PSP has been shown to manifest immunomodulatory and anticancer properties in both pre-clinical experiments and clinical trials. It has been
shown to reduce the side effects of radiotherapy and chemotherapy and has been used as an adjunct medical modality to conventional cancer treatment. Experiments suggest that PSP can boost the immune system and alleviate the symptoms of chemotherapy.
Based on the PSP´s significant findings in the investigated cancers of the Phase II trial, permission was granted by the Chinese Administration of Health Bureau to carry out a multi-center Phase III clinical trial. Fourteen hospitals including the eight who participated in the phase II trial conducted this randomized study from April 1996 to September 1997.
Polysaccharide-peptide (PSP) is a protein bound polysaccharide 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.
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.
PSP is an anticarcinogen and immunological regulator identified as a polysaccharide peptide which has been extracted from the deep layer cultivated mycelia of Coriolus versicolor. Infrared spectrophotometer at wavelenghts of 3432 cm-1, 1621 cm-1 and 1073 cm-1 produces three absorption bands.
The N.M.R. of PSP has the characteristic to show absorption at 1.0-2.5 ppm, 3.0-3.4, 4.5, 5.4 ppm and broad absorption in the region of 3.0-4.3 ppm.
Use spectrophotometer to determine the effluent separated from the column of gel chromatography (Sephadex G-75), The results shown that maximum absorption peaks of polypeptide and polysaccharides are found in the homeo-collecting tubes.
The polysaccharide portion is composed of the five monsaccharides, galactose, glucose, mannose, xylose, and fucose. The amino acids most frequently found in the polypeptide are aspartic and glutamic. PSP has no sharply defined fusion point. It is insoluble in methyl alcohol, pryridine, benzene, hexane, and chloroform but is very soluble in hot water. The pH value of its 1% water solution is 6.6. It is heat and light stable. &nbp; When kept at a temperature of 100oC for 48 hours or irradiated with ultraviolet light for 30 hours there is essentially no change in composition. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) the molecular weight has been calculated at about 1×105 Dalton.
A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-¯uorouracil (tegafur) and uracil at a molar ratio of 1:4, to be e€ective for poorly di€erentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly di€erentiated gastric cancer following a curative resection. We determined the e€ect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly di€erentiated stage II±IV gastric cancer were entered into this study after undergoing a curative resection. No di€erences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-speci®c survival (P < 0.05). UFT at 12 mg/ kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly di€erentiated gastric cancer, and is also cost-e€ective for outpatients.
C.Y. Hoa, Clara B.S. Laua, C.F. Kima, K.N. Leungb, K.P. Fungb, T.F. Tsec, Helen H.L. Chanc, Moses S.S. Chowa
Being one of the commonly used Chinese medicinal herbs, Coriolus versicolor (CV), also named as Yunzhi, was known to possess both anti-tumor and immunopotentiating activities. The present study aimed to investigate the in vitro immunomodulatory effect of a standardized ethanol–water extract prepared from CV on the proliferation of murine splenic lymphocytes using the MTT assay, and the production of six T helper (Th)-related cytokines using the enzyme-linked immunosorbent assay (ELISA) technique. The results showed that the CV extract significantly augmented the proliferation of murine splenic lymphocytes in a time- and dose-dependent manner, maximally by 2.4-fold. Moreover, the production of two Th1-related cytokines, including interleukin (IL)-2 and IL-12, in culture supernatants from the CV extract-activated lymphocytes was prominently upregulated at 48 and 72 h. Positive correlations were found between the levels of these two cytokines and the MTT-based proliferative response. In contrast, the production of two other Th1-related cytokines, including interferon (IFN)-g and IL-18, was significantly augmented only at 24 h, but not at 48 and 72 h. On the other hand, the levels of two Th2-related cytokines such as IL-4 and IL-6 were undetectable in the culture supernatants of lymphocytes treated with the CVextract. The CVextract was suggested to be a lymphocyte mitogen by differentially enhancing the production of Th1-related cytokines.
Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 Ag/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 F 15.2 Ag/ml), Raji (253.8 F 60.7 Ag/ml) and NB-4 (269.3 F 12.4 Ag/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 Ag/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.
Kodama Y, Kano T, Tamada R, Kumashiro R, Okamura T, Inokuchi K.
Effectiveness of prophylactic extensive lymph node dissection (PELD) plus postoperative long term combination chemotherapy (PLCC) for patients with curatively resected gastric carcinoma was assessed in terms of the degree of serosal invasion and lymph node metastasis. Either the Group 1 and Group 2 lymph nodes were eradicated by PELD. PLCC included intermittent intravenous administration of mitomycin C (0.4 mg/kg intraoperatively followed by 0.2 mg/kg every 3 months) and oral administration of Tegafur (600-800 mg/day) and PSK (3.0 g/day), an immunostimulator, for as long a period as possible. PELD alone resulted in a cure when the malignancy was confined to the mucosal and muscular layers of the stomach as well as to the Group 1 lymph nodes. In cases when the carcinoma involved the serosa and/or the Group 2 lymph nodes, the 5 year survival rate was about 55 per cent the PELD and PLCC groups, such being significantly higher than about 27 per cent in the PELD alone group. Therefore, PELD plus PLCC is highly effective for advanced gastric carcinoma, under a condition of curative resection.
To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSKtreated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.
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