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Effect of Beta Glucan on White Blood Cell Counts and Serum Levels of IL-4 and IL-12 in Women with Breast Cancer Undergoing Chemotherapy: A Randomized Double-Blind Placebo-Controlled Clinical Trial

  • Ostadrahimi, Alireza (Nutrition Research Center. Faculty of Nutrition, Tabriz University of Medical Sciences) ;
  • Ziaei, Jamal Eivazi (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • Esfahani, Ali (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • Jafarabadi, Mohammad Asghari (Road Traffic Injury Prevention Research Center, Faculty of Health, Tabriz University of Medical Sciences) ;
  • Movassaghpourakbari, Aliakbar (Hematology and Oncology Research Center, Tabriz University of Medical Sciences) ;
  • Farrin, Nazila (Student Research Committee. Faculty of Nutrition, Tabriz University of Medical Sciences)
  • 발행 : 2014.07.30

초록

Background: Breast cancer is the most common female malignancy in the world. Beta glucan can be a hematopoietic and an immune modulator agent in cancer patients. The aim of this trial was to determine the effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy. Materials and Methods: This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study. Results: In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007). Conclusions: The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation.

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참고문헌

  1. Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis, E (2007). Effects of beta-glucans on the immune system. Medicina, 43, 597-606.
  2. Asharijafarabadi M, Mohammadi S (2013). Statistical series: summarizing and displaying data. J Diabetes Lipid Dis, 12, 83-100.
  3. Baran J, Allendorf DJ, Hong F, Ross GD (2007). Oral beta-glucan adjuvant therapy converts nonprotective Th2 resp:mse to protective Thl cell-mediated immune response in mammary tumor-bearing mice. Folia Histochem Cytobiol, 45, 107-14.
  4. Brown GD, Taylor PR, Reid DM, et al (2002). Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med, 196,407-12. https://doi.org/10.1084/jem.20020470
  5. Budak F, Goral G, Oral HB (2008). Saccharomyces cerevisiae beta-glucan induces interferon-gamma production in human t cells via IL-12. Turk J Immunol, 13, 21-6.
  6. Chan GC, Chan WK, Sze DM (2009). The effects of beta-glucan on human immune and cancer cells. J Hematol Oncol, 2, 25. https://doi.org/10.1186/1756-8722-2-25
  7. Cramer DE, Wagner S, Li B, et al (2008). Mobilization of hematopoietic progenitor cells by yeast-derived $\beta$-glucan requires activation of matrix metalloproteinase 9. Stem Cells, 26,1231-40. https://doi.org/10.1634/stemcells.2007-0712
  8. Demir G, Klein HO, Mandel-Molinas N, Tuzuner N (2007). Beta glucaninduces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer. Int Immunopharmacol, 7, 113-6. https://doi.org/10.1016/j.intimp.2006.08.011
  9. DeNardo DG, Coussens LM (2007). Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res, 9, 212. https://doi.org/10.1186/bcr1746
  10. Foa R, Guarini A, Gansbacher B (1992). IL2 treatment for cancer: from biology to gene therapy. Br J Cancer, 66, 992-8. https://doi.org/10.1038/bjc.1992.400
  11. Goodridge HS, Wolf AJ, Underhill DM (2009). Beta-glucan recognition by the innate immune system Immunol Rev, 230,38-50. https://doi.org/10.1111/j.1600-065X.2009.00793.x
  12. Goto S, Sato M, Kaneko R, et al (1999). Analysis of Th1 and Th2 cytokine production by peripheral blood mononuclear cells as a parameter of immunological dysfunction in advanced cancer patients. Cancer Immunol Immunother, 48, 435-42. https://doi.org/10.1007/s002620050620
  13. Herre J, Gordon S, Brown GD (2004). Dectin-1 and its role in the recognition of $\beta$-glucans by macrophages. Molecular immunology, 40, 869-76. https://doi.org/10.1016/j.molimm.2003.10.007
  14. Jafari-Koshki T, Schmid VJ, Mahaki B (2014). Trends of breast cancer incidence in Iran during 2004-2008: A Bayesian space-time model. Asian Pac J Cancer Prev, 15,1557-61. https://doi.org/10.7314/APJCP.2014.15.4.1557
  15. Karaca H, Bozkurt O, Ozaslan E, et al (2014). Positive effects of oral beta-glucan on mucositis and leukopenia in colorectal cancer patients receiving adjuvant folfox-4 combination chemotherapy. Asian Pac J Cancer Prev, 15, 3641-4. https://doi.org/10.7314/APJCP.2014.15.8.3641
  16. Li B, Allendorf DJ, Hansen R, et al (2006). Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol, 177, 1661-9. https://doi.org/10.4049/jimmunol.177.3.1661
  17. Li B, Cai Y, Qi C, et al (2010). Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer. Clin Cancer Res, 16,5153-64. https://doi.org/10.1158/1078-0432.CCR-10-0820
  18. Li XH, Ma J, Wu XX, et al (2009). Effect of various combinations of IL2, IL 12 and IL 15 on function of human peripheral blood derived NK cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 17, 918-23.
  19. Lin H, Cheung SW, Nesin M (2007). Enhancement of umbilical cord blood cell hematopoiesis by maitake beta-glucan is mediated by granulocyte colony-stimulating factor production. Clin Vaccine Immunol, 14, 21-7. https://doi.org/10.1128/CVI.00284-06
  20. Magnani M, Castro-Gomez RH, Aoki MN, et al (2010). Effects of carooxymethyl-glucan from Saccharomyces cerevisiae on the peripheral blood cells of patients with advanced prostate cancer. Exp Ther Med, 1, 859-62.
  21. Majeed W, Aslam B, Javed I, et al (2014). Breast cancer: major risk factors and recent developments in treatment. Asian Pac J Cancer Prev, 15, 3353-8. https://doi.org/10.7314/APJCP.2014.15.8.3353
  22. Moore MA (2009). Diverse influences of dietary factors on cancer in Asia. Asian Pac J Cancer Prev, 10, 981-6.
  23. Mousavi SM, Montazeri A, Mohagheghi MA, et al (2007). Breast cancer in Iran: an epidemiological review. Breast J, 13, 383-91. https://doi.org/10.1111/j.1524-4741.2007.00446.x
  24. Nishimura T, Nakui M, Sato M, et al (2000). The critical role of Th1-dominant immunity in tumor immunology. Cancer Chemother Pharmacal, 46, 52-61. https://doi.org/10.1007/PL00014051
  25. Patchen ML, MacVittie TJ (1986). Hemopoietic effects of intravenous soluble glucan administration. J Immunopharmacol, 8, 407-25. https://doi.org/10.3109/08923978609026497
  26. Pellegrini P, Berghella AM, Del Beato T, et al (1996). Disregulation in TH1 and TH2 subsets of CD4+ T cells in peripheral blood of colorectal cancer patients and involvement in cancer establishment and progression. Cancer Immunol Immunother, 42, 1-8. https://doi.org/10.1007/s002620050244
  27. Pirouzpanah S, Taleban FA, Atri M, Abadi AR, Mehdipour P (2010). The effect of modifiable potentials on hypennethylation status of retinoic acid receptor-beta2 and estrogen receptor-alpha genes in primary breast cancer. Cancer Causes Control, 21, 2101-11. https://doi.org/10.1007/s10552-010-9629-z
  28. Pospisil M, Sandula J, Pipalova I, Hofer M, Viklicka S (1991). Hemopoiesis stimulating and radioprotective effects of carboxymethylglucan. Physiol Res, 40, 377-80.
  29. Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J (1999). Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology, 42, 61-74. https://doi.org/10.1016/S0162-3109(99)00013-2
  30. Seliger B (2005). Strategies of tumor immune evasion. BioDrugs, 19, 347-54. https://doi.org/10.2165/00063030-200519060-00002
  31. Suzuki Y, Adachi Y, Ohno N, Yadomae T (2001). Th1/Th2- Balancing immunomodulating activity of gel-forming (1-->3)-beta-glucans from fungi. Biol Pharm Bull, 24, 811-9. https://doi.org/10.1248/bpb.24.811
  32. Taylor PR, Brown GD, Reid DM, et al (2002). The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol, 169, 3876-82. https://doi.org/10.4049/jimmunol.169.7.3876
  33. Vetvicka V (2011). Glucan-immunostimulant, adjuvant, potential drug. World J Clin Oncol, 2, 115-9. https://doi.org/10.5306/wjco.v2.i2.115
  34. Vetvicka V, Dvorak B, Vetvickova J, et al (2007). Orally administered marine (l-->3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity. Int J BioI Macromol, 40, 291-8. https://doi.org/10.1016/j.ijbiomac.2006.08.009
  35. Wang JL, Bi Z, Zou JW, Gu XM (2012). Combination therapy with lentinan improves outcomes in patients with esophageal carcinoma. Mol Med Rep, 5, 745-8.
  36. Weitberg AB (2008). A phase I/II trial of beta-(1,3)/(1,6) D-glucan in the treatment of patients with advanced malignancies receiving chemotherapy. J Exp Clin Cancer Res, 27, 40. https://doi.org/10.1186/1756-9966-27-40
  37. Yan J, Vetvicka V, Xia Y, et al (1999). Beta-glucan, a "specific" biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD 11b/CD18). J Immunol, 163, 3045-52.
  38. Yoon TJ, Kim TJ, Lee H, et al (2008). Anti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces cerevisiae. Int Immunopharmacol, 8, 36-42. https://doi.org/10.1016/j.intimp.2007.10.005
  39. Yoshino S, Tabata T, Hazama S, et al (2000). Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/ Th2 balance in patients with digestive cancers. Anticancer Res, 20, 4707-11.

피인용 문헌

  1. Effect of Immune-Enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically Ill Patients vol.8, pp.6, 2016, https://doi.org/10.3390/nu8060336
  2. Consumption of β-glucans to spice up T cell treatment of tumors: a review vol.18, pp.10, 2018, https://doi.org/10.1080/14712598.2018.1523392