Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx.

A controlled study using adjuvant PSK immunotherapy in patients with nasopharyngeal carcinoma was initiated with the aim of improving survival by enhancing the host immune system against tumour cells. A total of 38 patients were randomly selected, all of whom had previously received radiotherapy with or without chemotherapy. Eight patients in the PSK immunotherapy group (n = 21) developed local recurrence, three of whom later died due to distant metastasis. In the control group (n = 17) three patients developed local recurrence while six patients developed distant metastasis. All of these six patients later died due to disease progression. It seems that PSK exerts its antitumour effect systemically; the risk of distant metastasis occurring is decreased, but it is apparently ineffective in improving local disease control. The estimated median survival time of the PSK-treated group compared with the control was significantly increased (35 months versus 25 months, P = 0.043). The 5-year survival rate was also significantly better in the PSK immunotherapy group (28% versus 15%, P = 0.043). It is concluded that PSK deserves careful consideration as an important immunotherapeutic agent in the management of nasopharyngeal carcinoma.

Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study

Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n¼123) or III (n¼82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6–80.4%) with PSK (n¼137) and 58.8% (95% CI 47.1–70.5%) in the controls (n¼68) (P¼0.016). POLYSACCHARIDE K reduced the recurrence by 43.6% (95% CI 4.5–66.7%) and mortality by 40.2% (95% CI _12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3–88.2%) in the PSK group and 72.1% (95% CI 61.4–82.7%) in the control group (P¼0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1–72.9%) and 74.6% (95% CI 63.0–86.1%) in the PSK group as compared with 32.1% (95% CI 14.8–49.4%) and 46.4% (95% CI 28.0–64.9%) in the controls (P¼0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P¼0.02; odds ratio 0.27; 95% CI 0.09–0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712–5.165; Po0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221–3.633; P¼0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017–19.014; P¼0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.

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Activation of peritoneal macrophages by polysaccharopeptide from the mushroom, Coriolus versicolor.

Polysaccharopeptide (PSP) is a substance produced by an edible mushroom, Coriolus versicolor which has been claimed to possess antitumor activity.  However, neither tumoricidal activity nor cytotoxicity was observed when five tumor cell lines and mouse peritoneal macrophages were cultured in vitro in the presence of 2.5-10 ?g/ml PSP.  An increase in the production of reactive nitrogen intermediates, reactive oxygen intermediates (superoxide anions) and tumor necrosis factor was measured in peritoneal macrophages collected from inbred C57 mice which had received PSP in the drinking water for 2 weeks.  Northern blot analysis also demonstrated that PSP activated the transcription of tumor necrosis factor gene in these cells, indicating that PSP exerted an immunomodulatory effect on the defensive cells.

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Activation of human natural killer cells by the protein-bound polysaccharide PSK

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 ÷ large granular lymphocytes (LGL) were treated in vitro overnight with PSK, they demonstrated enhanced NK cell activity against K562. The PSK-activated killer cells also lysed NK-resistant targets and freshly isolated autologous and allogeneic tumor cells. The PSK effect was observed with concentrations that could be obtained in the blood of cancer patients receiving oral administration of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal antibodies (mAb) that neutralized interferon (IFN)o~, IFN3,, or interleukin-2 (IL-2). In addition, mAb reactive with p55 (~ chain) or p75 (/3 chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK activity even when used simultaneously. These results indicate that the PSK could activate human NK cells independently of IFN and IL-2/IL-2R systems.

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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.


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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