Z.Y. Sun et al
Shanghai Medical University
Abstract
28 late cases of malignancy of all pathologically proven were evaluated. Among them are one case of melanoma, two cases of non-Hodgkin lymphoma (NHL), twenty cases of gastro-intestinal cancers, three cases of bronchogenic carcinoma, one case each of primary hepatocellular carcinoma and multiple peritoneal malignancies of unknown origin respectively.
Cloud mushroom contains several saccharides including polysaccharide peptide (PSP) and polysaccharide-K (PSK, krestin). The protein bound polysaccharides have been found to be immune-modulating and anti-tumor, and their polypeptide moieties are rich in aspartic acid and glutamic acid. By gas chromatography and HPLC, PSP has proved that in addition to glucose, it also contains five other monosaccharides – mannose, xylose, galactose, rhamnose and arabinose. The polysaccharide peptides can be found in the mycelium, while the fruiting body mainly contains polysaccharides
Coriolus mushroom is a fungus. People have used the fruiting body and other parts as folk medicine for a long time. Recently, researchers have started to isolate and identify substances in coriolus that might act like pharmaceutical drugs. Two of these substances are polysaccharide peptide (PSP) and polysaccharide krestin (PSK). Scientists think these chemicals might be able to fight cancer and boost the immune system. Coriolus mushroom, PSP, and PSK are used for stimulating the immune system; treating herpes, chronic fatigue syndrome (CFS), hepatitis, and pulmonary disorders; reducing phlegm; improving bodybuilding results; increasing energy; curing ringworm and a skin condition called impetigo; treating upper respiratory, urinary, and digestive tract infections; curing liver disorders including hepatitis; reducing the toxic effects and pain of chemotherapy and radiation therapy; increasing the effectiveness of chemotherapy; prolonging life and raising the quality of life of cancer patients; and increasing appetite.
Display Settings: Abstract
Int J Oncol. 2004 Aug;25(2):453-9.
Ogihara T, Iinuma H, Okinaga K.
Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.
Abstract
Biological response modifiers (BRMs) augment the cytotoxic activity of various effector cells by the induction of multiple
cytokines and suppression of immunosuppressive factors. BRMs are used extensively in adjuvant therapy for gastric
cancer in Japan. In dendritic cell (DC)-based vaccine therapy, the quality of DCs is important in inducing strong antitumor
immunity. A good manufacturing practice (GMP) grade agent for DCs maturation is desirable for safety. Here we report
the effects of two BRMs, OK432 and PSK, which are GMP grade agents for the functional maturation of DCs. OK432 and
PSK were examined in vitro, and compared with lipopolysaccharide (LPS) and a cytokine cocktail (IL-1beta, TNF-alpha,
IL-6 and PGE2). In the immunophenotypical analysis, the expression of CD80 and CD83 of DCs stimulated with OK-432
increased significantly compared with PSK and medium, and this up-regulation was the same as levels of DCs stimulated
with cytokine cocktail. DCs stimulated with OK-432 showed significantly higher production of IL-12 and Th1-type cytokines
(IL-2 and IFN-gamma) compared with DCs stimulated with LPS or cytokine cocktail. OK-432 stimulated DCs could induce
the significantly high level of cytotoxic T cell activity compared with PSK-stimulated or unstimulated DCs. These results
suggest that OK432 is a GMP-grade reagent that promotes functional maturation of DCs and could be applied in
DC-based vaccinations.
PMID: 15254744 [PubMed – indexed for MEDLINE]
Anai H, Sakaguchi Y, Emi Y, Kohnoe S, Maehara Y, Sugimachi K.
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
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.
Keizo Sugimachi, Yoshihiko Maehara, Michio Ogawa, Teruo Kakegawa, Masao Tomita
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.
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.
Ichihashi H, Kondo T, Nakazato H.
A randomized controlled study was carried out on curatively resected gastric cancer patients in a cooperative study involving 16 institutions in order to evaluate the effect of an alternative long-term adjuvant immunochemotherapy using Esquinon (CQ) and Krestin (PSK). One week after surgery, CQ was given at a dose of 2mg/m2 once a week for 3 weeks and this was repeated every 6 weeks. CQ was administered intravenously in the 1st course and thereafter orally up to 9 courses. Three postoperative week, immunotherapy was then started in which PSK was given orally in 3 divided doses of
2g/m2/day from the day when CQ therapy ended for 4 consecutive weeks, and this performed for every course. Estimated survival rate and cumulative survival curves were compared utilizing the data up to 7 years after surgery in the chemotherapy group given CQ alone and in the immunochemotherapy group given CQ + PSK. The survival curve in all cases showed a favorable form in the CQ + PSK group for up to 36 months, and thereafter it crossed with that of the CQ group for up to 68 months. Both curves twisted at 68 months and then deviated from each other, showing that the effect in the CQ + PSK group beneficial. The curve showed a twisting configuration throughout the treatment period. There was no statistically significant difference between the survival curves of the two groups. Retrospective survival analysis was then performed on separate subgroups classified into the category of S1, S2, N1, and N2. The CQ + PSK group was better than the CQ alone group in its survival rate for the S1 + S2 (N1-2) group, the percentage being 11.5%, and a statistically significant difference was observed between the two groups (p = 0.089).
Masahiko Shibata Takeshi Nezu Shigeru Fujisaki Katsuyuki Andou
Ryouichi Tomita Masahiro Fukuzawa
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.
To evaluate the efficacy of PSK for adjuvant immuno-chemotherapy in patients who had undergone radical gastrectomy, a randomized controlled trial has been in progress in collaboration with 46 institutions in the Chubu district of Japan. A total of 262 patients were registered for this trial during the two years from July 1985 to June 1987 with a centralized registration system, and were allocated into the 5-FU+PSK group (Group P) and 5-FU alone group (Group C) by the minimization method following the random permuted blocks method. Between the two groups, the parameters of sex, age, serosal invasion (S), lymph-node metastasis (N), and the combination of S . N factor levels were distributed without significant differences. An induction treatment with MMC 6 mg/m2 was given to all patients following curative mastectomy and on the 7th post-operative day. Two weeks after surgery, Group P received alternately PSK 3 g/day for 4 week and 5-FU 150 mg/day for 4 weeks as one course, and 10 courses were given. Group C received 5-FU alone for 4 weeks using alternate rest interval for 4 weeks. Since both experimental and clinical studies suggested that alternate treatments using PSK and anticancer agents were effective, treatment in this trial alternated PSK and 5-FU. A final follow-up study will be completed in June 1992, when all patients shall have survived more than 5 years after surgery. The administration of 5-FU was completed by January. 1989, but PSK has been administered to group P. The period from 18 to 42 months after surgery was reached in all eligible patients (253) at the end of December 1988. The disease-free survival curves and overall survival curves of group P were significantly (p = 0.018 and p = 0.045,) better than those of group C.