Implications of a novel glioblastoma classification defined by miR-21-Sox2 status

由 miR-21-Sox2 状态定义的新型胶质母细胞瘤分类的意义

基本信息

批准号：
8431523
负责人：
SADHAN MAJUMDER
金额：
$ 37.92万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8431523
关键词：
Age Applications Grants B Cell Proliferation Basic Science Biochemical Bioinformatics Biological Assay Brain Neoplasms Caring Cell Death Cell Proliferation Classification Clinic Clinical Research Combined Modality Therapy Consensus CpG Island Methylator Phenotype D Cells Data Databases Detection Diagnostic Differentiation Inducer Doctor of Medicine FDA approved Glioblastoma Glioma Goals Histopathology Housing Human Immunoglobulin Class Switching In Vitro Karnofsky Performance Status Magnetic Resonance Imaging Measures Messenger RNA MicroRNAs Modeling Molecular Molecular Profiling Mus Newly Diagnosed Oncogenic Outcome PTEN gene Parents Pathway interactions Patient Care Patients Performance Pharmaceutical Preparations Predictive Value Process Property Radiation Resistance Reverse Transcriptase Polymerase Chain Reaction Sampling Stem cells System TP53 gene Testing The Cancer Genome Atlas Therapeutic Translations Treatment Protocols Tretinoin Tumor Subtype Work Xenograft Model arm base chemotherapy design effective therapy improved in vivo innovation insight mouse model novel prognostic relating to nervous system research study self-renewal stemness temozolomide tumor tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Glioblastoma multiforme (GBM) is the most common and most aggressive human brain tumor. However, despite decades of basic science and clinical research, there is no quick, widely used prognostic criterion for GBM patients (except for non-molecular parameters, such as age; lower survival is correlated with older age) and the outcome for GBM patients remains dismal, with an average survival duration of only 15 months. Thus, new innovative, mechanism-based approaches are necessary for the management of patients with GBM. We have discovered a new regulatory axis based on a novel miR-21-Sox2 axis in GBM patients and patient glioblastoma-derived stem cells through bioinformatic and biochemical studies. This axis appears to classify GBM patients into distinct classes. Based on these results, here we propose to prove or disprove the novel central hypothesis that our GBM classification based on the miR-21-Sox2 axis can produce new prognostic approaches for GBM patients and that this mechanism can also be utilized to develop more effective, less toxic "personalized" treatment regimens for GBM patient care PUBLIC HEALTH RELEVANCE: The mean survival duration of patients with glioblastoma multiforme (GBM), the most common form of glioma, is approximately 15 months and there is no effective therapy. If the Specific Aims of this grant application are completed, not only we wil have the understanding of a new mechanistic axis of GBM tumorigenesis, but this information will also have potentially novel and unconventional translational impact in terms of detection, predict patient outcome and design more effective therapeutic approaches than what is currently used.

描述（由申请人提供）：多形胶质母细胞瘤（GBM）是最常见和最具侵略性的人脑肿瘤。但是，尽管经过数十年的基础科学和临床研究，但GBM患者没有快速使用的预后标准（除了非分子参数，例如年龄；较低的生存率与年龄相关），GBM患者的结果仍然令人沮丧，平均存活持续时间仅为15个月。因此，对于GBM患者的管理，必须采用新的创新，基于机制的方法。我们通过生物学和生物化学研究发现了基于GBM患者的新型miR-21-SOX2轴和患者胶质母细胞瘤衍生的干细胞的新调节轴。该轴似乎将GBM患者分为不同的类别。基于这些结果，我们在这里建议证明或反驳新的中心假设，即我们的GBM分类基于miR-21-SOX2轴可以为GBM患者产生新的预后方法，并且该机制也可以用于开发更有效的，更有效，毒性较低的“个性化”治疗方案的GBM患者护理护理治疗方案公共卫生相关性：胶质瘤最常见的胶质母细胞瘤（GBM）患者的平均存活持续时间约为15个月，没有有效的治疗。如果完成了本赠款申请的具体目的，我们不仅将了解GBM肿瘤发生的新机械轴，而且该信息还将在检测方面具有潜在的新颖和非常规的翻译影响，预测患者结果和设计更有效的治疗方法。