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

• 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
• 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

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）：多形性胶质母细胞瘤（GBM）是最常见和最具侵袭性的人脑肿瘤。然而，尽管有几十年的基础科学和临床研究，没有快速，广泛使用的GBM患者的预后标准（除了 非分子参数，如年龄;较低的存活率与年龄相关），GBM患者的结果仍然令人沮丧，平均存活期仅为15个月。因此，新的创新，机制为基础的方法是必要的GBM患者的管理。通过生物信息学和生物化学研究，我们在GBM患者和患者胶质母细胞瘤源性干细胞中发现了基于新的miR-21-Sox 2轴的新调控轴。该轴似乎将GBM患者分为不同的类别。基于这些结果，我们在此提出证明或反驳新的中心假设，即我们基于miR-21-Sox 2轴的GBM分类可以为GBM患者产生新的预后方法，并且这种机制也可以用于开发更有效、毒性更小的GBM患者护理“个性化”治疗方案。 公共卫生相关性：多形性胶质母细胞瘤（GBM）是最常见的胶质瘤形式，其患者的平均生存期约为15个月，目前尚无有效的治疗方法。如果该资助申请的具体目标完成，我们不仅将了解GBM肿瘤发生的新机制轴，而且这些信息还将在检测方面具有潜在的新颖和非传统的翻译影响，预测患者结局并设计比目前使用的更有效的治疗方法。