Category Archives: PSK

[Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum]

[Article in Japanese]

Mitomi T, Tsuchiya S, Iijima N, Aso K, Suzuki K, Nishiyama K, Amano T, Takahashi T, Murayama N, Oka H, et al.

Dept. of Surgery II, Tokai University.

Abstract

To evaluate of adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer, randomized controlled

study by 35 institutions in Kanagawa prefecture was conducted. From March 1985 till February 1987, 462 patients were

assigned one of two different regimens. 448 patients (97.0%) of them satisfied the eligibility criteria. Control group

received mitomycin C intravenously on the day and the day after the operations respectively followed by 5-FU orally over

for 6 months. PSK group received in addition to mitomycin C and 5-FU as in control group, PSK orally for over 3 years. By

February 1989, follow up studies of the patients after their operations had been carried out for two years to four years.

The disease free curve and the survival curve of PSK group were higher than those of control group, differences between

the two groups were statistically significant (Disease free curve: P = 0.0096, survival curve: p = 0.0391). From these

results, adjuvant immunochemotherapy with PSK was considered beneficial for curatively resected colorectal cancer.

PMID: 2500070 [PubMed – indexed for MEDLINE]

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Usefulness of immunomodulators for maturation of dendritic cells.

Ogihara T, Iinuma H, Okinaga K.

Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.

Abstract

Biological response modifiers (BRMs) augment the cytotoxic activity of various effector cells by the induction of multiple

cytokines and suppression of immunosuppressive factors. BRMs are used extensively in adjuvant therapy for gastric

cancer in Japan. In dendritic cell (DC)-based vaccine therapy, the quality of DCs is important in inducing strong antitumor

immunity. A good manufacturing practice (GMP) grade agent for DCs maturation is desirable for safety. Here we report

the effects of two BRMs, OK432 and PSK, which are GMP grade agents for the functional maturation of DCs. OK432 and

PSK were examined in vitro, and compared with lipopolysaccharide (LPS) and a cytokine cocktail (IL-1beta, TNF-alpha,

IL-6 and PGE2). In the immunophenotypical analysis, the expression of CD80 and CD83 of DCs stimulated with OK-432

increased significantly compared with PSK and medium, and this up-regulation was the same as levels of DCs stimulated

with cytokine cocktail. DCs stimulated with OK-432 showed significantly higher production of IL-12 and Th1-type cytokines

(IL-2 and IFN-gamma) compared with DCs stimulated with LPS or cytokine cocktail. OK-432 stimulated DCs could induce

the significantly high level of cytotoxic T cell activity compared with PSK-stimulated or unstimulated DCs. These results

suggest that OK432 is a GMP-grade reagent that promotes functional maturation of DCs and could be applied in

DC-based vaccinations.

PMID: 15254744 [PubMed – indexed for MEDLINE]

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

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Anticancer Res. 1990 Jan-Feb;10(1):55-8.

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]

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Usefulness of immunomodulators for maturation of dendritic cells.

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Int J Oncol. 2004 Aug;25(2):453-9.

Ogihara T, Iinuma H, Okinaga K.

Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.

Abstract

Biological response modifiers (BRMs) augment the cytotoxic activity of various effector cells by the induction of multiple

cytokines and suppression of immunosuppressive factors. BRMs are used extensively in adjuvant therapy for gastric

cancer in Japan. In dendritic cell (DC)-based vaccine therapy, the quality of DCs is important in inducing strong antitumor

immunity. A good manufacturing practice (GMP) grade agent for DCs maturation is desirable for safety. Here we report

the effects of two BRMs, OK432 and PSK, which are GMP grade agents for the functional maturation of DCs. OK432 and

PSK were examined in vitro, and compared with lipopolysaccharide (LPS) and a cytokine cocktail (IL-1beta, TNF-alpha,

IL-6 and PGE2). In the immunophenotypical analysis, the expression of CD80 and CD83 of DCs stimulated with OK-432

increased significantly compared with PSK and medium, and this up-regulation was the same as levels of DCs stimulated

with cytokine cocktail. DCs stimulated with OK-432 showed significantly higher production of IL-12 and Th1-type cytokines

(IL-2 and IFN-gamma) compared with DCs stimulated with LPS or cytokine cocktail. OK-432 stimulated DCs could induce

the significantly high level of cytotoxic T cell activity compared with PSK-stimulated or unstimulated DCs. These results

suggest that OK432 is a GMP-grade reagent that promotes functional maturation of DCs and could be applied in

DC-based vaccinations.

PMID: 15254744 [PubMed – indexed for MEDLINE]

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Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK

Masahiko Fujii, Takayoshi Fujii, Ken Saito, Norio Takahashi, Chikao Yoshikumi, Junji Kakuchi and Yoshio Kawai Biomedical Research Laboratories, Kureha Chemical Industry Co., Tokyo, Japan

The administration of PSK caused the mean tumor size to decrease slightly and the duration of survival to be prolonged in comparison with control group. In tumor-bearing animals treated with IS, the administration of PSK significantly decreased the tumor size and prolonged the survival rate.

Further studies are required to clarify the origin of IS and its function in the body. For that purpose, the experimental model used in the present study is useful. Serum levels of IS may serve as a parameter to monitor the efficacy of immunotherapy

cont. in link…

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Suppression of in vivo tumor-induced angiogenesis by the protein-bound polysaccharide PSK.

U.S. National Library of Medicine

National Institutes of Health

In Vivo. 1994 Mar-Apr;8(2):247-50.

Kanoh T, Matsunaga K, Saito K, Fujii T.

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

Abstract

The anti-angiogenic effects of an antitumor protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus

versicolor in basidiomycetes were examined by the mouse dorsal air sac assay. PSK suppressed the mouse hepatoma

MH134-induced angiogenesis when assessed by morphological and biochemical examinations. This finding suggested that

the anti-metastatic effect of PSK is attributed to the suppression of tumor-induced angiogenesis.

PMID: 7522606 [PubMed – indexed for MEDLINE]

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Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions.

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Anticancer Res. 1990 May-Jun;10(3):697-702.

Sakagami H, Kim F, Konno K.

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

Abstract

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, stimulated the

iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear

cells (PMN), human promyelocytic leukemic HL-60 cells and human myeloblastic leukemic ML-1 cells. In contrast, PSK did

not significantly increase the iodination of other cultured cell lines (U-937, THP-1, L-929, T98G, BALB 3T3). The PSK

stimulation of iodination of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly

suppressed by the presence of myeloperoxidase inhibitors. Among various PSK subfractions, the highest molecular weight

fraction (MW greater than 200 kD), or the fraction precipitated at pH 4.0-4.5, stimulated the iodination most. In contrast,

natural and chemically modified glucans had little or no stimulation activity. The active PSK subfractions synergistically

enhanced TNF stimulation of PMN iodination. The data suggest the presence of some unique components in PSK which

directly stimulate the iodination of myeloperoxidase-positive cells.

PMID: 2369086 [PubMed – indexed for MEDLINE]

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

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Reversal of Inhibition of Reactive Oxygen Species Macrophages

These results suggest that the immunological functions of macrophages is related to the activity of glutathione peroxidase. The non-specific immune-polysaccharide might protect macrophages by the damage induced by reactive oxygen species by enhancing anti-oxidative capacity.

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Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

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Cancer. 1992 Nov 15;70(10):2475-83.

Toi M, Hattori T, Akagi M, Inokuchi K, Orita K, Sugimachi K, Dohi K, Nomura Y, Monden Y, Hamada Y, et al.

Department of Surgery, Hiroshima University, Japan.

Abstract

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition

of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with

estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy

for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM

daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day

of operation. METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and

staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914

(94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS)

times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American

Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with

ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in

patients with ER-negative disease. RESULTS: Results of subset analyses suggested a benefit from TAM in

postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with

node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS: The 5-year results of the current trial showed a

survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

PMID: 1423177 [PubMed – indexed for MEDLINE]

U.S. National Library of Medicine

National Institutes of Health

Publication Types, MeSH Terms, Substances

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Tumor cytostasis mediated by LPS- or PSK-activated human plastic-adherent peripheral blood mononuclear cells.

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Cell Immunol. 1992 Oct 15;144(2):358-66.

Kobayashi Y, Yoshikawa T, Watanabe N.

Department of Biomolecular Science, Faculty of Science, Toho University, Chiba, Japan.

Abstract

We investigated the mechanism of cytostasis mediated by activated human plastic-adherent peripheral blood mononuclear

cells (PBMC) in two cell lines, L.P3 cells (TNF alpha sensitive) and A375 cells (TNF alpha insensitive), using two biological

response modifiers, lipopolysaccharide (LPS) and a protein-bound polysaccharide extracted from a fungus, PSK. In

L.P3/LPS, L.P3/PSK, and A375/LPS cultures, the cytostatic effects were significantly reversed by anti-TNF alpha

antibody, while in the A375/PSK culture they were not. In concordance with this, LPS was a good inducer of TNF alpha,

but PSK was not. In A375/PSK culture, PSK-activated cells arrested A375 cells at the boundary between G1 and S,

presumably through inhibition of polyamine synthesis. This growth inhibition may be mediated by an unknown soluble factor

which is different from TNF alpha, IL-1, IL-6, and TGF beta.

PMID: 1394447 [PubMed – indexed for MEDLINE]

U.S. National Library of Medicine

National Institutes of Health

MeSH Terms, Substances

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