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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]

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.[…]

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.[…]

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.[…]

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][…]

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 immunopolysaccharide might protect macrophages by the damage induced by reactive oxygen species by enhancing anti-oxidative capacity.[…]

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.

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.[…]

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

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.[…]