Improving Phenylbutyrate-based Anticancer Therapy

改善基于丁酸苯酯的抗癌疗法

• 批准号: 6937639
• 负责人: ASHOK S BHAGWAT
• 金额: $ 3.36万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937639
• 关键词: antineoplastics; apoptosis; athymic mouse; bioluminescence; cell cycle; glioma; molecular /cellular imaging; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; nonhuman therapy evaluation; oncoprotein p21; phenylbutyrates; radiation sensitivity; radiosensitizer; small interfering RNA; tissue /cell culture

DESCRIPTION (provided by applicant): The long-term goal of this work is to develop novel anticancer therapies that utilize inhibitors of histone deacetylases (HDACs) to sensitize tumors to anticancer treatments. Inhibition of HDACs results in chromatin remodeling and alteration of expression of several genes. HDAC inhibitor phenylbutyrate (PB) has been shown to sensitize glioma cells to ionizing radiation. A principal problem in this approach to chemotherapy is that PB treatment induces a G1 block that reduces the number of cells susceptible to radiation. I propose to use siRNA specific for p21 to release the G1 block and to test the cells in culture for sensitivity towards ionizing radiation as well chemotherapeutic agents. The goal of this work is to find an optimal combination therapy involving PB that is effective against gliomas. In the second part of this work, I will use a bioluminescence imaging system available at the University of Michigan to monitor tumors in live mice as they undergo apoptosis or undergo G1 arrest. This work will create the tools necessary for the monitoring of tumor cells in live animals when they are treated with PB as part of combination chemotherapy.

描述（由申请人提供）：这项工作的长期目标是开发使用组蛋白脱乙酰基酶（HDACS）抑制剂的新型抗癌疗法，以使肿瘤对抗癌治疗敏感。 HDAC的抑制作用会导致几种基因表达的染色质重塑和改变。 HDAC抑制剂苯丁酸（Pb）已显示可使神经胶质瘤细胞对电离辐射敏感。这种化学疗法方法的主要问题是，PB处理诱导了G1块，从而减少了容易受到辐射的细胞数量。我建议使用针对p21的siRNA释放G1块并测试培养物中的细胞，以使其对电离辐射以及化学治疗剂的敏感性。这项工作的目的是找到一种有效抗神经胶质瘤的PB的最佳组合疗法。在这项工作的第二部分中，我将使用密歇根大学使用的生物发光成像系统来监测活小鼠的肿瘤，因为它们会发生凋亡或经历G1停止。这项工作将创造出用PB治疗的作为组合化疗的一部分，以监测活动物中肿瘤细胞的必要工具。