Osteopontin-CD44 role in the malignancy of lateral ventricle infiltrating glioblastoma

骨桥蛋白-CD44在侧脑室浸润性胶质母细胞瘤恶性肿瘤中的作用

• 批准号: 10628557
• 负责人: Hugo Guerrero-Cazares
• 金额: $ 21.06万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10628557
• 关键词: Adult; Affect; Animal Model; Applications Grants; Binding; Bioinformatics; Biological; Biopsy; Blocking Antibodies; Brain Neoplasms; CD44 gene; Cell Proliferation; Cell Survival; Cells; Cerebrospinal Fluid; Chemotherapy and/or radiation; DNA Damage; Data; Diagnosis; Distal; Encapsulated; FDA approved; Family; Gene Expression Profile; Genes; Glioblastoma; Glioma; Glycoproteins; Goals; Human; Hydrogels; Implant; In Vitro; Intrathecal Injections; Lead; Location; Malignant - descriptor; Malignant Neoplasms; Mentored Research Scientist Development Award; Operative Surgical Procedures; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Primary Brain Neoplasms; Proteins; Recombinants; Recurrence; Reporting; Role; Sampling; Scientist; Secure; Speed; Testing; Translational Research; base; career; cell motility; differential expression; experimental study; gain of function; genetic signature; in vivo; inhibitor; lateral ventricle; loss of function; malignant phenotype; member; migration; neoplastic cell; nerve stem cell; osteopontin; overexpression; pluripotency; pre-clinical; prenylation; response; self-renewal; skills; stemness; subventricular zone; targeted treatment; therapy resistant; transcriptome sequencing; tumor; tumor progression; whole genome

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with a median survival of only 14 months after diagnosis, despite optimal surgery, chemotherapy, and radiation. Patients whose GBMs infiltrate the wall of the lateral ventricles (LV) have a substantially shorter survival than those whose tumors are located away from the LV, for reasons that remain unknown. Cerebrospinal fluid (CSF) in the LV can regulate the differentiation and migration of normal neural progenitor cells. We propose by analogy that LV-infiltrating GBMs also can interact with components of the CSF, and that this interaction makes these tumors more malignant. This proposal will study the interaction of human GBM cells and CSF. Particularly it will be focused on determining whether the osteopontin-CD44 axis plays a role in the response of GBM cells to CSF. This K01 award will allow Dr. Hugo Guerrero-Cazares to solidify his career as an independent scientist, develop bioinformatics and translational research skills and secure the preliminary information for a successful R01 grant application

胶质母细胞瘤(GBM)是成人最常见和最具侵袭性的原发脑肿瘤， 确诊后的中位生存期只有14个月，尽管手术是最好的， 化疗和放射治疗。基底膜渗入外侧壁的患者 脑室(LV)的存活期比肿瘤所在的脑室短得多 离开LV，原因不明。左心室内脑脊液(CSF) 能调节正常神经前体细胞的分化和迁移。我们 以此类推地提出，LV渗透的GBM也可以与 这种相互作用会使这些肿瘤更加恶性。这项提议将 研究人GBM细胞与脑脊液的相互作用。特别是它将重点放在 确定骨桥蛋白-CD44轴是否在GBM的反应中起作用 细胞到脑脊液。这一K01奖项将使雨果·格雷罗-卡萨雷斯博士的职业生涯更加稳固 作为一名独立科学家，发展生物信息学和转化研究技能，并 保护成功的R01拨款申请的初步信息