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Open Access 01-01-2012 | Review Article

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN^®): review of development and future perspectives

Authors: Yoshihiko Maehara, Shunichi Tsujitani, Hiroshi Saeki, Eiji Oki, Keiji Yoshinaga, Yasunori Emi, Masaru Morita, Shunji Kohnoe, Yoshihiro Kakeji, Tokujiro Yano, Hideo Baba

Published in: Surgery Today | Issue 1/2012

Abstract

The mechanism of action of protein-bound polysaccharide K (PSK; KRESTIN^®) involves the following actions: (1) recovery from immunosuppression induced by humoral factors such as transforming growth factor (TGF)-β or as a result of surgery and chemotherapy; (2) activation of antitumor immune responses including maturation of dendritic cells, correction of Th1/Th2 imbalance, and promotion of interleukin-15 production by monocytes; and (3) enhancement of the antitumor effect of chemotherapy by induction of apoptosis and inhibition of metastasis through direct actions on tumor cells. The clinical effectiveness of PSK has been demonstrated for various cancers. In patients with gastric or colorectal cancer, combined use of PSK with postoperative adjuvant chemotherapy prolongs survival, and this effect has been confirmed in multiple meta-analyses. For small-cell lung carcinoma, PSK in conjunction with chemotherapy prolongs the remission period. In addition, PSK has been shown to be effective against various other cancers, reduce the adverse effects of chemotherapy, and improve quality of life. Future studies should examine the effects of PSK under different host immune conditions and tumor properties, elucidate the mechanism of action exhibited in each situation, and identify biomarkers.

van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254:1643–7.PubMedCrossRef

Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001;411:380–4.PubMedCrossRef

Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52.PubMedCrossRef

Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2001;2:675–80.PubMedCrossRef

Yoshimura K, Olino K, Edil BH, Schulick RD, Oka M. Immuno- and gene-therapeutic strategies targeted against cancer (mainly focusing on pancreatic cancer). Surg Today. 2010;40:404–10.PubMedCrossRef

Sargent DJ, Köhne CH, Sanoff HK, Bot BM, Seymour MT, de Gramont A, et al. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer. J Clin Oncol. 2009;27:1948–55.PubMedCrossRef

Donaldson SS, Lenon RA. Alterations of nutritional status: impact of chemotherapy and radiation therapy. Cancer. 1979;43:2036–52.PubMedCrossRef

Sakamoto J, Teramukai S, Koike A, Saji S, Ohashi Y, Nakazato H. Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma: findings from three independent clinical trials. Cancer. 1996;77:2206–12.PubMedCrossRef

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.PubMedCrossRef

10.

Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K. Krestin (PSK). Cancer Treat Rev. 1984;11:31–55.CrossRef

11.

Fujii M. Krestin (PSK). Biotherapy. 1996;10:315–7 (in Japanese with English abstract).

12.

Matsunaga K, Morita I, Iijima H, Endo H, Oguchi Y, Yoshimura M, et al. Competitive action of biological response modifier, PSK, on a humoral immunosuppressive factor produced in tumor-bearing hosts. J Clin Lab Immunol. 1990;31:127–36.PubMed

13.

Hattori T, Nakajima T, Nakazato H, Tanabe T, Kikuchi K, Abe O, et al. Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy. Jpn J Surg. 1990;20:127–36.PubMedCrossRef

14.

Harada M, Matsunaga K, Oguchi Y, Iijima H, Tamada K, Abe K, et al. Oral administration of PSK can improve the impaired anti-tumor CD4⁺ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice. Int J Cancer. 1997;70:362–72.PubMedCrossRef

15.

Matsunaga K, Hosokawa A, Oohara M, Sugita N, Harada M, Nomoto K. Direct action of a protein-bound polysaccharide, PSK, on transforming growth factor-β. Immunopharmacology. 1998;40:219–30.PubMedCrossRef

16.

Inokuchi K, Kumashiro R. Chemotherapy for gastric cancer. Surg Therapy. 1980;42:40–6 (in Japanese).

17.

Yamanaka M, Takahata K, Oka H, Yoshino F, Sugita N, Yoshikumi C. Studies on the mechanisms of antitumor activities of PSK (Krestin): effects on prostaglandin metabolism of tumor cells. In: Ishigami J, editor. Recent advances in chemotherapy. Proceedings of the 14th ICC. Tokyo: University of Tokyo Press; 1985. p. 896–7.

18.

Kobayashi Y, Kariya K, Saigenji K, Nakamura K. Oxidative stress relief for cancer-bearing hosts by the protein-bound polysaccharide of Coriolus versicolor Quel with SOD mimicking activity. Cancer Biother. 1994;9:55–62.PubMedCrossRef

19.

Yamaguchi Y, Minami K, Ohshita A, Kawabuchi Y, Noma K, Toge T. Enhancing effect of PS-K on IL-2-induced lymphocyte activation: possible involvement of antagonistic action against TGF-beta. Anticancer Res. 2004;24:639–48.PubMed

20.

Shibata M, Abe H, Kanou H, Azuhata T, Nezu T, Ohara M, et al. In vitro and in vivo immune-modulating effects of polysaccharide-K (PSK) in patients with colorectal cancer. Proc AACR. 2002;43:448.

21.

Shibata M, Nezu T, Kanou H, Nagata Y, Kimura T, Takekawa M, et al. Immunomodulatory effects of low dose cis-diaminedichloroplatinum (cisplatin) combined with UFT and PSK in patients with advanced colorectal cancer. Cancer Invest. 2002;20:166–73.PubMedCrossRef

22.

Tsujitani S, Ozaki T, Saito H, Fukuda K, Tatebe S, Ikeguchi M. The NKG2D expression on CD8⁺ T cells and efficacy of polysaccharide K (PSK) in gastric cancer. J Clin Oncol. 2008;26:148s.

23.

Okuzawa M, Shinohara H, Kobayashi T, Iwamoto M, Toyoda M, Tanigawa N. PSK, a protein-bound polysaccharide, overcomes defective maturation of dendritic cells exposed to tumor-derived factors in vitro. Int J Oncol. 2002;20:1189–95.PubMed

24.

Sugiyama Y, Saji S, Kunieda K, Yamada M, Nagata M, Ri S, et al. Effect of PSK on either immunocytes or tumor cells. Biotherapy. 1996;10:18–25 (in Japanese with English abstract).

25.

Ooshiro M, Sugishita Y, Tanaka H, Koide K, Nagashima M, Katoh R. Regulation of perioperative immunological changes following laparotomy: effects of biological response modifier (BRM) on surgical stress. Immunol Lett. 2004;93:33–8.PubMedCrossRef

26.

Tsukagoshi S. Fundamental approaches to cancer immunotherapy using a protein-bound polysaccharide, PS-K, with special reference to its clinical application. In: Mizuno D, Chihara G, Fukuoka F, Yamamoto T, Yamamura Y, editors. Host defense against cancer and its potentiation. Tokyo: University of Tokyo Press; 1975. p. 365–77.

27.

Kono K, Kawaguchi Y, Mizukami Y, Mimura K, Sugai H, Akaike H, et al. Protein-bound polysaccharide K partially prevents apoptosis of circulating T cells induced by anti-cancer drugs S-1 in patients with gastric cancer. Oncology. 2008;74:143–9.PubMedCrossRef

28.

Kariya Y, Okamoto N, Fujimoto T, Inoue N, Kihara T, Sugie K, et al. Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK. Jpn J Cancer Res. 1991;82:1044–50.PubMedCrossRef

29.

Nio Y, Shiraishi T, Tsubono M, Morimoto H, Tseng CC, Imai C, et al. In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer. Cancer Immunol Immunother. 1991;32:335–41.PubMedCrossRef

30.

Vánky F, Wang P, Klein E. The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumor cells. Cancer Immunol Immunother. 1992;353:193–8.CrossRef

31.

Ebina T, Kohya H. Antitumor effector mechanism at a distant site in the double grafted tumor system of PSK, a protein-bound polysaccharide preparation. Jpn J Cancer Res. 1988;79:957–64.PubMedCrossRef

32.

Tsuru S, Nomoto K. Effects of PSK on specific tumor immunity to syngeneic tumor cells. J Clin Lab Immunol. 1983;10:215–9.PubMed

33.

Algarra I, Collado A, Garrido F. Protein bound polysaccharide PSK abrogates more efficiently experimental metastasis derived from H-2 negative than from H-2 positive fibrosarcoma tumor clones. J Exp Clin Cancer Res. 1997;16:373–80.PubMed

34.

Ueda Y, Naito K, Kobayashi M, Omori K, Shimode Y, Matsuda A, et al. In vitro induction of LAK cells with PSK. Biotherapy. 1991;5:861–3 (in Japanese with English abstract).

35.

Baba N, Yamaguchi Y, Sato Y, Takayama T, Yanagawa E, Toge T. The enhancement of tumoricidal activities of macrophages by protein-bound polysaccharide in tumor bearing mice. Biotherapy. 1990;4:123–8 (in Japanese with English abstract).

36.

Kato H, Kin R, Yamamura Y, Tanigawa M, Sano H, Sugino S, et al. Tumor inhibitory effect of polymorphonuclear leukocytes (PMN) induced by PSK in the peritoneal cavity of tumor-bearing mice. J Kyoto Pref Univ Med. 1987;96:927–38.

37.

Hirose K, Zachariae C, Oppenheim J, Kouji M. Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. Lymphokine Res. 1990;94:475–83.

38.

Asai K, Kato H, Kimura S, Mukai S, Kawahito Y, Sano H, et al. Induction of gene expression for nitric oxide synthase by immunomodulating drugs in the RAW264.7 murine macrophage cell line. Cancer Immunol Immunother. 1996;42:275–9.PubMedCrossRef

39.

García-Lora A, Pedrinaci S, Garrido F. Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. Cancer Immunol Immunother. 2001;50:191–8.PubMedCrossRef

40.

García-Lora A, Martinez M, Pedrinaci S, Garrido F. Different regulation of PKC isoenzymes and MAPK by PSK and IL-2 in the proliferative and cytotoxic activities of the NKL human natural killer cell line. Cancer Immunol Immunother. 2003;52:59–64.PubMed

41.

Asai H, Iijima H, Matsunaga K, Oguchi Y, Katsuno H, Maeda K. Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4⁺ T cells by modulating T cell receptor signaling. Cancer Immunol Immunother. 2008;57:1647–55.PubMedCrossRef

42.

Kanazawa M, Mori Y, Yoshihara K, Iwadate M, Suzuki S, Endoh Y, et al. Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes. Immunol Lett. 2004;91:229–38.PubMedCrossRef

43.

Ogihara T, Iinuma H, Okinaga K. Usefulness of immunomodulators for maturation of dendritic cells. Int J Oncol. 2004;25:453–9.PubMed

44.

Schoof DD, Terashima Y, Peoples GE, Goedegebuure PS, Andrews JV, Richie JP, et al. CD4⁺ T cell clones isolated from human renal cell carcinoma possess the functional characteristics of Th2 helper cells. Cell Immunol. 1993;150:114–23.PubMedCrossRef

45.

Sugiyama Y, Osada S, Yamaguchi K, Nagao N, Takahashi T, Sakashita F. Evidence-based biotherapy by use of PSK. Biotherapy. 2006;20:396–402 (in Japanese with English abstract).

46.

Yoshino S, Hazama S, Shimizu R, Fukuda S, Kudoh A, Mizuta E, et al. Usefulness in predicting parameters for the selection of responders who received immunochemotherapy with PSK in patients with colorectal cancer. Jpn J Cancer Chemother. 2005;32:1568–70 (in Japanese with English abstract).

47.

Kanoh T, Saito K, Matsunaga K, Oguchi Y, Taniguchi N, Endoh H, et al. Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody the protein-bound polysaccharide PSK in mice bearing a human cancer cell line. In Vivo. 1994;8:241–5.PubMed

48.

Nomoto K, Yoshikumi C, Matsunaga K, Fujii T, Takeya K. Restoration of antibody-forming capacities by PS-K in tumor bearing mice. Gann. 1975;66:365–74.PubMed

49.

Maruyama S, Akasaka T, Yamada K, Tachibana H. Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1. Biomed Pharmacother. 2009;63:409–12.PubMedCrossRef

50.

Liu A, Klein G, Bandobashi K, Klein E, Nagy N. SH2D1A expression reflects activation of T and NK cells in cord blood lymphocytes infected with EBV and treated with the immunomodulator PSK. Immunol Lett. 2002;80:81–8.CrossRef

51.

Liu A, Arbiser JL, Holmgren A, Klein G, Klein E. PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12. Blood. 2005;105:1606–13.PubMedCrossRef

52.

Liu A, Claesson HE, Mahshid Y, Klein G, Klein E. Leukotrien B₄ activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures. Blood. 2008;111:2693–703.PubMedCrossRef

53.

Klein E, Liu A, Claesson HE. Activation of innate immunity by the leukotriene B₄ inhibits EBV induced B-cell transformation in cord-blood derived mononuclear cultures. Immunol Lett. 2008;116:174–7.PubMedCrossRef

54.

Akagi J, Baba H. PSK may suppress CD57⁺ T cells to improve survival of advanced gastric cancer patients. Int J Clin Oncol. 2010;15:145–52.PubMedCrossRef

55.

Asai Y, Takaori K, Yamamoto T, Ogawa T. Protein-bound polysaccharide isolated from basidiomycetes inhibits endotoxin-induced activation by blocking lipopolysaccharide-binding protein and CD14 functions. FEMS Immunol Med Microbiol. 2005;43:91–8.PubMedCrossRef

56.

Miki C, Tanaka K, Inoue Y, Araki T, Ohi M, Mohri Y, et al. Perioperative host–tumor inflammatory interactions: a potential trigger for disease recurrence following a curative resection for colorectal cancer. Surg Today. 2008;38:579–84.PubMedCrossRef

57.

Tsutsumi N, Kohnoe S, Sonoda H, Guntani A, Rikimaru T, Taguchi K, et al. Protein-bound polysaccharide-K reduces colitic tumors and improves survival of inflammatory bowel disease in vivo. Oncol Lett. 2011;2:791–6.

58.

Yanagawa T, Oguro M, Takagi T, Takenaga K. Direct antitumor activity of biological response modifiers (B.R.M.) proven by an in vitro sensitivity test. Jpn J Cancer Chemother. 1984;11:2155–62 (in Japanese with English abstract).

59.

Yefenof E, Gafanovitch I, Oron E, Bar M, Klein E. Prophylactic intervention in radiation-leukemia-virus-induced murine lymphoma by the biological response modifier polysaccharide K. Cancer Immunol Immunother. 1995;41:389–96.PubMedCrossRef

60.

Araya S, Nio Y, Hayashi H, Masai Y, Tsubono M, Ishigami S, et al. Various plant-derived polysaccharides augment the expression of HLA on Colo 205 human colonic cancer line. J Jpn Soc Cancer Ther. 1994;29:1965–73 (in Japanese with English abstract).

61.

Hattori ST, Komatsu N, Shichijo S, Itoh K. Protein-bound polysaccharide K induced apoptosis of the human Burkitt lymphoma cell line, Namalwa. Biomed Pharmacother. 2004;58:226–30.PubMedCrossRef

62.

Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, et al. The immunomodulator PSK induces in vitro cytotoxic activity in tumor cell lines via arrest of cell cycle, induction of apoptosis. BMC Cancer. 2008;8:78.PubMedCrossRef

63.

Kobayashi H, Matsunaga K, Oguchi Y. Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from Basidiomycetes: an overview. Cancer Epidemiol Biomarkers Prev. 1995;4:275–81.PubMed

64.

Zhang H, Morisaki T, Matsunaga H, Sato N, Uchiyam A, Hashizume K, et al. Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-β1 and MMPs. Clin Exp Metastasis. 2000;18:343–52.PubMed

65.

Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7:131–42.PubMedCrossRef

66.

Hayashida T, Konagi A, Hasegawa H, IshiiY, Endo T, Okabayashi K, et al. Inhibitory ability of a protein-bound polysaccharide, PSK, on transforming growth factor beta pathway and EMT. In: Proceedings of the JCA. 2009; p. 47.

67.

Kumar S, Saitoh K, Kumar P. Angiogenesis: key principles–science–technology–medicine. In: Steiner R, Weisz PB, Langer R, editors. Antiangiogenesis strategies in cancer therapy with special reference to Krestin. Basel: Birkhauser Verlag; 1992. p. 463–70.

68.

Wada T, Wakamatsu Y, Bannai K, Kato M, Oguchi Y, Matsunaga K, et al. Suppression mechanism of angiogenesis by PSK. Ann Cancer Res Ther. 2002;10:93–106.

69.

Konno H, Yamamoto M, Ohta M. Recent concepts of antiangiogenic therapy. Surg Today. 2010;40:494–500.PubMedCrossRef

70.

Yoshikawa R, Yanagi H, Hashimoto-Tamaoki T, Morinaga T, Nakano Y, Noda M, et al. Gene expression in response to anti-tumour intervention by polysaccharide-K (PSK) in colorectal carcinoma cells. Oncology Rep. 2004;12:1287–93.

71.

Zhang H, Morisaki T, Nakahara C, Matsunaga H, Sato N, Nagumo F, et al. PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene. 2003;22:2088–96.PubMedCrossRef

72.

Kinoshita J, Fushida S, Harada S, Makino I, Nakamura K, Oyama K, et al. PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-kappaB activation and survivin expression. Int J Oncol. 2010;36:593–600.PubMedCrossRef

73.

Sakurai Y, Azuma I, Ishihara K, Ogura T, Saito T, Simoyama M, et al. Method for evaluation of efficacy of immunopotentiating agent on malignant tumor. Pharm Regul Sci. 1980;11:764–8 (in Japanese).

74.

Nakao I, Yokoyama T, Urushizaki I, Wakui A, Furue H, Koyama Y, et al. Clinical outcome of PSK for advanced gastric cancer—results of randomized control trial. Oncologia. 1985;14:163–9 (in Japanese).

75.

Maehara Y, Baba H, Sugimachi K. Adjuvant chemotherapy for gastric cancer: a comprehensive review. Gastric Cancer. 2001;4:175–84.PubMedCrossRef

76.

Kondo M, Torisu M, Evaluation of an anticancer activity of a protein-bound polysaccharide PS-K (Krestin). In: Torisu M, Yoshida T, editors. Basic mechanisms and clinical treatment of tumor metastasis. Orlando: Academic Press; 1985. p. 623–36.

77.

Maehara Y, Moriguchi S, Sakaguchi Y, Emi Y, Kohnoe S, Tsujitani S, et al. Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. J Surg Oncol. 1990;45:169–72.PubMedCrossRef

78.

Nakajima T, Inokuchi K, Hattori T, Inoue K, Taguchi T, Kondou T, et.al. Multi-institutional cooperative study of adjuvant immunochemotherapy for gastric cancer—five-year survival rate. Jpn J Cancer Chemother. 1989;16:799–806 (in Japanese with English abstract).

79.

Niimoto M, Hattori T, Tamada R, Sugimachi K, Inokuchi K, Ogawa N. Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Jpn J Surg. 1988;18:681–6.PubMedCrossRef

80.

Kondo T, Ichihashi H, Nakazato H, Ogawa N. Results of adjuvant immunochemotherapy on 8-year survival using KRESTIN^® and Futraful^® for gastric cancer patients who underwent radical gastrectomy—a randomized controlled trial by cooperative study group. Biotherapy. 1989;3:655–64 (in Japanese with English abstract).

81.

Sakamoto J, Nakazato H, Koike A, Saji S. Pitfalls in the clinical evaluation of surgical adjuvant immunochemotherapy for the multidisciplinary treatment of gastrointestinal cancers. Biotherapy. 1993;7:1759–64 (in Japanese with English abstract).

82.

Kondo T, Sakamoto J, Nakazato H. Alternating immunochemotherapy of advanced gastric carcinoma: a randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection. Biotherapy. 1991;3:287–95.PubMedCrossRef

83.

Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet. 1994;343:1122–6.PubMedCrossRef

84.

Ogawa M, Kako H, Kitano K, Matsukane H, Nagao K, Misumi A, et al. Cooperative study of adjuvant immunochemotherapy using HUFU (Mifurol^®) for gastric cancer patients who underwent curative resection. Rinsyo To Kenkyu. 1994;71:201–6 (in Japanese).

85.

Oba K, Teramukai S, Kobayashi M, Matsui T, Kodera Y, Sakamoto J. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother. 2007;56:905–11.PubMedCrossRef

86.

Sugimachi K, Maehara Y, Ogawa M, Kakegawa T, Tomita M. Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer. Cancer Chemother Pharmacol. 1997;40:233–8.PubMedCrossRef

87.

Fujii M, Kochi M, Takayama T. Recent advances in chemotherapy for advanced gastric cancer in Japan. Surg Today. 2010;40:295–300.PubMedCrossRef

88.

Torisu M, Hayashi Y, Ishimitsu T, Fujimura T, Iwasaki K, Katano M, et al. Significant prolongation of disease-free period gained by oral polysaccharide K(PSK) administration after curative surgical operation of colorectal cancer. Cancer Immunol Immunother. 1990;31:261–8.PubMedCrossRef

89.

Takashima S, Kinami Y, Miyazaki I. Clinical effect of postoperative adjuvant immunochemotherapy with FT-207 suppository and PSK for colo-rectal cancer patients. Jpn J Cancer Chemother. 1988;15:2229–36 (in Japanese with English abstract).

90.

Mitomi T, Tsuchiya S, Iijima N, Aso K, Nishiyama K, Amano T, et al. Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer—5 years follow-up after surgery (a final report). J Jpn Soc Cancer Ther. 1993;28:71–83 (in Japanese with English abstract).

91.

Ito K, Nakazato H, Koike A, Takagi H, Saji S, Baba S, et al. Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up. Int J Colorectal Dis. 2004;19:157–64.PubMedCrossRef

92.

Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, et al. Adjuvant immunochemotherapy with oral tegafur/uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer. 2004;90:1003–10.PubMedCrossRef

93.

Sakamoto J, Morita S, Oba K, Matsui T, Kobayashi M, Nakazato H, et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother. 2006;55:404–11.PubMedCrossRef

94.

Konno K, Motomiya M, Oizumi K, Sato M, Yamamoto F, Tamiya K, et al. Effects of protein-bound polysaccharide preparation (PSK) in small cell carcinoma of the lung. JJLC. 1988;28:19–28 (in Japanese with English abstract).

95.

Ikeda T, Sakai T, SuitoT, Kosaki G. Evaluation of postoperative immunochemotherapy for lung cancer patients. Jpn J Cancer Chemother. 1986;13:1044–9 (in Japanese with English abstract).

96.

Hayakawa K, Mitsuhashi N, Saito Y, Nakayama Y, Furuta M, Nakamoto S, et al. Effect of Krestin as adjuvant treatment following radical radiotherapy in non-small cell lung cancer patients. Cancer Detect Prev. 1997;21:71–7.PubMed

97.

Go P, Chung CH. Adjuvant PSK immunotherapy in patients with carcinoma of the nasopharynx. J Int Med Res. 1989;17:141–9.PubMed

98.

Matsumoto K, Nakagami Y, Kishimoto T. The prevention of recurrence of superficical bladder tumours with immunochemotherapy. In: deKernion JB, editor. International society of urology reports. Immunotherapy of urological tumours. Edinburgh: Churchill Livingstone; 1990. p. 149–55.

99.

Ogoshi K, Satou H, Isono K, Mitomi T, Endoh M, Sugita M. Immunotherapy for esophageal cancer. A randomized trial in combination with radiotherapy and radiochemotherapy. Am J Clin Oncol. 1995;18:216–22.PubMedCrossRef

100.

Iino Y, Yokoe T, Maemura M, Horiguchi J, Takei H, Ohwada S, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res. 1995;15:2907–11.PubMed

101.

Pharmaceutical Affairs Bureau, Ministry of Health and Welfare (Japan). Ethical drug side effect information no. 48. 1982; p. 220–3 (in Japanese).

102.

Kohara K, Arima S, Tamesue N, Shimura H. Toxicities in single chemotherapy with 5-fluorouracil dry syrup and combination chemotherapy with 5-fluorouracil dry syrup and PSK for cancer patients. Jpn J Cancer Chemother. 1979;6:379–85 (in Japanese with English abstract).

103.

Sadahiro S, Suzuki T, Maeda Y, Tanaka A, Kamijo A, Murayama C, Nakayama Y, Akiba T, et al. Effects of preoperative immunochemoradiotherapy and chemoradiotherapy on immune responses in patients with rectal adenocarcinoma. Anticancer Res. 2010;30:993–9.PubMed

104.

Yoshimura A, Asakawa M, Nakai H, Sakai H, Nishiwaki Y, Furuse K, et al. Combined effects of PSK with chemotherapy in the treatment of adenocarcinoma of the lung. Assessment of quality of life (QOL). Biotherapy 1992;6:256–7 (in Japanese with English abstract).

105.

Motai H. PSK effectiveness for cancer pain relief: clinical study covering the last 11 years. Biotherapy. 1992;6:950–6 (in Japanese with English abstract).

106.

Nomoto K, Matsuo K. Role of immunopotentiators in immunotherapy. Jpn J Cancer Chemother. 1978;5:1135–41 (in Japanese with English abstract).

107.

Sakamoto J, Koike A, Saji S, Teramukai S, Ohashi Y, Nakazato H. Preoperative serum immunosuppressive acidic protein (IAP) test for the prognosis of gastric cancer: a statistical study of the threshold level and evaluation of the effect of the biological response modifier PSK. Surg Today. 1992;22:530–6.PubMedCrossRef

108.

Toge T, Yamaguchi Y. Protein-bound polysaccharide increases survival in resected gastric cancer cases stratified with a preoperative granulocyte and lymphocyte count. Oncol Rep. 2000;75:1157–61.

109.

Tsujitani S, Kakeji Y, Orita H, Watanabe A, Kohnoe S, Baba H, et al. Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer. Anticancer Res. 1992;12:645–8.PubMed

110.

Ogoshi K, Tajima T, Mitomi T, Makuuchi, Tsuji K. HLA-A2 antigen status predicts metastasis and response to immunotherapy in gastric cancer. Cancer Immunol Immunother. 1997;45:53–9.

111.

Yoshikawa R, Yanagi H, Shen CH, Fujiwara Y, Noda M, Yagyu T, et al. ECA39 is a novel distant metastasis-related biomarker in colorectal cancer. World J Gastroenterol. 2006;12:5884–9.PubMed

112.

Yamashita K, Ougolkov AV, Nakazato H, Ito K, Ohashi Y, Kitakata H, et al. Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic β-catenin activation. Dis Colon Rectum. 2007;50:1169–81.PubMedCrossRef

113.

Takahashi Y, Mai M, Nakazato H. Preoperative CEA and PPD values as prognostic factors for immunochemotherapy using PSK and 5-FU. Anticancer Res. 2005;25:1377–84.PubMed

114.

Ohwada S, Ogawa T, Makita F, Tanahashi Y, Ohya T, Tomizawa N, et al. Beneficial effects of protein-bound polysaccharide K plus tegafur/uracil in patients with stage II or III colorectal cancer: analysis of immunological parameters. Oncol Rep. 2006;15:861–8.PubMed

115.

Sugimachi K, Maehara Y, Kusumoto T, Okamura T, Korenaga D, Kohnoe S, et al. In vitro reactivity to a protein-bound polysaccharide PSK of peripheral blood lymphocytes from patients with gastrointestinal cancer. Anticancer Res. 1995;15:2175–80.PubMed

116.

Yoshinaga K, Saeki H, Endo K, Morita M, Emi Y, Kakeji Y, et al. Biomarker research of Krestin (PSK) therapy in gastric and colorectal cancer patients. J Jpn Soc Clin Oncol. 2008;43:900.

117.

Sugiyama M, Yoshino I, Kakeji Y, Maehara Y. Gene expression profile in human peripheral blood mononuclear cells upon PSK stimulation. In: Proceedings of the JCA. 2008; p. 452.

Title: Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN®): review of development and future perspectives
Authors: Yoshihiko Maehara
Shunichi Tsujitani
Hiroshi Saeki
Eiji Oki
Keiji Yoshinaga
Yasunori Emi
Masaru Morita
Shunji Kohnoe
Yoshihiro Kakeji
Tokujiro Yano
Hideo Baba
Publication date: 01-01-2012
Publisher: Springer Japan
Published in: Surgery Today / Issue 1/2012
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI: https://doi.org/10.1007/s00595-011-0075-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Biological mechanism and clinical effect of protein-bound polysaccharide K (KRESTIN^®): review of development and future perspectives

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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