MATRIX-ATTACHMENT THERAPY: A STRATEGY TO DELIVER 5-FLUOROURACIL TO TUMOR

基质附着疗法：向肿瘤输送 5-氟尿嘧啶的策略

• 批准号: 7955488
• 负责人: FRANCIS C. SZOKA
• 金额: $ 0.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955488
• 关键词: Binding; Body Fluids; Breast; CD44 Antigens; CD44 gene; Chimera organism; Chimeric Proteins; Computer Graphics; Computer Retrieval of Information on Scientific Projects Database; Cytosine deaminase; Extracellular Matrix; Flucytosine; Fluorouracil; Funding; Glioblastoma; Glycosaminoglycans; Grant; Hyaluronan; Imagery; Informatics; Institution; Laboratories; Link; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Normal tissue morphology; Ovary; Research; Research Personnel; Resources; Sequence Analysis; Source; Structure; United States National Institutes of Health; Vertebrates; Yeasts; biocomputing; cancer cell; improved; melanoma; tool; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hyaluronan is a ubiquitous glycosaminoglycan found in all tissues and body fluids of vertebrates. The basal levels of HA is low in normal tissues, but elevated levels of hyaluronan are found in various malignant tumors, including melanoma, ovaries, breast, glioblastoma, and bladder cancer cells. CD44 and TSG-6 are two hyaluronan binding proteins that are well characterized, both functionally and structurally. We are creating fusion proteins that contain the hyaluronan binding domain (also known as the Link domain) from either CD44 or TSG-6 and yeast cytosine deaminase (yCD). Our hypothesis is that the fusion protein Link-yCD will bind to hyaluronan in the extracellular matrix and covert the orally available 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). We believe this will create a chemotherapeutic fence around the tumor and improve antitumor therapy. Currently, we use various sequence analysis tools that are available from the Computer Graphics Laboratory and we plan to use Chimera to visualize the structures of functional domains for modified fusion proteins.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 透明质酸是一种普遍存在于脊椎动物所有组织和体液中的糖胺聚糖。 正常组织中透明质酸的基础水平较低，但在各种恶性肿瘤中发现透明质酸水平升高，包括黑色素瘤、卵巢癌、乳腺癌、胶质母细胞瘤和膀胱癌细胞。 CD44 和 TSG-6 是两种透明质酸结合蛋白，其功能和结构均已得到充分表征。 我们正在创建包含来自 CD44 或 TSG-6 和酵母胞嘧啶脱氨酶 (yCD) 的透明质酸结合域（也称为 Link 域）的融合蛋白。 我们的假设是融合蛋白 Link-yCD 将与细胞外基质中的透明质酸结合，并将口服可用的 5-氟胞嘧啶 (5-FC) 转化为 5-氟尿嘧啶 (5-FU)。 我们相信这将在肿瘤周围建立化疗围栏并改善抗肿瘤治疗。 目前，我们使用计算机图形实验室提供的各种序列分析工具，并计划使用 Chimera 来可视化修饰融合蛋白的功能域结构。