Category Archives: Cancer

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Coriolus versicolor is a mushroom used in traditional Asian herbal remedies (see Chinese Herbal Medicine). Two substances extracted from
the mushroom, polysaccharides K (PSK) and polysaccharides-peptide (PSP), are being studied as possible complementary cancer treatments.
Versicolor polysaccharides (VPS), another extract from the mushroom that is sold as a dietary supplement in the United States, is also being studied. A polysaccharide is a carbohydrate formed by a large number of sugar molecules.

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

Abstract
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.

PMID: 12168863 [PubMed – indexed for MEDLINE]
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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.

Antimetastatic Effects of PSK (Krestin), a Protein-bound Polysaccharide Obtained from Basidiomycetes: An Overview….. View more here:

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Coriolus versicolor extracts: relevance in cancer management

M. Szeto BSc RD

Cancer patients are increasingly seeking options in complementary and alternative medicine. Natural health products have by far become the most popular modality. Mainstream health care professionals need to engage in an open dialogue with their patients as cancer care becomes more multifaceted.

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

Cheuk-Lun Lee, Xiaotong Yang, Jennifer Man-Fan Wan

Department of Zoology, Kardoorie Biological Science Building, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China

Received 24 December 2003; accepted 5 October 2004

Abstract

Polysaccharopeptide (PSP) derives from the medicinal mushroom Coriolus versicolor is considered a biological response modifier with potential pharmaceutical applications. Significant literatures support the immune and anticancer functions of PSP; however, standardization is of big concern because variable biotechnological factors can affect both the chemical and biological properties of PSP. In this study, the extracts of PSP obtained at different days from the Coriolus versicolor culture were tested in vitro for their immune function on human normal peripheral blood mononuclear cells (PBMC) and cytotoxicity on the human leukemia Molt 4 cells. Over the 10-days culture period, both biomass and peptide/polysaccharide content were increased with time. The increase in proliferation index of PBMC and their production of interleukin 1 beta (IL-1_), tumor necrosis factor alpha (TNF-_) and gamma interferon (IFN-_) in the presence of PHA strengthens the correlation between culture duration and biological potency of PSP. The growth inhibition of the Molt 4 cells by PSP also depended on its maturity. 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.

© 2005 Elsevier Inc. All rights reserved. Keywords: Coriolus versicolor; Polysaccharopeptide; Flow cytometry; High performance liquid chromatography; Peripheral blood mononuclear cells; Molt 4

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[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]

[Article in Japanese]

Mitomi T, Tsuchiya S, Iijima N, Aso K, Suzuki K, Nishiyama K, Amano T, Takahashi T, Murayama N, Oka H, et al.

Dept. of Surgery II, Tokai University.

Abstract

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.

PMID: 2500070 [PubMed – indexed for MEDLINE]

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Usefulness of immunomodulators for maturation of dendritic cells.

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

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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]

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