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Glycosphingolipids of various human ovarian tumors

各种人卵巢肿瘤的鞘糖脂

基本信息

批准号：
03807109
负责人：
KIGUCHI Kazushige
金额：
$ 1.22万
依托单位：
Keio University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

1. Glycosphingolipids (GSLs) of Various Human Ovarian Tumors:Among the human ovarian tumors, mucinous cystadenocarcinoma, serous cystadenocarcinoma, and clear cell adenocarcinoma, the mucinous cystadenocarcinoma showed a unique GSL composition. More than 90% of the acidic GSL in the mucinous cystadenocarcinoma was comprised of sulfolipids, rarely detected in normal ovary and found in concentrations of less than 40% in the other types of ovarian tumors. By means of negative ion fast atom bombardment mass spectrometry (FABMS) and gas-liquid chromatography(GLC), the major sulfolipid in mucinous cystadenocarcinoma was confirmed as I^3SO_3-GalCer with N-cerebronyl phytosphingosine, rather than I^3SO_3-GalCer with N-nonhydroxy fatty acyl sphingosine, the major molecular species in the other ovarian cancers.2. a Monoclonal Antibody, MRG-1:A murine monoclonal antibody, MRG-1, established by immunizing mouse with human ovarian carcinoma-derived cells, reacted preferentially with the cells' Golgi complexes and microsome fractions, but not with the plasma membranes, whereas the antigen was distributed in the intercellular matrix of normal human cervical epithelium. The antigen was identified as neutral GSLs with blood group A-determinant by TLC-immunostaining. Using FABMS and NMR, the structure was found to be ceramide-Glc4-Gal3-GlcNAc4-Gal(2-Fuc)3-GalNAc3-Gal(2-Fuc)3-GalNAc, type IIIA GSLs.3. Galactosyltransferase Associated with Tumor (GAT):GAT was studied clinically in ovarian cancer patients. The GAT positive rate for different histologic types of ovarian carcinoma was relatively high for each type, e. g., 55.0% for clear cell carcinoma and 66.7% for endometrioid adenocarcinoma. In patients with benign diseases, in particular endometriosis, the GAT positive rate was lower than the positive rate with any other simultaneously definite markers. These results indicate the usefulness of GAT in distinguishing malignant from benign ovarian tumors.

1.各种人卵巢肿瘤的鞘糖脂（GSL）：在人卵巢肿瘤、粘液性囊腺癌、浆液性囊腺癌和透明细胞腺癌中，粘液性囊腺癌显示出独特的GSL组成。粘液性囊腺癌中90%以上的酸性GSL由硫脂组成，在正常卵巢中很少检测到，在其他类型的卵巢肿瘤中浓度低于40%。通过负离子快原子轰击质谱（FABMS）和气液色谱（GLC）分析，证实粘液性囊腺癌中主要的硫脂分子是I^3SO_3-GalCer和N-脑酰基植物鞘氨醇，而不是其他卵巢癌中主要的I^3SO_3-GalCer和N-非羟基脂肪酰基鞘氨醇. a单克隆抗体MRG-1：通过用人卵巢癌衍生细胞免疫小鼠而建立的鼠单克隆抗体MRG-1，优先与细胞的高尔基复合体和微粒体组分反应，但不与质膜反应，而抗原分布在正常人宫颈上皮的细胞间基质中。经薄层层析免疫组化鉴定，该抗原为中性GSL，具有A血型决定簇。使用FABMS和NMR，发现结构为神经酰胺-Glc 4-Gal 3-GlcNAc 4-Gal（2-Fuc）3-GalNAc 3-Gal（2-Fuc）3-GalNAc，IIIA型GSL。与肿瘤相关的半乳糖基转移酶（GAT）：对卵巢癌患者进行了GAT的临床研究。不同组织学类型的卵巢癌GAT阳性率均较高，其中卵巢癌GAT阳性率最高。例如，在一个实施例中，透明细胞癌55.0%，类囊腺癌66.7%。在良性疾病，特别是子宫内膜异位症患者中，GAT阳性率低于任何其他同时确定的标志物的阳性率。这些结果表明GAT在鉴别卵巢肿瘤的良恶性方面是有用的。