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糖タンパク質糖鎖の癌性変化とその臨床への応用

糖蛋白糖链的癌变及其临床应用

基本信息

批准号：
62614509
负责人：
木幡陽
金额：
$ 9.6万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
1987
资助国家：
日本
起止时间：
1987 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62614509/
关键词：
糖タンパク質糖鎖がん腫瘍マーカー hCG アルカリホスファターゼ CEA

项目摘要

1)絨毛性性腺刺激ホルモン(hcG)糖鎖の癌性変化の臨床応用破壊奇胎患者の尿から精製したhcGが絨毛癌hcGで発見された5種の異常糖鎖のうち3種をもっているが, 2種の異常2本鎖を一切含んでいないこと, 又糖鎖は常にシアル酸を含んでいることを発見した. この知見はhcG糖鎖の癌性変化がGlcNACβ1→4Man残基を作り出すN-アセチルグルコサミン転移酵素IVの異所性発現とその基質特異性変化の二段階によって起ること, この酵素の異所性発現が起っている異常破壊奇胎は明日に前癌状態にあると結論されることを意味している. これらhcG糖鎖の癌性変化を検出する目的で, 広く各種の市販不溶化レクチンカラムを用いた探索研究を進めた結果, シロバナチヨウセンアサガオのレクチン(DSA)が破壊奇胎と絨毛癌のhcGに共通に含まれるGal_<β1>→4GlcNAc_<β1>4(Gal_<β1>→4GlcNA_<cβ1>→2)Manという5糖残基を持った小糖群と, これを持たない小糖群を区別する上で有効に使えることを発見した. そこでDSA-セファロースカラムに患者尿を通してELISAでhcGをモニターした結果, 健常妊婦並びに胞状奇胎患者のhcGはシアリダーゼ処理の有無に関係なくカラムを素通りするのに対し, 破壊奇胎患者のhcGはシアリダーゼ処理後にのみカラムに結合すること, 絨毛癌患者のhcGは一部そのままでもカラムに結合するが, シアリダーゼ処理後には全てカラムに結合するようになることを見出した. この方法は従来不可能であったhcGによる絨毛性疾患の判別診断を可能にするものなので, 更に臨床検査室でも使えるようにAssay法の簡便化を急いでいる.2)CEA関連正常抗原の糖鎖構造の解析NCA-2に続いてNFA-2の糖鎖構造の解析を進めた結果, 同抗原には前者と同様Galβ1→3GlcNAcを母核にする糖鎖が多く含まれ, これを利用したCEAとの判別法開発の見通しが出て来た.

1)5 kinds of abnormal glycogen lockers were found in urine of patients with chorionic gonadal stimulation (hcG), 3 kinds of abnormal glycogen lockers were found in urine, 2 kinds of abnormal glycogen lockers were found in urine of patients with chorionic gonadal stimulation (hcG), 3 kinds of abnormal glycogen lockers were found in urine, 2 kinds of abnormal glycogen lockers were found in urine of patients with chorionic gonadal stimulation (hcG), 3 kinds of abnormal glycogen lockers were found in urine, 2 kinds of abnormal glycogen lockers were found in urine of patients with chorionic gonadal stimulation (hcG), 3 kinds of abnormal glycogen lockers were found in urine, 2 kinds of abnormal glycogen lockers were found in urine of patients with chorionic gonadal stimulation (hcG), 3 kinds of abnormal glycogen lockers were found in urine, 3 kinds of abnormal glycogen lockers were found in urine, 2 kinds of abnormal glycogen lockers were found in urine, 3 kinds of abnormal glycogen lockers were found in urine, 3 kinds of abnormal glycogen lockers were found in The results showed that the oncogenic transformation of hcG glycolate lock was caused by GlcNAC β 1 → 4 Man residues, and the heterogeneic development of N-terminal-isoenzyme IV and the two-stage heterogeneic transformation of stroma specific transformation were caused by the heterogeneic development of this enzyme. The purpose of this study is to explore the application of various market insolubles in the detection of carcinogenesis of hcG. The results of this study are as follows: Gal <β 1> → 4GlcNAc <β 1> 4 (Gal_<β 1> → 4GlcNA_<c β 1> → 2) Man_(5) sugar residues are maintained in small sugar groups. The results of the DSA-10 ELISA showed that hcG in normal pregnant women and patients with choriocarcinoma had no relationship with the treatment. The results showed that hcG in patients with choriocarcinoma had no relationship with the treatment. All right. 2) Analysis of the glycan lock structure of CEA associated normal antigen NCA-2 and NFA-2. The results showed that the glycan lock structure of CEA associated normal antigen Gal β 1 → 3GlcNAc contained many glycan locks. The method of CEA discrimination was used to open up the possibility of discovery.