PubMed · 10778178
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T Kamigaki, Y Kuroda. 1999. [KMO1].. https://pubmed.ncbi.nlm.nih.gov/10778178/
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The first total synthesis of alpha-(2-->3)/alpha-(2-->6)-disialyl lactotetraosyl (DSLc4) ceramide and alpha-(2-->3)/alpha-(2-->6)-disialyl Lewis A (DSLe(a)) ganglioside as cancer-associated antigens is described. The suitably protected lactotriose (Lc3) derivatives were successively glycosylated with sialic acid, sialyl-alpha-(2-->3)-D-galactose and/or L-fucose donors in a regio- and stereo-selective manner, to give the protected type I hexa- and hepta-saccharides, respectively, which were then converted to the target gangliosides by the introduction of ceramide and subsequent complete deprotection.
The structure of the tetrameric Vicia villosa isolectin B4 (VVLB4) in complex with a cancer antigen, the Tn glycopeptide (GalNAc-O-Ser), was determined at 2.7 A resolution. The N-acetylgalactoside moiety of the ligand binds to the primary combining site of VVLB4 in a similar way as observed for other Gal/GalNAc-specific plant lectins. The amino acid moiety of the Tn antigen is largely exposed to the solvent and makes few contacts with the protein. The structure of the complex provides a framework to understand the differences in the strength of VVLB4 binding to different sugars and emphasizes the role of a single protein residue, Tyr127, as a structural determinant of Tn-binding specificity.
BACKGROUND: The prognosis of cancer patients with distant metastases is extremely poor. CASE: A 51-year-old Japanese woman with Stage IIIc serous cystoadenocarcinoma of the ovary achieved complete remission. At 30 and 39 months after the initiation of therapy, solitary brain and then spleen metastases without intraperitoneal lesions were found, respectively. A simultaneous elevation in tumor markers (CA125 and CA72-4) was noted at the spleen metastasis; however, only a marked elevation in CA 72-4 levels at the brain metastasis was noted. Immunohistochemical studies revealed that although CA125-positive cells could be observed in both the original tumor and the spleen metastasis, CA125-positive cells could not be observed in the brain metastasis and that CA72-4-positive cells could be observed in both the original ovarian tumor and the metastatic tumor. CONCLUSION: It is important to monitor with tumor markers with different characteristics, such as CA125 and CA72-4.