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

基本信息

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
项目类别：
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

项目摘要

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）是成人中最常见和最具侵袭性的原发性脑肿瘤，尽管进行了最佳手术，诊断后中位生存期仅为 14 个月，化疗和放疗。 GBM 浸润侧脑室壁的患者脑室 (LV) 的生存期比肿瘤所在的患者要短得多远离 LV，原因尚不清楚。左心室中的脑脊液 (CSF) 可以调节正常神经祖细胞的分化和迁移。我们通过类比提出，LV 浸润性 GBM 也可以与 CSF，并且这种相互作用使这些肿瘤更加恶性。该提案将研究人类 GBM 细胞和脑脊液的相互作用。特别是它将重点关注确定骨桥蛋白-CD44轴是否在GBM反应中发挥作用细胞至脑脊液。这个 K01 奖项将使 Hugo Guerrero-Cazares 博士能够巩固他的职业生涯作为一名独立科学家，培养生物信息学和转化研究技能，确保获得成功 R01 拨款申请的初步信息