frequently diagnosed in the advanced stages of the disease, where curative treatments are either unavailable or provide only modest survival improvement. As recent studies have uncovered the natural and beneficial role of bacteria throughout the human body, as well as their proclivity to grow inside solid tumors, bacteria emerge as a natural delivery vehicle for novel therapeutics against the disease. Here we will use synthetic biology to engineer bacteria that produce high local concentrations of therapeutics targeting pathways commonly dysregulated in hepatocellular carcinoma (HCC), and that are only capable of growing within a tumor’s unique microenvironment, thereby minimizing systemic effects. Using in vitro and in vivo humanized mouse models, we aim to develop an effective, safe, and novel treatment option for HCC.

项目摘要/摘要肝癌是全球癌症相关死亡的第二大原因，经常在该疾病的晚期阶段，治愈性治疗不可用或仅提供适度的生存改善。由于最近的研究发现了整个人体的细菌，以及它们在实体瘤内生长的倾向，细菌成为一种自然送货工具，用于针对该疾病的新型治疗。在这里我们将使用合成生物学对工程师细菌的合成生物学，产生局部浓度高的靶向靶向通常在肝细胞癌（HCC）中通常失调的途径，而这些途径仅能在肿瘤独特的微环境中生长，从而最大程度地减少全身效果。在体外使用在体内人性化的鼠标模型中，我们旨在开发有效，安全和新颖的治疗选择对于HCC。