THE MOLECULAR BIOLOGY OF RETINOBLASTOMA

视网膜母细胞瘤的分子生物学

• 批准号: 6476290
• 负责人: DANIEL M ALBERT
• 金额: $ 32.4万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6476290
• 关键词: angiogenesis; eye neoplasms; genetically modified animals; laboratory mouse; melanoma; molecular oncology; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplasm /cancer remission /regression; nonhuman therapy evaluation; nutrition related tag; oncogenic virus; polymerase chain reaction; retinoblastoma; tumor antigens; vitamin D; vitamin D receptors; vitamin therapy

DESCRIPTION: (from abstract). The PI proposes to continue with studies regarding the molecular biology of retinoblastoma, focusing on the evaluation of chemotherapeutic and chemopreventative actions of vitamin D analogs (Specific Aim 1) and the identification of the mechanism of action of these compounds on retinoblastoma (Specific Aim 2). The subaims are: (I a) Determine the effectiveness and toxicity of Ia-hydroxyvitamin D2 (Ia-hydroxy-D2), and compare its potency and toxicity to 1,25-dihydroxy-16-ene-23-yne-vitarnin D3 (16,23-D3) in the treatment of transgenic and athvmic models of retinoblastoma. (Ib) Study the ability of these compounds to induce reduction tumor mass. (Ic) Compare the effectiveness of these analogs to standard chemotherapy used in the treatment of retinoblastoma and evaluate the effectiveness of vitamin D analogs as adjuvant therapy. (Id) Determine the effectiveness of these compounds on the midbrain tumors in "trilateral" retinoblastoma. (Ie) Evaluate the emergence of drug-resistant subpopulations of retinoblastoma cells. Subaims to Specific Aim 2 are: (2a) Study the relationship of vitamin D receptors to drug therapy effectiveness. (2b) Determine the mechanism by which cell proliferation arrest is mediated by vitamin D analogs with regard to cell cycle proliferation and cell death. (2c) Establish whether the mechanism of tumor growth arrest is regulated by p53 -dependent gene expression. (2d) Determine whether I a-hydroxy-D2 and 16,23 -D3 inhibit angiogenesis in a transgenic mouse model. These studies will complete the pre-clinical investigation of the efficacy of vitamin D analogs for human treatment.

描述：（来自摘要）。 PI建议继续研究有关分子生物学的研究 视网膜细胞瘤，重点是评估化学治疗和 维生素D类似物的化学预防作用（特定目标1）和 鉴定这些化合物对视网膜细胞瘤的作用机理 （特定目标2）。 Subiaim是：（i a）确定有效性和 IA-羟基维生素D2（IA-Hydroxy-D2）的毒性，并比较其效力和 毒性对16-二氢-16-Ene-23-enne-vitarnin D3（16,23-D3）的毒性 视网膜母细胞瘤的转基因和ATHVMIC模型的处理。 （IB）研究 这些化合物诱导减少肿瘤质量的能力。 （IC）比较 这些类似于治疗中使用的标准化疗的有效性 视网膜细胞瘤并评估维生素D类似物的有效性 辅助治疗。 （id）确定这些化合物在 “三侧”视网膜母细胞瘤中的中脑肿瘤。 （即）评估 视网膜细胞细胞的药物耐药亚群。特定目标 2是：（2a）研究维生素D受体与药物治疗的关系 效力。 （2b）确定细胞增殖停滞的机制 是由维生素D类似物介导的，与细胞周期增殖和 细胞死亡。 （2C）确定肿瘤生长停滞的机制是否为 受p53依赖性基因表达调控。 （2d）确定我是否 A-羟基-D2和16,23 -D3在转基因小鼠模型中抑制血管生成。 这些研究将完成临床前研究的疗效 维生素D类似物用于人类治疗。