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V P Skipski

Publications and source records attributed to V P Skipski.

At least 19 recordsLinked to original sources

Ganglioside profiles of metastases and of metastasizing and nonmetastasizing rat primary mammary carcinomas.

The possible relationship between ganglioside levels and ganglioside profiles in malignant tumors and the formation of metastasis was investigated by the analysis of gangliosides in metastasizing SMT-2A and nonmetastasizing MT-W9a mammary carcinomas as well as in metastases formed from SMT-2A tumors. The extracted lipid of SMT-2A tumors contained 3.3-fold more lipid-bound sialic acid than did that of MT-W9a tumors. THe differences were also substantial in the ganglioside profiles in these 2 tumors. Plasma membranes isolated from SMT-2A tumors also contained 1.8-fold more lipid-bound sialic acid than did plasma membranes from MT-W9a tumors. Ganglioside profiles in two types of SMT-2A secondary tumors were investigated. The lipid-bound sialic acid content was 1.5-fold higher in tumor nodules in the lung and 1.9-fold higher in axillary lymph node tumors than it was in primary SMT-2A tumors. The ganglioside pattern in these 2 secondary tumors generally reflected that found in SMT-2A: high levels of gangliosides containing three or four sialic acid molecules. The lung nodule retained its specificity with respect to lipid-bound sialic acid content and ganglioside pattern after the lung nodule was sequentially transplanted three times to the site of the original SMT-2A tumor growth.

Animals↗

Possible relationship between glycosphingolipids and the formation of metastasis in certain human experimental tumors.

Two tumors, human sarcoma #1 (HS #1) and human epidermoid carcinoma #3 (HEp #3), were cultured on the chorioallantoic membrane of chick embryos. Under experimental conditions, HS #1 does not metastasize, whereas HEp #3 metastasizes extensively to chick embryo lungs and other organs. The glycosphingolipid profiles of these tumors were studied and HEp #3 wad found to contain about 2.5-fold less lipid-bound sialic acid per 100 mg of total lipid extracted than did HS #1, due mainly to smaller levels of monosialoganglioside (3.7-fold) and disialoganglioside (3.8-fold) in HEp #3. The total amount of neutral glycosphingolipids was approximately the same in both tumors, but their profiles differed. Treatment of these tumors with 6,7,8,9-tetrahydro-1-mercapto-1,2,4-triazolo-[4,3-a]quinazolin-5-ol (2.5 mg/egg/tumor) completely inhibited the formation of metastases in HEp #3 and increased the total content of lipid-bound sialic acid in the tumor by 63% (hematoside, monosialoganglioside, and disialoganglioside by 71, 99, and 67%, respectively). No change was seen in the content of lipid-bound sialic acid in HS #1. Treatment of HEp #3 with a smaller dose of te quinazolinol derivative (1.25 mg/egg) caused an average of 88% inhibition of metastasis, with a 37% increase in lipid-bound sialic acid. Another compound, 2,5-diphenylthiazolo-[5,4-d]thiazole (500 microgram/egg), completely inhibited the formation of metastasis and caused a substantial increase in the amount of lipid-bound sialic acid (77%). The data showed the existence of a correlation between the level of gangliosides in HEp #3 and the ability of these tumors to metastasize.

Animals↗

Glycosphingolipids of subcellular fractions from normal rat liver and Morris hepatoma 5123TC.

Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from plasma membranes, mitochondria, microsomes, and nuclei isolated from normal rat liver and Morris hepatoma 5123TC. Results showed a higher content of glycosphingolipids, especially gangliosides, in hepatomas and differences in the distribution of glycosphingolipids among subcellular fractions. Differences in the glycosphingolipid composition of the hepatoma, namely, the absence of trisialogangliosides and an increase in the lower molecular weight gangliosides, reflected an altered metabolism of glycosphingolipids in this tumor. The results indicated that changes in membrane glycosphingolipids were not restricted to the cell surfaces of malignant cells, inasmuch as intracellular membrane fractions also exhibited altered glycosphingolipid profiles.

Animals↗

Alterations in glycosphingolipids of plasma membranes from Morris hepatoma 5123TC.

Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from normal rat liver and Morris hepatoma 5123TC and their isolated plasma membranes to determine differences in these components in the cell surface membranes of malignant cells. Glycosphingolipids present in rat liver and hepatoma were concentrated in plasma membranes, and glycosphingolipid patterns in plasma membranes reflected those of their respective whole cells. Neutral glycospingolipids of plasma membranes from normal liver and from hepatoma consisted of ceramide mono- and dihexosides, together accounting for 83 to 86% of the total neutral glycosphingolipids and some ceramide tri- and tetrahexosides. In plasma membranes from hepatoma, the concentration of neutral glycosphingolipids was generally greater than in plasma membranes from normal liver. Gangliosides of plasma membranes from hepatoma were altered more drastically, since trisialogangliosides, present in plasma membranes from normal liver, were absent, while hematosides, monosialogangliosides, and disialogangliosides were increased an average eight-fold. These data are compatible with a concept of incomplete synthesis of trisialogangliosides in hepatoma and an accumulation precursor gangliosides.

Animals↗

Plasma membranes of rat liver: isolation of lipoprotein macromolecules.

Three high-denisity lipoprotein classes and one protein were separated from rat-liver plasma in membranes that had been treated with mild sonic oscillation. The lipoproteinis were separated and identified by techniques in which ultracentrifugation was used. Enzyme markers and electron-microscopic examination revealed membrane preparations essentially free of contaminating cellular partictulates.

Adenosine Triphosphatases↗