A Review of Research on the Protein-Bound Polysaccharide from the Mushroom Coriolus Versicolor

Mushrooms are known for their nutritional and medicinal value (Breene, 1990) and also for the diversity of bioactive compounds they contain. The mushroom Coriolus versicolor (Yun Zhi) was recorded in the Compendium of Materia Medica by Li Shi Zhen during the Ming Dynasty in China, as being beneficial to health and able to bring longevity if consumed regularly. Various products derived from this mushroom and claimed to have medicinal value are commercially available. Among them, PSK (Sakagami et al., 1991) and PSP are the most prominent. It is the intent of this article to summarize research data pertaining to PSP.

PSK (Sakagami et al., 1991) and PSP are two chemically related products of the mushroom Coriolus versico~or isolated from deeplayer cultivated mycelia of the COV-1 and CM-101 strains, by Chinese and Japanese investigators, respectively. The similarities and differences of the two products have been pointed out by the Fungi Research Institute (1993a). Both possess a molecular weight of approximately 100 kDa and their polypeptide moieties are rich in aspartic acid and glutamic acid. Monosaccharides with o~-1,4 and [3-1,3 glucosidic linkages constitute the pol~saccharide moieties of PSP and PSK: fucose is found in the latter¢ whereas arabinose and rhamnose occur in the former. Both PSP and PSK have been found to be immunoenhancing and effective against tumor cells.

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PSK does not surpress conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer.

Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.

A BIOLOGICAL RESPONSE MODIFIER, PSK, INHIBITS

We found that PSK has an antiviral effect on human immunodeficiency virus (HIV) in vitro. One of the mechanisms of this effect is attributable to the inhibition of binding of HIV with lymphocytes. Here, we found that PSK inhibits reverse transcriptase in a non-competitive way in vitro. Such inhibition may be important in its anti-HIV effect as well as its inhibitory effect on the binding of HIV with lymphocytes.

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PSP Coriolus Extract – How It Works (Mechanism Of Action) – MD Anderson, Texas

The multiple and complex mechanisms of action of Coriolus Versicolor PSP have been demonstrated through in vitro and animal studies. Coriolus PSP has suppressed the growth of human cancer cell lines in mice (sarcoma 180, lung adenocarcinoma and Lewis lung cancer).

It has also inhibited incorporation of two structural units of DNA (uridine and thymidine) in Ehrlich ascites tumor cells, inhibited the growth of P388 leukemia cells, and demonstrated anti-proliferative activity against cell lines of human gastric cancer, lung cancer, lymphoma, and mononuclear leukemia.

Coriolus PSP has reversed tumor-induced immunodeficiencies in sarcoma-bearing mice by increasing immunoglobulin G and C3 complement levels9. It has also been associated with increases in white blood cell count, serum IgG, CD4, CD8, B-lymphocytes, and neutrophils, along with a higher survival rate of tumor bearing mice3. Many of these effects have been attributed to PSP being a strong scavenger of superoxide and hydroxyl radicals. Coriolus Versicolor PSP has also been found to restrict the cell cycle of HL-60 leukemic cells through apoptosis.
These and other immune effects of PSK and PSP are described in reviews by Fisher and Yang, Ooi and Liu and Chu, Ho and Chow.

Source: (mdanderson.org)

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)

Coriolus Versicolor – The Miracle Mushroom

This extract taken from quantumhealing.co.za details various trials and treatments of Coriolus Veriscola.

It shrank his liver tumor by 90%––after his doctor gave up on him.

A man describes his oncologist as “the most negative man I ever met.” The doctor treated Mr. G. for liver cancer for six years, then gave him up as untreatable. “After the chemo failed, he threw up his hands, shrugged his shoulders, wished me good luck, and said there was nothing else he could do,” according to Mr. G. “And surgery couldn’t be performed either, because the consulting surgeon saw that the tumor was wrapped around my vena cava blood vessel.”

Mr G. told his oncologist, “I totally reject what you are telling me. I do not accept that nothing can be done to affect the outcome of this disease.” The doctor said, “Well, I know what I’m talking about when it comes to cancer. I’m a scientist.”

Mr G. shot back, “Yes, but you’re not God!” Four years later the patient was healthy again after using the type of therapies known as CAIM (complementary/ alternative/integrative medicine), especially including capsules containing the powdered extract of a mushroom, Coriolus versicolor. Mr G. learned about the remedy on the Internet and he can tell you all about it, having downloaded nearly 400 studies.

Amazingly, Mr. G.’s liver cancer reduced to less than ten percent of its original size. His CEA (carcinoembryonic antigen) cancer marker fell more than two-thirds from 296 to 97.9.

What is Coriolus Versicolor?

Like all mushrooms, Coriolus versicolor is a fungus, one of more than a half million varieties worldwide. Many of them have been known for thousands of years to have medicinal properties. And as you may know, gourmets the world over prize both wild and commercially grown mushrooms. Some European cookbooks even call them “flowers of the fall.” Whatever you call them, certain mushrooms are a perfect food for staying trim and healthy. They have little or no fat and some species, like Coriolusversicolor, boast valuable therapeutic and nutritional benefits. But a few fungi are poisonous and we do not recommend that nonexperts attempt to harvest their own. Coriolus versicolor goes by a number of botanical names, including Trametes versicolor and Boletus versicolor.

“Versicolor” refers to the mushroom’s various colors. In North America, the common name is “turkey tail,” while in Japan it is called by a name meaning “mushroom by the river bank” and in China its name indicates it’s a cloud fungus that grows best in the rain.

Over 400 clinical studies have shown that a purified extract derived from the mushroom Coriolus versicolor offers strong benefits for the immune system. Clinical studies indicate the extract’s ingredients are especially effective against stomach, uterine, colon and lung cancer.

Anecdotal evidence and clinical experience suggest it also works well against prostate, breast, liver and colorectal  cancer. Studies of rats and mice show that this mushroom is effective against many experimental animal cancers such as sarcoma and hepatoma.

Martha I.’s lung cancers disappear

“Of course,” says Dr. Bailey, “some cancer patients take Coriolus versicolor even while they engage in radiation treatment or chemotherapy. Or the patients don’t submit to chemotherapy or radiotherapy at all but rely, instead, exclusively on nutritional therapies with the medicinal mushroom as the main treatment ingredient.

“For example, one of my patients, Martha I., a 34-year-old woman working in the health field, consulted me with a cancer spreading at two sites in her lungs. Orthodox treatment had been tried but no longer was effective. She discontinued her smoking of two cigarette packs a day and embarked on nutritional therapies.

The nutrients included Martha’s completing six months of taking Coriolus versicolor. After this halfyear, radiological examination showed that all of her lung tumors had disappeared. Seeing her current progress, orthodox medicine probably would declare this patient to be cured.”

Blood tests show how the mushroom boosts immunity

I spoke with a doctor who measures natural killer cell (NK) counts and considers them a valuable cancer

marker. Kenneth Bock, M.D., is the medical director of two holistic medical clinics, one in Rhinebeck, New York and the other in Albany. “Because it increases natural killer (NK) cell activity, I think of using Coriolus versicolor mainly when I’m confronted with a patient suffering from cancer or a viral infection,” he says. “This mushroom is one of the main medicinal compounds I use to boost a diminished blood reading which records NK activity. The mushroom’s active biological response modifier produces a marked improvement in NK cell function and number, something I monitor by blood testing. If the blood reading is low, my patient takes greater amounts of PSK capsules. And, although it’s an expensive and sophisticated assay, I repeat my NK cell testing inside of a month or two. In a number of patients, I’ve seen some nice blood test improvement.”

Dr. Bock finds that a few patients with advanced metastatic cancer see their NK counts jump from 2 or 3 to a normal 20 to 50.

Patient’s immune system recovers

“I can illustrate what I’m saying by providing a before-and-after case history plus the literature that backs my claim,” Dr. Bock states. His patient was a white, married computer consultant named Marty E., sixty years old and suffering from high blood pressure and arteriosclerosis when he was also found to have polyps on his larynx. These were removed, with radiation therapy as a follow-up. But then Marty E. was also found to have prostate cancer.

“His blood test showed diminished natural killer cell activity at the level of 6 m/u,” Dr. Bock states. “Still, Marty wanted no conventional therapy for prostate cancer. So I started him on alternative medical therapies for prostate cancer and to improve his deficient NK cell activity. Coriolus versicolor was a definite part of his treatment regimen.

“Within two months, the patient’s NK cell activity elevated to 18 m/u. And two months after that his NK cell activity increased to a normal 31 m/u. Now the man is doing well physically, and he tells me he feels great! I would say this type of response to the  PSK therapy is usual; the patient’s quality of life does improve dramatically and he or she feels asense of well-being,” according to Dr. Bock.

A naturpathic doctor named Tori Hudson told of her clinical experience using PSK for breast cancer patients during and after chemotherapy. “My impression is that patients taking Coriolus versicolor are experiencing less side effects from chemotherapy such as diminished fatigue, less nausea (but not less hair loss), and more stable white blood cell counts. I have not measured natural killer cell counts,” she states.

Animal studies confirm what patients see for themselves

Animal studies show PSK is effective against a long list of cancers including melanoma, sarcoma, mammary cancer, colon cancer and lung cancer. Studies also show it inhibits metastasis to other sites. The studies indicate PSK enhances the immune system and battles cancer cells. It’s been shown to prolong the survival time and stimulate the production of cancer antibodies in mice with cancer.

PSK is also a potent antiviral remedy that may hold new hope for HIV-AIDS. It even lowers cholesterol in animals and speeds up recovery from burns in rabbits when used in combination with the herb Astragalus membranaceus.

Can be used in combination with conventional treatments

Human patients who have decided to stick with conventional chemotherapy and radiation therapy need to know that PSK renders these toxic treatments much more effective, as shown by a number of clinical studies.

A Japanese study looked at the effectiveness of 200 phytochemicals (plant substances) when used in combination with chemotherapy and radiation. Coriolus versicolor was found to be the best of the bunch. The researchers suggest that this medicinal mushroom seems to protect the immune system from being suppressed by prolonged use of chemotherapy drugsand by the cancer itself.

Further investigations indicate a marked improvement in the survival rates of chemo and radiationpatients taking the mushroom therapy when compared with those who did not. For patients with Stage I lung cancer observed over ten years, the tumor shrinkage and survival rate was 39 percent for those taking PSK compared to only 16 percent for patients receiving the toxic therapies without the mushroom extract. That’s a huge difference––more than twice as many survived and/or improved with the help of PSK.

Those lung cancer patients with more serious Stage II cancer experienced a 22 percent tumor shrinkage and survival rate over ten years when they took Coriolus versicolor orally while being treated with chemo or radiation. Among the people who didn’t take the herbal remedy the figure was a mere five percent.

From this study of 185 lung cancer patients it appears the mushroom extract can make the toxic therapies anywhere from two to four times more effective.

A Japanese study of 262 gastric cancer patients tested the mushroom’s efficacy following surgery. During a follow-up period ranging from five to seven years, the half who received the mushroom extract survived at substantially higher rates. The researchers concluded that PSK was a useful adjunctive therapy to surgery and chemo.

A Japanese study of breast cancer patients found similar results: Those who received PSK along with chemotherapy had better outcomes than those who did not. And a study of 28 patients suffering from acute leukemia––all on chemotherapy––showed an average survival time of 21 months for those who took the mushroom extract and 12 months for those who did not.

Hartford Hospital, Conneticut & Coriolus Vericolor PSK/PSP

What Hartford Hospital in Conneticut has to say about Coriolus Versicolor

“Currently, extracts of Coriolus versicolor called polysaccharide-K (PSK) and polysaccharopeptide (PSP) are under study as immune stimulants for use alongside chemotherapy in the treatment of cancer. These two related substances, made from slightly different strains of the fungus, are thought to act as “biological response modifiers,” meaning that they affect the body’s response to cancer.

According to most but not all reported trials, most of which were performed in Asia, both PSK and PSP can enhance the effects of various forms of standard cancer treatment. For example, in a 28-day double-blind , placebo-controlled study of 34 people with advanced non–small-cell lung cancer, use of Coriolus extracts along with conventional treatment significantly slowed the progression of the disease.

It is thought that Coriolus extracts work by stimulating the body’s own cancer-fighting cells. PSK and PSP may also have cancer-preventive effects.
In addition, very weak evidence hints that extracts of Coriolus versicolor might be helpful for HIV infection.”

(Source: www.hartfordhospital.org)

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