Category Archives: Why It Works

Clinical trail China phase 1

Polysaccharide-peptide (PSP) is a protein bound polysaccharides isolated from the COV-1 strain of Yunzhi (Coriolous versicolor mushroom) and made from modern alcohol extraction techniques. Each capsule contains 0.34 grams of PSP. Experimental in-vitro and in-vivo studies have shown PSP inhibits the proliferation of cancer cells including P338 leukemia cells, S 180 cells, Ehrlich ascites, and stomach and lung cancer cells. It also inhibits the growth of some tumors such as the lymphatic tumor of human skin tissue cells. In addition, PSP affects the immune system of mice by stimulating the production of ?\interferons, increasing the phagocytic index and metabolic rate of the reticuloendothilial system and by raising the HC 50 (median hemolytic dose), IgG and PFC (plaque forming cell) values. Human in-vivo experiments have also shown PSP can modulate the immune system by helping to prevent and partly eliminate the side effects of radiation and chemotherapeutic agents used by cancer patients.

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Basty University herbal monographs

PSK fights cancers and tumors by inhibiting the growth of cancer cells and by “stimulating a host mediated response.” Natural Killer cells are also promoted to enhance the immune system. It is often used in conjunction with chemotherapy to increase cancer survival rates.  PSP is being proposed as an inhibitor of HIV replication based on an in vitro study

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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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The immunomodulator PSK induces in vitro cytotoxic activity in tumor cell lines via arrest of cell cycle and induction of apoptosis

Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.

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

Fisher M, Yang LX.

Radiobiology Laboratory, St. Mary’s Medical Center, California Pacific Medical Center Research Institute, San Francisco

94118, USA.

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

Display Settings: Abstract

Anticancer Res. 1990 Jan-Feb;10(1):55-8.

Kim F, Sakagami H, Tanuma S, Konno K.

First Department of Biochemistry, School of Medicine, Showa University, Tokyo, Japan.

Abstract

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor

necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced

differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of

cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. 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.

PMID: 2110432 [PubMed – indexed for MEDLINE]

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Usefulness of immunomodulators for maturation of dendritic cells.

Display Settings: Abstract

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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Study on Anti-tumor Action of PSP

R.T. Chen, A.M. Zhou, B. Xu Department of Pharmacology I Shanghai Institute of Materia Medica, Academia Sinica

Abstract

It has been reported that some polysaccharides possess antitumor action. PSP is a glycopeptide isolated from Coriolus versicolor by Yang et al. Its physiological properties have been investigated. In the present work we studied the antitumor action of PSP in vitro experiments.

Summary

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.

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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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