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Usefulness of immunomodulators for maturation of dendritic cells.

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[…]

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

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.[…]

Usefulness of immunomodulators for maturation of dendritic cells.

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

DC-based vaccinations.[…]

Study on Anti-tumor Action of PSP

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.[…]

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

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

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

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.[…]

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

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.[…]

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

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.[…]

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

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.[…]

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

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][…]