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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。透明质酸（HA）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HA的基础水平较低，但在各种恶性肿瘤中发现HA水平升高，包括黑素瘤、卵巢癌、乳腺癌、胶质母细胞瘤和膀胱癌细胞。CD 44大分子是一种膜蛋白，可通过其胞外结构域与透明质酸结合。我们正在创建一个融合蛋白之间的细胞外结构域的CD 44和胞嘧啶脱氨酶。我们的假设是，融合蛋白将结合HA的细胞外基质和转化的口服可用的5-氟胞嘧啶5-氟尿嘧啶。我们相信这将在肿瘤周围建立一个化疗围栏，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，我们计划使用嵌合体来可视化修饰融合蛋白的功能结构域的结构。

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 (HA) 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 HA are found in various malignant tumors, including melanoma, ovaries, breast, glioblastoma, and bladder cancer cells. The CD44 macromolecule is a membrane protein that can bind to hyaluronan via its extraceullar domain. We are creating a fusion protein between the extracellular domain of CD44 and cytosine deaminase. Our hypothesis is that the fusion protein will bind to HA in the extracellular matrix and covert the orally available 5-fluorocytosine to 5-fluorouracil. 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.