Liver Cancer and the Role of Protein Hyper-Fucosylation

肝癌和蛋白质高岩藻糖基化的作用

• 批准号: 9011170
• 负责人: Timothy M Block
• 金额: $ 0.62万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-19 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9011170
• 关键词: Liver; Cancer; Role; Protein; Hyper

DESCRIPTION (provided by applicant): This is a re-submission of a proposal to gain an understanding about the nature of the hyper-fucosylation of glycoproteins associated with primary human hepatocellular carcinoma (HCC). Compared to healthy individuals, the circulation of people with HCC contains an abundance of glycoproteins with fucosylation at their N-glycan cores. Little is known about why this modification is so elevated, if it relates to protein function and/or plays a role in disease. There is even uncertainty about whether or not it is the cancer cells that are producing the fucosylated glycoforms. This modified application will systematically determine which cells are producing three "sentinel" hyper-fucosylated glycoproteins, as well as the functional consequences of fucosylation, in comparative studies with fucosylated and unfucosylated glycoforms. The proteins hemopexin, kininogen and GP73, each determined to correlate in the fucosylated glycoform with HCC, are chosen to represent different categories. In doing this, the important hypothesis that fucosylation plays a role in directing the sorting of hepatocytes glycoproteins will also be tested. The results of this work are thus intended to answer the fundamental question as to why fucosylation seems to be a common feature in HCC and help in developing early detection and possibly therapeutic interventions.

描述（由申请人提供）：这是一项提议的重新提出，以了解与原代人肝细胞癌（HCC）相关的糖蛋白过度凝血蛋白的性质。与健康的个体相比，HCC患者的循环含有大量的糖蛋白在其N-聚糖核心处具有诱导化的糖蛋白。如果这种修饰与蛋白质功能相关和/或在疾病中起作用，那么对于为什么这种修饰如此之高的知识知之甚少。甚至是癌细胞是否产生构造糖基化的糖型，甚至存在不确定性。这种修饰的应用将系统地确定哪些细胞在与葡萄糖基化和不降糖基化的糖基型的比较研究中，在比较研究中，将产生三个“前哨”过度关糖基化的糖蛋白以及岩藻糖基化的功能后果。蛋白质蛋白质，依诺原和GP73确定在岩藻糖基化的糖基中与HCC相关，以代表不同的类别。在此过程中，还将测试岩藻糖基化在指导肝细胞分类糖蛋白方面起作用的重要假设。因此，这项工作的结果旨在回答有关为什么岩藻糖基化似乎是HCC中的一个常见特征，并有助于开发早期检测和可能的治疗干预措施。

项目成果

Is chronic hepatitis B being undertreated in the United States?

• DOI: 10.1111/j.1365-2893.2010.01401.x
• 发表时间: 2011-06-01
• 期刊: JOURNAL OF VIRAL HEPATITIS
• 影响因子: 2.5
• 作者: Cohen, C.;Holmberg, S. D.;Block, T. M.
• 通讯作者: Block, T. M.

Chronic hepatitis B: what should be the goal for new therapies?

• DOI: 10.1016/j.antiviral.2013.01.006
• 发表时间: 2013-04
• 期刊: ANTIVIRAL RESEARCH
• 影响因子: 7.6
• 作者: Block, Timothy M.;Gish, Robert;Guo, Haitao;Mehta, Anand;Cuconati, Andrea;London, W. Thomas;Guo, Ju-Tao
• 通讯作者: Guo, Ju-Tao