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Why It Works

Treatment of cancer with mushroom products.

The author describes a study which shows that natural killer cells can double in number with 8 wk of treatment with Coriolus versicolor. Also described is an epidemiological survey of cancer deaths among Flammulina velutipes farmers in Japan, which found that the mushroom farmers had lower rates of cancer deaths than controls who were not involved in mushroom farming?.[…]

Clinical Experience in the Use of PSP

W.C. Xue and T.F. Liu
Cancer Hospital, Shanghai Medical University

Abstract

There is no really effective treatment for moderate and advanced stages of esophageal
carcinoma. Although surgery for the earlier cases has been able to give a 5 years survival
rate of 28.7%, such operable cases are relatively few. By far the greater majority are
already in stage III to IV when first seen in the clinic, and radiotherapy alone in these cases
has given a 5 years survival rate of only 8-14%. In order to improve treatment results, a
variety of chemotherapeutic agents have been used in combination surgery, but so far no
really effective drug has been found.

The drug PSP (polysaccharide-peptide of Coriolus versicolor) has been discovered and
produced by Professor Qing-yao Yang of. It is a new anti-cancer and immuno-regulatory
drug, similar to PSK (Krestin) but the effective component has been found to be larger
than PSK. Experimental data has proved these properties of PSP, and in vitro as well as
in vivo studies have all proved that PSP is superior to PSK. Of course, as is the case with
all new drugs, the ultimate proof of its value will have to be shown by clinical application.

Data on Krestin suggest that this family of drugs when used in combination with
radiotherapy, there might be an increase of the biological effects of radiation. To do a
pilot study on such a possibility, the authors have treated 41 moderate to advanced cases of
esophageal carcinoma with a combination of PSP and radiotherapy.[…]

Blastoid transformation of human lymphocytes cultured with protein-bound polysaccharide preparation, PS-K, in vitro.

The protein-bound polysaccharide preparation, PS-K, isolated from a mushroom, Coriolus versicolor, was found to stimulate human lymphocytes and induce them into blastogenesis in vitro. This stimulatory effect seemed to be nonspecific since lymphocytes from cord blood of newborn babies were also stimulated by PS-K. The highest lymphocyte blastogenesis by PS-K was observed after 5 days in culture.[…]

The effect of a protein-bound polysaccharide from Coriolus versicolor on immunological parameters and experimental infections in mice.

The influence of PSK, a protein bound polysaccharide from Coriolus versicolor on various immunological parameters was studied, PSK was found to enhance B cell activity as measured by the spleen plaque-forming cell assay in mice, and to stimulate mouse macrophages as determined by an enhancement of carbon clearance and an increase in the phagocytosis of opsonized sheep red blood cells by peritoneal mouse macrophages in vitro. The activation of mouse macrophages by PSK appeared to correlate with the therapeutic effects of the compound. In mice made granulocytopenic with cyclophosphamide and subsequently infected with a variety of garm-negative pathogens or with Candida albicans, PSK prolonged the average survival time of the animals. The compound also led to a drastic increase in the number of animals surviving such experimental infections as compared to untreated controls. Possible mechanisms responsible for these protective effects by PSK are discussed.[…]

[Restoration of depressed immune responses by PSK in C3H/He mice bearing the syngeneic X5563 tumor]

PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The effects of PSK on immunologic responsiveness were investigated in C3H/He mice bearing syngeneic X5563 tumor. The results were as follows. elayed foot pad reaction and antibody-forming capacity to sheep erythrocytes were depressed in tumor bearing mice, and such depression was prevented by oral or intraperitoneal administration of PSK. In vitro cytotoxic activity of splenic lymphocytes against the tumor was augmented by PSK administration. Antitumor effect was augmented by combination of PSK and X-irradiation. Delayed foot pad reaction to sheep erythrocytes was suppressed in normal C3H/He mice given immunosuppressive substance obtained from tumor-bearing mice, and the depressed reaction recovered to the normal level following PSK administration. These results show that PSK is effective in the syngeneic murine tumor system.[…]

Restoration of immune responsiveness by a biological response modifier, PSK, in aged mice bearing syngeneic transplantable tumor.

PSK (Krestin) is a protein-bound polysaccharide isolated from cultured mycelia of Coriolus versicolor in basidiomycetes. PSK is a biological response modifier which possesses unique characteristics. We investigated the effects of PSK on the immune response of aged C57BL/6 mice bearing a syngeneic transplantable tumor adenocarcinoma 755. (a) In C57BL/6 mice, the delayed foot pad reaction against sheep erythrocytes and resistance to syngeneic tumor challenge reached a peak when the mice were at 30 weeks of age, and decreased at 50-60 weeks of age. The serum of normal mice exerts a modifying effect on blastogenesis of lymphocytes to phytohemagglutinin. The positive effect reached a peak at 30 weeks of age, and thereafter declined with age. (b) When adenocarcinoma 755 was inoculated to C57BL/6 mice at 10-, 30- and 60-weeks of age, immune responses were depressed in 10-week-old and 60-week-old mice. PSK prevented such depression. However, in 30-week-old mice, tumor-induced suppression was slight, and administration of PSK to them increased proportion of mice which did not develop a tumor. (c) In 60-week-old tumor-bearing mice, the antitumor effects was increased with a combination of PSK and adoptive transfer of spleen cells from 10-week-old normal mice. The immune responses of mice, which change with the progress of age, are depressed by tumor burden. The administration of PSK to aged mice is effective to restore immune responses from tumor-induced suppression.[…]

Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.[…]

Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.

We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.[…]

Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor.

Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus versicolor which has been claimed to possess antitumor activity. However, neither tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10 micrograms/ml PSP. An increase in the production of reactive nitrogen intermediates, reactive oxygen intermediates (superoxide anions) and tumor necrosis factor was measured in peritoneal macrophages collected from inbred C57 mice which had received PSP in the drinking water for 2 weeks. Northern blot analysis also demonstrated that PSP activated the transcription of tumor necrosis factor gene in these cells, indicating that PSP exerted an immunomodulatory effect on the defensive cells.[…]

Improved recovery of myelosuppression following chemotherapy in mice by combined administration of PSK and various cytokines.

Granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) were used in combination with PSK, a protein-bound polysaccharide extracted from mycelium of Coriolus versicolor (strain CM101), in myelosuppressed mice. The myelosuppression model consisted of BDF1 mice who received 150 mg/kg 5-fluorouracil (5-FU) intravenously. The peripheral blood leukocyte count during the recovery stage was significantly increased when these cytokines were administered with PSK compared to when the cytokines were used individually. In vitro colony assay revealed that the combination of PSK and any of GM-CSF, IL-3 or stem cell factor (SCF) showed a greater increase in colony numbers than when these materials were administered individually, although G-CSF did not show a synergistic effect with PSK. When bone marrow cells were obtained from mice which had been given PSK or IL-3, the colony assays were made in the presence of PSK or IL-3 in vitro. The greatest increase in the numbers was observed in colonies of the cultured group in the presence of IL-3 after the PSK priming. However, the colony formation potential of PSK was not inhibited by addition of anti-SCF antibody. The above results indicate that the combined administration of PSK with G-CSF, GM-CSF or IL-3 increased the hematological recovery of myelosuppressed mice. Moreover, the phase at which PSK has effects on hematopoietic cells seems to be at a more immature level than with IL-3. The combined administration of PSK and the above cytokines may improve myelosuppression after chemotherapy in patients with malignancy.[…]