| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1991: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1990: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Research Abstract |
Cell surface glycoconjugates are related to recognition, growth, and differentiation of cells, and changes in sugar cliains of these conjugates have been associated with malignant transformation. We analyzed biochemically the glycoconjugates in various organs of the female genital tract, and also developed new diagnostic methods for endometrial cancer by using a newly established monoclonal antibody directed against a certain glycoconjugate. The following results were obtained from our studies :
1.) The concentration of IV ^3NeuAc alpha-nLc_4Cer, a major ganglioside along with II ^3NeuAcLacCer (GM3) in human placental villi, was found to decrease gradually there during gestation, suggesting that this characteristic alteration might be related to the function of the villi.
2.) Sulfatide, one of tlie acidic glycolipids, was found in normal endometrial tissue, and its amount was larger in normal secretory endometrium than in the proliferative-phase type. In secretory endometrium, the cerami
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des of neutral glycolipids were shown to be hydroxylated. Sulfatide was also detected in endoinetrial cancer cells, and long-chain sugars and hydroxylated ceramides of neutral glycolipids were also found in well-differentiated endometrial cancers. In the cervical glands the composition of glycolipids was similar to that in the endometrium at the different phases of the menstrual cycle, but in the fallopian tubes sulfatide and hydroxylated ceramides were expressed uniformly throughout the cycle. These analyses revealed that the behavior of some endometrial glicolipids was influenced by the hormonal environment and by malignant transformation.
3.) We established MSN-1, monoclonal antibody that recognizes a Leb-related sugar moiety of glycolipids in endometrial cancer, and used it to develop new diagnostic methods for endometria cancer. Flow cytometric analysis and Endometrial Glycolipid Assay revealed that MSN-1 seldom reacted with normal endometrial cells but that it was reactive with about 70% of endometrial cancer specimens. By Endometrial Cell-EIA, in which endometrial cells obtained by Endocyte or Endosearch were used directly, similar results were noted. These methods detecting glycoconjugate changes associated with malignant transformation were considered useful in differentiating endometrial cancer from normal endometrium.
4.) CA54/61, determined in our laboratory to be a mucin-type sugar chain-related antigen like CA72-4 and sialil Tn (STN), was established as a novel tumor marker of ovarian cancer. The localization of A54/61 was compared with that of CA72-4 and STN immunohistochemically, and the results indicated that these three antigens were not the saine ones but were closely related. Also, their serum levels resembled each other. Less
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