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Specific inhibitors of hyaluronan (HA) biosynthesis can be valuable therapeutic agents to prevent cancer invasion and metastasis. We have found previously that 4-methylumbelliferone (MU) inhibits HA synthesis in human skin fibroblasts and in group C Streptococcus. In this paper, the inhibition mechanism in mammalian cells was investigated using rat 3Y1(More)
The structure of 4-methylumbelliferone (MU) consists of coumarin with 4-methyl group and 7-hydroxy group. MU inhibits HA synthesis and pericellular HA matrix formation. In this study, we used 10 MU derivatives which have hydroxy groups and methyl groups at various positions of coumarin to investigate a more effective HA inhibitor than MU. First, human(More)
The effects of xylosyl-beta-D-(4-methylumbelliferone) and its aglycone, 4-methylumbelliferone, on hyaluronic acid synthesis were investigated in cultured human skin fibroblasts. Xylosyl-beta-D-(4-methylumbelliferone) added to the medium of cultured cell reduced the synthesis of hyaluronic acid. Furthermore, 4-methylumbelliferone reduced the production of(More)
Oligosaccharides from hyaluronic acid and chondroitin 6-sulfate were prepared by digestion with testicular hyaluronidase and separated according to their degree of polymerization by gel-permeation chromatography. These materials were successively analyzed by negative-mode ion-spray mass spectrometry with an atmospheric-pressure ion source. An ion-spray(More)
Prognostic factors for breast cancer include axillary lymph node status, tumor size, histology, nuclear grade, presence of estrogen and progesterone receptors, HER2/neu status, and mean microvessel density (MVD). In this study, we evaluated the usefulness of a new marker, D2-40, by investigating lymph vascular invasion of the tumor immunohistochemically in(More)
4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver(More)
In the present study the complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein was determined. This protein whose biological function is unknown consists of a single polypeptide chain of 276 amino acid residues including 8 tryptophan residues and has a pyroglutamyl residue at the amino terminus. The location of the two disulfide bonds in the(More)
Hyaluronan (HA) is a ubiquitous, major component of the pericellular matrix and is necessary for various physiological processes. It plays a very important role in biological barriers. We previously reported that 4-methylumbelliferone (MU) inhibits HA synthesis and pericellular HA matrix formation in cultured human skin fibroblasts, Streptococcus equi(More)
Hyaluronan (HA) is a ubiquitous, major component of the extracellular matrix. It is involved in cell adhesion and locomotion, and hence in tumor metastasis. We have previously reported that 4-methylumbelliferone (MU) inhibits HA synthesis and may be a useful tool for examining the functions of HA. We here demonstrate that the formation of cell surface HA by(More)
The effects of progesterone, dehydroepiandrosterone sulfate and 17beta-estradiol on the synthesis and degradation of hyaluronate were investigated using human uterine cervix fibroblasts. The cells were incubated with [3H]glucosamine in the presence of the hormones and then [3H]hyaluronate was isolated from the medium. The changes in the radioactivity of(More)