Medical Studies, PSK

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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Cytokines, Leukemia, Medical Studies, PSK, Tumor

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

Display Settings: Abstract

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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Cancer, Cytokines, Gastric Cancer, Medical Studies, PSK

Usefulness of immunomodulators for maturation of dendritic cells.

Display Settings: Abstract

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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in vitro, Medical Studies, PSP, Tumor

Study on Anti-tumor Action of PSP

R.T. Chen, A.M. Zhou, B. Xu Department of Pharmacology I Shanghai Institute of Materia Medica, Academia Sinica

Abstract

It has been reported that some polysaccharides possess antitumor action. PSP is a glycopeptide isolated from Coriolus versicolor by Yang et al. Its physiological properties have been investigated. In the present work we studied the antitumor action of PSP in vitro experiments.

Summary

PSP at the doses of 500 or 1000ug/ml produced inhibitory effect on P388 luekemia cells by 79-96%. At the dose of 1000 or 2000ug/ml PSP caused the inhibition of [3H]UR or [3H]TdR incorporation into RNA and DNA in Ehrlich ascites carcinoma cells was found to be the inhibition rate 50-80% or 27-47% respectively.

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Medical Studies, PSP

The Influence of PSP on the Behavior and Growth of the Fetus in Rats.

Zheng-de Zhang1, Zhen-bin Qian2, Lan-feng Zhou2 and Bin Xu1 1 Shanghai Institute of Materia Medica, Academia Sinica 2 Department of Toxicology, Shanghai Institute of Labour Health and Occupational Diseases

Abstract

PSP is a new immunomodulating agent prepared and developed by Professor Qing-yao Yang. In the present work its influence on the behavior and growth of fetus in 1st and 2nd generation of rats was investigated.

For behavior study the squirrel wheel test, rotating cylinder test and passive avoidance test were performed, PSP was administered orally at 60, 600 and 6000mg/kg. The results showed that no marked difference in the change of behavior was found between the control and treatment groups. The brain weights of two-generation rats had no marked change either.

For teratogeny test 110 rats were involved PSP was administered orally at 60, 600 and 6000mg/kg in different groups for 10 days. The conditions of the maternal body, embryonic survival and the function and growth of the fetuses were examined. After statistical tests no marked difference was observed in the control and treatment groups.

The data observed showed that PSP has no noticeable toxicity on fetus growth and on the behavioral performance of 1st and 2nd generation rats

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Cancer, Medical Studies, PSK, Tumor

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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Cancer, Chemotherapy, Medical Studies, Melanoma, PSP

The Preliminary Appraisal of Polysaccharide Peptide (PSP) in Malignant and Non-malignant Diseases

Z.Y. Sun et al Shanghai Medical University

Abstract

28 late cases of malignancy of all pathologically proven were evaluated. Among them are one case of melanoma, two cases of non-Hodgkin lymphoma (NHL), twenty cases of gastro-intestinal cancers, three cases of bronchogenic carcinoma, one case each of primary hepatocellular carcinoma and multiple peritoneal malignancies of unknown origin respectively.

Most of the cases had surgery, irradiation or anticancer chemotherapy in combination. PSP were taken orally in capsules, total dose ranged from 20g to more than 800g.

A case of malignant melanoma of back was operated for five times, she was operated for the first time in Jan 1982, lymphadenopathy of right iliac and inguired glands began, consequently wide dissections of the involved nodes were done. In August 1983, the disease metastatized to right chest wall and st. axillary glands and resected specimen showed one of three subseapular nodes and one of the eight axillary nodes were metastatic melanoma lesions, the estrogen receptor content of the specimen was 125F mol/mg. On September 10, the same year a total hysterectomy was done. She received 7 courses of CCNU, PCZ and VCR regime beginning from October 1983. Despite the stable condition of her disease, she had to give up further chemotherapy on account of distinct leucopenia. In April 1985, she was found to have GI bleeding, GI bladder, condition improved after Tamoxifen and symphomate treatments. Half year later melana reappeared and right hemicolectomy and partial resection of the jijunum were done. PSP was given postoperatively, and there was no chemotherapy for already more than 2 years. She is apparently well and can participate ordinary heavy work without difficulty.

Another case of multiple peritoneal metastasis of unknown origin was benefited by PSP also. She had mass of 5x5cm in RLQ of abdomen and quite massive ascites. Ager 100g

of PSP, ascites disappeared and the mass decreased to 3x3cm. White count went up to 5200 from 3800, lymphocytic mitosis increased from 28 to 36%.

Two cases of NHL were apparently benefited too by PSP in spite of the fact one each had received systemic chemotherapy and radiotherapy of waldegers ring respectively.

All the 28 cases except 2, the general conclitims of patients and appetite improved 2/3 of the cases showed an increase of white count of 1000 at least. Around half of the patients had an increased of function of cellular immunity. One case of liver cancer showed marked amelioration of abdominal pain 80 that he could abandon dolantin injection and one case of lung cancer had conspicuous decrease of the malignant pleural effusion.

Five cases of chronic gastrites and three cases of chronic active hepatitis showed remarkable improvement in symptoms and liver function test. HBsAg declined in two of three hepatitis patients.

So far no adverse drug reaction has been observed, there were no impairment of liver and renal functions after the long term administration of PSP even up to years.

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Medical Studies

The Comparative Analysis of the Extracts of the Mycelia and the Fruitbodies of Yun Zhi (Coriolus versicolor)

Qing-yao Yang1, Ji-nian Fang2, Xiu-ping Qian1 Xiao-tong Yang1, Ping Yuan1, Ke Mi1 and Hui-qin Feng1 1 Shanghai Teachers University 2 Institute of Materia Medica, Academia Sinica

Abstract

After Yun Zhi mycelia or fruitbodies are extracted by hot water and precipitated by alcohol, the Yun Zhi mycelium extract (MWA) or Yun Zhi fruitbody extract (FWA) is obtained. Then they are respectively developed by anthrone and phenolsulfate, and an analysis is made by means of ultraviolet/visible light spectra. The result shows that the maximum absorption wavelengths of MWA are 420 and 487nm respectively and those of FWA are 671 and 486 respectively. After the water solution of MWA is developed by ninhydrin, we see that its maximum absorption wavelength is 586nm; but there is no obvious absorption of FWA. Through a comparison of the infrared spectra of MWA and FWA, we discover that there is an obvious absorption of MWA at 1380nm, while there is no obvious absorption of FWA at that place. By phenol suplfate and Lowry methods to determine the contents of polysaccharide and protein, we find that the glucose contents of MWA and FWA are 36% and 48% respectively and the protein contents are 33% and 21% respectively. With a rotatory instrument to measure the specific rotatory power of MWA and FWA, we find that MWA is -0.04 and that of FWA is -0.69. With DEAE-cellulose for column chromatography, we find that the eluant of MWA contains 3 kinds of monosaccharide: galactose, mannose and rhamnose while that of FWA contains only 2 kinds of monosaccharide: galactose and rhamnose. The 0-2 mol of eluant of MWA contains 6 monosaccharide: glucose, mannose, arabinose, xylose and rhamnose while that of FWA contains 5 monosaccharide: glucose, mannose, arabinose, xylose and rhamnose. The main ingredient of FWA is not absorbed on DEAE-cellulose. Its molecular weight is 6200 Da, while that of MWA is absorbed on DEAE-cellulose. its molecular weight is 26000 Da.

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Medical Studies, PSK, Tumor

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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Cancer, Leukemia, Medical Studies, PSK

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

Display Settings: Abstract

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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