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Cancer

American Cancer Society

Available scientific evidence does not support claims that the raw mushroom itself is an effective anti-cancer agent in humans. But there is some scientific evidence that substances derived from parts of the mushroom may be useful against cancer. Clinical trials suggest that PSK may help people with certain types of cancer by increasing survival rates and lengthening periods of time without disease, without causing major side effects. PSK is commonly used with other cancer treatments in Japan. PSP and VPS have not been studied as thoroughly.[…]

Anticancer effects and mechanisms of polysaccharide?K (PSK): implications of cancer immunotherapy.

Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant
treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the “host versus tumor response,” thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy, in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer, immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery, chemotherapy and/or radiotherapy.[…]

Antimetastatic Effects of PSK (Krestin), a Protein-bound Polysaccharide Obtained from Basidiomycetes: An Overview

PSK is currently used as an immuno therapeutic agent for gastric colorectal, and lung cancers in Japan. It has virtually no adverse effects, and it can be administered P. over a long term. Consequently, its use need not be limited to the treatment of Cancer, and, as our previous paper suggested, it should in the future prove valuable as a general chemopreventive agent and, as this review shows, as anti metastatic agent. The principal mechanisms of PSK may act as an inhibitor of the motility, invasion, and progression of tumor cells, in addition to its role as an immunomodulator.[…]

Coriolus versicolor extracts: relevance in cancer management

The existing evidence on C. versicolor extracts is positive. The role of PSK as a BRM in cancer therapy is well established in Japan, and preliminary research on PSP is promising. Communities in North America are becoming more globally diverse and multicultural.[…]

The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor

Flow cytometry analysis on cell cycle and cell death (apoptosis) of Molt 4 cells indicated that the anticancer mechanism of PSP is related to its ability to induce S-phase cell arrest and apoptosis, respectively. Together, these results suggest that monitor the harvest duration is critical for the quality control of polysaccharopeptide in the biotechnological industry.[…]

[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.

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.[…]

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.[…]

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][…]