The CVP (Coriolus versicolor polysaccharide) is well known as anti-tumor drug in clinical applications.

INTRODUCTION
Coriolus versicolor, also known as Yun Zhi (YZ), belonging to the family Basidiomycotina, is a mushroom widely used in traditional Chinese herbal remedies. Its medical value correlate to C. versicolor extracts. Of the C. versicolor-derived therapeutics extracts, polysaccharopeptides are commercially the best established. The *Corresponding author. E-mail: xuanweizhou@sjtu.edu.cn. Tel: +86-21-62932002. Fax: +86-21- 65643552,
Abbreviations: YZ, Yun Zhi; CVP, Coriolus versicolor polysaccharides; PSK, polysaccharopeptide Krestin; PSP,
polysaccharopeptide; and MTT, 3-(4, 5-dimethylthiazolyl)-2, 5- diphenyl- tetrazolium bromide. polysaccharopeptides were obtained from C. versicolor known as C. versicolor polysaccharides (CVP), is a complicated protein-bound polysaccharide extracted from its mycelium or fruiting body. The composition of the polysaccharopeptide appears to depend on the source of  the material and the method of recovery used, such as polysaccharopeptide Krestin (PSK) obtained from the extraction of C. versicolor (CM-101) strains in China and polysaccharopeptide (PSP) obtained from the extraction of C. versicolor (Cov-1) strains in Japan. Both products have similar physiological activities but are structurally different (Chu et al., 2002). The major bioactive CVP is a _-(1_3)-glucan branching at 4’ and 6’ positions. The CVP mainly consists of neutral polysaccharides of glucose units; the main chain of _-1-3 consisted of _-D-1, 4-
Glc and _-D-1, 3-Glc, and branch chains were situated, _-D-1, 3, 6-Glc and _-D-1, 4, 6-Glc (Zhang et al., 2001).
The substance contained a branched glucan core with (1_3)-_-, (1_4)-_- and/or (1_6)-_-linkages, has a molecular weight of about 100 KDa and is highly watersoluble
(Ng, 1998; Wang et al., 1996).
The CVP have many pharmacological activities, including immunopotentiation, immunosuppressive, improvement
of appetite and liver function, calming of the central nervous system and enhancement of pain threshold. Historically, the CVP have been considered as important remedies for maintaining health, enhancing overall immune status, and prevention and treatment of chronic diseases (Ng, 1998). Presently, CVP is considered as a potential candidate for drug development in treatment and prevention of human cancers because of its immunological properties as well as its ability to distinguish cancerous cells from normal cells. Based on a statistics and analysis of anti-tumor plant drugs in a
hospital of Guangdong province, the frequency of using CVP is the highest in various fungal polysaccharides during the years of 2000-2002 (Liu et al., 2005). In vitro studies reveal that PSP acts selectively on B-cell lymphoma cell line (Raji), human promyelocytic leukemia cell lines (HL-60, NB-4) (Lau et al., 2004; Hsieh et al., 2002), human breast cancer cell lines (T-47D, MCF-7, MDA-MB-231) (Aoyagi et al., 1997; Chow et al., 2003), prostate cancer cell lines (PC-3, DU-145) (Hsieh and Wu, 2001). Although the CVP suppress proliferation of many human cancer cell lines in vitro and in vivo, not all cancers seem to respond to C. versicolor polysaccharopeptides. Normal lymphocytes, human
normal liver cell line (WRL) and human breast cancer cell line (BT20) are not affected by PSP (Hsieh et al., 2002;
Lau et al., 2004; Ho et al., 2005). The anti-tumor activity of the extract from C. versicolor appears to depend on
the strains-derived (Yang et al., 2000), the habitat in which it grows (Monro, 2003), the source material (Matsunaga et al., 1996) and the method of recovery used (Chen et al., 2003). The CVP can be produced from C. versicolor mushrooms harvested in the wild or cultivated commercially or from mycelial growth of C. versicolor in submerged fermentation. The polysaccharopeptides isolated from different sources (mushroom, mycelium, and biomass-free broth) differ somewhat in structure, composition, and physiological activity. The present study aimed to examine the in vitro cytotoxic activities of a culture-grown of C. versicolor hotwater extract in eight cell lines and to verify if the crude CVP can be extracted from the fruit body. This study provides a method of extract prepared CVP from
cultivated fruit bodies, and farther revealed that the CVP significantly suppressed the proliferation of four human
breast cancer cells in a dose-dependent manner, and four human liver cancer cells in a selectively manner in
vitro.

MATERIALS & METHODS
A biomass powder of Coriolus versicolor was chosen as it has significantly higher content of PSP’s to other mushroom preparations, specifically the biomass equivalents of Grifola frondosa (Maitake), Ganoderma lucidium (Reishi) and Cordyceps sinensis. This biomass form of Coriolus versicolor also has significantly greater peroxidase activity to biomass equivalents of
Grifola frondosa and Ganoderma lucidium specifically. Lastly, it has higher beta-glucanasase activity to Griofola frondosa (Maitake) and Cordyceps sinensis as well as increased glucose 2-oxidase activity (Karmali A, University of Lisbon 2002). The biomass powder contained the mycelium and the primordia (young fruitbody) of Coriolus versicolor, grown on a sterile substrate. The biomass
powder was then manufactured, into 500 mg tablets under to Pharmaceutical GMP standards in the United Kingdom. Thirty (30) patients were observed from the author’s clinical practice. They had a variety of solid tumours, mostly stage 3 or stage 4. The breakdown by tumour type is given in Table I:

Table I
Patients by Tumour Type and Secondary Tumors
Condition
Patient
Numbers Secondary Tumors
Number of
Secondaries
Hodgkin´s
Lymphoma 1 None 0
Prostate Cancer 8 Bone 6
Bowel Carcinoma 10 Liver 9
Breast Cancer 8 Metastases 8
Died During Study 3 Not Applicable 0
Total 30 23

Of the group of 30 patients who were selected to enter this study, 3 patients have died. Therefore this leaves us at 27 study results.

5.
Interleukin 5, interleukin 12 (both at gene expression level), tumour necrosis factor beta (also at gene expression level) and telomerase were recorded at day 0, day 60 and day 120. (See Appendices II, III, IV, and V ). The supplementation schedule for Coriolus versicolor supplementation was three tablets (500 mg each tablet) three times a day (9 tablets) for the first month (4.5 grams per day), six tablets three times a day (18 tablets) for the
second month (9.0 grams per day) and nine tablets three times a day (27 tablets) for the third (13.5 grams grams per day) and fourth (13.5 grams per day) months. (See Appendix I for outline of Coriolus versicolor supplementation schedule). Supplementation intake was conducted 30 minutes prior to every meal.

Table II
Coriolus versicolor
Supplementation Schedule Grams
per day
1 Month 1 4.5
2 Month 2 9.0
3 Month 3 13.5
4 Month 4 13.5

RESULTS
Based on the aforementioned four immunological parameters, over the 120 day supplementation period, the average change in Interleukin 5, interleukin 12 (both at gene expression level), tumour necrosis factor beta (also at gene expression level) and telomerase was encouraging. The summary of results was based on the recorded four (4) immunological parameters of 27 patients and outlined in Table III.

Table III
Summary of Results Average
Day 0 Day 60 Day 120 Change
1 Telomerase 1727 1034 417 -75.9%
2 Interleukin 5 * 22540 28516 4482 -80.1%
3 Interleukin 12 * 13931 20968 29489 111.7%
4
Tumour Necrosis Factor
Beta*(1) 27777 26113 31713 14.2%
6.
*Gene Expression Level
(1) only 26 data points

For patient specific information, please review the attached in Appendices II,  III, IV and V for the respective data points per measurement data.

Table IV
Statistical Data
Interleukin 5
0 – 60 days 0.589691
0 – 120 days 0.039371 Significant p< . 05
60 – 120 days 0.007972 Significant p< . 01
Telomerase
0 – 60 days 0.039307 Significant p< .05
0 – 120 days 1.78E-05 Significant p<. 00001

60 – 120 days 0.018498 Significant p< .05
Interleukin 12
0 – 60 days 0.478791
0 – 120 days 0.133005
60 – 120 days 0.439141
0 = 60 days starting value<3001
0.003306

Note: When the cut off of evaluation of interleukin 12 using any patients who has a starting value of less than 3,001, there was a significant increase in production of interleukin 12.

DISCUSSION
These results show a significant drop in telomerase activity (-75.9%) in the group except four cases (Patients 3, 8, 11 and 15-See Appendix II). The average decrease in Interleukin 5 was -80.1%, the majority showed an increase in Interleukin 12 (111.7%) and slight increase in tumour necrosis factor beta (14.2%). This therefore shows that there is a general move  towards a TH1 immune response in the majority of cases studied here.

Interleukin 5 was -80.1%, the majority showed an increase in Interleukin 12 (111.7%) and slight increase in tumour necrosis factor beta (14.2%). This therefore shows that there is a general move towards a TH1 immune response in the majority of cases studied here.

7.
To provide for greater ease of use, the use of tablet presentations of Coriolus versicolor should be replaced with a powder presentation in months 3 and 4 (13.5 gram per day).

CONCLUSION
This observational study on the use of Coriolus versicolor shows that there appears to be a differentiating effect on cancer cells by lowering telomerase activity and an encouragement of an immune function move towards a cell
mediated TH1 immune response, which is a more effective anti-tumour response. This is indeed remarkable, as the majority of these cases were stage 3 and 4 cancers, many of them chemotherapy and radiotherapy failures.
The use of Coriolus versicolor supplementation as adjuvant nutritional therapy to support the immune system in Stage 3 and 4 cancer patients should be further studied.
References:
Gotos.et al 1999 “Analysis of TH1 and TH2 cytokine production by peripheral
blood mononuclear cells as a parameter of immunological dysfunction in
advanced cancer patients.” Cancer Immunol.Immunother.48:435
Kazue Imai et al. “Natural cytotoxic activity of peripheral blood lymphocytes in
cancer incidents: an 11 year follow up study of a general population.”
The Lancet Vol. 356 – November 25th 2000 1795-1799.
Kenyon J N Observational Study on 32 Cancer Patients looking at TH1-TH2
response on www.doveclinic.com website.
Kidd, P.M. “The use of mushroom glucans and proteoglycans in cancer
treatment.” ( Kidd. P.M. Altern Med Red 2000: 5 (1): 4-27).
Rudin C M & Thompson C B 1997 “Apoptosis & Disease: Regulation and
clinical relevance of programmed cell death.” Rev.Med., 48,267-281
Shay J W & Wright W E “Telomerase activity in human cancer.” Current
opinion in oncology 8: 66-71 (1998).
Professor Amin Kamali. “The role of mushroom nutrition as a delivery agent
for enzyme therapy in cancer care- Chemical and biological properties in
mushroom nutrition”. Institute Superior de Engenharia de Lisboa. Rua
Conselheiro Emidio Navarro 1900-Lisboa. akarmali@isel.ipl.pt. Copy
available from www.mycologyresearch.com (R& D section)

A very interesting read!!! Part 1 of 2

OBSERVATIONAL NON-CONTROLLED STUDY OF THE USE OF CORIOLUS VERSICOLOR SUPPLEMENTATION IN 30 CANCER PATIENTS-Dr. Julian Kenyon (MD, MB ChB)

PSP, a polysaccharopeptide obtained from cultivated mycelia of the mushroom Coriolus versicolor, is a biological response modifier capable of howing diverse biological activities. It is a chemically homogenous substance possessing a molecular weight of approximately 100 kilodaltons. PSP is composed of 90% polysaccharides and 10% peptides. In addition to glucose, its polysaccharide constituents consist of five other sugars including arabinose, galactose, mannose, rhannose and xylose. The polypeptide constituents contain more than twenty different amino acids, notably aspartic and glutamic acids. PSP exhibits immunomodulatory and anti-tumour activities with low cytotoxicity. It has been used in Asia, particularly in China, as an adjuvant in the clinical treatment of cancer to boost the immunological
status of patients undergoing chemotherapy and/or radiotherapy. In addition, PSP exhibits analgesic, anti-viral and hepato-protective effects. Cancer is the result of changes in key regulatory genes which control cell proliferation, differentiation and survival. Cancer development is a multi step complex process in which normal cells gradually progress to malignancy. Both the activation of the oncogenes and the inactivity of the tumour suppresser genes are critical steps in tumour initiation and progression. The failure of cancer cells to undergo programmed cell death, known as apoptosis, is a critical factor in the development of tumours. The immune response mounted by the body is of major importance in preventing this process happening, or if it has happened, moving it towards the direction of normal apoptosis. (Rudin C M & Thompson C B 1997).

Dr. Kenyon is the founder of the Dove Clinic for Integrated Medicine, London and Twyford (near Winchester) / ( www.doveclinic.com ) The activity of the immune system is firstly non-specific, mediated by natural killer cells, and secondly tumour antigen specific by mounting a cell mediated

2. Immune response known as a thymic helper cell one (TH1) response. Most commonly cancer patients mount a marked thymic helper cell two (humoral immunity), a so-called TH2 response which involves production of large quantities of antibodies (Kenyon 2001 Gotos et al 1999). TH1 cells produce one set of cytokines whilst another set of cells, the TH2 cells, produce another set of cytokines. The cytokines produced by the two cell groups both influence the anti-cancer defence mechanism in a different way. Amongst the cytokines produced by the TH1 cells there is Tumour Necrosis Factor Beta which is known for it’s ability to destroy cancer cells. However, if the TH1 response is suppressed, Tumour Necrosis Factor Beta can be produced by natural killer cells. An effective anti-tumour response is a cell mediated TH1 immune response. If the TH2 humoral response is
excessively activated then a set of cytokines, amongst which is Interleukin 5, will be produced and these can negatively affect the anti-cancer defence mechanism either directly, or indirectly. A recent study has shown that medium and high cytotoxic activity of peripheral blood lymphocytes (mediated by TH1 lymphocytes and also natural killer cells in a non-specific way), is associated with reduced cancer risk. Whereas low activity is associated with increased cancer risk, suggesting a role for natural immunological host defence mechanisms against cancer (Kazue Imai et al 2000). Telomerase is a ribonucleo protein polymerase and is an enzyme whose function is to maintain the essential genetic element of telomeres, the eukaryotic ends of chromosomes. Telomerase activity becomes suppressed in the ageing process, but activation of telomerase is regarded as essential to
most cancers. This means that there is a specific association of human telomerase activity with cancer and usually it is high in cancer patients. There is clinical evidence to show that patients’ who have tumours that do not display telomerase activity are likely to eliminate the cancer, quite often spontaneously. It is considered that the repression of telomerase activity
3.
could be one of the mechanisms for cancer regression (Shay J W & Wright W E 1998). Several medicinal mushrooms are available for medical use at the present time. More than 50 mushroom species exhibit anti-cancer activity in-vitro, or in animal models, and of these, 6 have been investigated in human cancers. All are non-toxic and very well tolerated. Two proteoglycans from Corioulus versicolor-PSK (Polysachharide/K) and PSP (Polysachharide-peptide) – have demonstrated the most promise. Both have been subject to Phase II and Phase III trials in China, and PSP significantly extended 5 years survival in oesophageal cancer. PSP also significantly improved quality of life, provided substantial pain relief and enhanced immune status in 70-97% of patients with cancers of the stomach, oesophagus, lung, ovary and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms,
and enhanced tumour infiltration by dendritic and cytotoxic T-cells. They have extremely high tolerability, proven benefits to survival and quality of life, and their compatibility to chemotherapy and radiation therapy makes them well suited for cancer management regimens (Kidd, P.M. “The use of mushroom glucans and proteoglycans in cancer treatment”. P.M. Altern MedRed 2000: 5 (1): 4-27).

Here’s an interesting study re prostate cancer and Coriolus Versicolor from New York Medical College

Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells.

TC Hsieh, JM Wu.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.

The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary.

Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites.

The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action.

Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells.

Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively.

In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions.

Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state

(Source: http://www.yunzhi-psp.com/net_resources/res_papers/res2001-01.pdf)

Here’s what the University of California San Diego Medical Center has to say about Coriolus versicolor.

Complementary and Alternative Therapies For Cancer Patients
Coriolus Versicolor
This treatment modality is used in place of conventional therapies to treat cancer. Seek advice from a qualified physician before replacing standard cancer therapy with coriolus versicolor treatment.
What does coriolus versicolor treatment involve? Coriolus versicolor is a mushroom used in Asian cultures to treat cancer. Its active ingredient can be administered as a tea or in capsules.
How is coriolus versicolor thought to treat cancer? The coriolus versicolor mushroom has shown antimicrobial, antiviral and antitumor properties, which have been attributed to a protein-bound polysaccharide called Polysaccharide K (PSK), also known as Krestin. In Japan, PSK is currently used as a cancer treatment, in conjunction with surgery, chemotherapy and/or radiation.
What has been proven about the benefit of coriolus versicolor? Animal studies have reported that PSK prevents the induction of tumors by chemicals, radiation and other mutagens. The University of Texas M.D. Anderson Cancer Center performed an extensive human studies literature review of coriolus versicolor and found twenty-four studies relevant to cancer. After an in-depth review of the available literature, M.D. Anderson Cancer Center reported that PSK is a “promising candidate for chemoprevention due to the multiple effects on the malignant process, limited side effects and safety of daily oral doses for extended periods of time.”
(Source: http://cancer.ucsd.edu/outreach/PublicEducation/CAMs/coriolusversicolor.asp)