MedLine Search: PSK, a non-toxic anti-tumor polysaccharide
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This MedLine Search of the technical medical literature is from the early days of CancerGuide so it may not include the latest research. The articles referenced are still relevant but more recent ones may also be available. For more information on the incredibly powerful and freely available MedLine database see my Article on MedLine.
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THU SEP 22,1994 9:32 PM PaperChase Contains 8,517,714 References -- All References Found in the Following Databases of the National Library of Medicine and the National Cancer Institute*. You are searching all four databases simultaneously. Database Indexing Began Updated Current through MEDLINE 1966 weekly November 1994 Update, Part 3 HEALTH 1975 monthly October 1994 Update AIDSLINE 1980 monthly October 1994 Update *CANCERLIT 1980 monthly September 1994 Update LIST REFERENCES LIST REFERENCES A) PSK 196 C) *SUM AB 231 B) KRESTIN 35 *****BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS***** (REFERENCE 1 OF 41) 89334864 Sakagami H Ikeda M Konno K Stimulation of tumor necrosis factor-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction. In: Biochem Biophys Res Commun (1989 Jul 31) 162(2):597-603 The mouse macrophage-like cell line, J774.1, spontaneously released differentiation-inducing factor(s). When these cells were treated with a protein-bound polysaccharide, PSK, significantly higher amounts of differentiation-inducing activity were accumulated in the culture supernatant. PSK directly stimulated human myelogenous leukemic cell differentiation induced by J774.1 conditioned medium or by tumor necrosis factor. Among four subfractions of PSK, only the highest molecular weight fraction (MW greater than 200 kD) exerted such a stimulating effect. Institutional address: First Department of Biochemistry School of Medicine Showa University Tokyo Japan. *****JAPANESE JOURNAL OF CANCER RESEARCH***** (REFERENCE 2 OF 41) 92388016 Ebina T Murata K Antitumor effect of PSK at a distant site: tumor-specific immunity and combination with other chemotherapeutic agents. In: Jpn J Cancer Res (1992 Jul) 83(7):775-82 The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male- 1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti- metabolite, 5-fluorouracil. Institutional address: Department of Bacteriology Tohoku University School of Medicine Sendai. (REFERENCE 3 OF 41) 92041203 Kariya Y Okamoto N Fujimoto T Inoue N Kihara T Sugie K Yagita M Kanzaki H Mori T Uchida A Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK. In: Jpn J Cancer Res (1991 Sep) 82(9):1044-50 The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor- infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK- induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems. Institutional address: Department of Late Effect Studies Kyoto University. (REFERENCE 4 OF 41) 89254785 Ebina T Kohya H Ishikawa K Antitumor effect of PSK: role of regional lymph nodes and enhancement of concomitant and sinecomitant immunity in the mouse. In: Jpn J Cancer Res (1989 Feb) 80(2):158-66 PSK, a Coriolus preparation, inhibited the growth of not only the right but also the left, non-treated tumor in a double grafted tumor system. In order to examine the role of lymph nodes and the spleen in the antitumor activity of PSK, regional (axillary and inguinal) lymph nodes and spleen were resected. Since in resected mice the antitumor activity of PSK against the right and left tumors was weakened, the regional lymph nodes and the spleen probably have a very important role in the antimetastatic effect of intratumoral administration of PSK. TIL (tumor-infiltrating lymphocytes) obtained from left and right side tumors treated with PSK were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from both sides clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. A primary growth of Meth-A sarcoma inoculated into the right flank resulted in the generation of concomitant immunity to the growth of a second graft of the same tumor cells in the left flank. A significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily was shown in mice bearing a primary right tumor that had previously been inoculated with PSK 3 times. After surgical excision of the primary tumor on day 6, daily oral administration of PSK significantly inhibited the growth of the secondary tumor inoculated on day 21, that is, PSK treatment also enhanced sinecomitant immunity. These observations suggest that presurgical intratumoral injection and postoperative oral administration of PSK are highly effective in eradicating metastatic tumors. Institutional address: Department of Bacteriology Tohoku University School of Medicine Sendai. (REFERENCE 5 OF 41) 88186531 Kikuchi Y Kizawa I Oomori K Iwano I Kita T Kato K Effects of PSK on interleukin-2 production by peripheral lymphocytes of patients with advanced ovarian carcinoma during chemotherapy. In: Jpn J Cancer Res (1988 Jan) 79(1):125-30 The effects of PSK on OKT 4/OKT 8 cell ratio, interleukin-2 (IL-2) production and expression of IL-2 receptor were examined in peripheral blood lymphocytes (PBL) from patients with advanced ovarian cancer during the course of chemotherapy. Preoperative levels of OKT 4/OKT 8 cell ratio and IL-2 production in PBL from patients with advanced ovarian cancer were significantly lower than those in cases of benign ovarian tumor. However, the expression of IL-2 receptor did not show any significant difference between ovarian cancer and benign ovarian tumor patients. When a combination chemotherapy of cisplatin, adriamycin and cyclophosphamide was given, the OKT 4/OKT 8 cell ratio was significantly increased with a significant decrease of the absolute number of the OKT 8 cell subset, while the expression of IL-2 receptor and the absolute number of the OKT 4 cell subset remained unchanged. In contrast, the IL-2 production was markedly depressed after the first course of chemotherapy. When PSK was combined with combination chemotherapy, the degree of inhibition of IL-2 production was reduced (though the effect was not statistically significant). If treatment with PSK was initiated after completion of combination chemotherapy, in addition to a significant elevation of OKT 4/OKT 8 cell ratio the depressed IL- 2 production was restored to benign control levels. On the other hand, the expression of IL-2 receptor remained unchanged even if PSK was given after completion of chemotherapy. Institutional address: Department of Obstetrics and Gynecology National Defense Medical College Saitama. *****LANCET***** (REFERENCE 6 OF 41) 94239027 Nakazato H Koike A Saji S Ogawa N Sakamoto J Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. In: Lancet (1994 May 7) 343(8906):1122-6 In Japan the standard adjuvant treatment after resection of gastric cancer is intravenous mitomycin plus oral fluorouracil. We have assessed the efficacy of protein-bound polysaccharide (PSK) in addition to standard chemotherapy in patients who had undergone curative gastrectomy at 46 institutions in central Japan. 262 patients were randomly assigned standard treatment alone or with PSK. The minimum follow-up time was 5 years (range 5-7 years). PSK improved both the 5-year disease-free rate (70.7 vs 59.4% in standard treatment group, p = 0.047) and 5-year survival (73.0 vs 60.0%, p = 0.044). The two regimens had only slight toxic effects, consisting of nausea, leucopenia, and liver function impairment, and there were no significant differences between the groups. The treatments were clinically well tolerated and compliance was good. Addition of PSK to adjuvant chemotherapy with mitomycin and fluorouracil is beneficial as treatment after curative gastrectomy. Institutional address: Yokoyama Gastrointestinal Hospital Japan. *****RECENT RESULTS IN CANCER RESEARCH***** (REFERENCE 7 OF 41) 79224859 Taguchi T Clinical studies on PSK: combination therapy of PSK with surgery and chemotherapy. In: Recent Results Cancer Res (1978) 68:236-40 [No Abstract Available] (REFERENCE 8 OF 41) 79224849 Taguchi T Clinical studies on PSK: combination therapy of PSK with radiation in cancer of the uterine cervix. In: Recent Results Cancer Res (1978) 68:174-7 [No Abstract Available] *****ANTICANCER RESEARCH***** (REFERENCE 9 OF 41) 92675773 Sakagami H Kawazoe Y NOVEL ELUCIDATION OF THE MECHANISM OF INDUCTION OF VARIOUS IMMUNOPOTENTIATING ACTIVITIES BY A PROTEIN-BOUND POLYSACCHARIDE, PSK (MEETING ABSTRACT) In: Anticancer Res (1990) 10(5B):1472 A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr) Quel, has been recognized for its host- mediated antitumor and antimicrobial activity in mice. Since PSK is a plant extract, it could contain several active ingredients. However, intact PSK has been used in almost all experiments. We recently reported that, among the four subfractions separated by the mol wt, only the highest mol wt fraction, F4 (mol wt greater than 200 kD), induced significant antimicrobial activity in mice. PSK and F4 stimulated the differentiation of human myelogenous leukemia cell lines toward monocyte/macrophages, induced by various cytokines such as tumor necrosis factor (TNF) and interferon-r (IFN-r). Binding studies with 125I-TNF or 125I-IFN-r suggest that the stimulating effect of the active PSK subfractions might be associated with inhibition of the downregulation of receptor binding of these cytokines. PSK also stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN), and the NBT-reducing activity of mouse peritoneal resident macrophages. Among the subfractions of PSK, whether separated by mol wt or by isoelectric point precipitation, the highest mol wt fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. We recently found that iv administration of PSK significantly stimulated OK-432- elicited endogenous cytotoxic factor (possibly TNF) production in mouse serum. The data suggest that (1) immunopotentiation activity of PSK might be ascribed, at least in part, to the stimulation or production of various cytokines, and (2) PSK might have some unique component(s) which directly stimulate the macrophage/PMN function. Therefore, the necessity of an advanced structure-activity relationship is indicated and further studies of this need are underway in our laboratory. Institutional address: First Dept. of Biochemistry Sch. of Medicine Showa Univ. 1-5-8 Hatanodai Shinagawaku Tokyo 142 Japan (REFERENCE 10 OF 41) 87324781 Matsunaga K Morita I Oguchi Y Fujii T Yoshikumi C Nomoto K The effect of a biological response modifier, PSK, on the intestinal immune system in tumor-bearing mice. In: Anticancer Res (1987 May-Jun) 7(3 Pt B):509-12 We have previously shown that oral administration of PSK not only exerts antitumor activity, but also restores immune response in tumor- bearing mice. In order to analyze the immunomodulative effect of PSK, we investigated the effects of oral PSK on the intestinal immune systems in ICR mice bearing sarcoma 180. Oral administration of PSK increased the number of Peyer's patches that developed relatively well, and led to recovered mitogenic response of lymphocytes from gut- associated lymphatic tissue and responsiveness to oral preimmunization with SRBC in tumor-bearing mice. These results suggest that PSK modulates the immunity in intestinal tract of tumor- bearing mice. Institutional address: Biomedical Research Laboratories Kureha Chemical Industry Co. Ltd. Tokyo Japan. (REFERENCE 11 OF 41) 94091790 Hayakawa K Mitsuhashi N Saito Y Takahashi M Katano S Shiojima K Furuta M Niibe H Effect of krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. In: Anticancer Res (1993 Sep-Oct) 13(5C):1815-20 From 1976 to 1985, 185 patients with non-small cell lung cancer at stages I-III were treated with definitive radiotherapy in Gunma University Hospital. As a result of analyzing the long-term survivors treated with radiotherapy, suitable conditions of the patients for radical radiotherapy were as follows; 1) stage I or II, and some stage III, 2) as regards the histologic type epidermoid carcinoma or well-differentiated adenocarcinoma, 3) as regards the primary sites, the upper lobe and the superior segment of the lower lobe, 4) the optimum dose was 60-70Gy, 5) the size of the radiation fields given > 40Gy was 100 cm2 or less, and 6) the host condition was satisfactory (BRM combined use). In particular, as a result of administering PSK as adjuvant treatment to patients with epidermoid carcinoma of the lung showing satisfactory tumour shrinkage after radiotherapy, the five year survival rate of the patients with stages I or II disease, as well as stage III was 39% and 22% respectively, compared with the non-administered group's 16% and 5%. These differences are statistically significant. Although an improvement in the results of treatment with the combined use of appropriate BRMs is anticipated in the future, when clinical trials for combined BRM and radiotherapy are planned, the subjects should be patients with satisfactory tumour regression after radiotherapy. Institutional address: Department of Radiology and Radiation Oncology Gunma University School of Medicine Japan. (REFERENCE 12 OF 41) 93199236 Iino Y Takai Y Sugamata N Morishita Y PSK (krestin) potentiates chemotherapeutic effects of tamoxifen on rat mammary carcinomas. In: Anticancer Res (1992 Nov-Dec) 12(6B):2101-3 A total of 20 mg of 7,12-dimethylbenz[a]anthracene (DMBA) was administered orally to 41 female Sprague-Dawley (SD) rats (control group), and 60 mg/kg of Krestin (PSK) were orally administered daily to 38 rats (PSK group) after DMBA administration. The average development period (9.6 weeks) of DMBA-induced tumors in the PSK group was significantly longer (P < 0.02) than that (7.9 weeks) in the control group. Average estrogen receptor (ER) levels of established tumors were almost the same between these two groups. However, the chemotherapeutic effect of tamoxifen (TAM) was significantly enhanced by PSK pretreatment. Institutional address: Second Departmen of Surgery Gunma University School of Medicine Japan. (REFERENCE 13 OF 41) 91290790 Sakagami H Aoki T Simpson A Tanuma S Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review). In: Anticancer Res (1991 Mar-Apr) 11(2):993-9 A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host- mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features. Institutional address: First Department of Biochemistry School of Medicine Showa University Tokyo Japan. *****BIOTHERAPY***** (REFERENCE 14 OF 41) 92322392 Nio Y Tsubono M Tseng CC Morimoto H Kawabata K Masai Y Shiraishi T Imai S Ohgaki K Tobe T Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. In: Biotherapy (1992) 4(2):117-28 The present study was designed to assess the effects of the protein- bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration less than 14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (greater than or equal to 14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group. These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: First Department of Surgery Kyoto University Faculty of Medicine Japan. *****CANCER***** (REFERENCE 15 OF 41) 93046011 Toi M Hattori T Akagi M Inokuchi K Orita K Sugimachi K Dohi K Nomura Y Monden Y Hamada Y et al Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization. In: Cancer (1992 Nov 15) 70(10):2475-83 BACKGROUND. A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. METHODS. A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER- positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. RESULTS. Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS. The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer. Institutional address: Department of Surgery Hiroshima University Japan. *****CANCER EPIDEMIOLOGY, BIOMARKERS AND PREVENTION***** (REFERENCE 16 OF 41) 93306183 Kobayashi H Matsunaga K Fujii M PSK as a chemopreventive agent. In: Cancer Epidemiol Biomarkers Prev (1993 May-Jun) 2(3):271-6 PSK, a protein-bound polysaccharide preparation obtained from cultured mycelia of the CM-101 strain of Coriolus versicolor belonging to basidiomycetes, is a biological response modifier capable of exhibiting diverse biological activities. This agent has been used clinically for the treatment of postoperative cancer patients in Japan by oral use. In this paper, chemopreventive aspects of PSK were reviewed. Oral administration of PSK reduced the incidence of tumor and/or prolonged the survival period in the following chemical carcinogen-induced, radiation-induced, and spontaneously developed animal cancer models: rat gastrointestinal cancer induced by 1,2-dimethylhydrazine; rat hepatoma by 3'-methyl- dimethylaminobenzene; mouse thymic lymphoma by whole-body irradiation; mouse spontaneous mammary tumor; and so on. PSK did not interact and/or inhibit drug-metabolizing enzymes and had no effect on the Ames test. On the other hand, this agent scavenged active oxygen through the induction of manganese superoxide dismutase, prevented the increase in frequency of anticancer agent-induced sister chromatid exchange, and suppressed fetal deformation induced by transplacental injection of teratogen, suggesting an effect on the initiation or promotion process of carcinogenesis. Also, PSK regulated cytokine production and enhanced the antitumor activity of effector cells such as killer T-cells and natural killer cells, suggesting an effect on the growth process after the development of malignant cells. Thus, this agent seems to act at multiple steps during carcinogenesis rather than a particular step. The main mechanism may be an antiteratogenic effect attributed to radical trapping, preventive effects against chromosome injury, and immunomodulative effects attributed to the modulation of cytokine production and effector cell function.(ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: Higashi-Nihon Gakuen University Hokkaido Japan. *****CANCER IMMUNOLOGY, IMMUNOTHERAPY***** (REFERENCE 17 OF 41) 90329611 Torisu M Hayashi Y Ishimitsu T Fujimura T Iwasaki K Katano M Yamamoto H Kimura Y Takesue M Kondo M et al Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. In: Cancer Immunol Immunother (1990) 31(5):261-8 To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a protein-bound polysaccharide extracted from a Basidiomycetes fungus, a randomized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers. The rate of patients in remission (or disease- free) was significantly higher in the PSK group than in the placebo group; the difference between both groups was statistically significant at P less than 0.05 by the log-rank test. The survival rate of patients was also significantly (P less than 0.05) higher in the PSK group than in the control group. The most significant laboratory finding was that polymorphonuclear leukocytes from PSK- treated patients showed remarkable enhancement in their activities, such as random and/or chemotactic locomotion, and phagocytic activity, when compared with those in the control group. In conclusion, PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer. The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying (activities induced by PSK). Institutional address: First Department of Surgery Kyushu University School of Medicine Fukuoka Japan. *****CANCER TREATMENT REVIEWS***** (REFERENCE 18 OF 41) 85048816 Tsukagoshi S Hashimoto Y Fujii G Kobayashi H Nomoto K Orita K Krestin (PSK). In: Cancer Treat Rev (1984 Jun) 11(2):131-55 A polysaccharide preparation isolated from Coriolus versicolor (Fr.) Quel. of Basidiomycetes (PSK) predominantly consists of glucan and approximately 25% tightly bound protein. PSK was effective against various allogeneic and syngeneic animal tumors and has been given orally to cancer patients. Various suppressed or enhanced immune responses of tumor-bearing animals were restored to normal levels by the administration of PSK in the tumor models tested. The killer T cell activity was augmented in tumor-bearing mice by intraperitoneal or oral administration of PSK, and there was correlation between the PSK associated antitumor effect and the killer T cell activity. It was found that PSK competed with immunosuppressive substances isolated from tumor-bearing mice and that the intestinal immune system appeared to be modulated by oral administration of PSK. After oral administration of 14C- or 35S-labeled PSK to normal rats, it was found that small or large molecular substances appeared in the serum depending on the time elapsed after administration, an indication that large molecular size products were from the digestive tract. Institutional address: Cancer Chemotherapy Center Japanese Foundation for Cancer Research Tokyo. *****DISEASES OF THE COLON AND RECTUM***** (REFERENCE 19 OF 41) 92136955 Mitomi T Tsuchiya S Iijima N Aso K Suzuki K Nishiyama K Amano T Takahashi T Murayama N Oka H et al Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa). In: Dis Colon Rectum (1992 Feb) 35(2):123-30 A randomized, controlled trial of adjuvant immunochemotherapy with PSK (Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK group received PSK orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow-up time for this study was four years (range, three to five years). The disease-free survival curve and the survival curve of the PSK group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival, P = 0.013; survival, P = 0.013). These results indicate that adjuvant immunochemotherapy with PSK was beneficial for curatively resected colorectal cancer. Institutional address: Department of Surgery II Tokai University Kanagawa Japan. *****EXS***** (REFERENCE 20 OF 41) 92314622 Kumar S Saitoh K Kumar P Antiangiogenesis strategies in cancer therapy with special reference to Krestin. In: EXS (1992) 61:463-70 [No Abstract Available] Institutional address: Christie Hospital (NHS) Trust Manchester England. *****GAN TO KAGAKU RYOHO [JAPANESE JOURNAL OF CANCER AND CHEMOTHERAPY]***** (REFERENCE 21 OF 41) 80685645 Tanaka T Shirosaki H Kamimoto M Nishimura I Baba N Hirose M [LONG-TERM ADMINISTRATION OF PSK AS AN IMMUNOSTIMULANT: AN IMMUNOLOGICAL CONSIDERATION] In: Gan To Kagaku Ryoho (1980) 7(4):638-644 (Published in Japanese) Long-term administration of PSK was given to 35 patients with cancer of the digestive organs and breast during the so-called maintenance period or the follow-up period. The mean duration of administration was about 9 mo. Delayed skin tests (purified protein derivative, candida) and id phytohemagglutinin tests tended to be initially enhanced, slightly depressed after several mo, and then restored about 3 mo later, in spite of continuous administration. The peripheral lymphocyte counts were also increased after a decrease. Serum IgG, IgA, and IgM were less changed, but IgM and IgG were slightly increased, but only in the curatively resected cases. No side effect in the liver, bone marrow, or other organs was seen. These results indicate that PSK is useful as an immunostimulant in cancer therapy. Relatively short periods of alternation of PSK with some other stimulant is assumed to be better than continuous administration of PSK alone. (Author abstract) (7 Refs) Institutional address: Dept. Surgery Fukui Red Cross Hosp. Tsukimi Fukui 910 Japan (REFERENCE 22 OF 41) 80669104 Kato H Yokoe N Takemura S Hotta T Matsumura N Furukawa Y Wakamatsu Y Nishihori H Ikezaki M Hosokawa K Yoshikawa T Kondo M [EFFECT OF IMMUNOPOTENTIATORS OK-432 (PICIBANIL), PSK (KRESTIN), AND LEVAMISOLE ON HUMAN SERUM COMPLEMENT] In: Gan To Kagaku Ryoho (1979) 6(3):643-649 1979 (Published in Japanese) The mode of antitumor action of the so-called immunopotentiators has been explained as restoration of the impaired immune response through cellular immunity. Since most of the preparations available are of bacterial or plant origin, it is possible that they can activate the complement system mainly through its alternative pathway. The purpose of the present investigation is to demonstrate the effect of a streptococcal preparation Picibanil (OK-432), a protein polysaccharide from mycelia of Coriolus versicolor Krestin (PSK), and an aminothiazole derivative Levamisole on human serum complement in vivo. Aged patients without malignancy, who had a decreased immune response, as detected by purified protein derivative and phytohemagglutinin skin tests received sc injection of OK-432 0.l mg/day, po PSK 3 g/day or po Levamisole 150 mg/day on three consecutive days of each wk. The classical complement pathway was determined by the lysis of sensitized sheep RBC [50% hemolytic unit for complement hemolysis, (CHO-50)] and the alternative pathway by the lysis of unsensitized rabbit RBC [50% hemolytic unit for alternative complement hemolysis, (ACH-50)]. The complement components were measured by the single radial immunodiffusion method. It was found that the administration of OK-432, PSK, or Levamisole resulted in the elevation of serum CH50 and ACH50. Complement components were affected by the use of the preparations, while no specific tendency could be demonstrated, except for increased C3 level when OK-432 was given. Oral administration of PSK showed the conversion of C3 from beta 1C to beta 1A mobility, determined by crossed immunoelectrophoresis. Evidence that immunopotentiators increase the serum complement level in man leads to the conclusion that these drugs might have an additional function in potentiating the host-mediated immune response against malignant tumor via the complement system. (Author abstract) (22 Refs) Institutional address: Third Dept. Internal Medicine Kyoto Prefectural Univ. Medicine Kamikyo-ku Kyoto 602 Japan (REFERENCE 23 OF 41) 90120624 Nishiwaki Y Furuse K Fukuoka M Ota M Niitani H Asakawa M Nakai H Sakai S Ogawa N [A randomized controlled study of PSK combined immuno-chemotherapy for adenocarcinoma of the lung. The Advanced Lung Cancer Immuno- chemotherapy Study Group] In: Gan To Kagaku Ryoho (1990 Jan) 17(1):131-6 (Published in Japanese) In a randomized controlled study of chemotherapy (CDDP 100 mg/m2 day 1, VDS 3 mg/m2 day 1, 8, 15) vs. immuno-chemotherapy combined with PSK 3 g/day for adenocarcinoma of the lung (stage III, IV, p. s. 0, 1, 2), response rate for 169 cases with completed extramural review was 14.2%. As for the response rates for 138 complete cases, the chemotherapy group showed 17.9%, and the immuno-chemotherapy group was 16.9%. MST were 330 days and 331 days, respectively. In stage III cases, the response rates were 11.1% in the chemotherapy group and 37.5% in the immuno-chemotherapy group (p = 0.046). MST were 457 days (65.3 weeks) and 576 days (82.3 weeks), respectively. In terms of survival curve, it was suggested that the immuno-chemotherapy group was superior to the chemotherapy group (logrank test p = 0.075), but in stage IV cases, there was nothing outstanding in the immunochemotherapy group. Institutional address: National Matsudo Hospital Dept. of Internal Med. (REFERENCE 24 OF 41) 86294568 Oguchi Y Morita I Matsunaga K Fujii T Yoshikumi C Kawai Y Nomoto K [Involution of the thymus in tumor-bearing mice and its restoration by PSK (2)] In: Gan To Kagaku Ryoho (1986 Aug) 13(8):2645-52 (Published in Japanese) We examined the effect of PSK on involution of the thymus in tumor- bearing mice. The weight and cell number of the thymus decreased and the size distribution (scatter profile) of thymus cells was changed in X5563-bearing C3H/He mice. Also in these mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only by per organ but also by per 1 mg of thymus tissue. Such an involution was also observed in tumor-free mice injected with immunosuppressive substance, which had been obtained from ascites of X5563-bearing mice and revealed suppressive activity against lymphocyte proliferation. PSK administration prevented such modulation in the thymus of tumor-bearing mice and immunosuppressive substance-injected tumor-free mice. In other words, it is considered that the various changes in the thymus demonstrated in tumor-bearing mice may be attributable to the suppression of cell proliferation in the thymus, that such suppression is caused at least partly by an immunosuppressive substance which possesses inhibitory activity against lymphocyte proliferation, and that PSK has an antagonistic activity against such a substance so as to restore the function of the thymus in tumor-bearing hosts. Institutional address: Biomedical Research Laboratories Kureha Chemical Industries Co. Ltd. Tokyo. *****INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY***** (REFERENCE 25 OF 41) 89213090 Toge T Yamaguchi Y Kegoya Y Baba N Yanagawa E Hattori T Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK. In: Int J Immunopharmacol (1989) 11(1):9-12 The ability of protein-bound polysaccharide (PSK) to block the suppressive activity of soluble suppressor factor (SSF) was investigated. The suppressive activity of SSF derived from U-937 cells on phytohemagglutinin (PHA)-induced lymphocyte proliferative (LP) response was significantly reduced in the presence of PSK. The release of SSF was not inhibited by the treatment of U-937 cells with PSK. The suppressive activity of SSF on LP response to PHA was significantly decreased by the pretreatment of responder lymphocytes with PSK. Studies to determine lymphocyte receptor activity were performed. PSK competed with wheat germ agglutinin (WGA) which recognized the same receptor as SSF on the surface of the lymphocyte. Neither PSK nor serum competed with anti-CD4 monoclonal antibody. Thus, PSK may inhibit SSF-mediated suppression by competing for specific binding sites on the surface of responder lymphocytes. Institutional address: Department of Surgery Hiroshima University Japan. (REFERENCE 26 OF 41) 89007261 Ikuzawa M Matsunaga K Nishiyama S Nakajima S Kobayashi Y Andoh T Kobayashi A Ohhara M Ohmura Y Wada T et al Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). In: Int J Immunopharmacol (1988) 10(4):415-23 The fate of 14C-labelled PSK in the body was investigated. Although only substances with low mol. wt were observed in blood shortly after the administration, with time, substances with high mol. wt appeared, suggesting absorption of PSK in its original form from the digestive tract. 14C-labelled PSK was distributed in bone marrow, salivary gland, brain liver, spleen, pancreas and tumor. Approximately 70% of 14C-labelled PSK was excreted by expiratory air after 24 h and approximately 15-20% in urine after 72 h. Only a small amount of 14C- labelled PSK was transferred into lymph and bile. The present study on the in vivo behavior of PSK provides an important basis for further analysis of its pharmacological actions. Institutional address: Biomedical Research Laboratories Kureha Chemical Industries Co. Ltd. Tokyo Japan. (REFERENCE 27 OF 41) 94237660 Yunoki S Tanaka N Hizuta A Orita K Enhancement of antitumor cytotoxicity of hepatic lymphocytes by oral administration of PSK. In: Int J Immunopharmacol (1994 Feb) 16(2):123-30 We have studied the effects of oral administration of a biological response modifier (BRM), PSK, on hepatic lymphocytes. Many PSK positive cells were observed in the liver by anti-PSK antibody staining. Flow cytometric analysis revealed an increase in the number of OX8 (CD8) positive cells in the non-parenchymal nonadherent liver cells (NPNALCs) which were isolated from the liver enzymatically digested by perfusion with collagenase. NPNALCs were fractionated by discontinuous density gradient centrifugation, and the number and cytotoxic activity of these cells were examined in each fraction. Although the yield of lymphocytes in each fraction was not significantly increased by the oral administration of PSK, the natural killer (NK) activity was markedly enhanced in low density fractions. The present findings suggest that oral administration of PSK is effective for prevention of liver metastasis through the augmentation of organ-associated NK activity. Institutional address: First Department of Surgery Okayama University Medical School Japan. (REFERENCE 28 OF 41) 94011589 Hirai R Oguchi Y Sugita N Matsunaga K Nomoto K Enhancement of T-cell proliferation by PSK. In: Int J Immunopharmacol (1993 Aug) 15(6):745-50 Protein-bound polysaccharide, PSK, is a biological response modifier and influences various immunological functions in vivo, including those of T-cells. However, PSK has not been proved to stimulate proliferation of T-cells in vitro in contrast to various lines of evidence that indicate the proliferation of B-cells in vitro. PSK enhanced the proliferation of spleen cells in C3H/He and nude mice in vitro. In this study such proliferating cells were detected by monoclonal antibody to bromodeoxyuridine (BrdU) incorporated into DNA, and their subsets were determined by flowcytometry with monoclonal antibody to Thy1 as a cell surface marker of T-cells. When spleen cells from C3H/He mice were cultured with PSK for 3 days, the percentage of BrdU positive cells increased, and about 67% of BrdU positive cells were Thy1.2 positive. In addition, PSK also had the activity to enhance the proliferation in a T-cell-enriched fraction from spleen cells by nylon fiber columns as well as that in original spleen cells. These results suggest that PSK enhances the proliferation of T-cells as well as B-cells. Institutional address: Biomedical Research Laboratories Kureha Chemical Industry Co. Tokyo Japan. *****JOURNAL OF CLINICAL AND LABORATORY IMMUNOLOGY***** (REFERENCE 29 OF 41) 88141253 Oguchi Y Morita I Fujii T Matsunaga K Yoshikumi C Kawai Y Tsuru S Nomoto K Involution of the thymus in tumor-bearing mice and its restoration by PSK. II. Mechanism of the involution and its restoration. In: J Clin Lab Immunol (1987 Oct) 24(2):93-9 In C3H/He mice, the weight and cell number of the thymus were reduced and the size distribution (scatter profile measured by flow cytometer) of the thymus cells was changed 1 week after subcutaneous inoculation of X5563 plasmacytoma. This involution and change were prevented by intraperitoneal or oral administration of PSK. We examined the mechanism of this involution and change in thymus and the effect of PSK on them. In X5563-bearing C3H/He mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only per organ but also per 1 mg of thymus tissue. Such reduction was inhibited by PSK. The substance (IS substance) which possessed a suppressive activity against mitogen induced lymphocyte proliferation, was partially purified from the ascites of X5563-bearing mice by the combination of ammonium sulfate precipitation and Sephacryl S-200 chromatography. IS substance was demonstrated to suppress the antibody response and delayed type foot- pad response against sheep red blood cells in mice. The reduction of weight and cell number and the change of scatter profile in thymus were caused by injection of this substance even in tumor-free mice. The restorative effects of PSK were observed also in IS substance injected mice. These results suggested that the various changes in the thymus observed in tumor-bearing mice might be attributable to the suppression of cell proliferation in the thymus, that such suppression was caused at least partly by an immunosuppressive substance which possessed inhibitory activity against lymphocyte proliferation, and that PSK had an antagonistic activity against such a substance so as to restore the function of the thymus in tumor- bearing hosts. Institutional address: Biomedical Research Laboratories Kureha Chemical Industries Co. Ltd. Tokyo Japan. *****JOURNAL OF DERMATOLOGY***** (REFERENCE 30 OF 41) 88088208 Watanabe T Saito H Effects of PSK ointment and OK-432 ointment of Pseudomonas burn wound infection in mice. In: J Dermatol (1987 Aug) 14(4):346-51 [No Abstract Available] *****JOURNAL OF UROLOGY***** (REFERENCE 31 OF 41) 93059776 Mizutani Y Nio Y Yoshida O Effect of PSK and its subfractions on peripheral blood lymphocytes mediated cytotoxicity against urinary bladder tumor cells. In: J Urol (1992 Nov) 148(5):1571-6 Our previous studies have indicated that the protein-bound polysaccharide Kreha (PSK) enhances the cytotoxic activity of peripheral blood lymphocytes (PBL) against the T24 human urinary bladder tumor cell line in patients with bladder tumor. Since PSK consists of a mixture of various kinds of protein-bound polysaccharides, the present study was designed to examine which subfractions of PSK mediated the enhancement of cytotoxicity. When PSK was separated according to size, treatment of PBL with the 50 kilodalton (kd) or less fraction killed T24 cells more efficiently than unfractionated PSK-treated PBL. The higher molecular weight fractions did not enhance killing above the control level. PSK was fractionated on a diethylaminoethyl (DEAE)-cellulose column to obtain a protein rich fraction that absorbed onto the column and a polysaccharide rich fraction that did not. PBL treated with the polysaccharide rich fraction were able to kill T24 cells more effectively than unfractionated PSK-treated PBL. The protein rich fraction had no effect on the killing. Further fractionation of the polysaccharide rich fraction was performed by differential precipitation with ammonium sulfate. PBL treated with the precipitated fraction at 70-80% saturation (PSK Fraction D) enhanced cytotoxicity equal to that of the polysaccharide rich fraction. Treatment of PBL with the other fractions did not augment the cytotoxicity. These enhancement by PSK fractions were observed in healthy donors and also in patients with bladder tumor. An increase of the proliferative response of PBL to PSK Fraction D as well as unfractionated PSK was observed. Treatment of PBL with PSK Fraction D had no effect on the proportion of PBL binding to T24 cells, thus suggesting a post-binding effect. The structure of PSK Fraction D as inferred from the results of methylation analysis was mainly an alpha- glucan. These results demonstrate that PSK mediated enhancement of cytotoxicity and proliferation of PBL may be largely due to an alpha- glucan of less than 50 kd. Institutional address: Department of Urology Faculty of Medicine Kyoto University Japan. *****JAPANESE JOURNAL OF CLINICAL ONCOLOGY***** (REFERENCE 32 OF 41) 92318463 Sakamaki S Kohgo Y Nojiri S Kanisawa Y Ito Y Takahashi M Ueno Y Hirayama Y Niitsu Y Effect of Krestin (PSK) on the induction of IL-2 activated killer cells. In: Jpn J Clin Oncol (1992 Apr) 22(2):79-83 The effects of Krestin (PSK) on the generation of lymphokine- activated killer (LAK) cells were examined in tumor-bearing mice. BALB/c mice were inoculated subcutaneously with methylcholanthrene- induced fibrosarcoma (Meth A) cells, and PSK was administered intraperitoneally every other day. The reduced LAK activity in tumor- bearing mice was restored by the administration of PSK. Since involvement of the humoral immunosuppressive factor in the impairment of LAK activity has been suggested, the effect of PSK on the impaired LAK activity in the presence of an immunosuppressive factor isolated from the ascites of X5563 (plasmacytoma)-inoculated mice was examined. The activity reduced by the immunosuppressive factor in an in vitro induction of LAK was restored by incubation with PSK. The antimetastatic effect of IL-2 was also augmented by its combined use with PSK. The data provide a rational basis for using PSK in combination with recombinant IL-2 in cancer immunotherapy. Institutional address: Department of Internal Medicine (Section 4) Sapporo Medical College. *****NIPPON GAN CHIRYO GAKKAI SHI. JOURNAL OF JAPAN SOCIETY FOR CANCER***** (REFERENCE 33 OF 41) 82602506 Ogawa Y Kimura S Imajo Y Hamada F Inomata T Ichiyanagi A Miyaji C Imanaka K Oshitani T Takashima H Ohbayashi K Takada Y Kono M [CLINICAL SIGNIFICANCE OF CONCOMITANT USE OF PSK IN 121 CASES OF PRIMARY LUNG CANCER (STAGE III AND IV) TREATED WITH COMBINATIONS OF RADIOTHERAPY AND CHEMOTHERAPY] In: Nippon Gan Chiryo Gakkai Shi (1981) 16(4):713-723 (Published in Japanese) Effects of polysaccharide-Kureha (PSK) were studied in 121 patients (100 men, 21 women) with primary lung cancer that was also treated with surgery, radiotherapy, and/or chemotherapy. The PSK (3.0 g/day x 3 days, po) was administered at the same time as other initial therapies. Chemotherapeutic agents included bleomycin, mitomycin C, 5- fluorouracil, and urokinase. With respect to immunotherapy, the PSK was administered alone to 37 patients, PSK + picibanil (OK-432) were administered to 20, and no immunotherapy was administered to 64. Among the patients with Stage III lung cancer, 12-mo survival rates were significantly higher, and 50% survival period was 2x higher, in the patients given PSK + OK-432 than in those given no immunotherapy. Among the patients with Stage IV lung cancer, 50% survival periods and crude survival rates were better in patients given immunotherapy than in those not given immunotherapy, but significant differences were not observed due to severity of the disease and incomplete radiotherapy in the patients not given immunotherapy. Similar results were observed between the patients given immunotherapy and those not given immunotherapy when the tumors were analyzed according to histological types, but the differences were decreased mo 20 after treatment. (27 Refs) Institutional address: Dept. Radiology Kobe Univ. Sch. Medicine Kobe Japan *****NIPPON KETSUEKI GAKKAI ZASSHI. ACTA HAEMATOLOGICA JAPONICA***** (REFERENCE 34 OF 41) 90143619 Tsuji K Takagi M Kobayashi T Ishiguro A Naganuma K Koike K Nakahata T Akabane T [Effect of a protein-bound polysaccharide, PSK, on human hemopoietic progenitors] In: Nippon Ketsueki Gakkai Zasshi (1989 May) 52(3):594-600 (Published in Japanese) Using in vitro clonal culture assays, we investigated the effects of PSK, a protein-bound polysaccharide derived from the cultured mycelium of CM101, Coriolus versicolor (Fr.) Quel in Basidiomycetes, on human hemopoietic progenitors. PSK alone did not stimulate colony formation by human bone marrow progenitors. Although 1-100 micrograms/ml of PSK had no effects on colony formation stimulated by erythropoietin and medium conditioned by phytohemagglutinin- stimulated leukocytes, more than 1 mg/ml of PSK inhibited all types of colony formation. In contrast, medium conditioned by PSK- stimulated leukocytes significantly stimulated formation of various types of colonies including erythroid bursts, granulocyte and/or macrophage colonies, eosinophil colonies, megakaryocyte colonies and mixed hemopoietic colonies. It is speculated that administration of the optimal dose of PSK can reduce the hematological suppression of antitumor drugs. *****NIPPON RINSHO. JAPANESE JOURNAL OF CLINICAL MEDICINE***** (REFERENCE 35 OF 41) 82600014 Nomoto K [POLYSACCHARIDE AND LIPOPOLYSACCHARIDE IMMUNOREGULATING MECHANISMS - USE OF PSK AS AN EXAMPLE] In: Nippon Rinsho (1981) 39(4):110-115 (Published in Japanese) Characteristics of the mechanism and the effect of the polysaccharide Kureha (PSK) were investigated as an example of immunopotentiation by polysaccharides and lipopolysaccharides. Administration of PSK (50- 100 mg/kg ip or 1,000 mg/kg po, continuously) to sarcoma 180 or Ehrlich tumor-bearing ICR mice resulted in disappearance of tumors after transient growth of the tumor. Antitumor effects were also observed for various homogenic strains of methylcholanthrene-induced tumors. Administration of PSK in mice with sarcoma 180 tumors increased splenocyte cytotoxicity. PSK had an inhibiting effect on macrophage aggregation in normal mice, but had stimulating effect on macrophage aggregation in tumor-bearing mice. Ip administration of PSK in cancer bearing mice resulted in recovery of delayed-type foot pad response to sheep RBC, and po administration resulted in a slightly lower degree of recovery. Ip administration of PSK in sarcoma 180 tumor-bearing mice with decreased production of interferon due to poly I:C stimulation resulted in a certain degree of recovery of interferon production. PSK was also observed to effect (1) fluctuations in preventing infections due to cancer, (2) changes in thymus function due to cancer, (3) inhibitory effects of cancerous ascites, (4) fractions of immune-inhibiting factors from cancerous abdominal ascites, and (5) mixes of accelerating factors and inhibiting factors in cancerous ascites and serum. (5 Refs) Institutional address: Cancer Res. Inst. Kyushu Univ. Kyushu Japan *****NIPPON SANKA FUJINKA GAKKAI ZASSHI. ACTA OBSTETRICA ET GYNAECOLOGICA***** (REFERENCE 36 OF 41) 93286457 Ishii K Kita T Hirata J Tode T Kikuchi Y Nagata I [Antitumor effect of PSK and its combined effect with CDDP on ovarian serous adenocarcinoma-bearing nude mice] In: Nippon Sanka Fujinka Gakkai Zasshi (1993 Apr) 45(4):333-9 (Published in Japanese) Although the antitumor effect of PSK can be increased by potentiating the immune functions of PSK in tumor-bearing hosts, the mechanisms of its action are not fully understood. In this study, we examined the antitumor effect and CDDP combined effect of oral administration of PSK on nude mice bearing a human ovarian cancer cell line (KF cells). 1. PSK was observed to have a significant antitumor effect in tumor- bearing nude mice and subsequently to bring about an increase in the survival rate and prolongation of the life span. 2. The antitumor effect of CDDP was (but not significantly) enhanced by oral administration of PSK and the prolongation of the life span of the tumor-bearing nude mice was obtained. 3. Six weeks after tumor inoculation, no significant natural killer (NK) cell activity in spleen cells from untreated nude mice was observed. However, when PSK (100 mg/kg but not 500 mg/kg) was given every other day, significant NK activity was induced. 4. The serum immunosuppressive acid protein (IAP) value in nude mice treated with PSK alone was significantly higher than that in nude mice treated with a combination of PSK (100 mg/kg) and CDDP. These results suggest that CDDP prevents the increase in serum IAP that occurs when PSK is used and that consequently combinations of PSK and CDDP result in augmentation of antitumor effects. Institutional address: Department of Obstetrics and Gynecology National Defense Medical College Saitama. *****ONCOLOGY***** (REFERENCE 37 OF 41) 94268800 Matsunaga K Aota M Nyunoya Y Hakozaki M Ishikawa Y Ohhara M Sugita N Endo H Antitumor effect of biological response modifier, PSK, on C57BL/6 mice with syngeneic melanoma B16 and its mode of action. In: Oncology (1994 Jul-Aug) 51(4):303-8 The effects of PSK, a protein-bound polysaccharide, on the survival period and effector cell activity were examined using C57BL/6 mice with melanoma B16. PSK prolonged the survival period of the mice with tumors in a schedule- and dose-dependent manner. However, no life- prolonging effect was observed when carrageenan-treated mice or congenitally athymic mice were used as hosts. PSK enhanced the cytostatic activity and interleukin-1-producing capacity of peritoneal exudate plastic-adherent cells in C57BL/6 mice with tumors. These findings suggested that PSK prolongs the survival period of mice with B16 tumors through T-cell- and macrophage- dependent mechanisms. Institutional address: Biomedical Research Laboratories Kureha Chemical Industry Co. Tokyo Japan. (REFERENCE 38 OF 41) 94255178 Ueno Y Kohgo Y Sakamaki S Itoh Y Takahashi M Hirayama Y Niitsu Y Immunochemotherapy in B-16-melanoma-cell-transplanted mice with combinations of interleukin-2, cyclophosphamide, and PSK. In: Oncology (1994 May-Jun) 51(3):296-302 The effect of combination immunochemotherapy using interleukin-2 (IL- 2), PSK and cyclophosphamide (CY) was evaluated in a pulmonary metastasis model in BDF1 mice. B-16 melanoma cells were inoculated into a hind limb. On day 3 after inoculation, 20 mg/kg of CY was administered intraperitoneally, and IL-2 (3.75 x 10(4) BRM units/head) was injected into the tail vein on days 7, 8 and 9. PSK (1,000 mg/kg) was administered orally every day from day 1 to day 10 using a stomach tube. This treatment cycle was repeated three times. Using this combination therapy, the cytotoxicity of lymphokine- activated killer cells and tumor-infiltrating lymphocytes was enhanced. Pulmonary metastasis was remarkably suppressed and a prolongation of survival was obtained compared with the nontreated group and an IL-2+CY group. The effect was augmented by repeating the therapy protocol. By analyzing the killer activity and surface markers of tumor-infiltrating lymphocytes, it was recognized that increased numbers of Lyt-2-positive T cells with augmented cytotoxicity were obtained. This treatment modality should have clinical significance. Institutional address: Department of Internal Medicine (Section 4) Sapporo Medical University School of Medicine Japan. *****PROCEEDINGS, ANNUAL MEETING OF THE AMERICAN SOCIETY OF CLINICAL***** (REFERENCE 39 OF 41) 93694949 Nakazato H Koike A Saji S Ogawa N Sakamoto J A randomized clinical trial on adjuvant immunochemotherapy with protein bound polysaccharide (PSK) in gastric cancer with curative resection (Meeting abstract). In: Proc Annu Meet Am Soc Clin Oncol (1993) 12:A550 A randomized clinical trial was conducted by 46 participating institutions from July 1985 to June 1987 in Chubu district to evaluate the effect of biological response modifier PSK in curatively resected advanced gastric cancer. After stratifying by serosal invasion (T2, T3), 253 patients (pts) were randomly allocated into the 5-fluorouracil (5-FU) and PSK group (Group P, n=124) and 5-FU alone group (Group C, n=129). Bolus injections of mitomycin C (MMC) 6 mg/m2 were given to all pts on the first and seventh postoperative days. At 2 wk after surgery, Group P began to alternately receive PSK 3 g/day for 4 wk and oral 5-FU 150 mg/day for 4 wk as 1 course: 10 courses were given. Group C received 5-FU alone for 4 wk with an alternate rest interval for the same period. Pts characteristics (age, sex, depth of tumor invasion, degree of lymph node metastasis) were well balanced in the 2 groups. By June 30, 1992 the median follow-up was 72 mo and all pts were followed up for at least 5 yr. The 5-yr disease-free survival rate for Group P was 0.71 and was significantly superior to that of Group C, which was 0.59 (p=0.047). The 5-yr survival rate for Group P was 0.73 and for Group C 0.60 and overall survival with MMC+5-FU+PSK was also significantly superior to MMC+5-FU alone (p=0.044). In conclusion, addition of PSK to the standard MMC+5-FU regimen results in a significantly superior survival in pts who had undergone radical gastrectomy. Institutional address: Dept. of Gastroenterological Surgery Aichi Cancer Center Nagoya Japan (REFERENCE 40 OF 41) 92681197 Mitomi T Tsuchiya S Iijima N Noto T Ogawa N A RANDOMIZED CONTROLLED STUDY ON ADJUVANT IMMUNOCHEMOTHERAPY WITH PSK IN CURATIVELY RESECTED COLORECTAL CANCER (MEETING ABSTRACT) In: Proc Annu Meet Am Soc Clin Oncol (1992) 11:A466 In order to evaluate the adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer, a randomized controlled study by 35 institutions in Kanagawa Prefecture was conducted. From March 1985 to February 1987, 462 patients (pts) with colorectal cancer (any TN1-3M0 or T4N0M0) were assigned to one of two different regimens. Of these, 448 pts (97.0%) satisfied the eligibility criteria (colon, 249 cases; rectum, 199 cases). The control group received mitomycin C (6.0 mg/m2) on the day and the day after the surgery, followed by 5- FU (200 mg/day) given orally for over 6 mo. The PSK group received PSK (3 g/day) po for over 3 yr, as well as mitomycin C and 5-FU as in the control group. In February 1991, a follow-up study of these pts was carried out to evaluate the survival rate for a minimum of 4 yr after surgery. Both treatment groups were well matched, as they had almost the same background factors. Disease-free rate (DFS) and overall survival rate (OS) of the PSK group were significantly higher than those of the control group (DFS: p=0.0250, OS: p=0.0296). Still more, concerning colon cancers, in each subgroup with positive preoperative CEA serum levels or Dukes' C, the PSK group showed more advantageous effects than those shown in the control group. Institutional address: Dept. of Surgery II Tokai Univ. Japan *****PROC ANNU MEET JPN CANCER ASSOC***** (REFERENCE 41 OF 41) 91669458 Hirose K Zachariae CO Oppenheim JJ Matsushima K ACTIVATION OF HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) TO EXPRESS IMMUNOMODULATING CYTOKINE GENES BY PSK (MEETING ABSTRACT) In: Proc Annu Meet Jpn Cancer Assoc (1990) 49:342 The protein-bound polysaccharide, PSK, has been used as a biological response modifier in treating patients with cancer (Cancer Treat Rev 11:131-155 1984). Although the mechanism of its antitumor action is not well understood, PSK enhances various immune responses in vivo as well as in vitro. We have here examined the direct effect of PSK on cytokine gene expression and production in human PBMC in vitro. As determined by Northern blotting, PSK strongly induced gene expression for interleukin 1 alpha, 1 beta, 6, 8, tumor necrosis factor alpha and monocyte chemotactic and activating factor, but not for interleukin 2 and lymphotoxin. Expression of mRNA occurs in 1-6 hr using concentrations of 5-400 ug/ml of PSK. Furthermore, the production of these cytokines in response to PSK can be detected by ELISA or RIA. We conclude that these cytokines may mediate the immunoenhancing action of PSK in vivo. Institutional address: Lab. of Molecular Immunoregulation NCI-FCRF Frederick MD 21701-1013
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