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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 Hybryonan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透明质酸水平升高，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和TSG-6是两种透明质酸结合蛋白，其在功能和结构上都被充分表征。 我们正在创建包含来自CD 44或TSG-6的透明质酸结合结构域（也称为连接结构域）和酵母胞嘧啶脱氨酶（yCD）的融合蛋白。 我们的假设是融合蛋白Link-yCD将结合细胞外基质中的透明质酸，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 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.