Improved Ophthalmic Care for Retinoblastoma Patients

改善视网膜母细胞瘤患者的眼科护理

• 批准号: 6910647
• 负责人: JOAN M O'BRIEN
• 金额: $ 34.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910647
• 关键词: FK506; SDS polyacrylamide gel electrophoresis; antiviral agents; clinical research; cyclosporines; diagnosis design /evaluation; diagnosis quality /standard; drug screening /evaluation; early diagnosis; family genetics; gene mutation; genetic screening; human genetic material tag; human subject; immunoprecipitation; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplasm /cancer genetics; patient care management; pediatric neoplasm /cancer; polymerase chain reaction; prognosis; rapid diagnosis; retinoblastoma; retinoids; temozolomide

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to improve ophthalmic care for patients with a pediatric ocular tumor, retinoblastoma (RB). We propose to provide rapid diagnosis and improved prognosis for patients with heritable ocular RB through improved genetic testing, and to innovate more effective and less toxic therapies for this ophthalmic disease.In pursuit of these objectives, two specific aims are proposed. These are: I. To develop and validate a protein truncation test (PTT) for detection of germline retinoblastoma gene (RB1) mutations and to determine whether mutation analysis can be used to predict ocular disease expression.This aim will be accomplished in 3 stages. We propose to: A. Develop PTT. B. Perform focused DNA sequencing to characterize RB1 mutations detected by PTT. C. Determine whether mutation analysis can be used to predict ocular disease expression .II. To determine the potential clinical utility of selected new pharmacologic agents in RB. These are: A. Cyclosporin A, and two potential alternatives, PSC-833 and FK506. B. Retinoids, including all-trans retinoic acid, ALRT1550, AM80, fenretinide, Targretin, 9-cis retinoic acid, and 13-cis retinoic acid.C. The alkylating agent, temozolomide. D. The blood-brain barrier permeabilizer, RMP-7 (Cereport).E. The tumor-specific viral agents, ONYX-015 and ONYX-RB1.These agents are chosen for their relatively low toxicity and potential efficacy in the management of this ocular tumor. These agents also have potential utility in the management of other ophthalmic disorders.

描述（由申请人提供）：该提案的长期目标是改善小儿眼部肿瘤视网膜母细胞瘤（RB）患者的眼科护理。我们建议通过改进基因检测为遗传性眼部 RB 患者提供快速诊断和改善预后，并为这种眼科疾病创新更有效、毒性更低的疗法。为了实现这些目标，提出了两个具体目标。这些是： I.开发和验证用于检测种系视网膜母细胞瘤基因（RB1）突变的蛋白质截断测试（PTT），并确定突变分析是否可用于预测眼部疾病的表达。该目标将分三个阶段完成。我们建议： A、发展PTT。 B. 进行重点 DNA 测序以表征 PTT 检测到的 RB1 突变。 C. 确定突变分析是否可用于预测眼部疾病的表达。确定所选新药物在 RB 中的潜在临床效用。它们是：A. 环孢菌素 A，以及两种潜在的替代品：PSC-833 和 FK506。 B.类视黄酸，包括全反式视黄酸、ALRT1550、AM80、芬维A胺、塔格雷汀、9-顺式视黄酸和13-顺式视黄酸。烷化剂，替莫唑胺。 D. 血脑屏障透化剂，RMP-7 (Cereport)。肿瘤特异性病毒制剂 ONYX-015 和 ONYX-RB1。选择这些制剂是因为它们的毒性相对较低，并且在治疗眼部肿瘤方面具有潜在功效。这些药物在治疗其他眼科疾病方面也具有潜在的用途。