[A comparative study of sphingolipids in transplanted melanomas with high and low metastatic activity].

The content of sphingolipids in M3 and B16/F10 melanomas with a high metastatic potential and in Claudman's and B16/F1 melanomas with a low metastatic potential was studied. It was shown that the content of total lipid-bound sialic acids and ganglioside GM3 in melanomas with a high metastatic potential is considerably higher than that in melanomas with a low metastatic potential. On the other hand, the ceramide to glucosylceramide molar ratio is higher in melanomas with a low metastatic potential. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

[Biologically active sphingolipids in transplantable tumors of different histogenesis].

The composition of biologically active sphingolipids in hepatoma 22, breast adenocarcinoma, Lewis lung carcinoma, large intestine adenocarcinoma, cervical carcinoma, and melanomas M3 and B16 was compared to elucidate the similarity and differences in sphingolipids of subcutaneously transplantable murine tumors. The sphingolipid composition of the tumors was found to widely vary. The sphingomyelin, ceramide, glucosyl- and lactosylceramide, and ganglioside GD3 contents in hepatoma 22 are higher than those in normal tissue. No common regularities for tumors of different origin were observed in the ratios of bioeffectors inhibiting proliferation and stimulating apoptosis and bioeffectors stimulating cell growth and survival. However, the Cer/(GlcCer + LacCer) ratios were very low and practically equal in two melanoma strains, which probably indicates the degree of tumor malignancy. The results suggest that the content and composition of sphingolipids in tumors depend on their histogenesis.

[Melanoma cell lines as the basis for antitumor vaccine preparation].

The aim of the study was to obtain cell lines from tumor samples, and to determine phenotypic cell characteristics in order to choose the optimal line for vaccine preparation. 15 cell lines with stable growth, varying in cultural growth character and cytomorphology, were obtained from samples taken from patients with metastatic skin melanoma. Immunofluorescense method was used to determine the expression of T- and B-lymphocyte markers, antigens of major histocompatibility complex (MHC) class I and II, and CD86 co-stimulating molecule in the cell lines. The expression of melanocyte differentiation antigens and cancer/testicular antigens was evaluated using immunocytochemical assay. The results allowed the authors to distinguish three types of melanoma cell lines according to the expression of MHC molecules: MHC-negative; MHC class I positive; MHC classes I and II positive.

Dihydroceramide desaturase activity in tumors.

Dihydroceramide desaturase activity in the transplantable mouse hepatoma-22, rat hepatoma-27, M1 sarcoma, and RS1 rat cholangiocellular carcinoma has been investigated. It was found that the dihydroceramide desaturase activity in mouse hepatoma-22 is lower than that in normal mouse liver. However, the activity of this enzyme in subcutaneously and intrahepatically transplanted rat hepatoma-27 is increased compared to normal value. Dihydroceramide desaturase activity in subcutaneously and intrahepatically transplanted M1 sarcoma as well as in hepatoma-27 is dependent on the tumor microenvironment. The enzyme activity in RS1 tumor was not revealed. The data indicate that dihydroceramide desaturase activity depends on the tumor type and its microenvironment.

Phenotypic characteristics of lewis lung carcinoma cells.

We studied adhesive properties and physiological activity in vivo of cells from Lewis lung carcinoma and its metastases. These cells differed in tumorogenic activity and metastatic potential in the syngeneic system. In vivo non-metastasizing cells are characterized by a lower content of surface lectins to tetrasaccharides SiaLex [Neu5Aca2-3Galb1-4(Fuca1-3) GlcNAcb] and SiaLea [Neu5Aca2-3Galb1-3(Fuca1-4)GlcNAcb] and trisaccharide HSO3Lex [HSO32-3Galb1-4(Fuca1-3)GlcNAcb] compared to cells forming metastases in the syngeneic system. Metastatic cells with low tumorogenic activity weakly expressed lectins to disaccharide ligands 6-SiaLac [Neu5Aca2-6Galb1-4Glc], 6-HSO3LacNAc, and A-di [GalNAca 1-3Galb] and trisaccharides H-type 1 [Fuca1-2Galb1-3GlcNAc and Lex [Fuca1-3(Galb 1-4)GlcNAc] compared to cells that initiated tumor formation in the syngeneic system (similarly to transplanted tumors). We hypothesized that cell receptors to these carbohydrate determinates are involved in the development and growth of primary tumors, while lectins to SiaLex, SiaLea, and HSO3Lex play a role in the progress of tumor process and metastasizing.

Sphinganine in sphingomyelins of tumors and mouse regenerating liver.

Contents of sphingenine (sphingosine) and sphinganine were studied in sphingomyelins of transplantable mouse tumors (hepatoma-22, melanoma B16, Lewis lung carcinoma, intestine carcinoma) and rat nephroma RA. The content of sphinganine was increased in sphingomyelins of hepatoma-22 and nephroma RA compared to sphingomyelins of liver and kidneys. Significant contents of sphinganine were also found in sphingomyelins of other studied tumors. The content of sphinganine in regenerating mouse liver (30 h after hepatectomy) was normal. The data suggest that disorders should exist in biosynthesis of sphingoid bases in tumors but not in normal rapidly proliferating tissue.

Sphingolipids of transplantable rat nephroma-RA.

Contents of sphingolipids (ceramide, sphingomyelin, gangliosides) and the composition of their sphingoid bases were studied in the transplantable rat nephroma-RA and in rat kidneys. The content of sphingomyelin was about 1.3-fold decreased and the content of ceramide was about 1.4-fold increased in the nephroma compared to normal kidneys, and this correlated with a 1.4-fold increased activity of neutral sphingomyelinase; however, the activity of the acidic isoform of the enzyme was virtually unchanged. The content of gangliosides was also increased in the nephroma. Ceramide and sphingomyelin of the nephroma, in addition to sphingosine, contained a significant amount of sphinganine, although a considerable amount of the latter was also found in the renal ceramide. The ratio sphingosine/sphinganine in sphingomyelins changed from 65:1 in kidneys to 5:1 in the nephroma. Thus, the biosynthesis of sphingoid bases seems to be disturbed in the transplantable rat nephroma-RA compared to normal kidneys.

Content and structure of ceramide and sphingomyelin and sphingomyelinase activity in mouse hepatoma-22.

The relative content of phosphatidylcholine is lower and that of sphingomyelin is higher in transplantable fast growing mouse hepatoma-22, thus decreasing their ratio approximately 2.5-fold versus normal liver. The ceramide content and the neutral sphingomyelinase activity is markedly higher (3- and 6.5-fold, respectively), whereas the acid sphingomyelinase activity is 4-fold lower in hepatoma-22 versus normal liver. The content of saturated fatty acids in ceramide and sphingomyelin of hepatoma-22 is higher than in normal liver. All sphingolipids of hepatoma-22 contain a considerable amount (25-37%) of sphinganine (dihydrosphingosine) along with sphingenine (sphingosine), whereas sphingolipids of normal liver contain predominantly sphingenine (over 95%). These results indicate that the activity of enzymes involved in sphingolipid biosynthesis and catabolism is disturbed in the transplantable mouse hepatoma-22 compared to normal liver.

Antiproliferative activity of ceramides isolated from normal human ovary and ovarian tumor.

Ceramides modulate cell growth, differentiation and apoptosis. We have previously demonstrated that human epithelial ovarian tumors contain dihydroceramides that are absent from normal ovary. Dihydroceramides differ in their biological effects from ceramides; therefore antiproliferative activity of ceramides isolated from normal human ovary and ovarian tumors was studied. Ceramides (3 microM) of normal ovary are more potent inhibitors of [3H]thymidine incorporation into human ovarian carcinoma cells (CaOv) than ceramides of ovarian tumors. Effects of various pools of tumor ceramides were similar regardless of significant differences in the contents of sphingenine and sphinganine. It is suggested that antiproliferative activity of ceramides depends not only on the sphingoid base structure but also on the fatty acid structure.

[Selective shedding of gangliosides by cells of mouse ascitic sarcoma-37]. / Izbiratel'noe sbrasyvanie gangliozidov kletkami astsitnoi sarkoma-37 myshei.

The profile and content of gangliosides associated with tumour cells of mouse sarcoma-37 and exfoliated from the cell surface were determined. It was shown that 20% of tumour gangliosides shed from the cell surface and only about 7% of all the shed gangliosides were contained in plasma membrane fragments. When incubated in vitro at 37 degrees C for 1 hour, the tumour cells were found to release less than 2% of cellular gangliosides. The main components of cellular gangliosides corresponded in their chromatographic behaviour to GM2 (31-32% of the total ganglioside content), GD3 (17-18%), GD1a (9-11%), GD2 (16-17%) and hematosides (19-21%). The profiles of in vivo and in vitro shed gangliosides were similar but strongly differed from those of cellular gangliosides: the relative content of GM2 was 70-75% and the other gangliosides were found in negligible amounts. The data show that GM2 accumulation in extracellular spaces is rather the result of its selective shedding than the shedding of products of "incomplete" cellular ganglioside synthesis.

[Biological properties of glutamin-(asparagin-)ase from Pseudomonas boreopolis 526]. / Biologicheskie svoistva glutamin(asparagin)azy iz Pseudomonas boreopolis 526.

Glutamine(asparagine)ase from Ps. boreopolis 526 has an antineoplastic effect on lymphoid leukemia P-388. The enzyme half-life in the mouse serum is 8.5 hours. Glutamine(asparagine)ase has no cross-antigenicity with L-asparaginase from E. coli (Bayer, FRG). Specific antibodies against L-asparaginase (Bayer, FRG) do not influence the activity of glutamine(asparagine)ase.

[Effect of cyclophosphamide on the ganglioside content and profile in metastasizing and nonmetastasizing mammary carcinoma in mice]. / Vliianie tsiklofosfamida na soderzhanie i profil' gangliozidov v metastaziruiushchei i nemtastaziruiushchei kartsinome molochnoi zhelezy myshei.

The content and profile of gangliosides (Gs) were investigated in metastatic (HMC-L) and nonmetastatic (HMC-O) mouse mammary carcinomas before and after cyclophosphamide (CP) treatment. It was shown that the Gs content did not alter markedly during HMC-O growth, whereas in HMC-L, it increased to maximum on day 15 after tumor inoculation and then dropped. CP treatment led to a steady rise in the Gs content in both tumors. The main Gs in HMC-O corresponded to GDIa, GMI, GDIb and hematosides, while in HMC-L, the main Gs at days 9-15 after tumor inoculation corresponded to GDIa (50-65% of total Gs). The action of CP on HMC-O was not accompanied by any essential alterations in the Gs profile, whereas in HMC-L on days 3-6 after CP treatment the relative content of GDIa was significantly lowered and the GMI and hematoside content markedly increased. These findings indicate that there is an obvious relation between the Gs profile and tumor ability to form metastases.

The antitumor activity of oxoplatinum.

A coordination complex cis-dichlorodiamminedihydroxoplatinum (IV) (oxoplatinum) was first synthesized in the USSR by Chugaev and Khlopin in 1927 [3]. Its marked antitumor properties were revealed by one of the authors of this article at the All-Union Cancer Research Center of the Academy of Medical Sciences of the USSR. The paper gives data on the antiblastic and side effects of oxoplatinum and also on the results of pharmacokinetic studies of the drug. Particular attention was paid to the similarity and differences of biological properties of oxoplatinum and cis-dichlorodiammineplatinum(II) (DDP) which has found wide use in oncological practice. It has been established that, on principle, oxoplatinum differs from DDP in action on the body and tumors. The new drug is 10 times less toxic than DDP. Oxoplatinum has a wide spectrum of antineoplastic action resulting in marked inhibition of growth of solid and ascitic forms of transplantable tumors. The drug has a longer duration of antitumor effect after the end of the therapeutic course. An important property of oxoplatinum is its high therapeutic index. The new drug manifests high antitumor activity with different ways of its administration into the body. Oxoplatinum in therapeutic doses does not produce necrotic lesions in the kidneys. The new drug exerted no cross-resistance with DDP and the alkylating antitumor agent sarcolysin. At the present time oxoplatinum is undergoing preclinical investigation.