Investigation of a Novel Cancer Stem Cell Population in Ependymoma.

室管膜瘤中新型癌症干细胞群的研究。

基本信息

批准号：
10380564
负责人：
NICHOLAS K FOREMAN
金额：
$ 34.86万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10380564
关键词：
3-Dimensional Activities of Daily Living Address Adult Automobile Driving Biological Biology Brain Neoplasms Cancer Etiology Cell Line Cells Cessation of life Child Childhood Brain Neoplasm Childhood Ependymoma Classification Clinical Data Diagnosis Disease Ependymoma Excision Expression Profiling Flow Cytometry Gene Expression Profiling Grant Heterogeneity Histologic Histology In Vitro Investigation Knowledge Malignant Neoplasms Malignant neoplasm of brain Measures Modeling Modernization Molecular Molecular Profiling Neurosphere Operative Surgical Procedures Outcome Patients Phenotype Population Posterior Fossa Primary Neoplasm Property Radiation Recurrence Relapse Repeat Surgery Research Research Proposals Resected Resolution Sampling Techniques Technology Testing Time Transcript Tumor Biology Tumor Stem Cells base cancer stem cell chemotherapy childhood cancer mortality cohort deep sequencing design exhaustion improved improved outcome in vivo insight medulloblastoma methylomics molecular phenotype mortality mouse model neoplastic cell novel novel therapeutic intervention protein expression refractory cancer relapse risk self-renewal single-cell RNA sequencing stem stem cell population stem cells therapeutic target transcriptome transcriptomics tumor

项目摘要

PROJECT SUMMARY Brain tumors have become the leading cause of cancer-related death in children. Ependymoma (EPN) accounts for a substantial number of these deaths, and unlike in medulloblastoma, no effective chemotherapy has been identified. Most pediatric ependymomas, unlike in adults, occur in the posterior fossa. While aggressive surgery and radiation improve the initial results but even in completely resected and radiated posterior fossa ependymoma the 10-year progression survival is very poor with only approximately one third of these children being without relapse. All relapsed children with ependymoma will relapse again and all will die, often after multiple relapses with damaging repeated surgeries and radiation. There is a desperate need to understand the biology of these tumors better to understand the high, and often delayed, relapses. Bulk examination of childhood ependymoma samples has allowed classification within ependymoma which has had identified subpopulations with early relapse risk but has had no impact on therapy or long-term outcomes. Given that relapses are late, seen most frequently in children who have had complete surgeries and are radiated, we hypothesized that relapses occur from a relatively small number of resistant cancer stem cells present at diagnosis. Preliminary data using single cell RNA seq on posterior fossa ependymoma strengthens this hypothesis and identifies a putative cancer stem cell subpopulation amongst 4 distinct subpopulations. This grant rigorously explores whether we have indeed identified a cancer stem population in childhood ependymoma. Our research intends to fully characterizes the distinct ependymoma subpopulations identified in single cell RNA seq. Potentially targeting a stem cell population at diagnosis in addition to surgery and radiation may improved outcomes for a pediatric brain tumor that has substantial mortality.

项目摘要脑肿瘤已成为儿童与癌症有关的主要原因。室温瘤（EPN）这些死亡中有很大数量，与髓母细胞瘤不同，没有有效的化学疗法已经确定了。与成人不同的大多数儿科室性膜瘤发生在后窝。尽管侵略性手术和辐射改善了初始结果，但即使在完全切除和辐射中后窝室膜瘤10年的进展生存率非常差，只有大约三分之一这些孩子没有复发。所有复发儿童患有室管膜瘤的儿童将再次复发，所有人都将死亡，经常在多次复发后，重复手术和辐射。迫切需要更好地理解这些肿瘤的生物学，以了解高且经常延迟的复发。大部分检查儿童时期样品样本已允许在已室内室内进行分类确定了具有早期复发风险的亚群，但对治疗或长期结局没有影响。鉴于复发迟到了，在有完整手术并且是辐射，我们假设复发来自相对较少的抗性癌干细胞在诊断中存在。使用单细胞RNA SEQ在后窝室内室室瘤上使用的初步数据加强该假设并确定了4个不同的亚群中假定的癌症干细胞亚群。这项赠款严格探讨我们是否确实确定膜瘤。我们的研究旨在充分表征所确定的独特的转心瘤亚群在单细胞RNA中。除手术和辐射可能改善具有重大死亡率的小儿脑肿瘤的结局。