Tethered Cationic Lipoplex Nanoparticle Assay for Liver Cancer Detection and Surv

用于肝癌检测和生存的系留阳离子脂质复合物纳米颗粒测定

基本信息

批准号：
8689573
负责人：
Kalpana Ghoshal
金额：
$ 19.32万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689573
关键词：
Accounting Aflatoxin B1 Alcohol abuse Biological Assay Biological Markers Biometry Biopsy Blood Blood specimen Caliber Cancer Detection Cancer Etiology Cancer Patient Cause of Death Cell Count Cells Cessation of life Chemicals Chemoembolization Cirrhosis Clinic Complex Complicity Data Detection Development Diagnosis Diagnostic Diagnostic Neoplasm Staging Disease Doctor of Medicine Doctor of Philosophy Early Diagnosis Encapsulated Engineering Environmental Carcinogens Excision Fibrosis Fluorescence Functional disorder Gene Expression Goals Hemochromatosis Hepatitis Hepatitis B Virus Hereditary Disease Human Image Analysis In Situ Joints Knowledge Link Liposomes Liquid substance Liver Liver neoplasms Malignant Neoplasms Malignant neoplasm of liver Measurement Measures Mechanics Messenger RNA Methods MicroRNAs Modeling Molecular Molecular Probes Monitor Nanotechnology Neoplasm Circulating Cells Oncogene Activation Operative Surgical Procedures Pathology Patients Performance Phenotype Pilot Projects Play Primary carcinoma of the liver cells Problem Solving Procedures Progression-Free Survivals Publications RNA Research Personnel Risk Factors Role Sampling Screening for Hepatocellular Cancer Screening for cancer Signal Transduction Source Specific qualifier value Staging Surveillance Methods Techniques Testing Therapeutic Time Tissue Sample Transgenic Mice Transgenic Organisms Tumor Biology Tumor Tissue Tumor stage Tumor-Suppressor Gene Inactivation Unresectable Virus Diseases Work base biochip cancer cell cancer diagnosis chronic liver disease cohort cost design experience extracellular high risk innovative technologies liver transplantation meetings member microwave ablation mortality mouse model nanoparticle neoplastic cell nonalcoholic steatohepatitis novel public health relevance response screening tool tumor

项目摘要

DESCRIPTION (provided by applicant): Liver cancer is one of the leading causes of cancer deaths worldwide with fast growing rate in the US in recent years. A patient-friendly early detection and surveillance method would substantially reduce the mortality in this serious disease. 'Liquid biopsy' relying on detection of either circulating tumor cells (CTCs) or extracellular RNAs encapsulated in exosomes in patient blood samples has great potential to achieve this goal. But existing detection methods are far from perfection because CTCs are rare (~5-100 per 1 mL human blood) and exosomes are very small (<100 nm in diameter). Furthermore, none of the existing methods are able to simultaneously capture and detect both circulating exosomes and CTCs. We recently developed a novel and low-cost method 'Tethered Cationic Lipoplex Nanoparticle (TCLN) biochip' that, for the first time, may achieve this goal. In TCLN, molecular beacons (MBs) are pre-loaded in liposome nanoparticles to capture circulating exosomes and detect encapsulated extracellular RNAs from the patient blood or fluid sample without extra complicity. The in situ detection of target RNAs without diluting the sample leads to very high detection sensitivity not achievable by existing methods, e.g. qRT-PCR. The same biochip can also detect intracellular biomarkers in the captured CTCs by lipoplex internalization. Preliminary data in a MYC transgenic mouse model and HCC patient blood samples using miR-21 and miR-181b as biomarkers are very promising. TCLN can be extended to a multiplexing array design to allow the detection of a panel of target RNAs. In this proposal, we plan to evaluate its feasibility for liver cancer early detection and surveillance. Our primary objectives are (1) to compare a panel of target RNAs as biomarkers in tumor tissue and blood samples from MYC transgenic and miR-122 KO mouse models at different disease stages to evaluate the feasibility of using TCLN assay for early cancer detection, and (2) to identify target microRNA/mRNA biomarkers in liver cancer and to conduct a pilot study using blood samples from well-defined liver cancer patient groups to evaluate the relevancy of TCLN assay for cancer use in clinic.

描述（由申请人提供）：肝癌是近年来美国癌症死亡的主要原因之一。患者友好的早期检测和监视方法将大大降低这种严重疾病的死亡率。依靠检测循环肿瘤细胞（CTC）或封装在患者血液样本中外泌体中的细胞外RNA的“液体活检”具有实现这一目标的巨大潜力。但是现有的检测方法远非完美，因为CTC罕见（每1 ml人体血液约5-100），外泌体非常小（直径<100 nm）。此外，现有的方法都无法同时捕获和检测循环外泌体和CTC。我们最近开发了一种新型和低成本的方法“束缚阳离子脂肪纳米颗粒（TCLN）生物芯片”，这首先可能实现了这一目标。在TCLN中，将分子信标（MBS）预载于脂质体纳米颗粒中，以捕获循环外泌体并检测患者血液或液体样品中封装的细胞外RNA，而无需额外同谋。原位检测靶RNA而不稀释样品导致现有方法无法实现的非常高的检测灵敏度，例如QRT-PCR。相同的生物芯片还可以通过脂质内部化检测捕获的CTC中的细胞内生物标志物。使用miR-21和miR-181b作为生物标志物的MYC转基因小鼠模型和HCC患者血液样本中的初步数据非常有前途。 TCLN可以扩展到多重阵列设计，以允许检测一组目标RNA。在此提案中，我们计划评估其对肝癌早期发现和监测的可行性。 Our primary objectives are (1) to compare a panel of target RNAs as biomarkers in tumor tissue and blood samples from MYC transgenic and miR-122 KO mouse models at different disease stages to evaluate the feasibility of using TCLN assay for early cancer detection, and (2) to identify target microRNA/mRNA biomarkers in liver cancer and to conduct a pilot study using blood samples from well-defined liver cancer patient groups to evaluate TCLN分析在临床上使用癌症的相关性。