名古屋大学 · 医学
Nishida教授の研究室は、糖鎖の立体化学的特徴とその生物学的機能の解明を柱としており、特にグルコース誘導体のNMR的解析を通じて糖鎖の立体障害的配座の定量的評価を進めています。また、ヒアルロンアン(HA)の代謝制御ががんの転移や関節石灰化に与える影響を、細胞・動物モデルを用いて解明しており、HA合成阻害剤の治療的応用可能性にも注力しています。主な研究対象は、がん細胞におけるHAの役割と、関節形成におけるマトリックス保持機構の分子メカニズムです。
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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