Category Archives: Diseases

Enhanced induction of immune resistance by concanavalin A-bound L1210 vaccine and an immunopotentiator prepared from Coriolus versicolor.

Kataoka T, Oh-hashi F, Tsukagoshi S, Sakurai Y.

Abstract

Combined administration of a vaccine consisting of a small number (2 X 10(6)) of L1210 murine leukemic cells treated with glutaraldehyde and concanavalin A and a protein-bound polysaccharide preparation of Coriolus versicolor induced synergistic resistance to L1210 leukemia in BALB/c X DBA/2CrF1 mice. This effect was dependent on the dose and timing of the administration of the protein-bound polysaccharide preparation, being most effective at the time of or 1 day after the second vaccination. Induced resistance was not cross-reactive with P388 murine leukemia, indicating specificity of resistance. This immunopotentiation by the protein-bound polysaccharide did not occur when L1210 cells treated with glutaraldehyde, but not with concanavalin A, were used as a vaccine.

PMID: 922733 [PubMed – indexed for MEDLINE]Free Article

http://www.ncbi.nlm.nih.gov/pubmed/922733

Survival time of tumor-bearing rats as related to operative stress and immunopotentiators.

Hattori T, Hamai Y, Ikeda T, Takiyama W, Hirai T, Miyoshi Y.

Abstract

To investigate the mechanism of tumor growth enhancement induced by operative stress in rats, laparo-thoracotomy was performed on day 2 after tumor cell inoculation associated with administrations of various kinds of immunopotentiators. OK-432 (Streptococcal preparation), PS-K (extract from mycelium of Coriolus Versicolor), Lentinan (extract from Lentinus Edodus) and C. parvum were administered intravenously or intraperitoneally in the fractionated form prior to or after inoculation. In general, administration of each immunopotentiator, except for Lentinan, resulted in a recovery from the reduction in survival days after laparo-thoracotomy. In particular, OK-432 administration prior to inoculation showed a significant improvement.

PMID: 7109360 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/7109360

Krestin (PSK).

Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K.

Abstract

A polysaccharide preparation isolated from Coriolus versicolor (Fr.) Quél. of Basidiomycetes (PSK) predominantly consists of glucan and approximately 25% tightly bound protein. PSK was effective against various allogeneic and syngeneic animal tumors and has been given orally to cancer patients. Various suppressed or enhanced immune responses of tumor-bearing animals were restored to normal levels by the administration of PSK in the tumor models tested. The killer T cell activity was augmented in tumor-bearing mice by intraperitoneal or oral administration of PSK, and there was correlation between the PSK associated antitumor effect and the killer T cell activity. It was found that PSK competed with immunosuppressive substances isolated from tumor-bearing mice and that the intestinal immune system appeared to be modulated by oral administration of PSK. After oral administration of 14C- or 35S-labeled PSK to normal rats, it was found that small or large molecular substances appeared in the serum depending on the time elapsed after administration, an indication that large molecular size products were from the digestive tract.

PMID: 6238674 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/6238674

Cloning of sequences induced and suppressed by administration of PSK, antitumor protein-bound polysaccharide.

Hirose K, Hakozaki M, Matsunaga K, Yoshikumi C, Hotta T, Yanagisawa M, Yamamoto M, Endo H.

Abstract

To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSK-treated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.

PMID: 3977892 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/3977892

[Restoration of immunologic responsiveness by PSK in tumor-bearing animals]

[Article in Japanese]

Matsunaga K, Morita I, Oguchi Y, Fujii T, Yoshikumi C, Nomoto K.

Abstract

PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.

PMID: 3789758 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/3789758

Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production.

Mori H, Mihara M, Teshima K, Uesugi U, Xu Q, Sakamoto O, Koda A.

Department of Pharmacology, Gifu Pharmaceutical University, Japan.

Abstract

OK-432, a lyophilized preparation of Streptococcus pyogenes, showed a priming activity for TNF production in mice, associated with an increase of spleen weight. PSK, a protein-bound polysaccharide preparation from Coriolus versicolor, did not show such activity. Both OK-432 and PSK potentiated the TNF production in mice primed with Corynebacterium parvum (CP) and challenged with Escherichia coli endotoxin (LPS). Cytotoxic antitumor agents of 5-fluorouracil (5-FU), cyclophosphamide (CY) and bleomycin (BLM) suppressed TNF production in mice primed with CP and challenged with LPS. TNF production suppressed by 5-FU, CY and BLM was partially restored by the combined treatment with OK-432 or PSK. These results suggest that the administration of cytotoxic antitumor agents suppresses the intrinsic TNF production in cancer patients, and the combined use of immunostimulants such as OK-432 and PSK is advantageous in restoring TNF production suppressed by cytotoxic antitumor agents.

PMID: 2448255 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/2448255

Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

Kim F, Sakagami H, Tanuma S, Konno K.

First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.

Abstract

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report regarding direct PSK modulation of cytokine action.

PMID: 2110432 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/2110432

Competitive action of a biological response modifier, PSK, on a humoral immunosuppressive factor produced in tumor-bearing hosts.

Matsunaga K, Morita I, Iijima H, Endo H, Oguchi Y, Yoshimura M, Fujii T, Yoshikumi C, Nomoto K.

Biomedical Research Laboratories, Kureha Chemical Industries Co., Ltd., Tokyo, Japan.

Abstract

We investigated the effect of PSK, a protein-bound polysaccharide obtained from the basidiomycetes Coriolus versicolor, on an immunosuppressive factor produced in tumor-bearing animals. Oral administration of PSK suppressed the growth of the tumor in C3H/He mice bearing X5563 plasmacytoma or MH134 hepatoma, but affected mice bearing MM102 mammary tumor little. PSK prevented the reduction in splenic lymphocyte blastogenesis caused by phytohemagglutinin that occurs in mice bearing X5563 tumors or MH134 hepatoma. The lymphocyte blastogenesis affected little by tumor or PSK in mice bearing MM102 tumors. The effect of sera on the blastogenesis of lymphocytes caused by phytohemagglutinin was different with different tumors in the C3H/He mice. Serum of mice bearing X5563 tumors inhibited blastogenesis, but serum of mice bearing MH134 hepatoma or MM102 tumors promoted it. The sera of mice bearing MH134 hepatoma contained both inhibitory and promotive factors; those of mice bearing X5563 tumors contained an inhibitory factor, and those of mice bearing MM102 tumors contained a promotive factor. The oral administration of PSK reduced the inhibition caused by the sera of mice bearing X5563 tumors. The promotive activity of sera from mice bearing MH134 hepatoma was augmented by PSK; that of sera in mice bearing MM102 tumors was not affected by PSK. Living Bacillus Calmette-Guérin did not have such effects in any of these mice. Serum immunosuppressive activity was also reduced by PSK in various tumor lines of rodents. These results suggest that PSK acts by reducing the activity of immunosuppressive factors produced in tumor-bearing hosts.

PMID: 1966997 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/1966997

A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer.

Anai H, Sakaguchi Y, Emi Y, Kohnoe S, Maehara Y, Sugimachi K.

Cancer Center, Kyushu University Hospital, Fukuoka, Japan.

Abstract

Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.