Tag Archives: cancer studies

CORIOLUS MUSHROOM: Uses, Side Effects, Interactions and Warnings – WebMD

Coriolus mushroom is a fungus. People have used the fruiting body and other parts as folk medicine for a long time. Recently, researchers have started to isolate and identify substances in coriolus that might act like pharmaceutical drugs. Two of these substances are polysaccharide peptide (PSP) and polysaccharide krestin (PSK). Scientists think these chemicals might be able to fight cancer and boost the immune system. Coriolus mushroom, PSP, and PSK are used for stimulating the immune system; treating herpes, chronic fatigue syndrome (CFS), hepatitis, and pulmonary disorders; reducing phlegm; improving bodybuilding results; increasing energy; curing ringworm and a skin condition called impetigo; treating upper respiratory, urinary, and digestive tract infections; curing liver disorders including hepatitis; reducing the toxic effects and pain of chemotherapy and radiation therapy; increasing the effectiveness of chemotherapy; prolonging life and raising the quality of life of cancer patients; and increasing appetite.

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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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[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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Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.

Display Settings: Abstract

Cancer Biother. 1994 Spring;9(1):63-9.

Kobayashi Y, Kariya K, Saigenji K, Nakamura K.

Molecular Biology Laboratory, Kotasato University School of Medicine, Kanagawa, Japan.

Abstract

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide

dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The

SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney

fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells

increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was

consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and

glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based

on SOD activity in tumor tissue.

PMID: 7812358 [PubMed – indexed for MEDLINE]

PubMed

U.S. National Library of Medicine

National Institutes of Health

MeSH Terms, Substances

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Clinical Experience in the Use of PSP

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

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.


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Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I’m-Yunity (PSP).

Hsieh TC, Wu P, Park S, Wu JM.

Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. Tze-Chen_Hsieh@nymc.edu

Abstract

BACKGROUND: I’m-Yunity (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I’m-Yunity (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I’m-Yunity (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I’m-Yunity (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I’m-Yunity (PSP) elicits these effects.

METHODS: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I’m-Yunity (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins.

RESULTS: Aqueous extracts of I’m-Yunity (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G1/S and G2/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I’m-Yunity (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-kappaB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I’m-Yunity (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase).

CONCLUSION: Aqueous extracts of I’m-Yunity (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I’m-Yunity (PSP).

PMID: 16965632 [PubMed – indexed for MEDLINE]PMCID: PMC1574346Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/16965632

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

Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A.

Servicio de Análisis Clínicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Av, de las Fuerzas Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org

Abstract

BACKGROUND: 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.

METHODS: The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.

RESULTS: PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

CONCLUSION: These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

PMID: 18366723 [PubMed – indexed for MEDLINE]PMCID: PMC2291471Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/18366723

Coriolus Versicolor PSP Clinical Trials

PSP and clinical trials

While PSK has been almost exclusively developed and tested within Japan, PSP in contrast is a product of China and continues to be assessed for efficacy safety by their scientists and oncologists.  There is a close similarity between PSK and PSP polypeptides although PSP lacks fucose and instead contains arabinose and rhamnose.  Since the first development of PSP in 1983 there has been rapid progress through human clinical trials.  Phase I clinical trials were carried out by Xu (1993) and it was shown that an oral dose of up to 6g/day was well talented and lacking in side-effects.  Patients showed improvement in appetite and general condition, together with a stabilisation of haematopoietic parameters.

The Phase II study by the Shanghai PSP Research Group with 8 hospitals in Shanghai was carried out using patients with cancers of the stomach, lung and oesophagus. The dosage was 1g three times daily to a total of 190g.  Results confirmed the role of PSP as a biological response modifer improving the immunological status of the patients after surgery, radiotherapy and/or chemotherapy (Liu and Zhou, 1993).  Following the success of the Phase II clinical trials, a Phase III trial was conducted in a large cohort of patients (650) in Shanghai hospitals.  189 were randomised to taking PSP and placebo;  461 patients were unblinded to their therapy (Liu et al., 1999).  These trials showed that PSP improved disease-free survival of gastric, oesophageal and non-small-cell lung cancers while again substantially reducing the normal unpleasant side-effects of conventional treatments (Sun and Zhu, 1999; Sun et al., 1999).  PSP had a protective effect on the immunological functions of conventionally-treated patients, thus demonstrating that PSP can be classified as a clinical biological response modifier.  Other BRMs such as LAK cells, IL-2, ? y IFN or TNF are also being used in the treatment of advanced cancer cases (Liu, 1999).  Yet, these drugs at effective doses, in many cases, produce quite severe side-effects such as fevers, chills, rashes, arthralgia, hypotension, oliguria, pulmonary oedema, congestive heart failure and CNS toxicities.  Mao et al. (1998) have shown dramatic anti-tumour effects when PSP was combined with IL-2.  As side-effects of IL-2 are dosage and schedule dependent, it isreasonable to expect that with PSP, a lower dose of IL-2 could be used clinically withsubsequent decrease in the severity of the side-effects (McCune and Chang, 1993).

A further observation noted that PSP in combination with radiotherapy induced a significant increase in the percentage of apoptotic cells at 24h, compared with radiation alone, and it has been surmised that the antitumour mechanism of PSPaction may also involve the induction of DNA damage by apoptosis in the target cancer cells (Stephens et al., 1991). A common adverse reaction of radiotherapy and chemotherapy is haematopoietic toxicity.  Several studies have shown a strong amelioration of thesetoxic effects by PSP (Shiu et al., 1992; Sun et al., 1999).

In a double-blind Phase II trial in Shanghai hospitals almost 300 patients suffering from gastric, oesophageal or lung cancer  were treated with conventional radiotherapy and/or chemotherapy together with PSP or shark liver oil (batyl alcohol).  Quality of life was assessed by marked improvement of clinical symptoms as well as improvements in blood profiles and/or immune indices and significant improvement in Karnovsky performance status or body weight.   PSP improved overall clinical symptoms, together with most symptoms associated with cancer therapy.  PSP was found to be effective for 82% of the patients compared with 48%for batyl alcohol (Liu and Zhou, 1993).

Many Phase III clinical trials of PSP combined with conventional therapies have demonstrated significant benefits against cancers of the stomach, oesophagus and lung (Jong and Yang, 1999; Yang, 1999).  Most studies with PSP have not fullyexplored the long-term survival benefit although in an open-label, randomised trial in oesophageal cancer has shown that PSP did significantly improve one-year and three-year survival (Yao, 1999).  Liu (1999) has commented on the favourable action of PSP in patients receiving bone autologous marrow transplants.

The corpus of laboratory and clinical evidence that PSP offers considerable benefits to patients suffering from cancers of the stomach, oesophagus and lung have led to the Chinese Ministry of Public Health granting it a regulatory license.

Extracts taken from: THE ROLE OF POLYSACCHARIDES DERIVED FROM MEDICINAL MUSHROOMS IN CANCER (icnet.uk)