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新的抗癌疗法，利用组蛋白脱乙酰酶（HDAC）抑制剂使肿瘤对抗癌治疗敏感。 HDAC 的抑制会导致染色质重塑和多个基因表达的改变。 HDAC 抑制剂苯丁酸 (PB) 已被证明可使神经胶质瘤细胞对电离辐射敏感。这种化疗方法的一个主要问题是 PB 治疗会诱导 G1 阻滞，从而减少对辐射敏感的细胞数量。我建议使用 p21 特异性的 siRNA 来释放 G1 阻滞，并测试培养中的细胞对电离辐射以及化疗药物的敏感性。这项工作的目标是找到一种有效对抗神经胶质瘤的 PB 最佳联合疗法。在这项工作的第二部分中，我将使用密歇根大学提供的生物发光成像系统来监测活体小鼠体内发生细胞凋亡或 G1 期停滞时的肿瘤。这项工作将创建必要的工具，用于监测活体动物在接受 PB 作为联合化疗的一部分时的肿瘤细胞。