Blood group substances as potential therapeutic agents for the prevention and treatment of infection with noroviruses proving novel binding patterns in human tissues.

Blood group-related glycans determining ABO and Lewis blood groups are known to function as attachment factors for most of the norovirus (NoV) strains. To identify binding specificity of each NoV, recombinant norovirus-like particles (VLPs) and human saliva samples with different ABO, Lewis phenotypes and secretor status have been commonly applied. When binding specificities of VLPs prepared from 16 different genotypes of NoVs in GI and GII genogroups were characterized in samples of human gastric mucosa compared to human saliva based on blood group phenotypes, considerable differences were observed for several strains.

Development of a novel system for mass spectrometric analysis of cancer-associated fucosylation in plasma α1-acid glycoprotein.

Human plasma α1-acid glycoprotein (AGP) from cancer patients and healthy volunteers was purified by sequential application of ion-exchange columns, and N-linked glycans enzymatically released from AGP were labeled and applied to a mass spectrometer. Additionally, a novel software system for use in combination with a mass spectrometer to determine N-linked glycans in AGP was developed. A database with 607 glycans including 453 different glycan structures that were theoretically predicted to be present in AGP was prepared for designing the software called AGPAS.

Novel sugar-cholestanols as anticancer agents against peritoneal dissemination of tumor cells.

Chemically synthesized sugar-cholestanols with mono-, di-, and tri-saccharides attached to cholestanol showed strong inhibiting activity against the proliferation of colorectal and gastric cancer cells. In contrast, cholestanol without sugar moieties was totally ineffective. Furthermore, when cancer cells were exposed to GlcNAcRbetacholestanol (R=(-) or beta1-3Gal), the compound was rapidly taken up via the lipid rafts/microdomains on the cell surface.

Chemically synthesized sugar-cholestanols possess a preferential anticancer activity involving promising therapeutic potential against human esophageal cancer.

The understanding of the cell signaling pathways and the molecular events leading to cell death of cancer cells will provide in-depth perspective into the identification and development of potent anticancer agents. A balance between cell proliferation and cell death has been raised as a rational target for the management of malignant tumors. In the present study, the authors demonstrated that chemically synthesized sugar-cholestanols consisting of GlcNAcbeta-, Galbeta- and GlcNAcbeta1,3Galbeta-cholestanols exerted a strong inhibiting activity against cell proliferation of esophageal cancer cells, but cholestanol itself did not show such an activity against the same cancer cells at all.

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis.

Background: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains.

Methods: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody.

Tumor-related expression of alpha1,2fucosylated antigens on colorectal carcinoma cells and its suppression by cell-mediated priming using sugar acceptors for alpha1,2fucosyltransferase.

The accumulation of alpha1,2fucosylated antigens, such as Y (Fucalpha1,2Galbeta1,4 [Fucalpha1,3]GlcNAcbeta), Le(b) (Fucalpha1,2Galbeta1,3-[Fucalpha1,4]GlcNAcbeta), and H type 2 (Fucalpha1,2 Galbeta1,4GlcNAcbeta) occurs specifically within human colorectal tumor tissues and can be detected by an antifucosylated antigen antibody, such as the YB-2 antibody. In the present investigation, we found that the expression of these antigens bearing an alpha1,2-linked fucose correlated with the resistance of the tumor cells to anticancer treatments. Addition of an exogenous sugar acceptor for alpha1,2fucosyltransferase to the cell medium resulted in suppression of alpha1,2fucosylated antigen expression on the tumor cells and increased susceptibility to anticancer treatment.