MOLECULAR BIOLOGY OF RETINOBLASTOMA AND UVEAL MELANOMA

视网膜母细胞瘤和葡萄膜黑色素瘤的分子生物学

• 批准号: 3256332
• 负责人: DANIEL M ALBERT
• 金额: $ 32.45万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-07-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3256332
• 关键词: athymic mouse; cell type; disease /disorder model; electron microscopy; eye neoplasms; gene expression; genetically modified animals; histopathology; immunocytochemistry; in situ hybridization; melanoma; metastasis; microscopy; molecular pathology; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplasm /cancer nutrition therapy; neoplasm /cancer radiation therapy; nucleic acid hybridization; oncogenes; polymerase chain reaction; recombinant DNA; retinoblastoma; scanning electron microscopy; tissue /cell culture; vitamin D; vitamin therapy; western blottings

This laboratory proposes to continue its morphological and molecular biological studies of retinoblastoma and uveal melanoma and interface them with new technologies made available through recombinant DNA research. Specifically we plan the following studies: 1. We will study a transgenic mouse that develops heritable retinoblastoma due to the genomic integration of a gene coding for SV40 large T antigen. The morphology, molecular biologic features, site of large T antigen integration, and elucidation of transgenic regulatory elements will be determined. These studies should reveal similarities an differences between murine tumor and human retinoblastoma and will establish the transgenic mouse model's concordance with the human condition. 2. In situ hybridization will be utilized to study expression of retinoblastoma gene in developing mature retina and other tissues. Variations of expression for different cell types will be investigated in order to define the histogenesis of retinoblastoma and the role of the Rb gene in differentiating tissue. 3. We will assay for oncogene activations in naturally occurring human uveal melanoma and correlate presence of oncogene activation with cell type and prognosis. In addition we have described the inhibition of retinoblastoma growth by vitamin D compounds and sodium butyrate and we will continue to study potential therapeutic strategies in the transgenic mouse model of retinoblastoma.

该实验室建议继续其形态学和分子 视网膜细胞瘤和紫veal黑色素瘤的生物学研究并将其接触 通过重组DNA研究提供了新技术。 具体而言，我们计划以下研究： 1。我们将研究一种发展可遗传性视网膜母细胞瘤的转基因小鼠 由于SV40大抗原的基因编码的基因组整合。 形态，分子生物学特征，大抗原的位点 转基因调节元件的整合和阐明将是 决定。 这些研究应揭示相似性有所不同 在鼠肿瘤和人视网膜细胞瘤之间，将建立 转基因小鼠模型与人类状况的一致性。 2。原位杂交将用于研究 视网膜母细胞瘤基因在发展成熟的视网膜和其他组织中。 将研究不同细胞类型的表达变化 为了定义视网膜细胞瘤的组织发生和RB的作用 分化组织中的基因。 3。我们将测定自然发生的人类的癌基因激活 卵巢黑色素瘤并与细胞类型相关的癌基因活化的存在 和预后。 此外，我们描述了视网膜细胞瘤生长的抑制 维生素D化合物和丁酸钠，我们将继续研究 转基因小鼠模型的潜在治疗策略 视网膜母细胞瘤。