JIBTVA  Vol.1 No.3 , October 2012
The Natural Killer Cell: A Historical Perspective and the Use of Supplements to Enhance NKC Activity
ABSTRACT
The Natural Killer Cell (NKC) is the cell-mediated cornerstone of innate immunity. The purpose of this reviewis to give a historical perspective of the discovery of the Natural Killer Cell (NKC)and to apply the use of supplements in the enhancement of NKC in human cancers for the developmentof human health and well-being.Since the discovery of the NKC, as observed by Nomarski optics, scanning (SEM)/transmission electron microscopy (TEM) with cellular numeration and enrichment using bovine serum albumin (BSA) continuous gradients, there have been significant research and clinical studies to increase the effectiveness of NKC in the destruction of cancer cells. Based on significant research and clinical studies, at least 16 components have been identified that enhance or may enhance, based on their immune modulator activity, the NKC. These supplements include Alpha LipoicAcid, Arabinoxylin, Curcumin, Garlic, Genistein, Ginseng, Lentinan, Mistletoe, N-Acetylcysteine, Resveratrol, Selenium, Vitamin B, Vitamin C, Vitamin D3, Vitamin E and zinc.

Cite this paper
J. Thornthwaite, H. Shah, P. Shah and H. Respess, "The Natural Killer Cell: A Historical Perspective and the Use of Supplements to Enhance NKC Activity," Journal of Immune Based Therapies, Vaccines and Antimicrobials, Vol. 1 No. 3, 2012, pp. 21-51. doi: 10.4236/jibtva.2012.13004.
References
[1]   U. Winkler, et al., “Characterization, Application and Potential Uses of Biotin-Tagged Inhibitors for Lymphocyte Serine Proteases (Granzymes),” Molecular Immunology, Vol. 33, No. 7-8, 1996, pp. 615-623. doi:10.1016/0161-5890(96)00025-9

[2]   S. L. Woodard, et al., “Chymase-Directed Serine Protease Inhibitor that Reacts with a Single 30-kD: A Granzyme and Blocks NK-Mediated Cytotoxicity,” The Journal of Immunology, Vol. 153, No. 11, 1994, pp. 5016-5025.

[3]   K. Thornthwaite, “Immune System—Natural Killer Cell,” 2009. http://www.youtube.com/watch?v=HNP1EAYLhOs

[4]   J. T. Thornthwaite and R. C. Leif, “Characterization of Immune Cells Using the Plaque Cytogram Assay,” Reticulendothelial Society, 1972.

[5]   J. T. Thornthwaite and R.C. Leif, “The Plaque Cytogram Assay. I. Light and Scanning Electron Microscopy of Immunocompetent Cells,” The Journal of Immunology, Vol. 113, No. 6, 1974, pp. 1897-1908.

[6]   J. T. Thornthwaite, “The Buoyant Density Distribution and Plaque Cytogram Assay for Immunocompetent Cells,” Master’s Thesis, Florida State University, Tallahassee, 1974.

[7]   J. T. Thornthwaite, et al., “A Technique for Combined Light and Scanning Microscopy of Cells, Scanning Electron Microscopy,” Proceedings of the Workshop on Advances in Biomedical Applications of the SEM, IIT Research Institute, Chicago, 1976.

[8]   J. T. Thornthwaite, et al., “A New Method for Preparing Cells for Critical Point Drying,” Scanning Electron Microscopy, 1976, pp. 387-402.

[9]   J. T. Thornthwaite and R. C. Leif, “The Plaque Cytogram Assay. II. Correlation between Morphology and Density of Linear Bovine Serum Albumin Buoyant Density Grardient-Separated Immunocompetent Cells,” The Journal of Immunology, Vol. 114, No. 3, 1975. pp. 1023-1033.

[10]   R. C Leif, et al., “The Identification by Plaque Cytogram Assays and BSA Density Distribution of Immunocompetent Cells,” Critical Factors in Cancer Immunology, 1975, pp. 103-158.

[11]   J. T. Thornthwaite, “The Characterization of the Cells Involved in Cell-Mediated Immunity against Allogeneic and Syngeneic Tumor Cells,” Ph.D. Thesis, Florida State University, Tallahassee, 1977.

[12]   R. Kiessling, E. Klein and H. Wigzell, “Natural Killer Cells in the mouse. I. Cytotoxic Cells with Specificity for Mouse Moloney Leukemia Cells. Specificity and Distribution according to Genotype,” European Journal of Immunology, Vol. 5, No. 2, 1975, pp. 112-117. doi:10.1002/eji.1830050208

[13]   R. Kiessling, et al., “Natural Killer Cells in the Mouse. II. Cytotoxic Cells with Specificity for Mouse Moloney Leukemia Cells. Characteristics of the Killer Cell,” European Journal of Immunology, Vol. 5, No. 2, 1975, pp. 117-121. doi:10.1002/eji.1830050209

[14]   R. B. Herberman and H. T. Holden, “Natural Cell-Mediated Immunity,” Advances in Cancer Research, Vol. 27, 1978, pp. 305-377. doi:10.1016/S0065-230X(08)60936-7

[15]   R. B. Herberman and H. T. Holden, “Natural Killer Cells as Antitumor Effector Cells,” Journal of the National Cancer Institute, Vol. 62, No. 3, 1979, pp. 441-445.

[16]   M. J. Robertson and J. Ritz, “Biology and Clinical Relevance of Human Natural Killer Cells,” Blood, Vol. 76, No. 12, 1990, pp. 2421-2438.

[17]   R. B. Herberman, M. E. Nunn and D. H. Lavrin, “Natural Cytotoxic Reactivity of Mouse Lymphoid Cells against Syn-Geneic Acid Allogeneic Tumors. I. Distribution of reactivity and specificity,” International Journal of Cancer, Vol. 16, No. 2, 1975, pp. 216-229. doi:10.1002/ijc.2910160204

[18]   R. B. Herberman and H. T. Holden, “Natural Cell-Mediated Immunity,” Advances in Cancer Research, Vol. 27, 1978, pp. 305-377.

[19]   R. B. Herberman and J. R. Ortaldo, “Natural Killer Cells: Their Roles in Defenses against Disease,” Science, Vol. 214, No. 4516, 1981, pp. 24-30. doi:10.1126/science.7025208

[20]   R. B. Herberman, “Cancer Immunotherapy with Natural Killer Cells,” Seminars in Oncology, Vol. 29, No. 3, 2002, pp. 27-30. doi:10.1053/sonc.2002.33079

[21]   R. Kiessling, J. C. Roder and P. P. Biberfeld, “Ultrastructural and Cytochemical Studies of Mouse Natural Killer (NK) Cells,” Advances in Experimental Medicine and Biology, Vol. 121B, No. 3, 1979, pp. 155-163.

[22]   S. Salinthone, et al., “Lipoic Acid Attenuates Inflammation via cAMP and Protein Kinase a Signaling,” PLoS One, Vol. 5, No. 9, 2010, p. e13058. doi:10.1371/journal.pone.0013058

[23]   S. Salinthone, et al., “Lipoic Acid Stimulates cAMP Pro- Duction via the EP2 and EP4 Prostanoid Receptors and Inhibits IFN Gamma Synthesis and Cellular Cytotoxicity in NK Cells,” Journal of Neuroimmunology, Vol. 199, No. 1-2, 2008, pp. 46-55. doi:10.1016/j.jneuroim.2008.05.003

[24]   R. V. Schillace, et al., “Lipoic Acid Stimulates cAMP Production in T lymphocytes and NK Cells,” Biochemical and Biophysical Research Communications, Vol. 354, No. 1, 2007, pp. 259-264. doi:10.1016/j.bbrc.2006.12.195

[25]   N. A. Filatova, et al., “Effect of Alpha-Lipoic Acid on the Sensitivity of Transformed Fibroblasts to Lysis by Natural Killer Cells. Comparison with NAC Action,” Tsitologiia, Vol. 51, No. 5, 2009, pp. 398-402.

[26]   D. P. P. Belobrajdic, et al., “An Arabinoxylan-Rich Fraction from Wheat Enhances Caecal Fermentation and Protects Colonocyte DNA against Diet-Induced Damage in Pigs,” British Journal of Nutrition, 2011, pp. 1-9.

[27]   J. R. Pritchard, et al., “A Survey of Beta-Glucan and Arabi-Noxylan Content in Wheat,” Journal of the Sci- ence of Food and Agriculture, Vol. 91, No. 7, 2011, pp. 1298-1303. doi:10.1002/jsfa.4316

[28]   G. Muralikrishna and M. V. Rao, “Cereal Non-Cellulosic Polysaccharides: Structure and Function Relation- ship—an Overview,” Critical Reviews in Food Science and Nutrition, Vol. 47, No. 6, 2007, pp. 599-610. doi:10.1080/10408390600919056

[29]   M. Ghoneum and S. Agrawal, “Activation of Human Monocyte-Derived Dendritic Cells in Vitro by the Biological Response Modifier Arabinoxylan Rice Bran (MGN-3/Biobran),” International Journal of Immunopathology and Pharmacology, Vol. 24, No. 4, 2011, pp. 941-948.

[30]   M. Ghoneum and S. Gollapudi, “Synergistic Apoptotic Effect of Arabinoxylan Rice Bran (MGN-3/Biobran) and Curcumin (Turmeric) on Human Multiple Myeloma Cell Line U266 in Vitro,” Neoplasma, Vol. 58, No. 2, 2011, pp. 118-123. doi:10.4149/neo_2011_02_118

[31]   M. H. Bang, et al., “Arabinoxylan Rice Bran, (MGN-3) Enhances the Effects of Interventional Therapies for the Treatment of Hepatocellular Carcinoma: A Three-Year Randomized Clinical Trial,” Anticancer Research, Vol. 30, No. 12, 2010, pp. 5145-5151.

[32]   L. Cao, et al., “Antitumor and Immunomodulatory Activity of Arabinoxylans: A Major Constituent of Wheat Bran,” International Journal of Biological Macromolecules, Vol. 48, No. 1, 2011, pp. 160-164. doi:10.1016/j.ijbiomac.2010.10.014

[33]   A. P. P. Femia, et al., “Arabinoxylan-Oligosaccharides, (AXOS) Reduce Preneoplastic Lesions in the Colon of Rats Treated with 1,2-Dimethylhydrazine (DMH),” Euro- pean Journal of Nutrition, Vol. 49, No. 2, 2010, pp. 127- 132. doi:10.1007/s00394-009-0050-x

[34]   D. Cholujova, J. Jakubikova and J. Sedlak, “Bio- Bran-Augmented Maturation of Human Monocyte-Derived Dendritic Cells,” Neoplasma, Vol. 56, No. 2, 2009, pp. 89-95. doi:10.4149/neo_2009_02_89

[35]   E. Noaman, et al., “Antioxidant Potential by Arabinoxlan Rice Bran, MGN-3/Biobran, Represents a Mechanism for Its Oncostatic Effect against Murine Solid Ehrlich Carcinoma,” Cancer Letters, Vol. 268, No. 2, 2008, pp. 348-359. doi:10.1016/j.canlet.2008.04.012

[36]   N. K. Badr El-Din, E. Noaman and M. Ghoneum, “In Vivo Tumor Inhibitory Effects of Nutritional Rice Bran Supplement MGN-3/Biobran on Ehrlich Carcnoma-Bearing Mice,” Nutrition and Cancer, Vol. 60, No. 2, 2008, pp. 235-244. doi:10.1080/01635580701627285

[37]   S. Gollapudi and M. Ghoneum, “MGN-3/Biobran, Modified Arabinoxylan from Rice Bran, Sensitizes Human Breast Cancer Cells to Chemotherapeutic Agent, Daun- orubicin,” Cancer Detection and Prevention, Vol. 32, No. 1, 2008, pp. 1-6. doi:10.1016/j.cdpp.2008.02.006

[38]   M. Glei, et al., “Both Wheat, (Triticum aestivum) Bran Arabinoxylans and Gut Flora-Mediated Fermentation Products Protect Human Colon Cells from Genotoxic Activeties of 4-Hydroxynonenal and Hydrogen Peroxide,” Journal of Agricultural and Food Chemistry, Vol. 54, No. 6, 2006, pp. 2088-2095. doi:10.1021/jf052768e

[39]   M. Ghoneum and S. Gollapudi, “Synergistic Role of Ara- Binoxylan Rice Bran, (MGN-3/Biobran) in S. Cere- Visiae-Induced Apoptosis of Monolayer Breast Cancer MCF-7 Cells,” Anticancer Research, Vol. 25, No. 6B, 2005, pp. 4187-4196.

[40]   K. Ogawa, M. Takeuchi and N. Nakamura, “Immunological Effects of Partially Hydrolyzed Arabinoxylan from Corn Husk in Mice,” Bioscience, Biotechnology and Biochemistry, Vol. 69, No. 1, 2005, pp. 19-25. doi:10.1271/bbb.69.19

[41]   H. Maeda, et al., “Oral Administration of Hydrolyzed Rice Bran Prevents the Common Cold Syndrome in the Elderly Based on Its Immunomodulatory Action,” Biofactors, Vol. 21, No. 1-4, 2004, pp. 185-187. doi:10.1002/biof.552210138

[42]   M. Ghoneum and S. Abedi, “Enhancement of Natural Killer Cell Activity of Aged Mice by Modified Arabinoxylan Rice Bran, (MGN-3/Biobran),” Journal of Pharmacy and Pharmacology, Vol. 56, No. 12, 2004, pp. 1581-1588. doi:10.1211/0022357044922

[43]   M. Ghoneum and A. Jewett, “Production of Tumor NecroSis Factor-Alpha and Interferon-Gamma from Human Pe- Ripheral Blood Lymphocytes by MGN-3, a Modified Ara-Binoxylan from Rice Bran, and Its Synergy with Inter-Leukin-2 In Vitro,” Cancer Detection and Prevention, Vol. 24, No. 4, 2000, pp. 314-324.

[44]   L. M. Ferrucci, et al., “Measurement of Spices and Sea- Sonings in India: Opportunities for Cancer Epidemiology and Prevention,” Asian Pacific Journal of Cancer Prevention, Vol. 11, No. 6, 2010, pp. 1621-1629.

[45]   R. Kannappan, et al., “Neuroprotection by Spice-Derived Nutraceuticals: You Are What You Eat!” Molecular Neurobiology, Vol. 44, No. 2, 2011, pp. 142-159. doi:10.1007/s12035-011-8168-2

[46]   H. G. Zhang, et al., “Curcumin Reverses Breast Tumor Exosomes Mediated Immune Suppression of NK Cell Tumor Cytotoxicity,” Biochimica et Biophysica Acta, Vol. 1773, No. 7, 2007, pp. 1116-23. doi:10.1016/j.bbamcr.2007.04.015

[47]   M. A. Bill, et al., “The Small Molecule Curcumin Analog FLLL32 Induces Apoptosis in Melanoma Cells via Stat3 Inhibition and Retains the Cellular Response to Cytokines with Anti-Tumor Activity,” Molecular Cancer, Vol. 9, No., 2010, p. 165. doi:10.1186/1476-4598-9-165

[48]   S. Bhaumik, M. D. Jyothi and A. Khar, “Differential Modulation of Nitric Oxide Production by Curcumin in Host Macrophages and NK Cells,” FEBS Letters, Vol. 483, No. 1, 2000, pp. 78-82. doi:10.1016/S0014-5793, No. 00)02089-5

[49]   M. A. Bill, et al., “Curcumin Induces Proapoptotic Effects against Human Melanoma Cells and Modulates the Cellu-Lar Response to Immunotherapeutic Cytokines,” Molecular Cancer Therapeutics, Vol. 8, No. 9, 2009, pp. 2726-2735. doi:10.1158/1535-7163.MCT-09-0377

[50]   G. Sa and T. Das, “Anti Cancer Effects of Curcumin: Cycle of Life and Death,” Cell Division, Vol. 3, 2008, p. 14. doi:10.1186/1747-1028-3-14

[51]   C. C. Li, et al., “A Study on the Construction, Expression and Immunosterility of Lagurus Laguru Zona Pellucida 3 DNA Vaccine pVAX1-sig-LTB-LZP3-C3d3,” Chinese Journal of Cellular and Molecular Immunology, Vol. 27, No. 9, 2011, pp. 941-944.

[52]   J. J. Lu, Y. J. Cai and J. Ding, “The Short-Time Treatment with Curcumin Sufficiently Decreases Cell Viability, Induces Apoptosis and Copper Enhances These Effects in Multidrug-Resistant K562/A02 Cells,” Molecular and Cellular Biochemistry, Vol. 360, No. 1-2, 2012, pp. 253- 260. doi:10.1007/s11010-011-1064-2

[53]   M. Bright-Gbebry, et al., “Use of Multivitamins, Folic Acid and Herbal Supplements among Breast Cancer Survivors: The Black Women’s Health Study,” BMC Complementary and Alternative Medicine, Vol. 11, 2011, p. 30. doi:10.1186/1472-6882-11-30

[54]   C. A. Gonzalez, et al., “Fruit and Vegetable Intake and the Risk of Gastric Adenocarcinoma: A Reanalysis of the European Prospective Investigation into Cancer and Nu- Triation, (EPIC-EURGAST) Study after a Longer Follow-Upp,” International Journal of Cancer, Vol. 131, No. 12, 2012, pp. 2910-2919. doi:10.1002/ijc.27565

[55]   Y. Zhou, et al., “Consumption of Large Amounts of Allium Vegetables Reduces Risk for Gastric Cancer in a Meta-Analysis,” Gastroenterology, Vol. 141, No. 1, 2011, pp. 80-89. doi:10.1053/j.gastro.2011.03.057

[56]   T. Ghazanfari, et al., “In Vitro Cytotoxic Effect of Garlic Extract on Malignant and Nonmalignant Cell Lines,” Immunopharmacol and Immunotoxicol, Vol. 33, No. 4, 2011, pp. 603-608. doi:10.3109/08923973.2011.551832

[57]   M. S. Butt, M. T. Sultan and J. Iqbal, “Garlic: Nature’s Protection against Physiological Threats,” Critical Reviews in Food Science and Nutrition, Vol. 49, No. 6, 2009, pp. 538-551. doi:10.1080/10408390802145344

[58]   H. Ishikawa, et al., “Aged Garlic Extract Prevents a Decline of Nk Cell Number and Activity in Patients with Advanced Cancer,” Journal of Nutrition, Vol. 136, No. 3, 2006, pp. 816S-820S.

[59]   D. L. Lamm and D. R. Riggs, “Enhanced Immunocompe- Tence by Garlic: Role IN Bladder Cancer and Other Malign-Nancies,” Journal of Nutrition, Vol. 131, No. 3s, 2001, pp. 1067S-1070S.

[60]   D. L. Lamm and D. R. Riggs, “The Potential Application Of Allium Sativum, (Garlic) for the Treatment of Bladder Cancer,” Urologic Clinics of North America, Vol. 27, No. 1, 2000, pp. 157-162, doi:10.1016/S0094-0143, No. 05)70243-3

[61]   Z. M. Hassan, et al., “Immunomodulatory Affect of R10 Fraction of Garlic Extract on Natural Killer Activity,” International Immunopharmacology, Vol. 3, No. 10-11, 2003, pp. 1483-1489. doi:10.1016/S1567-5769, No. 03)00161-9

[62]   S. Kasuga, et al., “Pharmacologic Activities of Aged Garlic Extract IN Comparison with Other Garlic Preparations,” Journal of Nutrition, Vol. 131, No. 3s, 2001, pp. 1080S-1084S.

[63]   E. Kyo, et al., “Immunomodulatory Effects of Aged Garlic Extract,” Journal of Nutrition, Vol. 131, No. 3s, 2001, pp. 1075S-1079S.

[64]   Z. Tang, et al., “The Preventing Function of Garlic on Experimental Oral Precancer and Its Effect on Natural Killer Cells, T-Lymphocytes and Interleukin-2,” Bulletin of Hunan Medical University, Vol. 22, No. 3, 1997, pp. 246-248.

[65]   S.-H. Kim, A. Bommareddy and S. V. Singh, “Garlic Constituent Diallyl Trisulfide Suppresses X-Linked Inhibitor of Apoptosis Protein in Prostate Cancer Cellsin Culture and in Vivo,” Cancer Prevention Research, Vol. 4, No. 6, 2011, pp. 897-906. doi:10.1158/1940-6207.CAPR-10-0323

[66]   X. Wu, et al., “Proteasome Inhibitor Lactacystin Augments Natural Killer Cell Cytotoxicity of Myeloma Via Downregu-Lation of Hla Class I,” Biochemical and Biophysical Research Communications, Vol. 415, No. 1, 2011, pp. 187-192. doi:10.1016/j.bbrc.2011.10.057

[67]   P. P. Wu, et al., “Diallyl Trisulfide (DATS) Inhibits Mouse Colon Tumor in Mouse CT-26 Cells Allograft Model in Vivo,” Phytomedicine, Vol. 18, No. 8-9, 2011, pp. 672-676. doi:10.1016/j.phymed.2011.01.006

[68]   P. P. Wu, et al., “Diallyl Sulfide Induces Cell Cycle Arrest and Apoptosis in Hela Human Cervical Cancer Cells through the p53, Caspase- and Mitochondria-Dependent Pathways,” International Journal of Oncology, Vol. 38, No. 6, 2011, pp. 1605-1613.

[69]   H. Javed, et al., “S-allyl Cysteine Attenuates Oxidative Stress Associated Cognitive Impairment and Neurodegen- Eration in Mouse Model of Streptozotocin-Induced Expe- Rimental Dementia of Alzheimer’s Type,” Brain Re- search, Vol. 1389, 2011, pp. 133-142. doi:10.1016/j.brainres.2011.02.072

[70]   N. Morioka, et al., “A Protein Fraction from Aged Garlic Extract Enhances Cytotoxicity and Proliferation of Human Lymphocytes Mediated by Interleukin-2 and Concanavalin A,” Cancer Immunology, Immunotherapy, Vol. 37, No. 5, 1993, pp. 316-322. doi:10.1007/BF01518454

[71]   J. H. Cha, et al., “Allicin Inhibits Cell Growth and Induces Apoptosis in U87MG Human Glioblastoma Cells through an Erk-Dependent Pathway,” Oncology Reports, Vol. 28, No. 1, 2012, pp. 41-48. doi:10.1007/BF01518454

[72]   Y. M. Nkrumah-Elie, et al., “Diallyl trisulfide as an Inhibitor of Benzo (a) Pyrene-Induced Precancerous Carcinogenesis in MCF-10A Cells,” Food and Chemical Toxicology, Vol. 50, No. 7, 2012, pp. 2542-2530. doi:10.1016/j.fct.2012.04.010

[73]   J. E. Lee, et al., “Induction of Apoptosis with Diallyl Disul-Fide in Ags Gastric Cancer Cell Line,” Journal of the Korean Surgical Society, Vol. 81, No. 2, 2011, pp. 85-95. doi:10.4174/jkss.2011.81.2.85

[74]   J. H. Lee, et al., “1, 25-Dihydroxyvitamin D3 Enhances NK Susceptibility of Human Melanoma Cells via Hsp60-Mediated FAS Expression,” European Journal of Immunology, Vol. 41, No. 10, 2011, pp. 2937-2946. doi:10.1002/eji.201141597

[75]   Y. Lee, et al., “Anticancer Activity of S-Allylmercapto- L-Cysteine on Implanted Tumor of Human Gastric Cancer Cell,” Biological and Pharmaceutical Bulletin, Vol. 34, No. 5, 2011, pp. 677-681. doi:10.1248/bpb.34.677

[76]   Z. Liu, et al., “S-Allylcysteine Induces Cell Cycle Arrest and Apoptosis in Androgen-Independent Human Prostate Cancer Cells,” Molecular Medicine Reports, Vol. 5, No. 2, 2012, pp. 439-443.

[77]   E. J. Kim, et al., “Thiacremonone, a Sulfur Compound Isolated from Garlic, Attenuates Lipid Accumulation Partially Mediated via AMPK Activation in 3T3-L1 Adipo- cytes,” The Journal of Nutritional Bioch, 2012. doi:10.1016/j.jnutbio.2011.10.008

[78]   N. Morihara, M. Hayama and H. Fujii, “Aged Garlic Extract Scavenges Superoxide Radicals,” Plant Foods for Human Nutrition, Vol. 66, No. 1, 2011, pp. 17-21. doi:10.1007/s11130-011-0216-6

[79]   A. A. Powolny, et al., “The Garlic Constituent Diallyl Trisulfide Increases the Lifespan of C. Elegans via SKN-1 Activation,” Experimental Gerontology, Vol. 46, No. 6, 2011, pp. 441-442. doi:10.1016/j.exger.2011.01.005

[80]   R. Nepravishta, et al., “Oxidative Species and SGlutathionyl Conjugates in the Apoptosis Induction by Allyl Thiosulfate,” FEBS Journal, Vol. 279, No. 1, 2012, pp. 154-167. doi:10.1111/j.1742-4658.2011.08407.x

[81]   M. H. Pai, et al., “S-Allylcysteine Inhibits Tumour Progression and the Epithelial-Mesenchymal Transition in a Mouse Xenograft Model of Oral Cancer,” British Journal of Nutrition, Vol. 108, No. 1, 2011, pp. 1-11.

[82]   Y. Pei, et al., “Hydrogen Sulfide Mediates the Anti-Survival Effect of Sulforaphane on Human Prostate Cancer Cells,” ology and Applied Pharmacology, Vol. 257, No. 3, 2011, pp. 420-428. doi:10.1016/j.taapp.2011.09.026

[83]   Z. Wang, et al., “Resveratrol Induces Gastric Cancer Cell Apoptosis via Reactive Oxygen Species, but Independent of Sirtuin1,” Clinical and Experimental Pharmacology and Physiology, Vol. 39, No. 3, 2012, pp. 227-232. doi:10.1111/j.1440-1681.2011.05660.x

[84]   X. Wang, et al., “Aged Black Garlic Extract Induces Inhibittion of Gastric Cancer Cell Growth in Vitro and in Vivo,” Molecular Medicine Reports, Vol. 5, No. 1, 2012, pp. 66-72.

[85]   F. Wang, et al., “Long-Term Efficacy of 10-12 Years after Being Immunized with Chinese Hamster Ovary Cell Derived Hepatitis B Vaccine in Chinese Rural Communities,” Vaccine, Vol. 30, No. 12, 2012, pp. 2051-2053. doi:10.1016/j.vaccine.2012.01.052

[86]   M. O. Altonsy and S. C. Andrews, “Diallyl Disulphide, A Beneficial Component of Garlic Oil, Causes a Redistribution of Cell-Cycle Growth Phases, Induces Apoptosis, and Enhances Butyrate-Induced Apoptosis in Colorectal Adeno-Carcinoma Cells (HT-29),” Nutrition and Cancer, Vol. 63, No. 7, 2011, pp. 1104-1113. doi:10.1080/01635581.2011.601846

[87]   C. Y. Chen, et al., “Diallyl Disulfide Induces Ca2+ Mobi- Lization in Human Colon Cancer Cell Line SW480,” Archives of Toxicology, Vol. 86, No. 2, 2012, pp. 231-238. doi:10.1007/s00204-011-0748-4

[88]   K. Berginc and A. Kristl, “The Mechanisms Responsible for Garlic—Drug Interactions and Their in Vivo Rele- Vance,” Current Drug Metabolism, 2011.

[89]   B. Akgul, et al., “Garlic Accelerates Red Blood Cell Turnover and Splenic Erythropoietic Gene Expression in Mice: Evidence for Erythropoietin-Independent Erythropoiesis,” PLOS One, Vol. 5, No. 12, 2010, p. e15358. doi:10.1371/journal.pone.0015358

[90]   C. Cerella, et al., “Chemical Properties and Mechanisms Determining the Anti-Cancer Action of Garlic-Derived or Ganic Sulfur Compounds,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 11, No. 3, 2011, pp. 267-271.

[91]   C. Ma, et al., “Production, Characterisation and Immuno- Genicity of a Plant-Made Plasmodium Antigen—The 19 kDa C-Terminal Fragment of Plasmodium Yoelii Merozoite Surface Protein 1,” Applied Microbiology and Biotechnology, Vol. 94, No. 1, 2012, pp. 151-161. doi:10.1007/s00253-011-3772-7

[92]   J. L. Ma, et al., “Fifteen-Year Effects of Helicobacter Pylori, Garlic, and Vitamin Treatments on Gastric Cancer Incidence and Mortality,” Journal of the National Cancer Institute, Vol. 104, No. 6, 2012, pp. 488-492. doi:10.1093/jnci/djs003

[93]   Q. Ma and Y. Wang, “Comprehensive Analysis of the Prevalence of Hepatitis B Virus Escape Mutations in the Major Hydrophilic Region of Surface Antigen,” Journal of Medical Virology, Vol. 84, No. 2, 2012, pp. 198-206. doi:10.1002/jmv.23183

[94]   M. L. Antony and S. V. Singh, “Molecular Mechanisms and Targets of Cancer Chemoprevention by Garlic-Derived Bioactive Compound Diallyl Trisulfide,” Indian Journal of Experimental Biology, Vol. 49, No. 11, 2011, pp. 805-816.

[95]   M. Iciek, et al., “The Effects of Garlic-Derived Sulfur Compounds on Cell Proliferation, Caspase 3 Activity, Thiol Levels and Anaerobic Sulfur Metabolism in Human Hepato-Blastoma HepG2 Cells,” Cell Biochemistry and Function, Vol. 30, No. 3, 2012, pp. 198-204. doi:10.1002/cbf.1835

[96]   H. Shirzad, F. Taji and M. Rafieian-Kopaei, “Correlation between Antioxidant Activity of Garlic Extracts and WEHI-164 Fibrosarcoma Tumor Growth in BALB/c Mice,” Journal of Medicinal Food, Vol. 14, No. 9, 2011, pp. 969-974. doi:10.1089/jmf.2011.1594

[97]   R. B. Walter, et al., “Vitamin, Mineral, and Specialty Supplements and Risk of Hematologic Malignancies in the Prospective VITamins and Lifestyle (VITAL) Study,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 20, No. 10, 2011, pp. 2298-2308. doi:10.1158/1055-9965.EPI-11-0494

[98]   D. Liang, et al., “S-Allylmercaptocysteine Effectively In- Hibits the Proliferation of Colorectal Cancer Cells under in Vitro and in Vivo Conditions,” Cancer Letters, Vol. 310, No. 1, 2011, pp. 69-76. doi:10.1016/j.canlet.2011.06.019

[99]   S. Karmakar, et al., “Molecular Mechanisms of Anti-Cancer Action of Garlic Compounds in Neuroblastoma,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 11, No. 4, 2011, pp. 398-407.

[100]   Y. S. Huang, et al., “Diallyl Disulfide Inhibits the Proliferation of HT-29 Human Colon Cancer Cells by Inducing Differentially Expressed Genes,” Molecular Medicine Reports, Vol. 4, No. 3, 2011, pp. 553-559.

[101]   H. Hu, et al., “Identification of a Novel Function of Id-1 in Mediating the Anticancer Responses of Samc, a Water-Soluble Garlic Derivative, in Human Bladder Cancer Cells,” Molecular Medicine Reports, Vol. 4, No. 1, 2011, pp. 9-16.

[102]   A. Tsubura, et al., “Anticancer Effects of Garlic and Garlic-Derived Compounds for Breast Cancer Control,” Anti- Cancer Agents in Medicinal Chemistry, Vol. 11, No. 3, 2011, pp. 249-253.

[103]   C. H. Kaschula, et al., “Anti-Proliferation Activity of Synthetic Ajoene Analogues on Cancer Cell-Lines,” Anti- Cancer Agents in Medicinal Chemistry, Vol. 11, No. 3, 2011, pp. 260-266.

[104]   E. Viry, et al., “Antiproliferative Effect of Natural Tetrasul-Fides in Human Breast Cancer Cells Is Mediated Through the Inhibition of the Cell Division Cycle 25 Phosphatases,” International Journal of Oncology, Vol. 38, No. 4, 2011, pp. 1103-1111.

[105]   V. Karagianni, et al., “Risk Factors for Colorectal Polyps: Findings from a Greek Case-Control Study,” Revista Medico-Chirurgicala a Societatii de Medici Si Naturalisti Din Iasi, 2010, Vol. 114, No. 3, pp. 662-670.

[106]   T. Chihara, et al., “Inhibition of 1, 2-Dimethylhydra- Zine-Induced Mucin-Depleted Foci and O (6)-Methyl- Guanine DNA Adducts in the Rat Colorectum by Boiled Garlic Powder,” Asian Pacific Journal of Cancer Prevention, Vol. 11, No. 5, 2010, pp. 1301-1304.

[107]   E. Padilla-Camberos, et al., “Antitumoral Activity of Al- Licin in Murine Lymphoma L5178Y,” Asian Pacific Journal of Cancer Prevention, Vol. 11, No. 5, 2010, pp. 1241-1244.

[108]   S. Salem, et al., “Major Dietary Factors and Prostate Cancer Risk: a Prospective Multicenter Case-Control Study,” Nutrition and Cancer, Vol. 63, No. 1, 2011, pp. 21-27.

[109]   N. Ferrari, et al., “Diet-Derived Phytochemicals: From Cancer Chemoprevention to Cardio-Oncological Prevention,” Current Drug Targets, Vol. 12, No. 13, 2011, pp. 1909-1924. doi:10.2174/138945011798184227

[110]   B. Ray, N. B. Chauhan and D. K. Lahiri, “The Aged Garlic Extract (AGE) and One of Its Active Ingredients S-Allyl-L-Cysteine (SAC) as Potential Preventive and Therapeutic Agents for Alzheimer’s Disease (AD),” Current Drug Targets, Vol. 18, No. 22, 2011, pp. 3306-3313. doi:10.2174/092986711796504664

[111]   K. C. Lai, et al., “Diallyl Sulfide, Diallyl Disulfide, and Diallyl Trisulfide Inhibit Migration and Invasion in Human Colon Cancer Colo 205 Cells through the Inhibition of Matrix Metalloproteinase-2, -7, and -9 Expressions,” Environmental Toxicology, Vol. 3, 2011. doi:10.1002/tox.20737

[112]   M. Miroddi, F. Calapai and G. Calapai, “Potential Bene- Ficial Effects of Garlic in Oncohematology,” MiniReviews in Medicinal Chemistry, Vol. 11, No. 6, 2011, pp. 461-472. doi:10.2174/138955711795843293

[113]   A. Ogita, K. Fujita and T. Tanaka, “Enhancing Effects on Vacuole-Targeting Fungicidal Activity of Amphotericin B,” Frontiers in Microbiology,” Vol. 3, 2012, p. 100.

[114]   R. Marik, et al., “Potent Genistein Derivatives as Inhibitors of Estrogen Receptor Alpha-Positive Breast Cancer,” Cancer Biology & Therapy, Vol. 11, No. 10, 2011, pp. 883-892. doi:10.4161/cbt.11.10.15184

[115]   T. L. Guo, et al., “Genistein Modulates Splenic Natural Killer Cell Activity, Antibody-Forming Cell Response, and Phenotypic Marker Expression in F(0) and F(1) Generations of Sprague-Dawley Rats,” Toxicology and Applied Pharmacology, Vol. 181, No. 3, 2002, pp. 219-227.

[116]   M. F. Ullah, et al., “Soy Isoflavone Genistein Induces Cell Death in Breast Cancer Cells through Mobilization of Endogenous Copper Ions and Generation of Reactive Oxygen Species,” Mol Nutr Food Res Molecular Nutrition & Food Research, Vol. 55, No. 4, 2011, pp. 553-559. doi:10.1002/mnfr.201000329

[117]   R. J. Zhou, et al., “Anti-Tumor Effects of All-Trans Retinoic Acid Are Enhanced by Genistein,” Cell Biochemistry and Biophysics, Vol. 62, No. 1, 2012, pp. 177- 184.doi:10.1007/s12013-011-9279-0

[118]   X. Yu, et al., “Anti-Angiogenic Genistein Inhibits VEGF- Induced Endothelial Cell Activation by Decreasing PTK Activity and Mapk Activation,” Medical Oncology, Vol. 29, No. 1, 2012, pp. 349-357. doi:10.1007/s12032-010-9770-2

[119]   F. Polito, et al., “Genistein Aglycone, a Soy-Derived Isoflavone, Improves Skin Changes Induced by Ovariectomy in Rats,” British Journal of Pharmacology, Vol. 165, No. 4, 2012, pp. 994-1005. doi:10.1111/j.1476-5381.2011.01619.x

[120]   Y. Zhang and H. Chen, “Genistein Attenuates WNT Signaling by Up-Regulating sFRP2 in a Human Colon Cancer Cell Line,” Experimental Biology and Medicine (Maywood) Vol. 236, No. 6, 2011, pp. 714-722. doi:10.1258/ebm.2011.010347

[121]   M. B. van Duursen, et al., “Genistein Induces Breast Cancer-Associated Aromatase and Stimulates Estrogen-Dependent Tumor Cell Growth in Vitro Breast Cancer Model,” Toxicology, Vol. 289, No. 2-3, 2011, pp. 67-73. doi:10.1016/j.tox.2011.07.005

[122]   C. Sanchez, et al., “Chemotherapy Sensitivity Recovery of Prostate Cancer Cells by Functional Inhibition and Knock down of Multidrug Resistance Proteins,” Prostate, Vol. 71, No. 16, 2011, pp. 1810-1817. doi:10.1002/pros.21398

[123]   W. Qi, et al., “Genistein Inhibits Proliferation of Colon Cancer Cells by Attenuating a Negative Effect of Epidermal Growth Factor on Tumor Suppressor FOXO3 Activity,” BMC Cancer, Vol. 11, 2011, pp. 219. doi:10.1186/1471-2407-11-219

[124]   G. Ji, et al., “Anti-Inflammatory Effect of Genistein on Non-Alcoholic Steatohepatitis Rats Induced by High Fat Diet and Its Potential Mechanisms,” International Immunopharmacology, Vol. 11, No. 6, 2011, pp. 762-768. doi:10.1016/j.intimpp.2011.01.036

[125]   D. Hess and R. A. Igal, “Genistein Downregulates Denovo Lipid Synthesis and Impairs Cell Proliferation in Human Lung Cancer Cells,” Experimental Biology and Medicine, Vol. 236, No. 6, 2011, pp. 707-713. doi:10.1258/ebm.2011.010265

[126]   S. de Assis, et al., “Protective Effects of Prepubertal Gen- Istein Exposure on Mammary Tumorigenesis Are Depend-ENT on Brca1 Expression,” Cancer Prevention Re- search, Vol. 4, No. 9, 2011, pp. 1436-1448. doi:10.1158/1940-6207.CAPR-10-0346

[127]   F. G. Bottone Jr. and B. Alston-Mills, “The Dietary Com- Pounds Resveratrol and Genistein Induce Activating Transcription Factor 3 While Suppressing Inhibitor of DNA Binding/Differentiation-1,” Journal of Medicinal Food, Vol. 14, No. 6, 2011, pp. 584-593. doi:10.1089/jmf.2010.0110

[128]   Y. Zhang, et al., “Genistein Inhibits Osteolytic Bone Me- Tastasis and Enhances Bone Mineral in Nude Mice,” Environmental Toxicology and Pharmacology, Vol. 30, No. 1, 2010, pp. 37-44. doi:10.1016/j.etapp.2010.03.016

[129]   M. Yamasaki, et al., “Genistein Induced Apoptotic Cell Death in Adult T-Cell Leukemia Cells through Estrogen Receptors,” Bioscience, Biotechnology, and Biochemistry, Vol. 74, No. 10, 2010, pp. 2113-2115. doi:10.1271/bbb.100359

[130]   I. Hwang, et al., “An Acidic Polysaccharide of Panax Ginseng Ameliorates Experimental Autoimmune Encephalo-Myelitis and Induces Regulatory T Cells,” Immunology Letters, Vol. 138, No. 2, 2011, pp. 169-178. doi:10.1016/j.imlet.2011.04.005

[131]   J. L. Elam, et al., “Methodological Issues in the Investigation of Ginseng as an Intervention for Fatigue,” Clini- cal Nurse Specialist, Vol. 20, No. 4, 2006, pp. 183-189. doi:10.1097/00002800-200607000-00007

[132]   F. Y. Xie, Z. F. Zeng and H. Y. Huang, “Clinical Observation on Nasopharyngeal Carcinoma Treated with Combined Therapy of Radiotherapy and Ginseng Polysaccharide Injection,” Chinese Journal of Integrated Traditional and Western Medicine, Vol. 21, No. 5, 2001, pp. 332-334.

[133]   H. Nakata, et al., “Inhibitory Effects of Ginsenoside RH2 on Tumor Growth in Nude Mice Bearing Human Ovarian Cancer Cells,” Japanese Journal of Cancer Research, Vol. 89, No. 7, 1998, pp. 733-740. doi:10.1111/j.1349-7006.1998.tb03278.x

[134]   D. M. See, et al., “In Vitro Effects of Echinacea and Ginseng on Natural Killer and Antibody-Dependent Cell Cytotoxicity in Healthy Subjects and Chronic Fatigue Syndrome or Acquired Immunodeficiency Syndrome Patients,” Immunopharmacology, Vol. 35, No. 3, 1997, pp. 229-235. doi:10.1016/S0162-3109, No. 96)00125-7

[135]   S. Y. Lin, L. M. Liu and L. C. Wu, “Effects of Shenmai Injection on Immune Function in Stomach Cancer Patients after Chemotherapy,” Chinese Journal of Integrated Traditional and Western Medicine, Vol. 15, No. 8, 1995, pp. 451-453.

[136]   Y. S. Yun, et al., “Inhibition of Autochthonous Tumor by Ethanol Insoluble Fraction from Panax Ginseng as an Immunomodulator,” Planta Medica, Vol. 59, No. 6, 1993, pp. 521-524. doi:10.1055/s-2006-959752

[137]   F. Scaglione, et al., “Immunomodulatory Effects of Two Extracts of Panax Ginseng C. A. Meyer,” Drugs under Experimental and Clinical Research, Vol. 16, No. 10, 1990, pp. 537-542.

[138]   B. Kenarova, et al., “Immunomodulating Activity of Ginsenoside RG1 from Panax Ginseng,” The Japanese Journal of Pharmacology, Vol. 54, No. 4, 1990, pp. 447- 454. doi:10.1254/jjpp.54.447

[139]   S. P. Wasser, “Medicinal Mushrooms as a Source of Antitumor and Immunomodulating Polysaccharides,” Applied Microbiology and Biotechnology, 2002, Vol. 60, No. 3, pp. 258-274. doi:10.1007/s00253-002-1076-7

[140]   T. Mitamura, et al., “Effects of Lentinan on Colorectal Carcinogenesis in Mice with Ulcerative Colitis,” Oncology Reports, Vol. 7, No. 3, 2000, pp. 599-601.

[141]   M. Suzuki, et al., “Curative Effects of Combination Therapy with Lentinan and Interleukin-2 against Established Murine Tumors, and the Role of CD8-Positive T cells,” Cancer Immunology, Immunotherapy, Vol. 38, No. 1, 1994, pp. 1-8. doi:10.1007/BF01517163

[142]   M. Suzuki, et al., “Reconstitution of Anti-Tumor Effects of Lentinan in Nude Mice: Roles of Delayed-Type Hypersensitivity Reaction Triggered by CD4-Positive T cell Clone in the Infiltration of Effector Cells into Tumor,” Japanese Journal of Cancer Research, Vol. 85, No. 4, 1994, pp. 409-417. doi:10.1111/j.1349-7006.1994.tb02374.x

[143]   V. Vetvicka, et al., “Enhancing Effects of New Biological Response Modifier Beta-1,3 Glucan Sulfate PS3 on Immune Reactions,” Biomedicine & Pharmacotherapy, Vol. 62, No. 5, 2008, pp. 283-288. doi:10.1016/j.biopha.2007.05.011

[144]   V. Vetvicka, et al., “Immunological Effects of Yeast- and Mushroom-Derived Beta-Glucans,” Journal of Medicinal Food, Vol. 11, No. 4, 2008, pp. 615-622. doi:10.1089/jmf.2007.0588

[145]   J. Wang, Z. D. Zhou and D. J. Xia, “Study on Effect of Lentinan in Enhancing Anti-Tumor Action of Dendritic Cytoma Vaccine and Its Mechanism,” Chinese Journal of Integrated Traditional and Western Medicine, Vol. 27, No. 1, 2007, pp. 60-64.

[146]   V. Vetvicka and J. C. Yvin, “Effects of Marine Beta-1,3 Glucan on Immune Reactions,” International Immunopharmacology, Vol. 4, No. 6, 2004, pp. 721-730. doi:10.1016/j.intimpp.2004.02.007

[147]   M. L. Ng and A. T. Yap, “Inhibition of Human Colon Carcinoma Development by Lentinan from Shiitake Mushrooms (Lentinus Edodes),” Journal of Alternative and Complementary Medicine, Vol. 8, No. 5, 2002, pp. 581-589. doi:10.1089/107555302320825093

[148]   K. Hamano, et al., “The Preoperative Administration of Lentinan Ameliorated the Impairment of Natural Killer Activity after Cardiopulmonary Bypass,” International Journal of Immunopharmacology, Vol. 21, No. 8, 1999, pp. 531-540. doi:10.1016/S0192-0561, No. 99)00033-8

[149]   S. B. Han, et al., “Characteristic Immunostimulation by Angelan Isolated from Angelica Gigas Nakai,” Immunopharmacology, Vol. 40, No. 1, 1998, pp. 39-48. doi:10.1016/S0162-3109, No. 98)00026-5

[150]   J. F. Li, J. W. Guo and X. F. Huang, “Study on the Enhancing Effect of Polyporus Polysaccharide, Mycobacterium Polysaccharide and Lentinan on Lymphokine-Activated Killer Cell Activity in Vitro,” Chinese Journal of Integrated Traditional and Western Medicine, Vol. 16, No. 4, 1996, pp. 224-226.

[151]   M. Rafique and W. Adachi, “Effects of Intraportal Administration of Chemoimmunotherapeutic Agents on Natural Killer Cell Activity in the Rat Liver,” Journal of Surgical Oncology, Vol. 60, No. 3, 1995, pp. 154-159. doi:10.1002/jso.2930600304

[152]   H. Matsuoka, et al., “Usefulness of Lymphocyte Subset Change as an Indicator for Predicting Survival Time and Effectiveness of Treatment with the Immunopotentiator Lentinan,” Anticancer Research, Vol. 15, No. 5B, 1995, pp. 2291-2296.

[153]   S. Hazama, et al., “Clinical Effects and Immunological Analysis of Intraabdominal and Intrapleural Injection of Lentinan for Malignant Ascites and Pleural Effusion of Gastric Carcinoma,” Japanese Journal of Cancer and Chemotherapy, Vol. 22, No. 11, 1995, pp. 1595-1597.

[154]   E. Kobayashi, et al., “KRN7000, a Novel Immunomodulator, and Its Antitumor Activities,” Ology Research, Vol. 7, No. 10-11, 1995, pp. 529-534.

[155]   H. Morinaga, et al., “An in Vivo Study of Hepatic and Splenic Interleukin-1 Beta mRNA Expression Following Oral PSK or LEM Administration,” Japanese Journal of Cancer Research, Vol. 85, No. 12, 1994, pp. 1298-1303. doi:10.1111/j.1349-7006.1994.tb02943.x

[156]   J. Hamuro, et al., “Synergistic Antimetastatic Effects of Lentinan and Interleukin 2 with Pre- and Post-Operative Treatments,” Japanese Journal of Cancer Research, Vol. 85, No. 12, 1994, pp. 1288-1297. doi:10.1111/j.1349-7006.1994.tb02942.x

[157]   Z. B. Yang, “Effects of Pretreatment with Lentinan or Krestin on Antitumor Effector Cell Activities Suppressed by Cyclophosphamide,” Hokkaido Journal of Medical Science, Vol. 69, No. 1, 1994, pp. 137-145.

[158]   M. Tani, et al., “Augmentation of Lymphokine-Activated Killer Cell Activity by Lentinan,” Anticancer Research, Vol. 13, No. 5C, 1993, pp. 1773-1776.

[159]   S. Arinaga, et al., “Enhanced Induction of Lymphokine- Activated Killer Activity after Lentinan Administration in Patients with Gastric Carcinoma,” International Journal of Immunopharmacology, Vol. 14, No. 4, 1992, pp. 535- 539. doi:10.1016/0192-0561, No. 92)90114-Z

[160]   M. Tani, et al., “In Vitro Generation of Activated Natural Killer Cells and Cytotoxic Macrophages with Lentinan,” European Journal of Clinical Pharmacology, Vol. 42, No. 6, 1992, pp. 623-627. doi:10.1007/BF00265926

[161]   M. Takahashi, et al., “Two-Color Flow Cytometric Analysis of Splenic Lymphocyte Subpopulations in Patients with Gastric Cancer,” Surgery Today, Vol. 22, No. 1, 1992, pp. 35-39. doi:10.1007/BF00326123

[162]   T. Fujimoto, et al., “Evaluation of Basic Procedures for Adoptive Immunotherapy for Gastric Cancer,” Biotherapy, Vol. 5, No. 2, 1992, pp. 153-163. doi:10.1007/BF02171701

[163]   M. Oka, et al., “Immunological Analysis and Clinical Effects of Intraabdominal and Intrapleural Injection of Lentinan for Malignant Ascites and Pleural Effusion,” Biotherapy, Vol. 5, No. 2, 1992, pp. 107-112. doi:10.1007/BF02171695

[164]   H. Tanabe, N. Imai and K. Takechi, “Studies on Usefulness of Postoperative Adjuvant Chemotherapy with Lentinan in Patients with Gastrointestinal Cancer,” Journal of Japan Society for Magazine Subscription, Vol. 25, No. 8, 1990, pp. 1657-1667.

[165]   M. Suzuki, et al., “Induction of Endogenous Lymphokine-Activated Killer Activity by Combined Admini- stration of Lentinan and Interleukin 2,” International Journal of Immunopharmacology, Vol. 12, No. 6, 1990, pp. 613-623. doi:10.1016/0192-0561, No. 90)90098-8

[166]   H. Shimizu, M. Inoue and O. Tanizawa, “Adoptive Cellular Immunotherapy to the Endometrial Carcinoma Cell Line Xenografts in Nude Mice,” Gynecologic Oncology, Vol. 34, No. 2, 1989, pp. 195-199. doi:10.1016/0090-8258, No. 89)90141-8

[167]   S. Yoshino, et al., “Effect of Intrapleural and/or Intraperitoneal Lentinan Therapy on Carcinomatous Pleuritis and Peritonitis with Special Reference to Immunological Evaluation,” Nihon Geka Hokan, Vol. 58, No. 3, 1989, pp. 310-319.

[168]   K. Yamasaki, et al., “Synergistic Induction of Lymphokine, (IL-2)-Activated Killer Activity by IL-2 and the Polysaccharide Lentinan, and Therapy of Spontaneous Pulmonary Metastases,” Cancer Immunology, Immuno- therapy, Vol. 29, No. 2, 1989, pp. 87-92. doi:10.1007/BF00199282

[169]   T. Inagaki, K. Morise and H. Matsunaga, “Effects of Endoscopic Intratumoral Injection of Lentinan in Patients with Gastric Cancer,” Japanese Journal of Cancer and Chemotherapy, Vol. 15, No. 2, 1988, pp. 319-324.

[170]   G. Peter, et al., “Effects of Lentinan on Cytotoxic Functions of Human Lymphocytes,” Immunopharmacology and Immunotoxicology, Vol. 10, No. 2, 1988, pp. 157-163. doi:10.3109/08923978809014330

[171]   M. Akimoto, T. Nishihira and M. Kasai, “Modulation of the Anti-Tumor Effect of BRM under Various Nutritional or Endocrine Conditions,” Japanese Journal of Cancer and Chemotherapy, Vol. 13, No. 4, 1986, pp. 1270-1276.

[172]   H. Miyakoshi, T. Aoki and M. Mizukoshi, “Acting Mechanisms of Lentinan in Human—II. Enhancement of Non-Specific Cell-Mediated Cytotoxicity as an Interferon Inducer,” International Journal of Immunopharmacology, Vol. 6, No. 4, 1984, pp. 373-379. doi:10.1016/0192-0561, No. 84)90057-2

[173]   M. Amino, et al., “Studies on the Effect of Lentinan on Human Immune System. II. in Vivo effect on NK Activity, MLR Induced Killer Activity and Pha Induced Blastic Response of Lymphocytes in Cancer Patients,”. Japanese Journal of Cancer and Chemotherapy, Vol. 10, No. 9, 1983, pp. 2000-2006.

[174]   K. Kurita, et al., “Synthesis and Macrophage Activation of Lentinan-Mimic Branched Amino Polysaccharides: Curdlans Having N-Acetyl-D-Glucosamine Branches,” Biomacromolecules, Vol. 12, No. 6, 2011, pp. 2267-2274. doi:10.1021/bm200353m

[175]   K. Harada, et al., “Effects of Lentinan Alone and in Combination with Fluoropyrimidine Anticancer Agent on Growth of Human Oral Squamous Cell Carcinoma in Vitro and in Vivo,” International Journal of Oncology, Vol. 37, No. 3, 2010, pp. 623-631. doi:10.3892/ijo_00000711

[176]   E. McCormack, et al., “Lentinan: Hematopoietic, Immunological, and Efficacy Studies in a Syngeneic Model of Acute Myeloid Leukemia,” Nutrition and Cancer, Vol. 62, No. 5, 2010, pp. 574-583. doi:10.1080/01635580903532416

[177]   X. Wang, et al., “Effects of Potential Calcium Sensing Receptor Inducers on Promoting Chemosensitivity of Human Colon Carcinoma Cells,” International Journal of Oncology Vol. 36, No. 6, 2010, pp. 1573-1580.

[178]   Z. Wang and H. Chen, “Genistein Increases Gene Expression by Demethylation of Wnt5a Promoter in Colon Cancer Cell Line SW1116,” Anticancer Research, Vol. 30, No. 11, 2010, pp. 4537-45.

[179]   N. Isoda, et al., “Clinical Efficacy of Superfine Dispersed Lentinan, No. Beta-1,3-Glucan) in Patients with Hepatocellular Carcinoma,” Hepatogastroenterology, Vol. 56, No. 90, 2009, pp. 437-441.

[180]   S. Maruyama, et al., “Anti Tumor Activities of Lentinan and Micellapist in Tumor-Bearing Mice,” Japanese Journal of Cancer and Chemotherapy, Vol. 33, No. 12, 2006, pp. 1726-1729.

[181]   J. Hamuro, “Anticancer Immunotherapy with Perorally Effective Lentinan,” Japanese Journal of Cancer and Chemotherapy, Vol. 32, No. 8, 2005, pp. 1209-1215.

[182]   H. Mushiake, et al., “Dendritic Cells Might Be One of Key Factors for Eliciting Antitumor Effect by Chemoimmunotherapy in Vivo,” Cancer Immunology, Immunotherapy, Vol. 54, No. 2, 2005, pp. 120-128. doi:10.1007/s00262-004-0585-x

[183]   S. Yoshino, et al., “Immunoregulatory Effects of the Antitumor Polysaccharide Lentinan on TH1/TH2 Balance in Patients with Digestive Cancers,” Anticancer Research, Vol. 20, No. 6C, 2000, pp. 4707-4711.

[184]   F. Takatsuki, et al., “Improvement of Erythroid Toxicity by Lentinan and Erythropoietin in Mice Treated with Chemotherapeutic Agents,” Experimental Hematology, Vol. 24, No. 3, 1996, pp. 416-422.

[185]   S. Goto, et al., “A Case Report of Recurrent Cervical Cancer Which Responded to a Combination of Biological Therapies,” European Journal of Gynaecological Oncology, Vol. 15, No. 3, 1994, pp. 235-240.

[186]   S. Braedel-Ruoff, “Immunomodulatory Effects of Viscum Album Extracts on Natural Killer Cells: Review of Clinical Trials,” Forsch Komplementmed, Vol. 17, No. 2, 2010, pp. 63-73. doi:10.1159/000288702

[187]   E. Gunsilius, J. Clausen and G. Gastl, “Palliative Immunotherapy of Cancer,” Therapeutische Umschau, Vol. 58, No. 7, 2001, pp. 419-424. doi:10.1024/0040-5930.58.7.419

[188]   A. Bussing, et al., “Development of Lymphocyte Subsets in Tumor Patients after Subcutaneous Administration of Mistletoe Extracts,” Forsch Komplementarmed, Vol. 6, No. 4, 1999, pp. 196-204. doi:10.1159/000021253

[189]   W. Dohmen, M. Breier and U. Mengs, “Cellular Immunomodulation and Safety of Standardized Aqueous Mis- tletoe Extract PS76A2 in Tumor Patients Treated for 48 Weeks,” Anticancer Research, Vol. 24, No. 2C, 2004, pp. 1231-1237.

[190]   T. Hajto and C. Lanzrein, “Natural Killer and Antibody- Dependent Cell-Mediated Cytotoxicity Activities and Large Granular Lymphocyte Frequencies in Viscum Album-Treated Breast Cancer Patients,” Oncology, Vol. 43, No. 2, 1986, pp. 93-97. doi:10.1159/000226342

[191]   J. Hauer and F. A. Anderer, “Mechanism of Stimulation of Human Natural Killer Cytotoxicity by Arabinogalactan from Larix Occidentalis,” Cancer Immunology, Immunotherapy, Vol. 36, No. 4, 1993, pp. 237-244. doi:10.1007/BF01740905

[192]   G. Maier and H. H. Fiebig, “Absence of Tumor Growth Stimulation in a Panel of 16 Human Tumor Cell Lines by Mistletoe Extracts in Vitro,” Anticancer Drugs, Vol. 13, No. 4, 2002, pp. 373-379. doi:10.1097/00001813-200204000-00006

[193]   M. Schink, “Mistletoe Therapy for Human Cancer: The Role of the Natural Killer Cells,” Anticancer Drugs, Vol. 8, No. 1S, 1997, pp. S47-S51. doi:10.1097/00001813-199704001-00011

[194]   A. Thies, et al., “Binding of Mistletoe Lectins to Cutaneous Malignant Melanoma: Implications for Prognosis and Therapy,” Anticancer Research, Vol. 21, No. 4B, 2001, pp. 2883-2887.

[195]   C. Guerra, et al., “Control of Mycobacterium Tuberculosis Growth by Activated Natural Killer Cells,” Clinical & Experimental Immunology, Vol. 168, No. 1, 2012, pp. 142-152. doi:10.1111/j.1365-2249.2011.04552.x

[196]   M. Ardolino, et al., “DNAM-1 Ligand Expression on AG-Stimulated T Lymphocytes Is Mediated by ROS-Dependent Activation of DNA-Damage Response: Relevance for NK-T Cell Interaction,” Blood, Vol. 117, No. 18, 2011, pp. 4778-4786. doi:10.1182/blood-2010-08-300954

[197]   I. A. Gamalei, et al., “N-Acetylcysteine-Induced Reduction in Susceptibility of Transformed and Embryonic Cells to Lytic Activity of Natural Killer Cells,” Tsitologiia, Vol. 52, No. 7, 2010, pp. 555-561.

[198]   L. Weiss, et al., “N-Acetylcysteine Mildly Inhibits the Graft-vs.-Leukemia Effect but Not the Lymphokine Activated Cells (LAK) Activity,” Transplant Immunology, Vol. 17, No. 3, 2007, pp. 198-202. doi:10.1016/j.trim.2006.10.005

[199]   N. A. Filatova, K. M. Kirpichnikova and I. A. Gamalei, “N-Acetylcysteine Reduces Transformed 3T3-SV40 Fibroblast Sensitivity to Lysis by Natural Killer Cells,” Tsitologiia, Vol. 48, No. 5, 2006, pp. 438-442.

[200]   J. Zhao and X. J. Liu, “Antioxidative and Immunomodulatory Role of Melatonin, Sodium Selenite, N-Acetyl-L- Cysteine and Quercetin on Human Umbilical Blood,” Pharmazie, Vol. 60, No. 9, 2005, pp. 683-688.

[201]   N. Guayerbas, et al., “A Diet Supplemented with Thiolic Anti-Oxidants Improves Leucocyte Function in Two Strains of Prematurely Ageing Mice,” Clinical and Experimental Pharmacology and Physiology, Vol. 29, No. 11, 2002, pp. 1009-1014. doi:10.1046/j.1440-1681.2002.03758.x

[202]   M. de La Fuente, et al., “The Amount of Thiolic Antioxidant Ingestion Needed to Improve Several Immune Functions Is Higher in Aged than in Adult Mice,” Free Radical Research, Vol. 36, No. 2, 2002, pp. 119-126. doi:10.1080/10715760290006439

[203]   M. Viora, et al., “Redox Imbalance and Immune Functions: Opposite Effects of Oxidized Low-Density Lipoproteins and N-Acetylcysteine,” Immunology, Vol. 104, No. 4, 2001, pp. 431-438. doi:10.1046/j.1365-2567.2001.01334.x

[204]   S. Kojima, et al., “Elevation of Glutathione Induced by Low-Dose Gamma Rays and Its Involvement in Increased Natural Killer Activity,” Radiation Research, Vol. 157, No. 3, 2002, pp. 275-280. doi:10.1667/0033-7587,No.2002)157[0275:EOGIBL]2.0.CO;2

[205]   K. Dobashi, et al., “Regulation of LPS Induced IL-12 Production by IFN-Gamma and IL-4 through Intracellular Glutathione Status in Human Alveolar Macrophages,” Clinical & Experimental Immunology, Vol. 124, No. 2, 2001, pp. 290-296. doi:10.1046/j.1365-2249.2001.01535.x

[206]   R. Breitkreutz, et al., “Improvement of Immune Functions in HIV Infection by Sulfur Supplementation: Two Randomized Trials,” Journal of Molecular Medicine, Vol. 78, No. 1, 2000, pp. 55-62. doi:10.1007/s001090050382

[207]   W. Droge and R. Breitkreutz, “Glutathione and Immune Function,” Proceedings of the Nutrition Society, Vol. 59, No. 4, 2000, pp. 595-600. doi:10.1017/S0029665100000847

[208]   M. D. Ferrandez, et al., “Effects in Vitro of Several Antioxidants on the Natural Killer Function of Aging Mice,” Experimental Gerontology, Vol. 34, No. 5, 1999, pp. 675-685. doi:10.1016/S0531-5565, No. 99)00009-1

[209]   K. Furuke, et al., “Fas Ligand Induction in Human NK Cells Is Regulated by Redox through a Calcineurin-Nuclear Factors of Activated T Cell-Dependent Pathway,” The Journal of Immunology, Vol. 162, No. 4, 1999, pp. 1988-1993.

[210]   S. Suyuki, et al., “N-Acetylcysteine Improves Cytotoxic Activity of Cirrhotic Rat Liver-Associated Mononuclear Cells,” International Immunology, Vol. 10, No. 10, 1998, pp. 1501-8. doi:10.1093/intimm/10.10.1501

[211]   A. Yamauchi and E. T. Bloom, “Control of Cell Cycle Progression in Human Natural Killer Cells through Redox Regulation of Expression and Phosphorylation of Retinoblastoma Gene Product Protein,” Blood, Vol. 89, No. 11, 1997, pp. 4092-4099.

[212]   T. Chiba, et al., “Fas-Mediated Apoptosis Is Modulated by Intracellular Glutathione in Human T cells,” European Journal of Immunology, Vol. 26, No. 5, 1996, pp. 1164- 1169. doi:10.1002/eji.1830260530

[213]   W. Malorni, et al., “Thiol Supplier N-Acetylcysteine Enhances Conjugate Formation between Natural Killer Cells and K562 or U937 Targets but Increases the Lytic Function Only Against the Latter,” Immunology Letters, 1994, Vol. 43, No. 3, pp. 209-214. doi:10.1016/0165-2478, No. 94)90225-9

[214]   C. Y. Yim, et al., “Use of N-Acetyl Cysteine to Increase Intracellular Glutathione During the Induction of Antitumor Responses by IL-2,” The Journal of Immunology, Vol. 152, No. 12, 1994, pp. 5796-805.

[215]   A. Tsuji, et al., “Immune Stimulatory and Anti-Tumour Properties of Haemin,” Clinical & Experimental Immunology, Vol. 93, No. 3, 1993, pp. 308-312. doi:10.1111/j.1365-2249.1993.tb08177.x

[216]   V. Vetvicka and J. Vetvickova, “Combination of Glucan, Resveratrol and Vitamin C Demonstrates Strong Anti- Tumor Potential,” Anticancer Research, Vol. 32, No. 1, 2012, pp. 81-87.

[217]   H. Miki, et al., “Resveratrol Induces Apoptosis via Ros- Triggered Autophagy in Human Colon Cancer Cells,” International Journal of Oncology, Vol. 40, No. 4, 2012, pp. 1020-8.

[218]   R. Di Franco, et al., “Skin Toxicity from External Beam Radiation Therapy in Breast Cancer Patients: Protective Effects of Resveratrol, Lycopene, Vitamin C and Anthocianin (Ixor?),” Radiation Oncology, Vol. 7, 2012, pp. 12. doi:10.1186/1748-717X-7-12

[219]   J. H. Kim, C. Chen and A. N. Tony Kong, “Resveratrol Inhibits Genistein-Induced Multi-Drug Resistance Protein 2 (MRP2) Expression in HepG2 Cells,” Archives of Biochemistry and Biophysics, Vol. 512, No. 2, 2011, pp. 160-1666. doi:10.1016/j.abb.2011.06.004

[220]   Y. Hiroto, et al., “Resveratrol, a Phytoestrogen Found in Red Wine, Down-Regulates Protein S Expression in HepG2 Cells,” Thrombosis Research, Vol. 127, No. 1, 2011, pp. e1-e7. doi:10.1016/j.thromres.2010.09.010

[221]   B. Shao, et al., “Proteomics Analysis of Human Umbilical Vein Endothelial Cells Treated with Resveratrol,” Amino Acids, Vol. 43, No. 4, 2012, pp. 1671-1678. doi:10.1007/s00726-012-1248-4

[222]   I. Muqbil, et al., “Old Wine in a New Bottle: The Warburg Effect and Anticancer Mechanisms of Resveratrol. Current Pharmaceutical Design,” Vol. 18, No. 12, 2012, pp. 1645-1654. doi:10.2174/138161212799958567

[223]   E. Scott, et al., “Resveratrol in Human Cancer Chemoprevention—Choosing the ‘Right’ Dose,” Molecular Nutrition & Food Research,” Vol. 56, No. 1, 2012, pp. 7-13. doi:10.1002/mnfr.201100400

[224]   X. Xu, et al., “Resveratrol Attenuates Doxorubicin-Induced Cardiomyocyte Death via Inhibition of P70 S6 Kinase 1-Mediated Autophagy,” Journal of Pharmacol- ogy and Experimental Therapeutics, Vol. 341, No. 1, 2012, pp. 183-195. doi:10.1124/jpet.111.189589

[225]   W. Mo, et al., “Resveratrol Inhibits Proliferation and Induces Apoptosis through the Hedgehog Signaling Pathway in Pancreatic Cancer Cell,” Pancreatology, Vol. 11, No. 6, 2011, pp. 601-609. doi:10.1159/000333542

[226]   M. U. Nessa, et al., “Combinations of Resveratrol, Cisplatin and Oxaliplatin Applied to Human Ovarian Cancer Cells,” Anticancer Research, Vol. 32, No. 1, 2012, pp. 53-59.

[227]   J. Ryu, et al., “Resveratrol Reduces TNF-Alpha-Induced U373MG Human Glioma Cell Invasion through Regulating NF-KappaB Activation and uPA/uPAR Expression,” Anticancer Research, Vol. 31, No. 12, 2011, pp. 4223- 4230.

[228]   T. Erdem, et al., “The Effect of Resveratrol on the Prevention of Cisplatin Ototoxicity,” European Archives of Otorhinolaryngology, 2011.

[229]   C. C. Lu and J. K. Chen, “Resveratrol Enhances Perforin Expression and NK Cell Cytotoxicity through NKG2D- Dependent Pathways,” Journal of Cellular Physiology, Vol. 223, No. 2, 2010, pp. 343-351.

[230]   R. Falchetti, et al., “Effects of Resveratrol on Human Immune Cell Function,” Life Sciences, Vol. 70, No. 1, 2001, pp. 81-96. doi:10.1016/S0024-3205, No. 01)01367-4

[231]   Y. Fang, E. J. Herrick and M. B. Nicholl, “A Possible Role for Perforin and Granzyme B in Resveratrol Enhanced Radiosensitivity of Prostate Cancer,” Journal of Andrology, 2011.

[232]   C. Alvarado, et al., “Improvement of Leukocyte Functions in Young Prematurely Aging Mice after a 5-Week Ingestion of a Diet Supplemented with Biscuits Enriched in Antioxidants,” Antioxidants & Redox Signaling, Vol. 7, No. 9-10, 2005, pp. 1203-1210. doi:10.1089/ars.2005.7.1203

[233]   L. D. Koller, et al., “Immune Responses in Rats Supplemented with Selenium,” Clinical & Experimental Immunology, Vol. 63, No. 3, 1986, pp. 570-576.

[234]   M. Enqvist, et al., “Selenite Induces Posttranscriptional Blockade of HLA-E Expression and Sensitizes Tumor Cells to CD94/NKG2A-Positive NK Cells,” The Journal of Immunology, Vol. 187, No. 7, 2011, pp. 3546-3554. doi:10.4049/jimmunol.1100610

[235]   W. C. Hawkes, “A. Hwang, and Z. Alkan, The Effect of Selenium Supplementation on DTH Skin Responses in Healthy North American Men,” Journal of Trace Elements in Medicine & Biology, Vol. 23, No. 4, 2009, pp. 272-280. doi:10.1016/j.jtemb.2009.04.002

[236]   X. Chen, et al., “Effect of Excessive Iodine on Immune Function of Lymphocytes and Intervention with Selenium,” Journal of Huazhong University of Science and Technology-Medical Sciences, Vol. 27, No. 4, 2007, pp. 422-425. doi:10.1007/s11596-007-0418-1

[237]   M. F. McCarty and K. I. Block, “Toward a Core Nutraceutical Program for Cancer Management,” Integrative Cancer Therapies, Vol. 5, No. 2, 2006, pp. 150- 171. doi:10.1177/1534735406288443

[238]   C. Klein, et al., “From Food to Nutritional Support to Specific Nutraceuticals: A Journey across Time in the Treatment of Disease,” Journal of Gastroenterology, Vol. 35, No. Suppl. 12, 2000, pp. 1-6.

[239]   A. D. Smith, Y. I. Kim and H. Refsum, “Is Folic Acid Good for Everyone?” The American Journal of Clinical Nutrition, Vol. 87, No. 3, 2008, pp. 517-533.

[240]   M. A. Erkurt, et al., “Effects of Cyanocobalamin on Immunity in Patients with Pernicious Anemia,” Medical Principles and Practice, Vol. 17, No. 2, 2008, pp. 131- 135. doi:10.1159/000112967

[241]   J. Tamura, et al., “Immunomodulation by Vitamin B12: Augmentation of CD8+ T Lymphocytes and Natural Killer (NK) Cell Activity in Vitamin B12-Deficient Patients by Methyl-B12 Treatment,” Clinical & Experimental Im- munology, Vol. 116, No. 1, 1999, pp. 28-32. doi:10.1046/j.1365-2249.1999.00870.x

[242]   F. Brivio, et al., “Preoperative Interleukin-2 Subcutaneous Immunotherapy May Prolong the Survival Time in Advanced Colorectal Cancer Patients,” Oncology, Vol. 53, No. 4, 1996, pp. 263-268. doi:10.1159/000227571

[243]   P. H. Nichols, et al., “The Effect of 5-Fluorouracil and Alpha Interferon and 5-Fluorouracil and Leucovorin on Cellular Anti-Tumour Immune Responses in Patients with Advanced Colorectal Cancer,” British Journal of Cancer, Vol. 70, No. 5, 1994, pp. 946-949. doi:10.1038/bjc.1994.426

[244]   M. K. Baum, et al., “Association of Vitamin B6 Status with Parameters of Immune Function in Early HIV-1 Infection,” Journal of Acquired Immune Deficiency Syndromes, Vol. 4, No. 11, 1991, pp. 1122-1132.

[245]   C. Ha, L. T. Miller and N. I. Kerkvliet, “The Effect of Vitamin B6 Deficiency on Cytotoxic Immune Responses of T Cells, Antibodies, and Natural Killer Cells, and Phagocytosis by Macrophages,” Cellular Immunology, Vol. 85, No. 2, 1984, pp. 318-329. doi:10.1016/0008-8749, No. 84)90246-6

[246]   K. L. Erickson, E. A. Medina and N. E. Hubbard, “Micronutrients and Innate Immunity,” The Journal of Infectious Diseases, Vol. 182, No. Suppl. 1, 2000, pp. S5-S10. doi:10.1086/315922

[247]   B. Atasever, et al., “In Vitro Effects of Vitamin C and Selenium on NK Activity of Patients with Beta-Thalassemia Major,” Journal of Pediatric Hematology/On- cology, Vol. 23, No. 3, 2006, pp. 187-197. doi:10.1080/08880010500506420

[248]   M. De la Fuente, A. Hernanz and M. C. Vallejo, “The Immune System in the Oxidative Stress Conditions of Aging and Hypertension: Favorable Effects of Antioxidants and Physical Exercise,” Antioxidants & Redox Signaling, Vol. 7, No. 9-10, 2005, pp. 1356-1366. doi:10.1089/ars.2005.7.1356

[249]   G. Heuser and A. Vojdani, “Enhancement of Natural Killer Cell Activity and T and B Cell Function by Buffered Vitamin C in Patients Exposed to Toxic Chemicals: The Role of Protein Kinase-C,” Immunopharmacol and Immunotoxicol, Vol. 19, No. 3, 1997, pp. 291-312. doi:10.3109/08923979709046977

[250]   D. C. Nieman and B. K. Pedersen, “Exercise and Immune Function. Recent Developments,” Sports Medicine, Vol. 27, No. 2, 1999, pp. 73-80. doi:10.2165/00007256-199927020-00001

[251]   E. W. Petersen, et al., “Effect of Vitamin Supplementation on Cytokine Response and on Muscle Damage after Strenuous Exercise,” American Journal of Physiology— Cell Physiology, Vol. 280, No. 6, 2001, pp. C1570- C1575.

[252]   D. See, S. Mason and R. Roshan, “Increased Tumor Necrosis Factor Alpha (TNF-Alpha) and Natural Killer Cell (NK) Function Using an Integrative Approach in Late Stage Cancers,” Immunological Investigations, Vol. 31, No. 2, 2002, pp. 137-153. doi:10.1081/IMM-120004804

[253]   K. Suresh and D. M. Vasudevan, “Augmentation of Murine Natural Killer Cell and Antibody Dependent Cellular Cytotoxicity Activities by Phyllanthus Emblica, a New Immunomodulator,” Journal of Ethnopharmacology, Vol. 44, No. 1, 1994, pp. 55-60. doi:10.1016/0378-8741, No. 94)90099-X

[254]   I. K. Toliopoulos, et al., “Inhibition of Platelet Aggregation and Immunomodulation of NK Lymphocytes by Administration of Ascorbic Acid,” Indian Journal of Experimental Biology, Vol. 49, No. 12, 2011, pp. 904-908.

[255]   A. Vojdani, et al., “New Evidence for Antioxidant Properties of Vitamin C,” Cancer Detection and Prevention Journal, Vol. 24, No. 6, 2000, pp. 508-523.

[256]   E. S. Wintergerst, S. Maggini and D. H. Hornig, “Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions,” Annals of Nutrition and Metabolism, Vol. 50, No. 2, 2006, pp. 85-94. doi:10.1159/000090495

[257]   A. E. El-Shazly and P. P. Lefebvre, “Modulation of NK Cell Autocrine-Induced Eosinophil Chemotaxis by Interleukin-15 and Vitamin D3: A Possible NK-Eosinophil Crosstalk via IL-8 in the Pathophysiology of Allergic Rhinitis,” Mediators of Inflammation, Vol. 2011, 2011, Article ID: 373589.

[258]   K. N. Lee, et al., “VDUP1 Is Required for the Develop- ment of Natural Killer Cells,” Immunity, Vol. 22, No. 2, 2005, pp. 195-208. doi:10.1016/j.immuni.2004.12.012

[259]   J. H. Ooi, J. Chen, and M. T. Cantorna, “Vitamin D Regulation of Immune Function in the Gut: Why Do T Cells Have Vitamin D Receptors?” Molecular Aspects of Medicine, Vol. 33, No. 1, 2012, pp. 77-82. doi:10.1016/j.mam.2011.10.014

[260]   A. Rohner, et al., “Differentiation-Promoting Drugs Up- Regulate NKG2D Ligand Expression and Enhance the Susceptibility of Acute Myeloid Leukemia Cells to Natural Killer Cell-Mediated Lysis,” Leukemia Research, Vol. 31, No. 10, 2007, pp. 1393-1402. doi:10.1016/j.leukres.2007.02.020

[261]   X. Wang, N. M. Ponzio and G. PP. Studzinski, “Long-Term Exposure of HL60 Cells to 1,25-DihydroxyVitamin D3 Reduces Their Tumorigenicity: A Model for Cancer Chemoprevention,” Proceedings of the Society for Experimental Biology and Medicine, 1997, Vol. 215, No. 4, pp. 399-404.

[262]   S. Yu and M. T. Cantorna, “Epigenetic Reduction in Invariant NKT Cells Following in Utero Vitamin D Deficiency in Mice. The Journal of Immunology, Vol. 186, No. 3, 2011, pp. 1384-1390. doi:10.4049/jimmunol.1002545

[263]   S. R. Hafid, A. K. Radhakrishnan and K. Nesaretnam, “Tocotrienols Are Good Adjuvants for Developing Cancer Vaccines,” BMC Cancer, Vol. 10, 2010, p. 5. doi:10.1186/1471-2407-10-5

[264]   M. G. Hanson, et al., “A Short-Term Dietary Supplementation with High Doses of Vitamin E Increases NK Cell Cytolytic Activity in Advanced Colorectal Cancer Patients,” Cancer Immunology, Immunotherapy, Vol. 56, No. 7, 2007, pp. 973-984. doi:10.1007/s00262-006-0261-4

[265]   D. Bunout, et al., “Effects of a Nutritional Supplement on the Immune Response and Cytokine Production in Free- Living Chilean Elderly,” Journal of Parenteral and Enteral Nutrition, Vol. 28, No. 5, 2004, pp. 348-354. doi:10.1177/0148607104028005348

[266]   M. A. Beck, D. Williams-Toone and O. A. Levander, “Coxsackievirus B3-Resistant Mice Become Susceptible in Se/Vitamin E Deficiency,” Free Radical Biology & Medicine, Vol. 34, No. 10, 2003, pp. 1263-1270. doi:10.1016/S0891-5849, No. 03)00101-1

[267]   C. Y. Lee and J. M. Wan, “Immunoregulatory and Antioxidant Performance of Alpha-Tocopherol and Selenium on Human Lymphocytes,” Biological Trace Element Rese, Vol. 86, No. 2, 2002, pp. 123-136. doi:10.1385/BTER:86:2:123

[268]   W. J. Evans, “Vitamin E, Vitamin C, and Exercise,” The American Journal of Clinical Nutrition, Vol. 72, No. 2, 2000, pp. 647S-52S.

[269]   A. S. Prasad, et al., “Zinc in Cancer Prevention,” Nutrition and Cancer, Vol. 61, No. 6, 2009, pp. 879-887. doi:10.1080/01635580903285122

[270]   M. Stefanidou, et al., “Zinc: A Multipurpose Trace Element,” Archives of Toxicology, Vol. 80, No. 1, 2006, pp. 1-9. doi:10.1007/s00204-005-0009-5

[271]   C. Alvarado, et al., “Dietary Supplementation with Antioxidants Improves Functions and Decreases Oxidative Stress of Leukocytes from Prematurely Aging Mice,” Nutrition, Vol. 22, No. 7-8, 2006, pp. 767-777. doi:10.1016/j.nut.2006.05.007

[272]   Y. K. Jeon, et al., “Expression of the Promyelocytic Leukemia Zinc-Finger in T-Lymphoblastic Lymphoma and Leukemia Has Strong Implications for Their Cellular Origin and Greater Association with Initial Bone Marrow Involvement,” Modern Pathology Advance Online Publication, 2012. doi:10.1038/modpathol.2012.82

[273]   PP. Pereira and L. Boucontet, “Innate NKTγδ and NKTαβ Cells Exert Similar Functions and Compete for a Thymic Niche,” European Journal of Immunology, 2012, Vol. 42, No. 5, pp. 1272-1281. doi:10.1002/eji.201142109

[274]   A. Shimada and S. Hasegawa-Ishii, “Senescence-Accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence,” Aging and Disease, Vol. 2, No. 5, 2011, pp. 414-435.

[275]   J. Yamashita, et al., “Murine Schnurri-2 Controls Natural Killer Cell Function and Lymphoma Development,” Leukemia & Lymphoma, Vol. 53, No. 3, 2012, pp. 479- 486. doi:10.3109/10428194.2011.625099

[276]   S. Y. Thomas, et al., “PLZF Induces an Intravascular Surveillance Program Mediated by Long-Lived LFA-1- ICAM-1 Interactions,” The Journal of Experimental Medicine, Vol. 208, No. 6, 2011, pp. 1179-1188. doi:10.1084/jem.20102630

[277]   E. Mocchegiani, et al., “Zinc, Metallothioneins and Immunosenescence,” Proceedings of the Nutrition Society, Vol. 69, No. 3, 2010, pp. 290-299. doi:10.1017/S0029665110001862

[278]   Xu, D., et al., Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate Immunity,” Immunity, Vol. 30, No. 6, 2009, pp. 802-816. doi:10.1016/j.immuni.2009.04.013

[279]   E. Mocchegiani, et al., “NK and NKT Cells in Aging and Longevity: Role of Zinc and Metallothioneins,” Journal of Clinical Immunology, Vol. 29, No. 4, 2009, pp. 416- 425. doi:10.1007/s10875-009-9298-4

[280]   M. Muzzioli, et al., “Zinc Improves the Development of Human CD34+ Cell Progenitors towards Natural Killer Cells and Induces the Expression of GATA-3 Transcription Factor,” The International Journal of Biochemistry & Cell Biology, Vol. 39, No. 5, 2007, pp. 955-965. doi:10.1016/j.biocel.2007.01.011

[281]   G. Cocchi, et al., “Immunological Patterns in Young Children with Down syndrome: Is There a Temporal Trend?” Acta Paediatrica, Vol. 96, No. 10, 2007, pp. 1479-1482. doi:10.1111/j.1651-2227.2007.00459.x

[282]   E. Mariani, et al., “Effect of Zinc Supplementation on Plasma IL-6 and MCP-1 Production and NK Cell Function in Healthy Elderly: Interactive Influence of +647 MT1a and ?174 IL-6 Polymorphic Alleles,” Experimen- tal Gerontology, Vol. 43, No. 5, 2008, pp. 462-471. doi:10.1016/j.exger.2007.12.003

[283]   V. Brazao, et al., “Zinc Supplementation Increases Resistance to Experimental Infection by Trypanosoma Cruzi,” Veterinary Parasitology, Vol. 154, No. 1-2, 2008, pp. 32- 37. doi:10.1016/j.vetpar.2008.02.015

[284]   C. H. Metz, et al., “T-Helper Type 1 Cytokine Release Is Enhanced by in Vitro Zinc Supplementation Due to Increased Natural Killer Cells,” Nutrition, Vol. 23, No. 2, 2007, pp. 157-163. doi:10.1016/j.nut.2006.10.007

[285]   O. DelaRosa, et al., “Immunological Biomarkers of Aging in Man: Changes in both Innate and Adaptive Immunity Are Associated with Health and Longevity,” Bio- gerontology, Vol. 7, No. 5-6, 2006, pp. 471-481. doi:10.1007/s10522-006-9062-6

[286]   C. F. Hodkinson, et al., “Zinc Status and Age-Related Changes in Peripheral Blood Leukocyte Subpopulations in Healthy Men and Women Aged 55-70 Y: the ZENITH Study,” European Journal of Clinical Nutrition, Vol. 59, No. Suppl. 2, 2005, pp. S63-S67. doi:10.1038/sj.ejcn.1602301

 
 
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