In the present study the anti-cancer effect of polysaccharide peptide of Coriolus versicolor Cov-1 (PSP) was compared with polysaccharide peptide of Coriolus versicolor CM-101 (PSK) on four human tumor cell line targets (SGC 7901, stomach cancer cell; SPC, human lung adenocarcinoma cell; SLY, human monocytic leukemia cell and Mei, human skin histiocytic lymphoma cell) in Vitro.
PSP had similar cytotoxic effects upon human tumor cells as PSK, both inhibiting cell growth. In comparison with control specimens, the SPC cell line treated with PSP (1000ug/ml) for 72 hours at 37oC showed marked morphological changes such as cell swelling, chromatin aggregation, formation of polynuclear cells and sawtooth on the surface of cell nuclei.
PSK as a new immunomodulative drug had been widely used for clinical anticancer therapy in Japan. When combined with chemotherapy, radiotherapy and surgical operation, PSK is found to be able to improve the therapeutic effects. In 1983, a polysaccharide peptide of Coriolus versicolor Cov-1 was isolated from the mycelia by Qing-yao Yang. It is possessed of physio-chemical characteristics similar to PSK and designated as PSP. In the present study the anti-cancer effect of PSP was compared with PSK using four human tumor cell line targets in vitro.
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.
Suto T, Fukuda S, Moriya N, Watanabe Y, Sasaki D, Yoshida Y, Sakata Y.
We conducted a randomized, controlled trial comparing 5-fluorouracil (5-FU) with or without biological response modifiers (BRMs) as a maintenance therapy for hepatocellular carcinoma (HCC) after treatment with percutaneous ethanol injection (PEI), transcatheter arterial embolization (TAE) or arterial infusion of antitumor agents (AI). A total of 58 cases of HCC were classified into 4 groups as follows: group I, PSK with 5-FU (n = 15); group II, lentinan with 5-FU (n = 15); group III, OK-432 with 5-FU (n = 12); and group IV, 5-FU alone as the control (n = 16). The mean survival time, mortality rate, time to progression, and T4/T8 ratio of lymphocytes in the peripheral blood were compared among the four groups. There was no significant difference in the background factors among the groups. In group I, the T4/T8 ratio of lymphocytes was reduced after the therapy. No significant difference was found among the groups in terms of the mean survival time, mortality rate, or time to progression. PEI for initial therapy was superior to the other therapies in terms of the mean survival time and mortality rate. These results suggest that the addition of BRM to maintenance therapy with 5-FU exerts no prognostic benefit on HCC patients treated with PEI, TAE, or AI.
The most effective treatment for gastric cancer is complete surgical resection with lymphadenectomy. However, a number of patients experience recurrence of the cancer even after curative surgery. This review focuses on comparative trials studying the use of adjuvant therapy with chemotherapy plus immunotherapy in the treatment of patients with curatively resected gastric cancer. Preoperative and intraperitoneal therapy, and therapy for advanced or recurrent gastric cancer are also discussed. At present, some subset analyses of adjuvant trials have shown favorable results suggesting that the biological response modifiers (BRMs), PSK or OK-432, add a benefit to chemotherapy. For advanced gastric cancer, although gastric cancer cells are generally not very sensitive to most of the currently available chemotherapeutic agents, it has been reported that biochemical modulation with treatments including low-dose cisplatin + 5-FU (fluorouracil) have high response rates and exert an immunomodulatory effect especially when used in combination with BRMs. The impact of splenectomy and some of the
promising newly developed drugs are discussed.
Up to now, the three main weapons against cancer have been surgery, radiotherapy and chemotherapy. Although these classical methods of treatment have given fairly good results in general, the results have yet to be improved, especially in late cases. Thus for many years, the search for a more effective means of anti-cancer treatment has been going on world-wide. An ideal drug would of course be one that could directly kill all the cancer cells without harming the normal tissues, and also without causing general toxicity. However, at present a more practical approach is to use drugs that would either enhance the biological effects of radiation or of cytotoxic agents, or strengthen the organism’s immunological defenses. In recent years, several such drugs have been undergoing clinical trials, for example, Misonidazole, RS 2508, OK-432, PSK, etc.
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.
Data on Krestin suggest that this family of drugs when used in combination with radiotherapy, there might be an increase of the biological effects of radiation. To do a pilot study on such a possibility, the authors have treated 41 moderate to advanced cases of esophageal carcinoma with a combination of PSP and radiotherapy.
The purpose of this study was to determine if immunotherapy with Krestin can prolong the durations of complete remission and survival. The patients were placed at random in the chemotherapy and chemoimmunotherapy groups. The median durations of complete remission and survival were longer in the chemoimmunotherapy group than in the chemotherapy group. The complete remission rate of the second induction was higher in the chemoimmunotherapy group than in the chemotherapy group. The cell-mediated immunity was somewhat enhanced in the chemoimmunotherapy group, while it was not enhanced in the chemotherapy group. These results suggested that Krestin administration for maintenance therapy was useful for prolongation of the durations of remission and survival time in patients with acute leukemia.
Cryoablation is a low-invasive surgical treatment for malignant tumors. It may induce an immunological response leading to the eradication of distant metastases or alternatively it might promote the growth of residual tumors. In this paper we confirm the occurrence of both phenomena and we describe the preventive effect of a protein-bound polysaccharide preparation. Metastatic liver tumors were produced in BALB/c mice by the intrasplenic inoculation of colon 26 cells and cryoablation was carried out usingliquid nitrogen ()170C) applied by a contact method. The value of combiningcryoablation with administration of the polysaccharide preparation in the prevention of growth of residual tumors was investigated. It was shown that the number of metastatic liver nodules and the size of the primary tumor at the site of inoculation in the spleen were significantly lower when the volume that was frozen was small. The production by splenocytes of the tumor necrosis factor TNF-a, interferon INF-c, and the interleukins IL-4 and IL-10 increased significantly after freezing and thawing of the tumor tissue. The polysaccharide treatment significantly reduced the production of IL-4 and IL-10 followingcryoablation; the production of TNF-a and INF-c was slightly promoted; the natural killer and cytotoxic T-cell activities of splenocytes were slightly enhanced. It was concluded that the polysaccharide preparation was beneficial by suppressing IL-4 and IL-10 production and might inhibit the growth of residual tumor that is sometimes induced by large-volume cryoablation.
RPSP, a refined polysaccharide peptide fraction isolated by fast performance liquid chromatography (FPLC) from the crude powder of total peptide-bound polysaccharides of cultivated Coriolus versicolor Cov-1 dose-dependently inhibited the proliferation of a human hepatoma cell line (HEPG2). The effective dose causing 50% inhibition following 3-day exposure to RPSP was 243 +/- 36 micrograms/ml for HEPG2. However, little or no inhibitory effects were detected in normal human foetal hepatocytes. On the other hand, in the pretreatment group, in which RPSP was administered i.p. for two weeks before sarcoma 180 inoculation in nude mice, the incidence of tumor growth was less (2 out of 5 mice) than that of the control group (all 5 mice). The tumor size of the control group was about 3-5 times bigger than that of the pretreatment group. In tumor bearing nude mice, 5 days after sarcoma 180 inoculation, i.v. administration of RPSP significantly suppressed the growth of tumor mass. The inhibition rate was 93.6% on day 13. Furthermore, administration of RPSP did not cause any pathological lesions in vital organs of rabbits such as heart, liver, spleen, lung and kidney. In conclusion, these results indicate that RPSP acts by directly suppressing tumor cell growth in vitro and the prevention of in vivo growth of tumor mass is probably mediated also via its immunomodulating effects.
Jin-Xu Zhou, Xin-li Shen, Zu-ming Shen, Xiao-yu Li
Polysaccharide peptide of Coriolus versicolor (PSP) is a new anti-tumor and immunomodulating drug. In this paper PSP showed direct inhibition on the cell proliferation of sarcoma 180 in vitro and inhibitory effect on the growth of murine sarcoma 180 in vivo. Owing to its direct cytotoxic effect was not strong, but at lower concentrations (10-20ug/ml) of PSP promoted the proliferation of T and pre-T cells of mouse thymus, increased the thymus weight, provided more number of lymphocytes, prevented the involuation of thymus in tumor bearing mice and antagonized the anti-tumor action of PSP combined with antilymphocyte serum. It is suggested the principal mechanism of anti-tumor activity of PSP was T-cell mediated cytotoxicity.
It has been known that some polysaccharides and polysaccharide peptide isolated from various natural sources, especially isolated from Basiodiomycetes have certain anti-tumor activities. The polysaccharide contained a main chain of an alpha and beta (1-4) glucan and a tightly bound 15-38% polypeptides (PSP) isolated from Coriolus versicolor (Fr) Quel. (Cov-1) by Professor Qing-yao Yang also exhibited antitumor action against mouse sarcoma 180 in vitro and in vivo. Recent experiments suggest three possible mechanism by which these PSP might act: (1) Potentiating of T-cell mediated cytotoxicity which killed more number of target-tumor cells. (2) Definite concentration of PSP produced direct cytotoxic activity in vitro. (3) Induction of tumorcidal macrophages killed more cancer cells. In this paper the antitumor action of PSP and its possible mechanism are reported.