Immunostimulatory properties and antitumor activities of glucans (Review)

Vannucci,Luca; Krizan,Jiri; Sima,Petr; Stakheev,Dmitry; Caja,Fabian; Rajsiglova,Lenka; Horak,Vratislav; Saieh,Mustafa

doi:10.3892/ijo.2013.1974

Immunostimulatory properties and antitumor activities of glucans (Review)

Authors:
- Luca Vannucci
- Jiri Krizan
- Petr Sima
- Dmitry Stakheev
- Fabian Caja
- Lenka Rajsiglova
- Vratislav Horak
- Mustafa Saieh
View Affiliations

Affiliations: Laboratory of Immunotherapy, Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., 142 20 Prague 4, Czech Republic, Laboratory of Tumour Biology, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, v.v.i., 277 21 Libechov, Czech Republic, Department of Biology, University of Al-Jabal Al-Gharbi, Gharyan Campus, Libya
Published online on: June 5, 2013 https://doi.org/10.3892/ijo.2013.1974
Pages: 357-364
Copyright: © Vannucci et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

New foods and natural biological modulators have recently become of scientific interest in the investigation of the value of traditional medical therapeutics. Glucans have an important part in this renewed interest. These fungal wall components are claimed to be useful for various medical purposes and they are obtained from medicinal mushrooms commonly used in traditional Oriental medicine. The immunotherapeutic properties of fungi extracts have been reported, including the enhancement of anticancer immunity responses. These properties are principally related to the stimulation of cells of the innate immune system. The discovery of specific receptors for glucans on dendritic cells (dectin-1), as well as interactions with other receptors, mainly expressed by innate immune cells (e.g., Toll-like receptors, complement receptor-3), have raised new attention toward these products as suitable therapeutic agents. We briefly review the characteristics of the glucans from mycelial walls as modulators of the immunity and their possible use as antitumor treatments.

View Figures

View References

1.	Tzianabos A: Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev. 13:523–533. 2000. View Article : Google Scholar : PubMed/NCBI
2.	Han SB, Lee CW, Jeon YJ, Hong ND, Yoo ID, Yang KH and Kim HM: The inhibitory effect of polysaccharides isolated from Phellinus liteus on tumor growth and metastasis. Immunopharmacology. 41:157–164. 1999. View Article : Google Scholar : PubMed/NCBI
3.	Ooi VE and Liu F: Immunomodulation and anticancer activity of polysaccharide-protein complex. Curr Med Chem. 7:715–729. 2000. View Article : Google Scholar : PubMed/NCBI
4.	Falch BH, Espevik T, Ryan L and Stokke BT: The cytokine stimulating activity of (1→3)-beta-D-glucans is dependent on the triple helix conformation. Carbohydr Res. 329:587–596. 2000.
5.	Barsanti L, Passarelli V, Evangelista V, Frassanito AM and Gualtieri P: Chemistry, physico-chemistry and applications linked to biological activities of β-glucans. Nat Prod Rep. 28:457–466. 2011.PubMed/NCBI
6.	Yap AT and Ng ML: An improved method for the isolation of lentina from the edible and medicinal shiitake mushroom, Lentinus edodes(Berk.) Sing. (Agaricomycetideae). Int J Med Mushr. 3:6–19. 2001.
7.	Riggi SJ and Di Luzio NR: Identification of a reticuloendothelial stimulating agent in zymosan. Am J Physiol. 200:297–300. 1961.PubMed/NCBI
8.	Wasser SP: Current findings, future trends and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol. 89:1323–1332. 2011. View Article : Google Scholar : PubMed/NCBI
9.	Chang ST and Wasser S: The role of culinary-medicinal mushrooms on human welfare with a pyramid model for human health. Int J Med Mushr. 14:95–134. 2012. View Article : Google Scholar : PubMed/NCBI
10.	Pillemer L and Ecker EE: Anticomplementry factor in fresh yeast. J Biol Chem. 137:139–142. 1941.
11.	Pillemer L, Blum L, Pensky J and Lepow IH: The requirement for magnesium ions in the inactivation of the third component of human complement (C'3) by insoluble residues of yeast cells (zymosan). J Immunol. 71:331–338. 1953.PubMed/NCBI
12.	Ohano N, Miura NN, Nakajima M and Yadomae T: Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa. Biol Pharm Bull. 7:866–872. 2000. View Article : Google Scholar : PubMed/NCBI
13.	Novak M and Vetvicka V: Glucans as biological response modifiers. Endocr Metab Immune Disord Drug Targets. 9:67–75. 2009. View Article : Google Scholar : PubMed/NCBI
14.	Hong F, Hansen RD, Yan J, Allendorf DJ, Baran JT, Ostroff CR and Ross GD: Beta-glucans functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res. 63:9023–9031. 2003.PubMed/NCBI
15.	Kamiryo Y, Yajima T, Saito K, Nishimura H, Fushimi T, Ohshima Y, Tsukamoto Y, Naito S and Yoshikai Y: Soluble branched (1,4)- β-D-glucans from Acetobacter species enhance antitumor activitiese against MHC class I-negative and postitive malignant melanoma through augmented NK activity and cytotoxic T-cell response. Int J Cancer. 115:769–776. 2005.
16.	Ryoyama K, Kidachi Y, Yamaguchi H, Kajiura H and Takata H: Antitumor activity of an enzymatically synthesized α-1,6 branched α-1,4-glucan, glycogen. Biosci Biotechnol Biochem. 68:2332–2340. 2004.
17.	Chan GC, Chan WK and Sze DM: The effects of beta-glucan on human immune and cancer cells. J Hematol Oncol. 2:252009. View Article : Google Scholar : PubMed/NCBI
18.	Aleem E: β-glucans and their applications in cancer therapy: focus on human studies. Anticancer Agents Med Chem. Nov 5–2012, (Epub ahead of print).
19.	Usui S, Tomono Y, Sakai M, Kiho T and Ukai S: Preparation and antitumor activities of beta-(1→6) branched (1→3)-beta-D-glucan derivatives. Biol Pharm Bull. 18:1630–1636. 1995.
20.	Synytsya A and Novák M: Structural diversity of fungal glucans. Carbohydr Polym. 92:792–809. 2013. View Article : Google Scholar : PubMed/NCBI
21.	Sawai M, Adachi Y, Kanai M, Matsui S and Yadomae T: Extraction of conformationally stable (1–6)–branched (1–3)-β-D-glucans from premixed edible mushroom powders by cold alkaline solution. Int J Med Mushr. 4:197–205. 2002.
22.	Kitamura S, Hori T, Kurita K, Takeo K, Hara C, Itoh W, Tabata K, Elgsaeter A and Stokke BT: An antitumor, branched (1→3)-beta-D-glucan from a water extract of fruiting bodies of Cryptoporus volvatus. Carbohydr Res. 263:111–121. 1994.
23.	Ohno N, Kurachi K and Yadomae T: Antitumor activity of a highly branched (1–3)-beta-D-glucan, SSG, obtained from Sclerotinia sclerotiorum IFO 9395. J Pharmacobiodyn. 10:478–486. 1987.
24.	Fujimoto S, Furue H, Kimura T, Kondo T, Orita K, Taguchi T, Yoshida K and Ogawa N: Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study. Eur J Cancer. 27:1114–1118. 1991. View Article : Google Scholar
25.	Ishibashi K, Miura NN, Adachi Y, Ohno N and Yadomae T: Relationship between solubility of grifolan, a fungal 1,3-beta-D-glucan and production of tumor necrosis factor by macrophages in vitro. Biosci Biotechnol Biochem. 65:1993–2000. 2001. View Article : Google Scholar : PubMed/NCBI
26.	Blecher P and Mackin W: Betafectin PGG-glucan: a novel carbohydrate immunodulator with anti-infective properties. J Biotechnol Healthcare. 2:207–222. 1995.
27.	Chihara G, Maeda Y, Hamuro J, Sasaki T and Fukuoka F: Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes. Nature. 222:687–696. 1969. View Article : Google Scholar : PubMed/NCBI
28.	Ohno N, Uchiyama M, Tsuzuki A, Tokunaka K, Miura NN, Adachi Y, Aizawa MW, Tamura H, Tanaka S and Yadomae T: Solubilization of yeast cell-wall β-(1–3)-D-glucans by sodium hypochlorite oxidation and dimethyl sulfoxide extraction. Carbohydr Res. 316:161–172. 1999.
29.	Majtan J: Pleuran (β-Glucan from Pleurotus ostreatus): an effective nutritional supplement against upper respiratory tract infections? Med Sport Sci. 59:57–61. 2013.
30.	Volman JJ, Helsper JP, Wei S, Baars JJ, van Griensven LJ, Sonnenberg AS and Plat J: Effects of mushroom-derived beta-glucan-rich polysaccharide extracts on nitric oxide production by bone marrow-derived macrophages and nuclear factor-kappaB transactivation in Caco-2 reporter cells: can effects be explained by structure? Mol Nutr Food Res. 54:268–276. 2010. View Article : Google Scholar
31.	Zhang P, Zhang L and Cheng S: Chemical structure and molecular weights of α-(1,3)-D-glucan from Lentinus edodes. Biosci Biotechnol Biochem. 63:1197–1202. 1999.
32.	Brown GD and Gordon S: Fungal β-glucans and mammalian immunity. Immunity. 19:311–315. 2003.
33.	Sasaki T and Takasuka N: Further study of the structure of lentinan, an antitumor polysaccharide from Lentinus edodes. Carbohydr Res. 47:99–104. 1976. View Article : Google Scholar : PubMed/NCBI
34.	Zhang M, Cui SW, Cheung PCK and Wang Q: Antitumor polysaccharides from mushrooms: a review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci Technol. 18:4–19. 2007. View Article : Google Scholar
35.	Zimmerman JW, Lindermuth J, Fish PA, Palace GP, Stevenson TT and DeMong DE: A novel carbohydrate-glycosphingolipid interaction between a beta-(1–3)-glucan immunomodulator, PGG-glucan and lactosylceramide of human leukocytes. J Biol Chem. 273:22014–22020. 1998.PubMed/NCBI
36.	Zimmermann G and Krueger K: Ultracentrifuge studies on properdin sera of zymosan-vaccinated cattle, rabbits, guinea pigs, rats and mice and on bovine properdin serum fractions. Acta Biol Med Ger. 11:902–917. 1963.(In German).
37.	Cassone A, Bistoni F, Cenci E, Pesce CD, Tissi L and Marconi P: Immunopotentiation of anticancer chemotherapy by Candida albicans, other yeasts and insoluble glucan in an experimental lymphoma model. Sabouraudia. 20:115–125. 1982.PubMed/NCBI
38.	Haggård L, Andersson M and Punga AR: β-glucans reduce LDL cholesterol in patients with myasthenia gravis. Eur J Clin Nutr. 67:226–227. 2013.
39.	Zhang Y, Xia L, Pang W, Wang T, Chen P, Zhu B and Zhang J: A novel soluble β-1,3-d-glucan Salecan reduces adiposity and improves glucose tolerance in high-fat diet-fed mice. Br J Nutr. 13:1–9. 2012.
40.	Di Luzio NR: Update on the immunomodulating activities of glucans. Springer Semin Immunopathol. 8:387–400. 1985.PubMed/NCBI
41.	Di Luzio NR: Immunopharmacology of glucan: a broadspectrum enhancer of host defence mechanisms. Trends Pharmacol Sci. 4:344–347. 1983.PubMed/NCBI
42.	Kaneko Y and Chihara G: Potentiation of host resistance against microbal infections by lentinan and its related polysaccharides. Microbal Infections: Role of Biological Response Modifers. Friedman H, Klein TW and Yamaguchi H: Plenum Press; New York, NY: pp. 201–215. 1992, View Article : Google Scholar : PubMed/NCBI
43.	Williams DL, Browder IW and Di Luzio NR: Immunotherapeutic modification of Escherichia coli-induced experimental peritonitis and bacteremia by glucan. Surgery. 93:448–454. 1983.
44.	Ling J, Melican D, Cafro L, Palace G, Fisette L, Armstrong R and Patchen ML: Enhanced clearance of a multiple antibiotic resistance Staphilococcus aureus in rats treated with PGG-glucans is associated with increased leukocyte counts and increased neutrophil oxidative burst activity. Int J Immunopharmacol. 20:595–614. 1998.
45.	Wakshull E, Brunke-Reese D, Lindermuth J, Fisette L, Nathans RS, Crowley JJ, Tufts JC, Zimmerman J, Mackin W and Adams DS: PGG-glucan, a soluble beta-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity and activates an NF-kappa B-like factor in human PMN: evidence for a glycosphingolipid beta-(1,3)-glucan receptor. Immunopharmacology. 41:89–107. 1999. View Article : Google Scholar
46.	Burgaletta C, Territo MC, Quan SG and Golde DW: Glucan activated macrophages: functional characteristics and surface morphology. J Reticuloendothel Soc. 23:195–104. 1978.PubMed/NCBI
47.	Chanput W, Reitsma M, Kleinjans L, Mes JJ, Savelkoul HF and Wichers HJ: β-glucans are involved in immune-modulation of THP-1 macrophages. Mol Nutr Food Res. 56:822–833. 2012.
48.	Adachi Y, Ohno N, Ohsawa S and Yadomae T: Change biological activities of (1–3)-beta-D-glucan from Grifola frondosa upon molecular weight reduction by heat treatment. Chem Pharm Bull (Tokyo). 38:477–481. 1990.
49.	Selijelid R, Bogwald J, Rasmussen LT, Larm O, Hoffman J, Berge A and Ugelstad J: In vivo activation of mouse macrophages with beta-1,3-D-glucan-derivatized plastic beads. Scand J Immunol. 6:601–605. 1985.PubMed/NCBI
50.	Patchen ML and Lotzova E: Modulation of murine hemopoiesis by glucans. Exp Hematol. 8:409–422. 1980.PubMed/NCBI
51.	Hofer M and Pospíšil M: Modulation of animal and human hematopoiesis by β-glucans: a review. Molecules. 16:7969–7979. 2011.
52.	Tsuzuki A, Tateishi T, Ohno N, Adachi Y and Yadomae T: Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1→3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice. Biosci Biotechnol Biochem. 63:104–110. 1999.
53.	Browder W, Williams D, Preutes H, Olivero G, Enrichens F, Mao P and Franchello A: Beneficial effect of enhanced macrophage function in the trauma patient. Ann Surg. 211:605–613. 1990.PubMed/NCBI
54.	Czop JK and Austen KF: Generation of leukotrienes by human monocytes upon stimulation of their beta-glucan receptor during phagocytosis. Proc Natl Acad Sci USA. 82:2751–2755. 1985. View Article : Google Scholar : PubMed/NCBI
55.	Goodridge HS, Wolf AJ and Underhill DM: Beta-glucan recognition by the innate immune system. Immunol Rev. 230:38–50. 2009. View Article : Google Scholar : PubMed/NCBI
56.	Czop JK and Austen KF: Properties of glycans that activate the human alternative complement pathway and interact with human monocyte beta-glucan receptor. J Immunol. 135:3388–3393. 1985.PubMed/NCBI
57.	Doita M, Rasmussen LT, Seljelid R and Lipsky PE: Effect of soluble aminated beta-1,3-D-polyglucose on human monocytes: stimulation of cytokine and prostaglandin E2 production but not antigen-presenting function. J Leukoc Biol. 49:342–351. 1991.PubMed/NCBI
58.	Konopski Z, Seljelid R and Eskeland T: Cytokines and PGE2 modulate the phagocytic function of beta-glucan receptor in macrophages. Scand J Immunol. 37:587–592. 1993. View Article : Google Scholar : PubMed/NCBI
59.	Volman JJ, Ramakers JD and Plat J: Dietary modulation of immune function by beta-glucans. Physiol Behav. 94:276–284. 2008. View Article : Google Scholar : PubMed/NCBI
60.	Senoglu N, Yuzbasioglu MF, Aral M, Ezberci M, Kurutas EB, Bulbuloglu E, Ezberci F, Oksuz H and Ciragil P: Protective effects of N-acetylcysteine and beta-glucan pretreatment on oxidative stress in cecal ligation and puncture model of sepsis. J Invest Surg. 21:237–243. 2008. View Article : Google Scholar : PubMed/NCBI
61.	Bedirli A, Kerem M, Pasaoglu H, Akyurek N, Tezcaner T, Elbeg S, Memis L and Sakrak O: Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock. 27:397–401. 2007. View Article : Google Scholar : PubMed/NCBI
62.	Sener G, Toklu H, Ercan F and Erkanli G: Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharmacol. 5:1387–1396. 2005. View Article : Google Scholar : PubMed/NCBI
63.	Williams DL, Sherwood ER, Browder IW, McNamee RB, Jones EL, Rakinic J and DiLuzio NR: Effect of glucan on neutrophil dynamics and immune function in Escherichia coli peritonitis. J Surg Res. 44:54–61. 1988. View Article : Google Scholar : PubMed/NCBI
64.	Onderdonk AB, Cisneros RL, Hinkson PL and Ostroff GR: Anti-infective effect of poly β1-6 glucotriosyle-β1-3glucopyranose glucan in vivo. Infect Immun. 60:1642–1647. 1992.
65.	Stashenko P, Wang CY, Riley E, Wu Y, Ostroff G and Niederman R: Reduction of infection-stimulated periapical bone resorption by the biological response modifier PGG-glucan. J Dent Res. 74:323–330. 1995. View Article : Google Scholar : PubMed/NCBI
66.	Berovic M, Habijanic J, Zore I, Wraber B, Hodzar D, Boh B and Pohleven F: Submerged cultivation of Ganoderm lucidum biomass and immunostimulatory effects of fungal polysaccharides. J Biotecnol. 103:77–86. 2003. View Article : Google Scholar : PubMed/NCBI
67.	Dellinger EP, Babineau TJ, Bleicher P, Kaiser AB, Seibert GB, Postier RG, Vogel SB, Norman J, Kaufman D, Galandiuk S and Condon RE: Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group Arch Surg. 134:977–983. 1999.
68.	Mueller A, Raptis J, Rice PJ, Kalbffleisch JH, Stout RD, Ensley HE, Browder W and Williams DL: The influence of glucan polymer structure and solution conformation on binding to (1–3)-β-D-glucans receptors in human monocyte-like cell line. Glycobiology. 10:339–346. 2000.
69.	Williams DL, Mueller A and Browder W: Glucan-based macrophages stimulators: a review of their anti-infective potential. Clin Immunother. 5:392–399. 1996. View Article : Google Scholar
70.	Hardison SE and Brown GD: C-type lectin receptors orchestrate antifungal immunity. Nat Immunol. 13:817–822. 2012. View Article : Google Scholar : PubMed/NCBI
71.	Saijo S and Iwakura Y: Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol. 23:467–472. 2011. View Article : Google Scholar : PubMed/NCBI
72.	Kapetanovic R and Cavaillon JM: Early events in innate immunity in the recognition of microbial pathogens. Expert Opin Biol Ther. 7:907–918. 2007. View Article : Google Scholar : PubMed/NCBI
73.	Tsoni SV and Brown GD: beta-glucans and dectin-1. Ann NY Acad Sci. 1143:45–60. 2008. View Article : Google Scholar : PubMed/NCBI
74.	Murphy EA, Davis JM and Carmichael MD: Immune modulating effects of β-glucan. Curr Opin Clin Nutr Metab Care. 13:656–661. 2010.
75.	Albeituni SH and Yan J: The effects of β-glucans on dendritic cells and implications for cancer therapy. Anticancer Agents Med Chem. Oct 18–2012, (Epub ahead of print).
76.	Józefowski S, Yang Z, Marcinkiewicz J and Kobzik L: Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages. Inflamm Res. 61:113–126. 2012.
77.	Chen JT and Hasumi K: Activation of peritoneal macrophages in patients with gynecological malignancies by sizofiran and recombinant interferon-gamma. Biotherapy. 6:189–194. 1993. View Article : Google Scholar : PubMed/NCBI
78.	Kelly EK, Wang L and Ivashkiv LB: Calcium-activated pathways and oxidative burst mediate zymosan-induced signaling and IL-10 production in human macrophages. J Immunol. 184:5545–5552. 2010. View Article : Google Scholar : PubMed/NCBI
79.	Kougias P, Wei D, Rice PJ, Ensley HE, Kalbfleisch J, Williams DL and Browder IW: Normal human fibroblasts express pattern recognition receptors for fungal (1→3)-beta-D-glucans. Infect Immun. 69:3933–3938. 2001.PubMed/NCBI
80.	Vetvicka V, Thornton BP and Ross GD: Soluble β-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complemet receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest. 98:50–61. 1998.
81.	Ross GD, Vetvicka V, Yan J, Xia Y and Vetvickova J: Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology. 42:61–74. 1999. View Article : Google Scholar : PubMed/NCBI
82.	Rice PJ, Kelley JL, Kogan G, Ensley HE, Kalbfleisch JH, Browder IW and Williams DL: Human monocyte scavenger receptors are pattern recognition receptors for (1→3)-beta-D-glucans. J Leukoc Biol. 72:140–146. 2002.
83.	Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L, Wong SY and Gordon S: Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med. 196:407–412. 2002. View Article : Google Scholar : PubMed/NCBI
84.	Ariizumi K, Shen GL, Shikano S, Xu S, Ritter R III, Kumamoto T, Edelbaum D, Morita A, Bergstresser PR and Takashima A: Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. J Biol Chem. 275:20157–20167. 2000. View Article : Google Scholar : PubMed/NCBI
85.	Willment JA, Gordon S and Brown GD: Characterization of the human beta-glucan receptor and its alternatively spliced isoforms. J Biol Chem. 276:43818–43823. 2001. View Article : Google Scholar : PubMed/NCBI
86.	Brown GD and Gordon S: Immune recognition: a new receptor for beta-glucans. Nature. 413:36–37. 2001. View Article : Google Scholar : PubMed/NCBI
87.	Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S and Wong SY: The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol. 169:3876–3882. 2002. View Article : Google Scholar
88.	Agrawal S, Gupta S and Agrawal A: Human dendritic cells activated via dectin-1 are efficient at priming Th17, cytotoxic CD8 T and B cell responses. PLoS One. 5:e134182010. View Article : Google Scholar : PubMed/NCBI
89.	Ozment-Skelton TR, Goldman MP, Gordon S, Brown GD and Williams DL: Prolonged reduction of leukocyte membrane-associated Dectin-1 levels following beta-glucan administration. J Pharmacol Exp Ther. 318:540–546. 2006. View Article : Google Scholar
90.	Brown GD, Herre J, Williams DL, Willment JA, Marshall AS and Gordon S: Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 197:1119–1124. 2003. View Article : Google Scholar : PubMed/NCBI
91.	Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, Haynes K, Steele C, Botto M, Gordon S and Brown GD: Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol. 8:31–38. 2007. View Article : Google Scholar : PubMed/NCBI
92.	Ni L, Gayet I, Zurawski S, Duluc D, Flamar AL, Li XH, O'Bar A, Clayton S, Palucka AK, Zurawski G, Banchereau J and Oh S: Concomitant activation and antigen uptake via human dectin-1 results in potent antigen-specific CD8⁺ T cell responses. J Immunol. 185:3504–3513. 2010. View Article : Google Scholar : PubMed/NCBI
93.	Ma J, Becker C, Lowell CA and Underhill DM: Dectin-1-triggered recruitment of light chain 3 protein to phagosomes facilitates major histocompatibility complex class II presentation of fungal-derived antigens. J Biol Chem. 287:34149–34156. 2012. View Article : Google Scholar
94.	Dragicevic A, Dzopalic T, Vasilijic S, Vucevic D, Tomic S, Bozic B and Colic M: Signaling through Toll-like receptor 3 and Dectin-1 potentiates the capability of human monocyte-derived dendritic cells to promote T-helper 1 and T-helper 17 immune responses. Cytotherapy. 14:598–607. 2012. View Article : Google Scholar : PubMed/NCBI
95.	Bulmer GS, Beneke ES and Stevens JA: Studies on Calvatia gigantea. III. Antitumor substances produced by mycelium from germinated spores and parent basidiocarps. Mycologia. 54:621–625. 1962.
96.	Lukas EH, Ringler RL, Byerrum RU, Stevens JA, Clarke DA and Stock CC: Tumor inhibitors in Boletus edulis and other holobasidiomycetes. Antibiot Chemother. 7:1–14. 1957.
97.	Tukonaka K, Ohano N, Adachi Y, Tanaka S, Tamura H and Yadomae T: Immunopharmacological and immunotoxicological activities of a water-soluble (1–3)-β-glucan, CSBG from Candiada spp. Int J Immunopharmacol. 5:383–394. 2000.PubMed/NCBI
98.	Suzuki I, Takeyama T, Ohano N, Oikawa S, Sato K, Suzuki Y and Yadomae T: Antitumor effect of polysaccharide griofolan NMF-5N on syngeneic tumor in mice. J Pharmacobiodyn. 2:72–77. 1987. View Article : Google Scholar : PubMed/NCBI
99.	Ren L, Perera C and Hemar Y: Antitumor activity of mushroom polysaccharides: a review. Food Funct. 3:1118–1130. 2012. View Article : Google Scholar : PubMed/NCBI
100.	Borchers AT, Keen CL and Gershwin ME: Mushrooms, tumors and immunity: an update. Exp Biol Med. 229:393–406. 2004.PubMed/NCBI
101.	Itoh H, Ito H, Amano H and Noda H: Inhibitory action of a (1→6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill (‘himematsutake’) on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol. 66:265–271. 1994.
102.	Mizuno M, Morimoto M, Minato K and Tsuchida H: Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice. Biosci Biotechnol Biochem. 62:434–437. 1998.
103.	Mizuno M, Minato K, Ito H, Kawade M, Terai H and Tsuchida H: Antitumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill. Biochem Mol Biol Int. 47:707–714. 1999.PubMed/NCBI
104.	Pinheiro F, Faria RR, de Camargo JLV, Spinardi-Barbisan ALT, da Eira AF and Barbisan LF: Chemoprevention of preneoplastic liver foci by dietary mushroom Agaricus blazei Murill in the rat. Food Chem Toxicol. 41:1543–1550. 2003. View Article : Google Scholar : PubMed/NCBI
105.	Alves de Lima PL, Delmanto RD, Sugui MM, da Eira AF, Salvadori DM, Speit G and Ribeiro LR: Letinula edodes(Berk.) Pegler (Shiitake) modulates genotoxic and mutagenic effects induced by alkylating agents in vivo. Mutat Res. 496:23–32. 2001.
106.	Sugui MM, Alves de Lima PL, Delmanto RD, da Eira AF, Salvadori DMF and Ribeiro LR: Antimutagenic effect of Lentinula edodes(BERK.) Pegler mushroom and possible variation among lineages. Food Chem Toxicol. 41:555–560. 2003.
107.	Zhang Y, Mills GL and Nair MG: Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa. J Agric Food Chem. 50:7581–7585. 2002. View Article : Google Scholar : PubMed/NCBI
108.	Prescott SM and Fitzpatrick FA: Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta. 1470:M69–M78. 2000.PubMed/NCBI
109.	Kodama N, Komuta K, Sakai N and Nanba H: Effects of D-fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells. Biol Pharm Bull. 25:1647–1650. 2002. View Article : Google Scholar : PubMed/NCBI
110.	Lin ZB and Zhang HN: Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin. 25:1387–1395. 2004.PubMed/NCBI
111.	Youn MJ, Kim JK, Park SY, Kim Y, Park C, Kim ES, Park KI, So HS and Park R: Potential anticancer properties of the water extract of Inonotus [corrected] obliquus by induction of apoptosis in melanoma B16-F10 cells. J Ethnopharmacol. 121:221–228. 2009.PubMed/NCBI
112.	Lavi I, Levinson D, Peri I, Tekoah Y, Hadar Y and Schwartz B: Chemical characterization, antiproliferative and antiadhesive properties of polysaccharides extracted from Pleurotus pulmonarius mycelium and fruiting bodies. Appl Microbiol Biotechnol. 85:1977–1990. 2010. View Article : Google Scholar : PubMed/NCBI
113.	Di Luzio NR, Williams DL, McNamee RB, Edwads BF and Kitahama A: Comparative tumor inhibitory and anti-bacterial activity of soluble and particlate glucan. Int J Cancer. 24:773–779. 1979.PubMed/NCBI
114.	Yoon TJ, Kim TJ, Lee H, Shin KS, Yun YP, Moon WK, Kim DW and Lee KH: Anti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces cerevisiae. Int Immunopharmacol. 8:36–42. 2008. View Article : Google Scholar : PubMed/NCBI
115.	Yamamoto K, Kimura T, Sugitachi A and Matsuura N: Anti-angiogenic and anti-metastatic effects of beta-1,3-D-glucan purified from Hanabiratake, Sparassis crispa. Biol Pharm Bull. 32:259–263. 2009. View Article : Google Scholar : PubMed/NCBI
116.	Ishihara Y, Fujii T, Iijima H, Saito K and Matsunaga K: The role of neutrophils as cytotoxic cells in lung metastasis: suppression of tumor cell metastasis by a biological response modifier (PSK). In Vivo. 12:175–182. 1998.PubMed/NCBI
117.	Lee IS and Nishikawa A: Polyozellus multiplex, a Korean wild mushroom, as a potent chemopreventive agent against stomach cancer. Life Sci. 73:3225–3234. 2003. View Article : Google Scholar : PubMed/NCBI
118.	Fujimiya Y, Suzuki Y, Oshiman K, Kobori H, Moriguchi K, Nakashima H, Matumoto Y, Takahara S, Ebina T and Katakura R: Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis. Cancer Immunol Immunother. 46:147–159. 1998. View Article : Google Scholar : PubMed/NCBI
119.	Chihara G, Hamuro J, Maeda Y, Arai Y and Fukuoka F: Antitumor polysaccharide derived chemically from natural glucan (pachyman). Nature. 225:943–944. 1970. View Article : Google Scholar : PubMed/NCBI
120.	Ohno N, Furukawa M, Miura NN, Adachi Y, Motoi M and Yadomae T: Antitumor betaglucan from the cultured fruit body of Agaricus blazei. Biol Pharm Bull. 24:820–828. 2001. View Article : Google Scholar : PubMed/NCBI
121.	Sasaki T, Abiko N, Sugino Y and Nitta K: Dependence on chain length of antitumor activity of (1→3)-β-D-glucan from Alcaligenes faecalis var. myxogenes, IFO 13140 and its acid-degraded products. Cancer Res. 38:379–383. 1978.
122.	Iino K, Ohno N, Suzuki I, Miyazaki T and Yadomae T: Structural characterization of a neutral antitumour beta-D-glucan extracted with hot sodium-hydroxide from cultured fruit bodies of Grifola Frondosa. Carbohyd Res. 141:111–119. 1985. View Article : Google Scholar
123.	Furusawa E, Chou SC, Furusawa S, Hirazum A and Dang Y: Antitumor activity of Gonoderma lucidum and edible mushroom, on interaperitoneally implanted Lewis lung carcinoma in synergeneic mice. Phytother Res. 6:300–304. 1992.
124.	Gelderman KA, Tomlinson S, Ross GD and Gorter A: Complement function in mAb-mediated cancer immunotherapy. Trends Immunol. 25:158–164. 2004. View Article : Google Scholar : PubMed/NCBI
125.	Akramiene D, Kondrotas A, Didziapetriene J and Kevelaitis EP: Effects of beta-glucans on the immune system. Medicina (Kaunas). 43:597–606. 2007.PubMed/NCBI
126.	Cheung NV and Modal S: Oral (1–3),(1–4)-β-D-Glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma. Clin Cancer Res. 8:1217–1223. 2002.
127.	Sier CFM, Gelderman KA, Prins FA and Gorter A: Beta-glucan enhanced killing of renal cell carcinoma micrometastases by monoclonal antibody G250 directed complement activation. Int J Cancer. 109:900–908. 2001. View Article : Google Scholar : PubMed/NCBI
128.	Modak S, Koehne G, Vickers A, O'Reilly RJ and Cheung NV: Rituximab therapy of lymphoma is enhanced by orally administered (1–3),(1–4)-D-β-glucan. Leuk Res. 29:679–683. 2005.PubMed/NCBI
129.	Hong F, Yan J, Baran JT, Allendorf DJ, Hansen RD, Ostroff GR, Xing PX, Cheung NK and Ross GD: Mechanism by which orally administered beta-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J Immunol. 173:797–806. 2004. View Article : Google Scholar
130.	Liu J, Gunn L, Hansen R and Yan J: Combined yeast-derived beta-glucan with anti-tumor monoclonal antibody for cancer immunotherapy. Exp Mol Pathol. 86:208–214. 2009. View Article : Google Scholar : PubMed/NCBI
131.	Huang H, Ostroff GR, Lee CK, Agarwal S, Ram S, Rice PA, Specht CA and Levitz SM: Relative contributions of dectin-1 and complement to immune responses to particulate β-glucans. J Immunol. 189:312–317. 2012.PubMed/NCBI
132.	Xiang D, Sharma VR, Freter CE and Yan J: Anti-tumor monoclonal antibodies in conjunction with β-glucans: a novel anti-cancer immunotherapy. Curr Med Chem. 19:4298–4305. 2012.
133.	Ina K and Ando T: The use of Lentinan for treating gastric cancer. Anticancer Agents Med Chem. Oct 18–2012.(Epub ahead of print).
134.	Kataoka H, Shimura T, Mizoshita T, Kubota E, Mori Y, Mizushima T, Wada T, Ogasawara N, Tanida S, Sasaki M, Togawa S, Sano H, Hirata Y, Ikai M, Mochizuki H, Seno K, Itoh S, Kawai T and Joh T: Lentinan with S-1 and paclitaxel for gastric cancer chemotherapy improve patient quality of life. Hepatogastroenterology. 56:547–550. 2009.PubMed/NCBI
135.	Chen J, Zhang XD and Jiang Z: The application of fungal beta-glucans for the treatment of colon cancer. Anticancer Agents Med Chem. Dec 24–2012.(Epub ahead of print).
136.	Hamuro J and Chihara G: Effect of antitumour polysaccharides on the higher structure of serum protein. Nature. 245:40–41. 1973. View Article : Google Scholar : PubMed/NCBI
137.	Soto ER, Caras AC, Kut LC, Castle MK and Ostroff GR: Glucan particles for macrophage targeted delivery of nanoparticles. J Drug Deliv. 2012:1435242012.PubMed/NCBI
138.	Huang H, Ostroff GR, Lee CK, Specht CA and Levitz SM: Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded beta-glucan particles. MBio. 1:e00164–102010.
139.	Lehtovaara BC and Gu FX: Pharmacological, structural and drug delivery properties and applications of 1,3-β-glucans. J Agric Food Chem. 59:6813–6828. 2011.
140.	Browder W, Williams D, Lucore P, Pretus H, Jones E and Mcnamee R: Effect of enhanced macrophage function on early wound-healing. Surgery. 104:224–230. 1988.PubMed/NCBI
141.	Portera CA, Love EJ, Memore L, Zhang L, Müller A, Browder W and Williams DL: Effect of macrophage stimulation on collagen biosynthesis in the healing wound. Am Surg. 63:125–131. 1997.PubMed/NCBI