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.
By proteins detected in the blood of people with a diagnosis of liver cancer contain the sugar, fucose. Understanding why will help in the development of new diagnostic methods, as well as provide clues for development of new therapies.
|Thio, Chloe L; Smeaton, Laura; Hollabaugh, Kimberly et al. (2015) Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks. AIDS 29:1173-82|
|Safaie, Parham; Ham, Maggie; Kuang, Peter et al. (2013) Lectin-reactive anti-?-gal in patients with Crohn's disease: correlation with clinical phenotypes. Inflamm Bowel Dis 19:2796-800|
|Block, Timothy M; Gish, Robert; Guo, Haitao et al. (2013) Chronic hepatitis B: what should be the goal for new therapies? Antiviral Res 98:27-34|
|Thio, Chloe L; Smeaton, Laura; Saulynas, Melissa et al. (2013) Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS 27:191-201|
|Evans, Alison A; London, W Thomas; Gish, Robert G et al. (2013) Chronic HBV infection outside treatment guidelines: is treatment needed? Antivir Ther 18:229-35|
|Parikh, Nirzari; Nonnemacher, Michael R; Pirrone, Vanessa et al. (2012) Substance abuse, HIV-1 and hepatitis. Curr HIV Res 10:557-71|
|Mehta, Anand; Norton, Pamela; Liang, Hongyan et al. (2012) Increased levels of tetra-antennary N-linked glycan but not core fucosylation are associated with hepatocellular carcinoma tissue. Cancer Epidemiol Biomarkers Prev 21:925-33|
|Liang, Hongyan; Block, Timothy M; Wang, Mengjun et al. (2012) Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73. Cancer Biomark 11:161-71|
|Nie, Hui; Evans, Alison A; London, W Thomas et al. (2012) Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion. J Hepatol 56:795-802|
|Jain, Surbhi; Chang, Ting-Tsung; Hamilton, James P et al. (2011) Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma. PLoS One 6:e26799|
Showing the most recent 10 out of 16 publications