GLYCOCONJUGATES IN PANCREATIC CANCER

胰腺癌中的糖结合物

基本信息

批准号：
3166390
负责人：
YOUNG S KIM
金额：
$ 12.46万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-01-01 至 1992-12-31
项目状态：
已结题

项目摘要

Early diagnosis of pancreatic cancer is important for increasing survival from this rapidly fatal disease. Promising immunossays for detection of pancreatic cancer recognize pancreatic cancer- associated mucins in serum. A monoclonal antibody that compares favorably in sensitivity and specificity to the available immunoassays, 19-9 and DU-PAN-2, has recently been developed in this laboratory. The pancreatic cancer mucin recognized by this antibody has also been purified from xenografts of the SW- 1990 pancreatic cancer cell line and characterized to a considerable extent. We propose to use the purified mucin to generate antibodies with increased specificity for different components of the mucin molecule and to further characterize the antibodies already produced. We also plan to isolate and characterize, by mass spectrometry, purified oligosaccharides from pancreatic mucin. Since little is known about the polypeptide sequence of pancreatic or other mucins, the purified mucin will be deglycosylated and used to obtain protein-specific antibodies and partial peptide sequences. This will be used to identify cDNA for pancreatic mucin, which should allow complete characterization of the mucin protein. Because the mechanisms that result in the appearance of pancreatic cancer mucin in serum are poorly understood, the biosynthesis, processing, and secretion of mucin in cultured pancreatic cancer cells will be investigated using metabolic labeling, mucin-specific antibodies, and cDNA probes. The availability of a cultured cell system, of a panel of mucin-specific antibodies, and of a continued source of purified mucin gives the opportunity to elucidate the immunochemistry, structure and molecular biology of pancreatic cancer mucin. These studies should prove useful in increasing our understanding of the biochemistry of pancreatic cancer cells and especially in improving the available diagnostic tools for detection of pancreatic cancer.

胰腺癌的早期诊断对于提高胰腺癌的治疗率非常重要从这种迅速致命的疾病中生存下来。有前途的免疫分析用于检测胰腺癌识别胰腺癌- 血清中相关粘蛋白。一种单克隆抗体与现有技术相比，其灵敏度和特异性均优于现有技术最近开发了免疫测定法 19-9 和 DU-PAN-2 在这个实验室里。胰腺癌粘蛋白被该抗体也已从 SW- 的异种移植物中纯化出来。 1990 胰腺癌细胞系并被鉴定为相当大的程度。我们建议使用纯化的粘蛋白产生针对不同类型具有更高特异性的抗体粘蛋白分子的成分并进一步表征已经产生的抗体。我们还计划隔离并通过质谱分析表征纯化的寡糖来自胰腺粘蛋白。由于人们对此知之甚少胰腺或其他粘蛋白的多肽序列，纯化的粘蛋白将被去糖基化并用于获得蛋白质特异性抗体和部分肽序列。这将用于鉴定胰腺粘蛋白的 cDNA，这应该允许完整的粘蛋白的表征。因为机制导致血清中出现胰腺癌粘蛋白对生物合成、加工和分泌知之甚少将研究培养的胰腺癌细胞中的粘蛋白使用代谢标记、粘蛋白特异性抗体和 cDNA 探针。培养细胞系统、一组细胞的可用性粘蛋白特异性抗体，以及纯化的持续来源粘蛋白提供了阐明免疫化学的机会，胰腺癌粘蛋白的结构和分子生物学。这些研究应该有助于增加我们的理解胰腺癌细胞的生物化学，特别是改进可用的诊断工具来检测胰腺癌。