Mechanisms of Brain Tumor Chemoresistance

脑肿瘤化疗耐药机制

• 批准号: 7969697
• 负责人: John Park
• 金额: $ 79.23万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969697
• 关键词: 19q; Brain; Brain Neoplasms; Cell Cycle; Cell division; Cell physiology; Cells; DNA; Genetic; Histologic; Lomustine; Loss of Heterozygosity; Malignant Glioma; Mediating; Methods; Microtubules; Morbidity - disease rate; Nitrosourea Compounds; Pathogenesis; Patients; Pharmaceutical Preparations; Primary Brain Neoplasms; Procarbazine; Proteins; Proteomics; Radiation; Reporting; Resistance; Role; Screening procedure; Vincristine; base; cell motility; chemotherapy; in vivo; migration; mortality; novel; oligodendroglioma; research study; stathmin; tumor

We previously reported that stathmin, a microtubule destabilizer required for the progression of cells through the cell cycle, also mediates the motility, migration, and invasion of malignant glioma cells. This was shown in experiments in which stathmin levels were experimentally increased or decreased with resulting changes in these cellular functions. We also demonstrated that nitrosoureas, DNA alkylating and protein carbamoylating drugs that inhibit stathmin and that are traditionally thought to inhibit only cell division, also inhibit motility, migration, and invasion. As invasion of surrounding brain by malignant glioma cells is one of the major causes of morbidity and mortality for patients with malignant glioma tumors, we have continued pursuing strategies to inhibit stathmin function in vivo, alone and in combination with nitrosourea therapy.

我们先前报道说，Stathmin是细胞通过细胞周期发展所需的微管衰减剂，还介导了恶性神经胶质瘤细胞的运动，迁移和侵袭。 这在实验中表明，在这些实验中，实验水平被实验增加或降低，导致这些细胞功能的变化。 我们还证明了硝基库，DNA烷基化和蛋白质氨基化药物，这些药物会抑制斯塔明蛋白，并且传统上被认为仅抑制细胞分裂，也抑制运动，迁移和侵袭。 由于恶性神经胶质瘤细胞对周围大脑的侵袭是恶性神经胶质瘤肿瘤患者发病率和死亡率的主要原因之一，因此我们继续采取策略以抑制体内，单独并与硝基含量结合使用硝基含量。