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M Kiso

Publications and source records attributed to M Kiso.

At least 109 records · Page 6Linked to original sources
PubMed1994

Analysis of oligosaccharides of human IgG from serum of leukemia patients.

The biantennary N-acetyllactosamine type oligosaccharide is attached to asparagine-297 of the human IgG heavy chain, which is an integral part of the tertiary structure of the Fc region, and is quite important in the role of IgG. Pyridylamination and analysis by HPLC can be performed more rapidly and simply than conventional carbohydrate analysis. We applied it to the analysis of the oligosaccharide structures of IgG from the serum of patients with leukemia, CLL and AML. The proportion of oligosaccharide from leukemia patients with a bisecting N-acetylglucosamine residue was almost equal to that of healthy individuals. However, the proportion of fucose and galactose residues differed. These data suggest that the analysis of the fucose and the terminal galactose residue of such oligosaccharides will be useful in the classification of leukemia.

Acetylglucosamine↗
PubMed1993

A distinct type of sialyl Lewis X antigen defined by a novel monoclonal antibody is selectively expressed on helper memory T cells.

A subset of human helper memory T cells is known to adhere to E-selectin expressed on cytokine-activated endothelial cells. However, sialyl Lex antigen, the carbohydrate ligand for E-selectin, has been hardly detectable on these cells, at least when typical anti-sialyl Lex antibodies were used for detection. One of the MoAbs (2F3, IgM), which we raised against a chemically synthesized sialyl Lex glycolipid preparation, is found to react selectively to CD4+ CD45RObright+ CD45RA- helper memory T cells among peripheral lymphocytes in healthy individuals. The specificity of the antibody is in clear contrast to that of the hitherto reported typical anti-sialyl Lex antibodies FH-6 and SNH-3. These classical anti-sialyl Lex antibodies were known to react to a subset of natural killer (NK) cells, but were not reactive with any particular subset of resting peripheral T or B cells of healthy individuals if the cells were not activated. On the other hand, the newly generated 2F3 antibody specifically reacted to helper memory T cells, and did not react to NK cells, B cells, or any T cells other than helper memory T cells. When tested against the sialyl Lex-active glycolipid antigen, the reactivity of 2F3 was not significantly different from that of the classical anti-sialyl Lex antibodies. But when tested against oligosaccharides prepared from cellular glycoproteins, 2F3 detected a distinct set of O-linked oligosaccharides, which were not reactive to the classical anti-sialyl Lex antibodies. Our results suggest that various molecular species of sialyl Lex antigens are present on carbohydrate side chains of cellular glycoproteins, and that helper memory T cells express a distinct type of sialyl Lex antigen that is defined by 2F3 but is not efficiently detected by other typical anti-sialyl Lex antibodies. Among cultured lymphocytic leukemia cells, the adult T-cell leukemia (ATL) cells preferentially expressed the 2F3-defined antigen, and acute lymphocytic leukemia cells rarely expressed the antigen. The cultured ATL cells expressing the 2F3-defined antigen showed a clear E-selectin-dependent adhesion to cytokin-activated endothelial cells, and the 2F3-defined sialyl Lex antigen served as a ligand for E-selectin as ascertained by the clear inhibition of adhesion with the 2F3 antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1993

A synthetic approach to polysialogangliosides containing alpha-sialyl-(2-->8)-sialic acid: total synthesis of ganglioside GD3.

A stereocontrolled, facile total synthesis of ganglioside GD3 is described as an example of a proposed systematic approach to the preparation of gangliosides containing an alpha-sialyl-(2-->8)-sialic acid unit alpha-glycosidically linked to O-3 of a D-galactose residue in their oligosaccharide chains. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-, 3-O-benzoyl-, or 3-O-benzyl-beta-D-galactopyrano-sides, or 2-(trimethylsilyl)ethyl 2,3,6,2',6'-penta-O-benzyl-beta-lactoside (7), with methyl [phenyl 5- acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9 lactone)- 4,7-di-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2-nonulopyrano sid] onate (3), using N-iodosuccinimide-trifluoromethanesulfonic acid as a promoter, gave the corresponding alpha glycosides 8 (32%), 13 (33%), 14 (48%), and 17 (31%), respectively. The glycosyl donor 3 was prepared from O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosy lonic acid)-(2-->8)-5-acetamido-3,5- dideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid by treatment with Amberlite IR-120 (H+) in methanol, O-acetylation, and subsequent replacement of the anomeric acetoxy group with phenylthio. Compound 8 was converted into the methyl beta-thioglycoside via O-benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group by reaction with methylthiotrimethylsilane. Compound 17 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the alpha-trichloroacetimidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol to give the beta-glycoside. This glycoside was easily transformed, via selective reduction of the azido group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester and lactone functions, into ganglioside GD3.

Carbohydrate Sequence↗
PubMed1993

Sulfated glycolipids are ligands for a lymphocyte homing receptor, L-selectin (LECAM-1), Binding epitope in sulfated sugar chain.

Specific sugar ligands which bind to rat L-selectin (LECAM-1, lymphocyte homing receptor)-IgG chimera were investigated by thin-layer chromatography-binding assay and ELISA. Rat L-selectin-IgG bound to native sulfated glycolipids such as sulfatide (I3SO3-GalCer), seminolipid, SM3(II3SO3-LacCer), SB2(III3SO3,II3SO3-Gg3Cer), SB1a (IV3SO3,II3SO3-Gg4Cer). The binding activity of the SM2 (II3SO3-Gg3Cer) carrying the internal sulfated Gal was very low, indicating that non-reducing terminal SO3H-3Gal beta 1- structure is essential for the binding. The reactivity of sulfatide was higher than that of sialyl Le(x) [Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-Ceramide] either in the presence of 1 mM Ca2+ or 1 mM Ca2+ and 5 mM EGTA. All the non-fucosylated gangliosides including ganglio-series and lacto-series type I and II chains tested gave a negative reaction. Neutral glycosphingolipids tested were all negative. Binding assay using synthetic sulfatide analogs indicated that the L-selectin-binding to its sulfated sugar ligands is position specific and depends on the number of the sulfate group, i.e., (SO3)3-3,4,6Gal- > (SO3)2-3,6Gal- > SO3-3Gal- > SO3-3Glc- > SO3-6Gal- > SO3-2Gal-. Lower reactivity of the chimera to SO3-3Glc-rather than SO3-3Gal- indicates that the chimera recognizes the configuration of hydroxyl group linked to the 4 carbon atom of the pyranose ring in galactose.

Amino Acid Sequence↗
PubMed1993

Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium.

The carbohydrate antigen, sialyl Lex, is known to be a ligand for the cell adhesion molecule called ELAM-1 (E-selectin, endothelial cell leukocyte adhesion molecule-1), which is present on cytokine-activated human endothelial cells. Recently, we reported that another carbohydrate antigen, sialyl Lea, can also serve as a ligand for ELAM-1 (A. Takada, K. Ohmori, N. Takahashi, K. Tsuyuoka, K. Yago, K. Zenita, A. Hasegawa, and R. Kannagi, Biochem. Biophys. Res. Commun., 179: 713-719, 1991). Both sialyl Lex and sialyl Lea are expressed in many human malignant cells. In order to assess the contribution of these carbohydrate antigens to the adhesion of human malignant cells to vascular endothelium, we selected a panel of 12 cultured human epithelial cancer cell lines and a panel of 12 human leukemia cell lines which express sialyl Lex and/or sialyl Lea antigens. All 12 epithelial cancer cell lines exhibited a clearly ELAM-1-dependent adhesion to cytokine-activated human umbilical vein endothelial cells, while only 3 of the 12 leukemia cell lines exhibited significant participation of ELAM-1 in the adhesion. With regard to epithelial cancer cells, the adhesion of 6 cancer cell lines, mostly of colon and pancreas origin, was dependent almost exclusively on sialyl Lea. A significant contribution of the sialyl Lex antigen was noted in the adhesion of the other 6 cell lines, including cancers of lung and liver origin. These results imply that the sialyl Lea/ELAM-1 adhesion system, as well as the sialyl Lex/ELAM-1 adhesion system, plays an important role in the adhesion of human cancer cells to human umbilical vein endothelial cells. With regard to leukemia cells, on the other hand, adhesion of the 3 leukemia cell lines that showed ELAM-1-dependent adhesion was mediated by the sialyl Lex antigen, and none of these leukemia cell lines expressed sialyl Lea or exhibited sialyl Lea-dependent adhesion.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Protective activity of lipid A analogue GLA-60 against murine cytomegalovirus infection in mice.

A chemically synthesized lipid A subunit analogue, GLA-60 (2-deoxy-4-O-phosphono-2-[(3R)-3-hydroxytetradecanamido]-3-O-[(3R) - 3-tetradecanoyloxytetradecanoyl]-D-glucose), has many of the activities of endotoxins but little, if any, toxicity. We investigated the protective activity of GLA-60 against murine cytomegalovirus (MCMV) infection in NMRI mice. Intraperitoneal administration of GLA-60 at 1 day before MCMV infection at doses of 1, 10, or 100 micrograms per mouse significantly reduced mortality. GLA-60 stimulated peritoneal natural killer (NK) cell and macrophage activities, and these activities were abolished by in vitro treatment with anti-asialo GM1 antibody and anti-Mac1 antibody, respectively. GLA-60 proved also protective against MCMV infection in mice in which either NK cells or macrophages were depleted by in vivo treatment with anti-asialo GM1 or anti-Mac1 antibody. The anti-MCMV activity of GLA-60 can at least be partially attributed to activation of NK cells and macrophages.

Adjuvants, Immunologic↗
PubMed1993

Synthesis of chemically modified sialic acid-containing sialyl-LeX ganglioside analogues recognized by the selectin family.

Sialyl Lewis X ganglioside analogues containing 5-acetamido-3,5-dideoxy-L-arabino-2-heptulopyranosylonic acid (C7-Neu5Ac), 5-acetamido-3,5-dideoxy-D-galacto-2-octulopyranosylonic acid (C8-Neu5Ac), and 5-acetamido-3,5-dideoxy-L-glycero-D-galacto-1-2-nonulopyranosylonic++ + acid (8-epi-Neu5Ac) in place of N-acetylneuraminic acid (Neu5Ac) have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl 6-O-benzoyl-beta-D-galactopyranoside with the phenyl or methyl 2-thioglycoside derivatives of the respective sialic acids, using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid as a promoter in acetonitrile, gave the three required 2-(trimethylsilyl)ethyl (2S)-sialyl-(2-->3)-beta-galactopyranosides. These were converted via O-benzoylation, selective transformation of the 2-(trimethylsilyl)ethyl group to acetyl, and introduction of the methylthio group with methylthiotrimethylsilane into the corresponding glycosyl donors. Glycosylation of 2-(trimethylsilyl)ethyl O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-(1-->3)-O-(2-acetamido-6-O- benzyl- 2-deoxy-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D- galactopyranoside with these donors in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) afforded the expected beta-glycosides, which were converted into the corresponding alpha-trichloroacetimidates, and these, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol, gave the required beta-glycosides. Finally, these were transformed via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and de-esterification into the target compounds in good yields.

Carbohydrate Sequence↗
PubMed1993

The vascular E-selectin binds to the leukocyte integrins CD11/CD18.

Leukocyte adhesion involves at least three molecular families of adhesion proteins: the leukocyte integrins CD11/CD18, the intercellular adhesion molecules (ICAMs) and the carbohydrate-binding L-, E- and P-selectins. The intercellular adhesion molecules are well-known ligands for the CD11/CD18 integrins. We now show that E-selectin specifically binds to the sialyl Lex carbohydrate epitopes of leukocyte integrins. Thus, the different families of leukocyte adhesion molecules form an integrated adhesion network.

Antigens, CD↗
PubMed1993

Structure-function studies on selectin carbohydrate ligands. Modifications to fucose, sialic acid and sulphate as a sialic acid replacement.

The selectins are a family of carbohydrate-binding proteins that have been implicated in the initial interaction between leukocytes and the vascular endothelium. The three members of this family will bind to the sialyl-Lewisx epitope [Sia alpha 2-3 Gal beta 1-4 (Fuc alpha 1-3) GlcNAc] and related oligosaccharides. In this report, we examine the molecular details of that recognition using synthesized carbohydrates with specific modifications on the sialyl-Lewisx epitope. E- and L-Selectin require hydroxyl groups at the 2, 3 and 4 positions of the fucose residue. P-Selectin, however, requires only the 3-position hydroxyl group, while tolerating removal of the oxygen at positions 2 or 4 of fucose residue. Modifications of the glycerol side chain or the N-acetyl group of the sialic acid have little effect on the binding of any of the selectins. All three selectins bind efficiently to an oligosaccharide with a sulphate replacement for the sialic acid [sulpho-Lewisx, or SO4-3Gal beta 1-4 (Fuc alpha 1-3) Glc-ceramide]. For E-Selectin, binding to sulpho-Lewisx appears to be equivalent to binding to sialyl-Lewisx, while for L- and P-Selectin binding to the sulphated structure shows characteristics distinct from sialyl-Lewisx recognition. Taken together, these data indicate that, while all three selectins can recognize sialyl-Lewisx, E-, L- and P-Selectin each display distinct carbohydrate ligand preferences.

Carbohydrate Metabolism↗
PubMed1993

Drift of the sialyl-linkage specific recognition of the sialidase of influenza B virus isolates.

Sialyl-linkage specificity of the sialidase of influenza B viruses isolated in different years from 1940 through 1990 (B/Lee/40,B/Setagaya/3/56,B/Tokyo/7/66,B/Kagoshima/1/68, B/Gifu/2/73, B/Kanagawa/3/76, B/Ibaraki/2/85, B/Yamagata/16/88, and B/Bangkok/163/90) was studied with N-acetylneuraminyl (alpha 2-3)- and (alpha 2-6)-lactoses, GM3 gangliosides containing the same sialyl-oligosaccharide sequences as sialyllactose, and also with type I and type II lacto-series gangliosides carrying Neu5Ac alpha 2-3Gal and NeuAc alpha 2-6Gal linkages as substrates. From an examination of up to nine strains, the sialidases of all viruses preferentially hydrolyze substrates with Neu5Ac alpha 2-3Gal linkage rather than the Neu5Ac alpha 2-6Gal linkage. It was found that the sialidase activity toward Neu5Ac alpha 2-6Gal linkage relative to Neu5Ac alpha 2-3Gal linkage is increased in later strains, whether sialyllactose or ganglioside is used as the substrate. These results suggested that the sialidase of influenza B virus isolates has shown a drift in linkage specificity which correlates with the year of isolation.

Animals↗
PubMed1993

Protective activity of the lipid A analogue GLA-60 against murine cytomegalovirus infection in immunodeficient mice.

The immunomodulating and murine cytomegalovirus (MCMV)-inhibiting effects of the synthetic lipid A subunit analogue GLA-60 were investigated in different strains of immunodeficient mice. Peritoneal natural killer (NK) cells obtained from nude (nu/nu) C57BL/6 mice or normal NMRI mice, which had been treated intraperitoneally with 10 micrograms of GLA-60 1 day earlier, exhibited a greater cytolytic activity than those from untreated mice. GLA-60 also stimulated NK cell activity in SCID (severe combined immune deficiency) mice (which are T and B cell-defective), but not in NK cell-defective beige (C57BL/6 bg/bg) mice. GLA-60 also enhanced the phagocytic activity of peritoneal macrophages in beige, nude and NMRI mice, but not in SCID mice. GLA-60, when administered as a single 150 micrograms dose 1 day before infection, completely protected beige mice against MCMV-associated mortality. It also caused a significant increase in the life-span of MCMV-infected nude and SCID mice.

Animals↗
PubMed1993

Binding of lysozyme to synthetic monosaccharide lipid A analogue, GLA60.

Recent studies by our group suggested that lysozyme (LZM) has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A, well-known as sharing large part of lipid A activities but with very low toxicity. In this study, we characterized the interaction of LZM with GLA60 in comparison to that with E. coli 0111 LPS (smooth form), taking a physicochemical approach. Using a dansylated lysozyme probe (DNS-LZM), LZM was found to bind to GLA60 in all 3 of its forms, free acid, triethylamine (TEA) salt and bovine serum albumin (BSA) complex of GLA60, as well as natural LPS. Compared with LPS, the complex formation of the TEA salt was weakly dependent on temperature and incubation time. LZM also bound to biologically inactive GLA analogues, GLA 64 and GLA69, at a high affinity, as well as to GLA 60. By using chemically modified LZM, it was found that the ionic as well as hydrophobic interactions are important for the complex formation.

Chemical Phenomena↗
PubMed1993

Systematic synthesis of sulfur-containing p-nitrophenyl alpha-maltopentaoside derivatives for a differential assay of human alpha-amylases.

For use in a differential assay of human alpha-amylases, a variety of 6(5)-S-substituted p-nitrophenyl alpha-maltopentaoside derivatives (6-54) were systematically synthesized via the key intermediate, p-nitrophenyl O-(2,3-di-O-acetyl-6-S-acetyl-4-O-benzoyl-6-thio-alpha-D-glucopyranosyl) - (-->4)-tris[O-(2,3,6-tri-O-acetyl-alpha-D-glucopyranosyl)-(1-->4)]-2,3,6 -tri-O-acetyl-alpha-D-glucopyranoside (4), which was easily prepared from p-nitrophenyl alpha-maltopentaoside (G5P) in four steps. The sulfoxide and sulfone derivatives were prepared by oxidizing the corresponding sulfides with m-chloroperbenzoic acid.

Carbohydrate Sequence↗
PubMed1992

Sphingolipids are essential for the growth of Chinese hamster ovary cells. Restoration of the growth of a mutant defective in sphingoid base biosynthesis by exogenous sphingolipids.

We previously isolated a temperature-sensitive Chinese hamster ovary cell mutant (strain SPB-1) with thermolabile serine palmitoyltransferase, which is involved in the first step of sphingolipid synthesis (Hanada, K., Nishijima, M., and Akamatsu, Y. (1990) J. Biol. Chem. 265, 22137-22142). In this study, sphingolipid-deficient culture medium was used to examine the effect of exogenous sphingolipids on the cell growth of SPB-1. When cultivated in the sphingolipid-deficient medium, SPB-1 cells ceased growing at non-permissive temperatures. Under these conditions, de novo sphingolipid synthesis ceased in the SPB-1 cells, resulting in a decrease in levels of sphingomyelin and ganglioside sialyl lactosylceramide (GM3), whereas the parental CHO-K1 cells grew logarithmically with normal sphingolipid synthesis. Exogenous sphingosine restored the contents of both sphingomyelin and GM3 in the SPB-1 cells near to the parental levels through metabolic utilization and allowed the mutant cells to grow even at the non-permissive temperature. Similarly, exogenous sphingomyelin restored the sphingomyelin levels and only partly the GM3 levels and also suppressed the temperature-sensitivity of the SPB-1 cell growth. In contrast, exogenous glucosylceramide, which restored the GM3 levels but not the sphingomyelin levels, failed to suppress the temperature sensitivity of the SPB-1 cell growth. Combination of exogenous sphingomyelin with ceramide, glucosylceramide, GM3, or sphingoid bases did not show any synergistic or additive effect on the SPB-1 cell growth enhancement, compared with sphingomyelin alone. The results indicated that the temperature sensitivity of the SPB-1 cell growth was due to the lack of cellular sphingolipids, possibly that of sphingomyelin.

Acyltransferases↗
PubMed1992

High affinity binding of the leucocyte adhesion molecule L-selectin to 3'-sulphated-Le(a) and -Le(x) oligosaccharides and the predominance of sulphate in this interaction demonstrated by binding studies with a series of lipid-linked oligosaccharides.

The binding of the leucocyte adhesion molecule L-selectin has been investigated toward several structurally defined lipid-linked oligosaccharides immobilized on silica gel chromatograms or plastic wells. In both assay systems the 3'-sulphated Le(a)/Le(x) type tetrasaccharides [formula: see text] were more strongly bound than 3'-sialyl analogues. A considerable binding was observed to the 3'-sulphated oligosaccharide backbone in the absence of fucose but not to a 3'-sialyl analogue or fuco-oligosaccharide analogues lacking sulphate or sialic acid. Affinity for other sulphated saccharides: 3'-sulphoglucuronyl neolactotetraosyl ceramide and glycolipids with sulphate 3'-linked to terminal or sub-terminal galactose or N-acetylgalactosamine was detected in the chromatogram assay only. These studies, together with earlier reports that L-selectin binding to endothelium is inhibited by sulphatide, highlight the relative importance of sulphate in the adhesive specificity of this protein.

Animals↗
PubMed1992

Synthesis of disialoganglioside GD1 alpha and its positional isomer.

The first total syntheses of disialoganglioside GD1 alpha and its alpha 2-6 positional isomer are described. Suitably protected pentasaccharide derivatives, derived from known pentasaccharide precursors, were selected as the glycosyl acceptors. Using our facile method of stereoselective alpha-glycosidation of sialic acid, these acceptors were coupled with methyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galact o-2- nonulopyranosid)onate in acetonitrile medium in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) to get the desired di-alpha-sialyl hexasaccharide derivatives in moderate yields. The hexasaccharide trichloroacetimidates upon coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol gave the corresponding beta-linked sphingosine glycosides in high yields. These were subjected in sequence to selective reduction of the azido group and coupling of the thus formed amino group with octadecanoic acid, O-deacylation, and saponification of the methyl ester groups to obtain ganglioside GD1 alpha and its positional isomer having the main-chain residue 2-6 linked.

Carbohydrate Conformation↗
PubMed1992

Inhibition of tumor-induced angiogenesis by the administration of recombinant interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60).

The effect of the administration of recombinant interferon-gamma (rIFN-gamma) and a synthetic lipid A subunit analog (GLA-60) on angiogenesis induced by B16-BL6 melanoma was examined in syngeneic C57BL/6 mice. Intravenous administration of rIFN-gamma followed by GLA-60 (referred to as rIFN-gamma/GLA-60) induced endogenous production of tumor necrosis factor (TNF). This treatment on day 3 after tumor inoculation caused a marked decrease in the number of vessels oriented towards the tumor mass (angiogenic response) and tumor size over a period of 9 days. In contrast, neither rIFN-gamma nor GLA-60 alone, nor GLA-60/rIFN-gamma (reverse sequence of administration), which is unable to induce the production of TNF in the serum, had any effect. Sera induced by the treatment with rIFN-gamma/GLA-60, and recombinant TNF, inhibited the in vitro growth of lung endothelial cells which is considered to be one of the essential events in tumor neovascularization. Multiple i.v. treatments with rIFN-gamma/GLA-60 on days 5, 8 and 11 after s.c. implantation of tumor significantly inhibited primary tumor growth by the amputation time (day 20) and lung metastasis of B16-BL6 cells on day 34, while other treatment modalities had no such effect. Our results indicate that inhibition of lung-tumor metastasis by rIFN-gamma/GLA-60 treatment may be partly due to the inhibition of tumor-associated angiogenesis.

Animals↗