Nagoya University · Medicine
Professor Yoshihiro Nishida's research lab focuses on the molecular mechanisms underlying extracellular matrix regulation in connective tissues and cancer progression, with a central emphasis on hyaluronan (HA) metabolism. The lab investigates the roles of hyaluronan synthases (HAS-1, HAS-2, HAS-3), HA turnover, and its interaction with receptors like CD44 in diseases such as osteoarthritis and breast cancer bone metastasis. Using molecular biology, NMR spectroscopy, and cell culture models, the lab explores how HA modulation affects tumorigenicity, matrix integrity, and tissue homeostasis. Recent work also examines pharmacological inhibition of HA synthesis as a therapeutic strategy, particularly using 4-methylumbelliferone in cancer and joint disorders.
Figures are computed from collected data and may differ slightly.
Abstract 1H NMR signals of H-6proR and H-6proS protons of D-glucoses and their per-O-acylated (acetyl and benzoyl) derivatives were unambiguously assigned by chiral deuteration at the C-6 position. The JH5,H-6proR and JH5,H-6proR values thus obtained enabled us to calculate the rotameric distributions of gg, gt and tg conformers. For the calculations, conventional equations (A and B) and novel equations accounting for possible departure of the three conformers from perfect staggering, were emplo
Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4-methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the pr
In order to define the role of cell-associated hyaluronan in cartilage matrix retention, human articular chondrocytes as well as cartilage slices were treated with phosphorothioate oligonucleotides comprised of sequence antisense to the mRNA of human HA synthase-2 (HAS-2). As a prerequisite for these studies, it was necessary to determine which HA synthase (HAS), of three separate human genes capable of synthesizing HA, designated HAS-1, HAS-2, or HAS-3, is primarily responsible for HA synthesis
OP-1 stimulates not only the synthesis of matrix macromolecules such as aggrecan, but also the synthesis of other molecules required for matrix retention, namely, HA and CD44.
These data demonstrate that IL-1alpha stimulates HAS-2 at the same time as it inhibits the expression of aggrecan. Although hyaluronan biosynthesis is up-regulated, so too is the expression of CD44 and the internalization/catabolism of hyaluronan. The net result is a loss of hyaluronan in areas of the articular cartilage where increases in CD44 expression are most prominent. This depletion of hyaluronan in the upper layers of the tissue likely facilitates the prominent loss of aggrecan from the
In pure myxoid liposarcoma located in the extremities and trunk wall, relatively few patients developed distant metastasis suggesting the tumor is generally low grade. Local control could be achieved with wide surgical margins without radiotherapy. Age was associated with lower survival but size and depth were not. Myxoid liposarcoma in older patients requires special consideration for treatment and followup.
[reaction: see text] A concept for the development of practical glycosylation is presented and demonstrated by one-pot alpha-glycosylation applying Appel agents for 2-O-benzyl-1-OH hexoses in DMF. The reaction, in situ giving the equilibrium of glycosyl bromides and more reactive O-glycoside intermediates, accomplishes a near-quantitative alpha-glycosylation removing the water molecules.
Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA-MB-231 cells. Based on the results of cell growth assay, we subsequently analyzed the effec
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