Abstract
To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a proteinbound 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 atP <0.05 by the logrank test. The survival rate of patients was also significantly (P <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).
Keywords: Gastric Cancer, Colorectal Cancer, Phagocytic Activity, Keyhole Limpet Hemocyanin, DNCB
References
- 1.Akiyama J, Kawamura T, Gotohda E, Yamada Y, Hosokawa M, Kodama T, Kobayashi H. Immunochemotherapy of transplanted KMT-17 tumor in WKA rats by combination of cyclophosphamide and immunostimulatory protein-bound polysaccharide isolated from basidiomycetes. Cancer Res. 1977;37:3042. [PubMed] [Google Scholar]
- 2.Easmon CSF, Cole PJ, Williams AJ, Hastings M. The measurement of opsonic and phagocytic function by Luminol-dependent chemiluminescence. Immunology. 1980;41:67. [PMC free article] [PubMed] [Google Scholar]
- 3.Hayashi Y, Torisu M. New approach to management of malignant ascites with a streptococcal preparation OK-432 III. OK-432 attracts NK cells through a chemotactic factor released from activated neutrophils. Surgery. 1990;107:74. [PubMed] [Google Scholar]
- 4.Ikeda T, Sakai T, Saito T, Kosaki G. Evaluation of Postoperative immunochemotherapy for lung cancer patients. Jpn J Cancer Chemother. 1986;13:1044. [PubMed] [Google Scholar]
- 5.Itoh I, Sakai T, Mori T. Aspects of immunological antitumor agent and its clinical use PSK. Jpn J Cancer Chemother. 1979;6:681. [Google Scholar]
- 6.Iwasaki K, Torisu M, Fujimura T. Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer. Cancer. 1986;58:1321. doi: 10.1002/1097-0142(19860915)58:6<1321::AID-CNCR2820580623>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
- 7.Japanese Research Society for Cancer of Colon and Rectum (1977) General rules for clinical and pathological studied on cancer of colon, rectum and anus.
- 8.Katano M, Torisu M. New approach to management of malignant ascites with a streptococcal preparation, OK-432. II. Intraperitoneal inflammatory cell-mediated tumor cell destruction. Surgery. 1983;93:365. [PubMed] [Google Scholar]
- 9.Katano M, Tanaka M, Okano H, Torisu M. Ambidextrous effect of PSK on motilities of both macrophages and tumor cells. Proc Am Soc Exp Biol. 1980;39:476. [Google Scholar]
- 10.Kataoka T, Oh-hashi F, Tsukagoshi S, Sakurai Y. Enhanced induction of immune resistance by concanavalin A-bound L1210 vaccine and an immunopotentiator prepared fromCoriolus versicolor . Cancer Res. 1977;37:4416. [PubMed] [Google Scholar]
- 11.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. New York: Academic Press; 1985. p. 623. [Google Scholar]
- 12.Kondo M, Kato H, Yokoe N, Natsumura N, Hotta T, Masuda M. Activation of the complement by immunostimulants, BCG, OK-432 (Picibanil), and PS-K (Krestin) in vivo. Gann. 1978;69:669. [PubMed] [Google Scholar]
- 13.Koshimura S, Shimizu R, Fujimura A, Okamoto H. Experimental anticancer studies. XXI. Effect of penicillin treatment of hemolyticStreptococcus on its anticancer activity. Gann. 1964;55:233. [PubMed] [Google Scholar]
- 14.Kumashiro R, Hiramoto Y, Okamura T, Kano T, Sano CC, Inokuchi K. Postoperative long-term immunostimulatory protein-bound polysaccharide Kureha (PSK) therapy for advanced gastric cancer. In: Torisu M, Yoshida T, editors. Basic mechanisms and clinical treatment of tumor metastasis. New York: Academic Press; 1985. p. 523. [Google Scholar]
- 15.Linell F, Mansson B. The prognostic value of eosinophilic leukocytes in the stroma of carcinoma of the cervix uteri. Acta Rasdiol. 1954;41:453. doi: 10.3109/00016925409175870. [DOI] [PubMed] [Google Scholar]
- 16.Mancini G, Carbonara AO, Heremans JF. Immunochemical quantitation of antigens by single radial immunodiffusion. Int J Immunochem. 1965;2:235. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
- 17.Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger LR, Mayat M, de Vassal F. Active immunotherapy for acute lymphoblastic leukemia. Lancet. 1969;1:697. doi: 10.1016/S0140-6736(69)92648-8. [DOI] [PubMed] [Google Scholar]
- 18.Mathé G, Schwarzenberg L, de Vassal F, Delgado M. Immunotherapy for acute lymphoid leukemia. Lancet. 1976;1:143. doi: 10.1016/S0140-6736(76)93179-2. [DOI] [PubMed] [Google Scholar]
- 19.Mayer MM. Experimental immunochemistry. 2nd edn. Springfield Ill: Thomas; 1961. p. 135. [Google Scholar]
- 20.Mitomi T, Ogoshi K. Clinical study of PSK as an adjuvant immunochemotherapeutic agent against gastric cancer. Jpn J Cancer Chemother. 1986;13:2532. [PubMed] [Google Scholar]
- 21.Morton DL, Eilber FR, Malmgren RA, Wood WC. Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery. 1970;68:158. [PubMed] [Google Scholar]
- 22.Morton DL, Eilber FR, Holmes EC, Sparkes FC, Ramming KP. Present status of BCG immunotherapy of malignant melanoma. Cancer Immunol Immunother. 1976;1:93. [Google Scholar]
- 23.Nagell JR, Donaldson ES, Wood EG, Parker JC. The significance of vascular invasion and lymphocytic infiltration in invasive cervical carcinoma. Cancer. 1978;41:228. doi: 10.1002/1097-0142(197801)41:1<228::AID-CNCR2820410131>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
- 24.Nakazato H, Ichihashi H, Kondo T. Clinical results of a randomized controlled trial on the effect of adjuvant immunochemotherapy using Esquinon and Krestin for patients with curatively resected gastric cancer. Jpn J Cancer Chemother. 1986;13:308. [PubMed] [Google Scholar]
- 25.Niimoto M, Toge T, Nakano A, Yanagawa E, Oride M, Hirano M, Nakanishi K, Nosou Y, Yamada Y, Hattori T. Adjuvant immunochemotherapy in patients with gastric cancer. Jpn J Gastroenterol Surg. 1981;14:704. doi: 10.5833/jjgs.14.704. [DOI] [Google Scholar]
- 26.Nishioka K, Linscott WD. Components of guinea pig complement I. Separation of a serum fraction essential for immune hemolysis and immune adherence. J Exp Med. 1963;118:767. doi: 10.1084/jem.118.5.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.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. [PubMed] [Google Scholar]
- 28.Okamoto H, Shoin S, Koshimura S, Shimizu R. Studies on the anticancer and streptolysin S-forming abilities of hemolytic streptococci. Jpn J Microbiol. 1973;11:323. doi: 10.1111/j.1348-0421.1967.tb00350.x. [DOI] [PubMed] [Google Scholar]
- 29.Pretlow TP, Keith EF, Cryar AK. Eosinophil infiltration of human colonic carcinomas as a prognostic indication. Cancer Res. 1983;43:2997. [PubMed] [Google Scholar]
- 30.Shiraki S, Mori H, Ito A, Kadomoto N, Yamagiwa S, Yamada Y, Noda K. Adjuvant immunotherapy for carcinoma of uterine cervix with PSK. Jpn J Cancer Chemother. 1982;9:1031. [PubMed] [Google Scholar]
- 31.Tachibana T, Ishikawa M. Quantitation of T and B lymphocyte. Jpn J Exp Med. 1973;43:227. [PubMed] [Google Scholar]
- 32.Taguchi T. Clinical studies on PSK: combination therapy of PSK with surgery and chemotherapy. Recent Results Cancer Res. 1979;68:236. doi: 10.1007/978-3-642-81332-0_36. [DOI] [PubMed] [Google Scholar]
- 33.Torisu M, Fukawa M, Nishimura M, Harasaki H, Kai S, Tanaka J. Immunotherapy of cancer patients with bacillus Calmette-Guérin: summary of four years of experience in Japan. Ann NY Acad Sci. 1976;277:160. doi: 10.1111/j.1749-6632.1976.tb41696.x. [DOI] [PubMed] [Google Scholar]
- 34.Torisu M, Katano M, Kimura Y, Itoh H, Takesue M. New approach to management of malignant ascites with a streptococcal preparation of survival. Surgery. 1983;93:357. [PubMed] [Google Scholar]
- 35.Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K, Orita K. Krestin (PSK) Cancer Treat Rev. 1984;11:131. doi: 10.1016/0305-7372(84)90005-7. [DOI] [PubMed] [Google Scholar]
- 36.Uchida A, Hoshino T. Clinical studies on cell-mediated immunity in patients with malignant disease. I. Effect of immunotherapy with OK-432 on lymphocyte subpopulation and phytomitogen responsiveness in vitro. Cancer. 1980;45:476. doi: 10.1002/1097-0142(19800201)45:3<476::AID-CNCR2820450311>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
- 37.Ward PA, Cochrane CG, Müller-Eberhard HJ. The role of serum complement in chemotaxis of leukocytes in vitro. J Exp Med. 1965;122:327. doi: 10.1084/jem.122.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Ward PA, Lepow IH, Newman LJ. Bacterial factors chemotactic for polymorphonuclear leukocytes. Am J Pathol. 1968;52:725. [PMC free article] [PubMed] [Google Scholar]
- 39.Watanabe Y, Iwa T (1984) Clinical value of immunotherapy by streptococcal preparation, OK-432, for lung cancer: a randomized study: In: Hoshino T, Uschida A (eds) Clinical and Experimental Studies in Immunotherapy Excerpta Medica, Amsterdam, p 120
- 40.Watanabe H, Enjohji M, Imai T. Gastric carcinoma with lymphoid stroma: Its morphologic characteristics and prognostic correlations. Cancer. 1976;38:232. doi: 10.1002/1097-0142(197607)38:1<232::AID-CNCR2820380135>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
- 41.Yoshikuni C., Nomoto K, Matsunaga K, Fujii T, Takeya K. Mouse strain difference in expression of antitumor activity of PS-K. Gann. 1975;66:649. [PubMed] [Google Scholar]