Lactoferrin and cancer disease prevention

Critical Reviews in Food Science and Nutrition

Volumn 49, Issue 3, 2009, Pages 203-217

  Rodrigues, Lígia ^a   Teixeira, Jose ^a   Schmitt, Fernando ^b,c   Paulsson, Marie ^d   Månsson, Helena Lindmark ^d,e  

^a UNIVERSITY OF MINHO   (Portugal)

^b UNIVERSITY OF PORTO   (Portugal)

^c University of Porto   (Portugal)

^d LUND UNIVERSITY   (Sweden)

^e Swedish Dairy Association   (Sweden)

Author keywords

Cancer; Chemoprevention; Infection; Inflammation; Lactoferrin

Indexed keywords

ANTINEOPLASTIC AGENT; IRON; LACTOFERRIN;

ANIMAL; ARTICLE; BREAST MILK; CHEMISTRY; CHEMOPROPHYLAXIS; HOMEOSTASIS; HUMAN; METABOLISM; NEOPLASM; PHYSIOLOGY;

ANIMALS; ANTICARCINOGENIC AGENTS; CHEMOPREVENTION; HOMEOSTASIS; HUMANS; IRON; LACTOFERRIN; MILK, HUMAN; NEOPLASMS;

EID: 57749195333     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408390701856157     Document Type: Article

References (235)

1. Abe, H., Saito, H., Miyakawa, H., Tamura, Y., Shimamura, S., Nagao, E., and Tomita, M. (1991). Heat stability of bovine lactoferrin at acidic pH. J. Dairy Sci. 74:65-71.
2. Adamik, B., Zimecki, M., Wlaszczyk, A., Berezowicz, P., and Kubier, A. (1998). Lactoferrin effects on the in vitro immune response in critically ill patients. Arch. Immunol. Ther. Exp. (Warsz). 46:169-176.
3. Al-Mashikhi, S. A. and Nakai, S. (1987). Isolation of bovine immunoglobulins and lactoferrin from whey proteins by gel filtration technique. J. Dairy Sci. 70:2486-2492.
4. Al-Mashikhi, S. A., Li-Chan, E., and Nakai, S. (1988). Separation of immunoglobulins and lactoferrin from cheese whey by chelating chromatography J. Dairy Sci. 71:1747-1755.
5. Al-Nabulsi, A. A. and Holley, R. A. (2006). Enhancing the antimicrobial effects of bovine lactoferrin against Eschericia coli 0157:H7 by cation chelation, NaCl and temperature. J. Appl. Microbiol. 100:244-255.
6. Ammendollia, M. G., Pietrantoni, A., Tinari, A., Valenti, P., and Superti, F. (2007). Bovine lactoferrin inhibits echovirus endocytic pathway by interacting with viral structural polypeptides. Antiviral Res.13 (3): 151-160.
7. Andersen, J. H., Osbakk, S. A., Vorland, L. H., Traavik, T., and Gutteberg, T. J. (2001). Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts. Antiviral Res. 51:141-149.
8. Andersson, J. and Mattiasson, B. (2006). Separation of lactoperoxidase and lactoferrin from whey protein concentrate. J. Chromatogr. A 1107 (1-2):88-95.
9. Babina, S. E., Tuzikov, F. V., Tuzikova, N. A., Buneva, V. N., and Nevinskii, G. A. (2006). The effect of nucleotides on oligomeric state of human lactoferrin Mol. Biol. (Most) 40:137-149.
10. Baker, E. N. (1994). Structure and reactivity of transferrins. Adv. Inorg. Chem. 41:389-463.
11. Baker, E. N. and Baker, H. M. (2005). Molecular structure, binding properties and dynamics of lactoferrin. Cell. Mol. Life Sci. 62:2531-2539.
12. Baker, E. N., Baker, H. M., and Kidd, R. D. (2002). Lactoferrin and transferrin: Functional variations on a common structural framework. Biochem. Cell Biol. 80:27-34.
13. Baumrucker, C. R., Schanbacher, F., Shang, Y., and Green, M. H. (2006). Lactoferrin interaction with, retinoid signalling: cell growth and apoptosis in mammary cells. Dom. Animal End.30 (4):289-303.
14. Baveye, S., Elass, E., Mazurier, J., Spik, G., and Legrand, D. (1999). Lactoferrin: a multifunctional glycoprotein, involved in the modulation of the inflammatory process. Clin. Chem. Lab. Med. 37:281-286.
15. Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., Kawase, K., and Tomita, M. (1992). Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta 1121:130-136.
16. Benaissa, M., Peyrat, J. P., Hornez, L., Mariller, C., Mazurier, J., and Pierce, A. (2005). Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer. Int. J. Cancer 114:299-306.
17. Bennett, R. M. and Davis, J. (1981). Lactoferrin binding to human peripheral blood cells: an interaction with a B-enriched population of lymphocytes and a subpopulation of adherent mononuclear cells. J. Immunol. 127:1211-1216.
18. Berliner, N., Hsing, A., Graubert, T., Sigurdsson, F., Zain, M., Bruno, E., and Hoffman, R. (1995). Granulocyte colony-stimulating factor induction of normal human bone marrow progenitors results in neutrophil-specific gene expression. Blood 85:799-803.
19. Berlutti, F., Schippa, S., Morea, C., Sarli, S., Perfetto, B., Donnarumma, G., and Valenti, P. (2006). Lactoferrin downregulates pro-inflammatory cytokines upexpressed in intestinal epithelial cells infected with invasive or non-invasive Escherichia coli strains. Biocliem. Cell Biol. 84:351-357.
20. Bezault, J., Bhimani, R., Wiprovnick, J., and Furmanski, P. (1994). Human lactoferrin inhibits growth of solid tumors and development, of experimental metastases in mice. Cancer Res. 54:2310-2312.
21. Birgens, H. S., Karle, H., Hansen, N. E., and Ostergaard Kristensen, L. (1984). Lactoferrin receptors in normal and leukaemic human blood cells. Scand. J. Haematol. 33:275-280.
22. Birgens, H. S., Kristensen, L. O., Borregaard, N., Karle, H., and Hansen, N. E. (1988). Lactoferrin-mediated transfer of iron to intracellular ferritin in human monocytes. Eur. J. Haematol. 41:52-57.
23. Bowman, B. H., Yang, F. M., and Adrian, G. S. (1988). Transferrin: evolution and genetic regulation of expression. Adv. Genet. 25:1-38.
24. Breton, M., Mariller, C., Benaissa, M., Caillaux, K., Browaeys, E., Masson, M., Vilain, J.-F., Mazurier, J., and Pierce, A. (2004). Expression of deltalactoferrin induces cell cycle arrest. Biometals 17:325-329.
25. Brisson, G., Britten, M., and Pouliot, Y. (2007). Electrically-enhanced crossflow microflltration for separation of lactoferrin from whey protein mixtures. J. Membrane Sci. 297:206-216.
26. Britigan, B. E., Serody, J. S., and Cohen, M. S. (1994). The role of lactoferrin as an anti-inflammatory molecule. Adv. Exp. Med. Biol. 357:143-156.
27. Britigan, B. E., Lewis, T. S., Waldschmidt, M., McCormick, M. L., and Krieg, A. M. (2001). Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells. J. Immunol. 167:2921-2928.
28. Brock, J. H. (1980). Lactoferrin in human milk: its role in iron absorption and protection against enteric infection in the newborn infant. Arch. Dis. Child. 55:417-421.
29. Brock, J. H. (2002). The physiology of lactoferrin. Biochem. Cell Biol. 80:1-6.
30. Bullen, J. J., Rogers, H. J., Spalding, P. B., and Ward, C. G. (2006). Natural resistance, iron and infection :a challenge for clinical medicine. J. Med. Microbiol. 55:251-258.
31. Campbell, T., Skilton, R. A., Coombes, R. C., Shousha, S., Graham, M. D., and Luqmani, Y. A. (1992). Isolation of a lactoferrin cDNA clone and its expression in human, breast cancer. Br. J. Cancer 65:19-26.
32. Cao, R., Farnebo, J., Kurimoto, M., and Cao, Y. (1999). Interleukin-18 acts as an angiogenesis and tumor suppressor. FASEB J. 13:2195-2202.
33. Castellino, F. J., Fish, W. W., and Mann, K. G. (1970). Strutural studies on bovine lactoferrin. J. Biol. Chem. 245:4269-4275.
34. Chaufer, B., Rabiller-Baudry, M., Lucas, D., Michel, F., and Timmer, M. (2000). Selective extraction of lysozyme from a mixture with lactoferrin by ultrafiltration. Role of the physico-chemical environment, Lait 80:197-203.
35. Chen, J. P. and Wang, C. H. (1991). Microfiltration affinity purification of lactoferrin and immunoglobulins from cheese whey. J. Food Sci. 56:701-706.
36. Chilukuri, V. V. S., Marshall, A. D., Munro, P. A., and Singh, H. (2001). Effect, of sodium dodecyl sulphate and cross-flow velocity on membrane fouling during cross-flow microfiltration of lactoferrin solutions. Chem. Eng. Process 40:321-328.
37. Chiu, C. K. and Etzel, M. R. (1997). Fractionation of lactoperoxidase and lactoferrin from bovine whey using a cation exchange membrane. J. Food Sci. 62:996-1000.
38. Cho E, Smith-Warner S. A., Spiegelman D, Beeson, W. L., van den Brandt, P. A., Colditz, G. A., Folsom, A. R., Fraser, G. E., Freudenheim, J. L., Giovannucci, E., Goldbohm, R. A., Graham, S., Miller, A. B., Pietinen, P., Potter, J. D., Rohan, T. E., Terry, P., Toniolo, P., Virtanen, M. J., Willett, W. C., Wolk, A., Wu, K., Yaun, S. -S., Zeleniuch-Jacquotte, A., and Hunter, D. J. (2004). Dairy foods, calcium, and colorectal cancer: A pooled analysis of 10 cohort studies. J. Natl. Cancer Inst. 96:1015-1022.
39. Close, M. J., Howlett, A. R., Roskelley, C. D., Desprez, P. Y., Bailey, N., Rowning, B., Teng, C. T., Stampfer, M. R., and Yaswen, P. (1997). Lactoferrin expression in mammary epithelial cells is mediated by changes in cell, shape and actin cytoskeleton. J. Cell. Sci. 110:2861-2871.
40. Crouch, S. P., Slater, K. J., and Fletcher, J. (1992). Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 80:235-240.
41. Damiens, E., El Yazidi, I., Mazurier, J., Duthille, I., Spik, G., and Boilly-Marer, Y. (1999). Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human, breast carcinoma cells. J. Cell. Biochem. 74:486-498.
42. Damiens, E., Mazurier, J., El Yazidi, I., Masson, M., Duthille, I., Spik, G., and Boilly-Marer, Y. (1998). Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and epithelial tumour cells. Biochim. Biophys. Acta 1402:277-287.
43. Das, P., Tiwari, G., Rupa, P., and Garg, L. C. (1999). Molecular cloning and sequence analysis of bubaline lactoferrin promoter. DNA Seq. 10:97-99.
44. Das, S. K., Taylor, J. A., Korach, K. S., Paria, B. C., Dey, S. K., and Lubahn, D. B. (1997). Estrogenic responses in estrogen receptoralpha deficient mice reveal a distinct estrogen signalling pathway. Proc. Natl. Acad. Sci. U.S.A. 94:12786-12791.
45. Davis, C. and Milner, J. (2004). Frontiers in nutrigenomics, proteomics, metabolomics and cancer prevention. Mutat. Res. 551:51-64.
46. Desai, D., Faubion, W. A., and Sandborn, W. J. (2007). Biological activity markers in inflammatory bowel disease. Aliment. Pliarmacol. Ther. 25:247-255.
47. Dhennin-Duthille, I., Masson, M., Damiens, E., Fillebeen, C., Spik, G., and Mazurier, J. (2000). Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen activated protein kinase in the human lymphoblastic T Jurkat cell line. J. Cell. Biochem. 79:583-593.
48. Mario, F., Aragona, G., Dal Bo, N., Cavestro, G. M., Cavallaro, L., Iori, V., Comparato, G., Leandro, G., Pilotto, A., and Franze, A. (2003). Use of bovine lactoferrin forHelicobacter pylori eradication. Dig. Liver.Dis. 35:706-710.
49. Elagamy, E. I., Ruppanner, R., Ismail, A., Champagne, C. P., and Assaf, R. (1996). Purification and characterization of lactoferrin, lactoperoxidase, lysozyme and immunoglobulins from camel's milk. Int. Dairy J. 6:129-145.
50. Elliot, R. and Ong, T. (2002). Nutritional genomics. Br. Med. J. 324:1438-1442.
51. Elliott, R. L., Elliott, M. C., Wang, F., and Head, J. F. (1993). Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study. Ann. N. Y. Acad. Sci. 698:159-166.
52. Ellison, R. T. III. and Giehl, T. J. (1991). Killing of Gram-negative bacteria by lactoferrin and lysozyme. J. Clin. Invest. 88:1080-1091.
53. Faulk, W. P., Hsi, B. L., and Stevens, P. J. (1980). Transferrin and transferrin receptors in carcinoma of the breast. Lancet 2:390-392.
54. Fischer, R., Debbabi, H., Dubarry, M., Boyaka, P., and Tome, D. (2006). Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin. Biochem. Cell Biol. 84:303-311.
55. Forozan, F., Mahlamaki, E. H., Monni, O., Chen, Y., Veldman, R., Jiang, Y., Gooden, G. C., Ethier, S. P., Kallioniemi, A., and Kallioniemi, O.- (2000). Comparative genomic hybridization analysis of 38 breast cancer cell lines: A basis for interpreting complementary DNA microarray datai. Cancer Res. 60:4519-4525.
56. Frydecka, I., Zimecki, M., Bocko, D., Kosmaczewska, A., Teodorowska, R., Ciszak, L., Krazel, M., Wlodarska-Polinska, J., Kuliczkowski, K., and Kornafel, J. (2002). Lactoferrin-induced up-regulation of zeta chain expression in peripheral blood T lymphocytes from cervical cancer patients. Anticancer Res. 22:1897-1901.
57. Fujita, K., Matsuda, E., Sekine, K., Iigo, M., and Tsuda H. (2004a). Lactoferrin modifies apoptosis-related gene expression in the colon of the azoxymethanetreated rat. Cancer Lett. 213:21-29.
58. Fujita, K., Matsuda, E., Sekine, K., ligo, M., and Tsuda, H. (2004b). Lactoferrin enhances Fas expression, and apoptosis in the colon mucosa of azoxymethanetreated rats. Carcinogenesis 25:1961-1966.
59. Fujita, K., Ohnishi, T., Sekine, K., ligo, M., and Tsuda H. (2002). Downregulation of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx)induced CYP1A2 expression is associated with bovine lactoferrin inhibition of MeIQx-induced liver and colon carcinogenesis in rats. Jpn. J. Cancer Res. 93:616-625.
60. Furmanski, P., Li, Z. P., Fortuna, M. B., Swamy, C. V., and Das, M. R. (1989). Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. J. Exp. Med. 170:415-429.
61. Geng, K., Li, Y., Bezault, J., and Furmanski, P. (1998). Induction of lactoferrin expression in murine ES cells by retinoic acid and estrogen. Exp. Cell Res. 245:214-220.
62. Ghio, A. J., Zhang, J., and Piantadosi, C. A. (1992). Generation of hydroxyl radical, by crocidolite asbestos is proportional to surface [Fe3+]. Arch. Biochem. Biophys. 298:646-650.
63. Giancotti, V. (2006). Breast cancer markers. Cancer Lett. 243:145-159.
64. Giansanti, F., Rossi, P., Massucci, M. T., Botti, D., Antonini, G., Valenti, P., and Seganti, L. (2002). Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activites of lactoferrin. Biochem. Cell Biol. 80:125-130.
65. Gill, H. S. and Cross, M. L. (2000). Anticancer properties of bovine milk. Br. J. Nutr. 84:S161-S166.
66. Giuffre, G., Arena, F., Scarfl, R., Simone, A., Todaro, P., and Tuccari, G. (2006). Lactoferrin immunoexpression in endometrial carcinomas: relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival. Oncology Rep. 16:257-263.
67. Goodman, S. A. and Young, L. G. (1981). Immunological identification of lactoferrin as a shared antigen on radioiodinated human sperm surface and in radioiodinated human seminal plasma. J. Reprod. Immunol. 3:99-108.
68. Goretzki, L. and Mueller, B. M. (1998). Low-density-lipoprotein receptor-related protein (LRP) interacts with a GTP-binding protein. Biochem. J. 336:381-386.
69. Grant, D. J., Shi, H., and Teng, C. T. (1999). Tissue and site-specific methylation correlates with expression of the mouse lactoferrin gene. J. Mol. Endocrinol. 23:45-55.
70. Green, M. R. and Pastewka, J. V. (1978). Lactoferrin is a marker for prolactin response in. mouse mammary expiants. Endocrinology 103:151-103.
71. Groves, M. L. (1960). The isolation of a red protein from milk. J. Am. Chem. Soc. 82:3345-3350.
72. Hangoc, G., Falkenburg, J. H. F., and Broxmeyer, H. E. (1991). Influence of T-lymphocytes and lactoferrin on. the survival-promoting effects of IL-1 and IL6 on human bone marrow granulocyte-macrophage and erythroid progenitor cells. Exp. Hematol. 19:697-703.
73. Hekman, A. and Rumke, P. (1969). The antigens of human seminal plasma with special reference to lactoferrin as a spermatozoacoating antigen. Fertil. Steril. 20:312-323.
74. Hirata, I., Hoshimoto, M., Saito, O., Kayazawa, M., Nishikawa, T., Murano, M., Toshina, K., Wang, F.-Y., and Matsuse, R. (2007). Usefulness of faecal lactoferrin and haemoglobin in diagnosis of colorectal diseases. World J. Gastroenterol. 13(10):1569-1574.
75. Horwitz, D. A., Bakke, A. C., Abo, W., and Nishiya, K. (1984). Monocyte and NK cell cytotoxic activity in human adherent cell preparations: discriminating effects of interferon and lactoferrin. J. Immunol. 132:2370-2374.
76. Hu, W. L., Regoeczi, E., Chindemi, P. A., and Bolyos, M. (1993). Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver. Am. J. Physiol. 264:112-117.
77. Hutchens, T. W., Henry, J. F., Yip, T. T., Hachey, D. L., Schanler, R. J., Motil, K. J., and Garza, C. (1991). Origin of intact lactoferrin and its DNA binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. Pediatr. Res. 29:243-250.
78. Iigo, M., Kuhara, T., Uchida, Y., Sekine, K., Moore, M. A., and Tsuda, H. (1999). Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. Clin. Exp. Metastasis 17:35-40.
79. ligo, M., Shimamura, M., Matsuda, E., Fujita, K., Nomoto, H., Satoh, J., Kojima, S, Alexander, D. B., Moore, M. A., and Tsuda, H. (2004). Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis. Cytokine25:36-44.
80. Ikeda, M., Nozaki, A., Sugiyama, K., Tanaka, T., Naganuma, A., Tanaka, K., Sekihara, H., Shimotohno, K., Saito, M., and Kato, N. (2000). Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells. Virus Res. 66:51-63.
81. Ismail, M. and Brock, J. H. (1993). Binding of lactoferrin and transferrin to the human, promonocytic cell line U937. J. Biol. Chem. 268:21618-21625.
82. Iwasa, M., Kaito, M., Ikoma, J., Takeo, M., Imoto, I., Adachi, Y., Yamauchi, K., Koizum, R., and Teraguchi, S. (2002). Lactoferrin inhibits hepatitis C virus viremia in chronic hepatitis C patients with high viral, loads and HGV genotype 1b. Am. J. Gastroenterol. 97:766-767.
83. Iyer, S. and Lonnerdal, B. (1993). Lactoferrin, lactoferrin receptors and iron metabolism. Eur. J. Clin. Nutr. 47:232-241.
84. Johanson, B. (1960). Isolation of an iron-containing red protein from human milk. Acta Chem. Scand. 14:510-512.
85. Johansson, B. G. (1969). Isolation of crystalline lactoferrin from human milk. Acta Chem. Scand. 23:683-684.
86. Jordan, V. C. and Morrow, M. (1999). Tamoxifen, raloxifene and the prevention of breast cancer. Eridocr. Rev. 20:253-278.
87. Kahler, S., Christophers, E., and Schroder, J. M. (1988). Plasma lactoferrin reflects neutrophil activation in psoriasis. Br. J. Dermatol. 119:289-293.
88. Katsuaki, T. (2006). Functionalities and usefulness of lactoferrins (2) Clinical application of lactoferrin for the treatment of chronic hepatitis C Foods & Food Ingred. J. Jpn. 211(9):748-753.
89. Kawakami, A., Hirayama, K., Kawakami, F., Kawakami, H., Fujihara, M., and Ohtsuki, K. (2006). Purification and biochemical characterization of fibroblast growth factor-binding protein (FGF-BP) from the lactoferrin fraction of bovine milk. Biochim. Biophys. Acta 1760:421-431.
90. Kawakami, H., Dosako, S., and Nakajima.I. (1993). Effect of lactoferrin on iron solubility under neutral conditions. Biochemistry 57:1376-1377.
91. Kawakami, H., Shinmoto, H., Dosako, S., and Sogo, Y. (1987). One-step isolation of lactoferrin using immobilized monoclonal antibodies. J. Dairy Sci. 70:752-759.
92. Khanna-Gupta, A., Zibello, T., Simkevich, C., Rosmarin, A. G., and Berliner, N. (2000). Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation. Blood 95:3734-3741.
93. Kim, C. W., Son, K.-N., Choi, S.-Y., and Kim, J. (2006). Human lactoferrin upregulates expression, of KDR/Flk-1 and stimulates VEGF-A-mediated endothelial cell proliferation and migration. FEBS Lett. 580:4332-4336.
94. Kim, S. J., Yu, D. Y., Pak, K. W., Jeong, S., Kim, S. W., and Lee, K. K. (1998). Structure of the human lactoferrin gene and its chromosomal localization. Mol. Cells 8:663-668.
95. Klintworth, G. K., Sommer, J. R., Obrian, G., Han, L., Ahmed, M. N., Qumsiyeh, M. B., Lin, P. Y., Basti, S., Reddy, M. K., Kanai, A., Hotta, Y., Sugar, J., Kumaramanickavel, G., Munier, F., Schorderet, D. F., Matri, L. E., Iwata, F., Kaiser-Kupfer, M., Nagata, M., Nakayasu, K., Hejtmancik, J. F., and Teng, C. T. (1997). Familial subepithelial corneal amyloidosis (gelationous droplike corneal dystrophy): exclusion of linkage to lactoferrin gene. Mol. Vis. 38:31-38.
96. Konishi, M., Iwasa, M., Yamauchi, K., Sugimoto, R., Fujita, N., Kobayashi, Y., Watanabe, S., Teraguchi, S., Adachi, Y., and Kaito, M. (2006). Lactoferrin inhibits lipid peroxidation in patients with chronic hepatitis C Hepatology Res. 36(1):27-32.
97. Krazel, M. L., Bacsi, A., Choudhury, B., Sur, S., and Boldogh, I. (2006). Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology .119:159-166.
98. Kuhara, T., ligo, M., Itoh, T., Ushida, Y., Sekine, K., Terada, N., Okamura, H., and Tsuda, H. (2000). Orally administered lactoferrin exerts an anti metastaticeffect and enhances production of IL-18 in. the intestinal epithelium. Nutr. Cancer 38:192-199.
99. Kuhara, T., Yamauchi, K., Tamura, Y., and Okamura, H. (2006). Oral administration of lactoferrin increases NK cell activity in mice via increased production of IL-18 and type I IFN in the small intestine. J. Interferon Cytokine Res. 26 (7):489-499.
100. Kuwata, H., Yamauchi, K., Teraguchi, S., Ushida, Y., Shimokawa, Y., Toida, T., and Hayasawa, H. (2001). Functional fragments of ingested lactoferrin are resistant to proteolytic degradation in the gastrointestinal tract of adult rats. J. Nutr. 131:2121-2127.
101. Kuwata, H., Yip, T. T., Tomita, M., and Hutchens, T. W. (1998a). Direct, evidence of the generation inhuman stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin. Biochim. Biophys. Acta 1429:129-141.
102. Kuwata, H., Yip, T. T., Yamauchi, K., Teraguchi, S., Hayasawa, H., Tomita, M., and Hutchens, T. W. (1998b). The survival of ingested lactoferrin in the gastrointestinal tract of adult mice. Biochem. J. 334:321-323.
103. Lampreave, F., Pineiro, A., Brock, J. H., Castillo, H., Sanchez, L., and Calvo, M. (1990). Interaction of bovine lactoferrin with other proteins of milk whey. Int. J. Biol. Macromol. 12:2-5.
104. Larkins, N. (2005). Potential implications of lactoferrin as a therapeutic agent. Am. J. Vet. Res. 66:739-742.
105. Law, B. A. and Reiter, B. (1977). The isolation and bacteriostatic properties of lactoferrin from bovine milk whey.J. Dairy Res. 44:595-561.
106. Lee, H. Y., Park, J. H., Seok, S. H., Back, M. W., Kim, D. J., Lee, B. H., Kang, P. D., Kim, Y. S., and Park, J. H. (2005). Potential antimicrobial effects of human lactoferrin against oral infection with Listeria monocytogenes in mice. J. Med. Microbiol. 54:1049-1054.
107. Legrand, D., Elass, E., Carpentier, M., and Mazurier, J. (2005). Lactoferrin: a modulator of immune and inflammatory responses. Cell Mol. Life Sci. 62:2549-2559.
108. Legrand, D., Elass, E., Pierce, A., and Mazurier, J. (2004). Lactoferrin and host defence: an overview of its immuno-modulating and anti-inflammatory properties. Biometals 17:225-229.
109. Levay, P. F. and Viljoen, M. (1995). Lactoferrin: a general review. Haematologica 80:252-267.
110. Liehr, J. G. and Jones, J. S. (2001). Role of iron in estrogen-induced cancer. Curr. Med. Chem. 8:839-849.
111. Longhi, G., Pietropaolo, V., Mischitelli, M., Longhi, C., Conte, M. P., Marchetti, M., Tinari, A., Valenti, P., Degener, A. M., Seganti, L., and Superti, F. (2006). Lactoferrin inhibits early steps of human BK Polyomavirus infection. Antiviral Res.72(2):l45-152.
112. Lönnerdal, B. (2003). Lactoferrin. In Advanced Dairy Chemistry, Vol I: Proteins. Eds. P. F. Pox and P. L. H. McSweeney. Kluwer Academic/Plenum Publishers, Norwell, MA, pp 449-466.
113. Lönnerdal, B. and Iyer, S. (1995). Lactoferrin: molecular structure and biological function. Annu. Rev. Nutr. 15:93-110.
114. Lu, R. R., Xu, S. Y., Wang, Z., and Yang, R. J. (2007). Isolation of lactoferrin from bovine colostrum by ultrafiltration coupled with strong cation exchange chromatography on a production, scale. J. Membrane Sci. 297:152-161.
115. Lund, L. G. and Aust, A. E. (1990). Iron mobilization from asbestos by chelators and ascorbic acid. Arch. Biochem. Biophys. 278:61-64.
116. Machnicki, M., Zimecki, M., and Zagulski, T. (1993). Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. Int. J. Exp. Pathol. 74:433-439.
117. Maher, R. J., Cao, D., Boxer, L. A., and Petty, H. R. (1993). Simultaneous calcium dependent delivery of neutrophil lactoferrin and reactive oxygen metabolites to erythrocyte targets: evidence supporting granule-dependent triggering of superoxide deposition. Am. J. Physiol., Cell Physiol. 156:226-234.
118. Mann, D. M., Romm, E., and Migliorini, M. (1994). Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin. J. Biol. Chem. 269:2366-23667.
119. Masuda, C., Wanibuchi, H., Sekine, K., Yano, Y., Otani, S., Kishimoto, T., Tsuda, H., and Fukushima, S. (2000). Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder carcinogenesis. Jpn. J. Cancer Res. 91:582-588.
120. Matsuda, Y., Saoo, K., Hosokawa, K., Yamakawa, K., Yokohira, M., Zeng, Y., Takeuchi, H., and Imaida, K. (2006). Post-initiation chemopreventive effects of dietary bovine lactoferrin on 4-(methylnitrosamino)-1-(3-pyridyl)1-butanone- induced lung tumorigenesis in female A/J mice. Cancer Lett. 246:41-46.
121. Matsue, M., Tomita, S., Nyui, S., Matayuma, J., and Kiyosawa, I. (1994). Suppressive effects of lactoferrin on bleomycin-dependent DNA damage by the iron ion and ascorbate. Biosci. Biotechnol. Biochem. 58:67-71.
122. Mcintosh, G. H. (1993). Colon cancer: dietary modification required for a balanced protective diet. Prev. Med.22:767-774.
123. McKeown, S. T., Lundy, F. T., Nelson, J., Lockhart, D., Irwin, C. R., Cowan, C. G., Marley, J. J. (2006). The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro. Oral Oncology 42(7):685-690.
124. Mehra, R. K., and Donnelly, W. J. (1993). Fractionation of whey-protein components through a large pore-size, hydrophilic, cellulosic membrane. J. Dairy Res. 60:89-97.
125. Metz-Boutigue, M. -H., Jolies, J., Mazurier, J., Schoentgen, F., Legrand, D., Spik, G., Montreuil, J., and Jolies, P. (1984). Human lactotransferrin: Amino acid sequence and structural comparisons with other transferrins. Eur. J. Biochem. 145:659-676.
126. Mikogami, T., Marianne, T., and Spik, G. (1995). Effect of intracellular iron depletion by picolinic acid on expression of the lactoferrin receptor in the human colon carcinoma subclone HT29-18-C1. Biochem. J. 308:391-397.
127. Min, S. and Krochta, J. (2005). Inhibition of Penicillium commune by edible whey protein films incorporating lactoferrin, lactoferrin hydrolysate, and lactoperoxidase systems. J. Food Sci. 70:87-94.
128. Mistry, N., Drobni, P., Naslund, J., Sunkari, V. G., Jenssen, H., and Evander, M. (2007). The anti-papillomavirus activity of human and bovine lactoferricin. Antiviral Res. 75:258-265.
129. Miyamoto, K., Fukutomi, T., Akashi-Tanaka, S., Hasegawa, T., Asahara, T., Sugimura, T., and Ushijima, T. (2005). Identification of 20 genes aberrantly methylated in human breast cancer. Int. J. Cancer 116:407-414.
130. Miyazawa.K., Mantel, C., Lu, L., Morrison, D. C., and Broxmeyer.H. E. (1991). Lactoferrin lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage differentiated HL-60 cells. J. Immunol 146:723-729.
131. Mohan, K. V., Devaraj, H., Prathiba, D., Hara, Y., and Nagini, S. (2006a). Antiproliferative and apoptosis inducing effect of lactoferrin and black tea polyphenol combination on hamster buccal pouch carcinogenesis. Biochim. Biophys. Acta 1760(10):1536-1544.
132. Mohan, K. V., Kumaraguruparan, R., Prathiba, D., and Nagini S. (2006b). Modulation of xenobiotic-metabolizing enzymes and redox status during chemoprevention of hamster buccal carcinogenesis by bovine lactctferrin. Nutrition 22:940-946.
133. Montreuil, J., Tonnelat, J., and Mullet, S. (1960). Preparation and properties of lactotransferrin of human milk. Biochim. Biophys. Acta 45:413-421.
134. Moore, S. A., Anderson, B. F., Groom, C. R., Haridas, M., and Baker, E. N. (1997). Three-dimensional structure of diferric bovine lactoferrin at 2-8 A resolution. J. Mol. Biol. 274:222-236.
135. Naidu, A. (2002). Activated lactoferrin - a new approach to meat safety. Food Technol. 56:40-45.
136. Nemet, K. and Simonovits, I. (1985). The biological role of lactoferrin. Haematologia 18:3-12.
137. Noppe, W., Plieva, F. M., Galaev, I. Y., Vanhoorelbeke, K., Mattiasson, B., and Deckmyn, H. (2006). Purification of lactoferrin from deffated milk. J. Chromatogr. A 1101 (1-2):79-85.
138. Norrby, K. (2004). Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. J. Vasc. Res. 41:293-304.
139. Norrby, K., Mattsby-Baltzer, I., Innocenti, M., and Tuneberg, S. (2001). Orally administrated bovine lactoferrin systematically inhibits VEGE165-mediated angiogenesis in the rat. Int. J. Cancer 91:236-240.
140. Nuijens, J. H., van Berkel, P. H., and Schanbacher, F. L. (1996). Structure and biological actions of lactoferrin. J. Mammary Gland Biol. Neoplasia 1:285-295.
141. Okada, S., Tanaka, K., Sato, T., Ueno, H., Saito, S. Okusaka, T., Sato, K. Yamamoto, S., and Kakizoe, T. (2002). Dose-response trial of lactoferrin in patients with chronic hepatitis C. Jpn. J. Cancer Res. 93:1063-1069.
142. Olofsson, T., Olsson, I., and Venge, P. (1977). Myeloperoxidase and lactoferrin of blood neutrophils and plasma in chronic granulocytic leukaemia. Scand. J. Haematol. 18:113-120.
143. Olsson, I., Lantz, M., Persson, A. M., and Arnljots, K. (1988). Biosynthesis and processing of lactoferrin in bone marrow cells, a comparison with processing of myeloperoxidase. Blood 71:441-447.
144. Pan, Y., Lee, A., Wan, J., Coventry, M. J., Michalski, W. P, Shiell, B., and Roginski, H. (2006). Antiviral properties of milkproteins and their derivatives. Int. Dairy J. 16:1252-1261.
145. Pan, Y., Rowney, M., Guo, P., and Hobman, P. (2007). Biological, properties of lactoferrin: an overview. Aust. J. Dairy Techn. 62 (1):31-42.
146. PanellaT. J., Liu Y. H., Huang A. T., and Teng C. T. (1991). Polymorphism and altered methylation of the lactoferrin gene in normal leukocytes, leukemic cells and breast cancer. Cancer Res. 51:3037-3043.
147. Penco, S., Caligo, M. A., Cipollini, G., Bevilacqua, G., and Garre C. (1999). Lactoferrin expression in human breast cancer. Cancer Biochem. Biophys. 17:163-178.
148. Pentecost, B. T. and Teng, C. T. (1987). Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions. J. Biol. Chem. 262:10134-10139.
149. Perou, C. M., Jeffrey, S. S., van de Rijn, M., Rees, C. A., Eisen, M. B., Ross, D. T., Pergamenschikov, A., Williams, C. F., Zhu, S. X., Lee, J. C., Lashkari, D., Shalon, D., Brown, P. O., and Botstein, D. (1999). Distinctive gene expression patterns in. human mammary epithelial cells and breast cancer. Proc. Natl. Acad. Sci. U.S.A. 96:9212-9217.
150. Peterson, N. A., Anderson, B. F., Jameson, G. B., Tweedie, J. W., and Baker, E. N. (2000). Crystal structure and iron-binding properties of the R210K mutant of the N-lobe of human, lactoferrin: implications for iron release from transferrins. Biocliemistry 39:6625-6633.
151. Petricoin, E. and Liotta, L. (2003). Clinical applications of proteomics. J. Nutr: 133:2476-2484.
152. Pierce, A., Colavizza, D., Benaissa, M., Maes, P., Tartar, A., Montreuil, J., and Spik, G. (1991). Molecular cloning and sequence analysis of bovine lactotransferrin. Eur. J. Biochem. 196:177-184.
153. Plate, K., Beutel, S., Buchholtz, H., Demmer, W., Fischer-Frahholz, S., Reif, O., Ulber, R., and Scheper, T. (2006). Isolation of bovine lactoferrin, lactoperoxidase and enzymatically prepared lactoferricin from proteolytic digestion of bovine lactoferrin using adsorptive membrane chromatography. J. Chromatogr. A 1117:81-86.
154. Qiu, J., Hendrixson, D. R., Baker, E. N., Murphy, T. F., St Geme, J. W., III and Plaut, A. G. (1998). Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae. Proc. Natl. Acad. Sci. USA. 95:12641-12646.
155. Querinjean, P., Masson, P. L., and Heremans, J. F. (1971). Molecular weight, single-chain structure and amino acid composition of human lactoferrin. Eur. J. Biochem. 20:420-425.
156. Rabiller-Baudry, M., Chaufer, B., Lucas, D., and Michel, F. (2001). Ultrafiltra-tion of mixed protein solutions of lysozyme and lactoferrin: role of modified inorganic membranes and ionic strength on the selectivity. J. Membr. Sci. 184:137-148.
157. Reddy,P. (2004). Interleukin-18: recent advances. Curr. Opin.Hematol. 11:405-410.
158. Roberts, A. K., Chierici, R., Sawatzki, G., Hill, M. J., Volpato, S., and Vigi, V. (1992). Supplementation of an adapted formula with bovine lactoferrin: 1. Effect on the infant faecal flora. Acta Paediatr. 81:119-124.
159. Rochard, E., Legrand, D., Mazurier, J., Montreuil, J., and Spik, G. (1989). The N-terminal domain I of human lactoferrin binds specifically to phylohemagglutinin-stimulated peripheral blood human lymphocyte recep-tor. FEBS Lett. 255:201-207.
160. Rossiello, R., Carriero, M. V., and Giordano, G. G. (1984). Distribution of ferritin, transferring and lactoferrin in breast cancer carcinoma tissue. J. Clin Pathol. 37:51-55.
161. Saito, H., Miyakawa, H., Tamura, Y., Shimamura, S., and Tomita, M. (1991). Potent bactericidal activity of bovine lactoferrin hydrolysate produced by heat treatment at acidic pH. J. Dairy Sci. 74:3724-3730.
162. Sakai, T., Banno, Y., Kato, Y., Nozawa, Y., and Kawaguchi, M. (2006). Pepsindigested bovine lactoferrin induces apoptotic cell death with JNK/SAPK activation in. oral cancer cells. J. Pharmacol. Sci. 98:41-48.
163. Saleh, Z. S. and Hossain, M. M. (2001). A study of the separation of proteins from multi-component mixtures by a semi-batch foaming process. Chem. Eng. Process 40:371-378.
164. Sanchez, L., Calvo, M., and Brock, J. H. (1992). Biological role of lactoferrin. Arch. Dis. Child. 67:657-661.
165. Santagati, M. G., La Terra Mulle, S., Amico, C., Pistone, M., Rusciano, D., and Enea, V. (2005). Lactoferrin expression by bovine ocullar surface epithelia: a primary cell culture model to study lactoferrin gene promoter activity. Ophthalmic Res. 37:270-278.
166. Sekine, K., Ushida, Y., Kuhara, T., ligo, M., Baba-Toriyama, H., Moore, M. A., Murakoshi, M., Satomi, Y., Nishino, H., Kakizoe, T., and Tsuda, H.
167. Sekine, K., Watanabe, E., Nakamura, J., Takasuka, N., Kim, D. J., Asamoto, M., Vladimir, K., Baba-Toriyama, H., Ohta, T., Moore, M. A., Masuda, M., Sugimoto, H., Nishino, H., Kakizoe, T., and Tsuda, H. (1997a). Inhibition of azoxymethane initiated colon tumour by bovine lactoferrin administration in F344 rats. Jpn. J. Cancer Res. 88:523-526.
168. Selby, J. V. and Friedman, G. D. (1988). Epidemiologic evidence of an association between, body iron stores and risk of cancer. Int. J. Cancer 41:677-682.
169. Senkovich, O., Cook, W. J., Mirza, S., Hollingshead, S. K., Protasevich, I. I., Brilles, D. E., and Chattopadhyay, D. (2007). Structure of a complex human lactoferrin. N-lobe with pneumococcal surface protein A provides insight into microbial defense mechanism. J. Mol. Biol. 370 (4):701-713.
170. Shah, N. P. (2000). Effects of milk-derived bioactives: an overview. Br. J. Nutr. 84:S3-S10.
171. Shan, L., He, M., Yu, M., and Qiu, C. (2002). cDNA microarray profiling of rat mammary gland carcinomas induced by 2-amino-1-methyl6-phenylimidazo[4,5- b]pyridine and 7,.12-dimethylbenz[a]anthracene. Carcinogenesis 23:1561-1568.
172. Shau, H., Kim, A., and Golub, S. H. (1992). Modulation of natural killer and lymphokine-activated killer cell cytotoxicity by lactoferrin. J. Leukoc. Biol. 51:343-349.
173. Shigeta, H., Newbold, R. R., McLachlan, J. A., and Teng, C. (1996). Estrogenic effect on the expression of estrogen receptor, COUPTF, and lactoferrin mRNA in developing mouse tissues. Mol. Reprod. Dev. 45:21-30.
174. Shimamura, M., Yamamoto, Y., Ashino, H., Oikawa, T., Hazato, T., Tsuda, H., and ligo, M. (2004). Bovine lactoferrin inhibits tumor induced angiogenesis. Int.J.Cancer 111:111-116.
175. Shimazaki, K. (2000). Lactoferrin: A marvellous protein in milk? Animal Sci. J. 71:329-347.
176. Shimazaki, K.-I. and Nishio, N. (1991). Interacting properties of bovine lactoferrin with immobilised cibacron blue Bga in column chromatography. J. Dairy Sci. 74:404-408.
177. Siciliano, R., Rega, B., Marchetti, M., Seganti, L., Antonini, G., and Valenti, P. (1999). Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection. Biochem. Biophys. Res. Commun. 264:19-23.
178. Siebert, P. D. and Huang, B. C. (1997). Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. Proc. Natl. Acad. Sci. U.S.A. 94:2198-2203.
179. Slater, K. and Fletcher, J. (1987). Lactoferrin derived from neutrophils inhibits the mixed lymphocyte reaction. Blood 69:1328-1333.
180. Spik, G., Coddeville, B., Mazurier, J., Bourne, Y., Cambillaut, C., and Montreuil, J. (1994). Primary and three-dimensional structure of lactotransferrin (lactoferrin) glycans. Adv. Exp. Med. Biol. 357:21-32.
181. Steijns, J. and van Hooijdonk, A. (2000). Occurrence, structure, biochemical properties technological characteristics of lactoferrin. Br. J. Nutr. 84:S 11-S17.
182. Stevens, R. G., Jones, D. Y., Micozzi, M. S., and Taylor, P. R. (1988). Body iron stores and the risk of cancer. N. Engl. J. Med. 319:1047-1052.
183. Suzuki, Y. and Lonnerdal, B. (2002). Characterization of mammalian receptors for lactoferrin. Biochem. Cell Biol. 80:75-80.
184. Tamura, Y. (2004). Production and application of bovine lactoferrin. Bulletin. IDF. 389:64-68.
185. Tanaka, K., Ikeda, M., Nozaki, A., Kato, N., Tsuda, H., Saito, S., and Sekihara, H. (1999). Lactoferrin inhibits hepatitis C virus viremia in patients with chronic hepatitis C: A pilot study. Jpn. J. Cancer Res. 90:367-371.
186. Tanaka, T., Kawabata, K., Kohno, H., Honjo, S., Murakami, M., Ota, T., and Tsuda, H. (2000). Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Jpn. J. Cancer Res. 91:25-33.
187. Teng, C. (2002). Lactoferrin gene expression and regulation: an overview. Biochem. Cell Biol. 80:7-16.
188. Teng, C., Gladwell, W., Raphiou, I., and Liu, E. (2004). Methylation and expression of the lactoferrin gene in human tissues and cancer cells. Biometals 17:317-323.
189. Teng, C. T. (2006). Factors regulating lactoferrin gene expression. Biochem. Cell Biol.84:263-267.
190. Teng, C. T., Gladwell, W., Raphiou, I., and Liu, E. (2004). Methylation and expression of the lactoferrin gene in human tissues and cancer cells. Biometals 17:317-323.
191. Teng, C. T., Pentecost, B. T., Chen, Y. H., Newbold, R. R., Eddy, E. M., and McLachlan, J. A. (1989). Lactotransferrin gene expression in the mouse uterus and mammary gland. Endocrinology 124:992-999.
192. Teng, C. T., Pentecost, B. T., Marshall, A., Solomon, A., Bowman, B. H., Lalley, P. A., and Naylor, S. L. (1987). Assignment of the lactotransferrin gene to human chromosome 3 and to mouse chromosome 9. Somat. Cell Mol. Genet. 13:689-693.
193. Teng, C. T., Walker, M. P., Bhattacharyya, S. N., Klapper, D. G., DiAugustine, R. P., and McLachlan, J. A. (1986). Purification and properties of an oestrogen-stimulated mouse uterine glycoprotein (approx. 70 kDa). Biochem. J. 240:413-422.
194. Teraguchi, S., Wakabayashi, H., Kuwata, H., Yamauchi, K., and Tamura, Y. (2004). Protection against infections by oral lactoferrin: evaluation in animal models. Biometals 17:231-234.
195. Teraguchi, S., Wakabayashi, H., Kuwata, H., Yamauchi, K., and Tamura, Y. (2004). Protection against infections by oral lactoferrin: evaluation in animal models. Biometals 17:231-234.
196. Tomita, M., Wakabayashi, H., Yamauchi, K., Teraguchi, S., and Hayasawa, H. (2002). Bovine lactoferrin and lactoferricin derived from milk: production and applications. Biochem. Cell Biol. 80:109-112.
197. Tomita, M., Wakabayashi, K., Yamauchi, K., Teraguchi, S., and Hayasawa, H. (2002). Bovine lactoferrin and lactoferricin derived from milk: production and applications.Biochem. Cell Biol. 80:109-112.
198. Troost, F. J., Steijns, J., Saris,W. H. M., and Brummer, R. J. M. (2001). Gastric digestion of bovine lactoferrin in vivo in adults. J. Nutr. 131:2101-2104.
199. Trumpler, U., Straub, P. W., and Rosenmund, A. (1989). Antibacterial prophylaxis with lactoferrin in neutropenic patients. Eur. J. Clin. Microbiol. Infect. Dis. 8:310-313.
200. Tsuda, H., Sekine, K., Fujita, K., and Iigo, M. (2002). Cancer prevention by bovine lactoferrin and underlying mechanisms - a review of experimental and clinical studies. Biochem. Cell Biol. 80:131-136.
201. Tsuda, H., Sekine, K., Ushida, Y., Kuhara, T., Takasuka, N., Iigo, M., Han, B. S., and Moore, M. A. (2000). Milk and dairy products in cancer prevention: focus on bovine lactoferrin. Mutat. Res. 462:227-233.
202. Ulber, R., Plate, K., Weiss, T., Demmer, W., Buchholz, H., and Scheper, T. (2001). Downstream processing of bovine lactoferrin from sweet whey. Acta Biotechnol. 21:27-34.
203. Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., and Tsuda, H. (1998). Inhibitory effects of bovine lactoferrin on intestinal polyposis in the ApcMin mouse. Cancer Lett. 134:141-145.
204. Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., Maeda, M., and Tsuda, H. (1999). Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat. Jpn. J. Cancer Res. 90:262-267.
205. Valenti, P., Marchetti, M., Superti, F., Amendolia, M. G., Puddu, P., Gessani, S., Borghi, P., Belardelli, F., Antonini, G., and Seganti, L. (1998). Antiviral activity of lactoferrin. Adv. Exp. Med. Biol. 443:199-203.
206. Van Berkel, P. H. C., Geerts, M. E. J., van Heen, H. A., Mericskay, M., de Boer, H. A., and Nuijens, J. H. (1997). N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme andDNA. Biochemistry J.328:145- 151.
207. Van Snick, J. L. and Masson, P. L. (1976). The binding of human lactoferrin to mouse peritoneal cells. J. Exp. Med. 144:1568-1580.
208. Van Snick, J. L., Masson, P. L., and Heremans, J. F. (1974). The involvement of lactoferrin in the hyposideremia of acute inflammation. J. Exp. Med. 140:1068-1084.
209. Varadhachary, A., Wolf, J. S., Petrak, K., O'Malley, B. W. Jr., Spadaro, M., Curcio, C., Forni, G., and Pericle, F. (2004). Oral lactoferrin inhibits growth of established tumors and potentiates conventional chemotherapy.Int. J. Cancer 111:398-403.
210. Wakabayashi, H., Kuwata, H., Yamauchi, K., Teraguchi, S., and Tamura, Y. (2004). No detectable transfer of dietary lactoferrin or its functional fragments to portal blood in healthy adult rats. Biosci. Biotechnol. Biochem. 68:853-860.
211. Wakabayashi, H., Yamauchi, K., and Takase, M. (2006). Lactoferrin research, technology and applications. Int. Dairy J. 16:1241-1251.
212. Wang,W. P., Iigo, M., Sato, J., Sekine, K., Adachi, I., and Tsuda H. (2000). Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Jpn. J. Cancer Res. 91:1022-1027.
213. Ward, P. P., Paz, E., and Conneely, O.M. (2005). Multifunctional roles of lactoferrin: a critical overview. Cell. Mol. Life Sci. 62:2540-2548.
214. Ward, P. P., Uribe-Luna, S., and Conneely, O. (2002). Lactoferrin and host defence. Biochem. Cell Biol. 80:95-102.
215. Weinberg, E. D. (1984). Iron withholding: a defense against infection and neoplasia. Physiol. Rev. 64:65-102.
216. Weinberg, E. D. (1992). Roles of iron in neoplasia. Promotion, prevention, and therapy. Biol. Trace Elem. Res. 34:123-140.
217. Weinberg, E. D. (1996). The role of iron in cancer. Eur. J. Cancer Prev. 5:19-36.
218. Weinberg, E. D. (2007). Antibiotic properties and applications of lactoferrin. Curr. Pharm. Design 13 (8):801-811.
219. Weinstein, R. E., Bond, B. H., and Silberberg, B. K. (1982). Tissue ferritin concentration in carcinoma of the breast. Cancer 50:2406-2409.
220. Wichmann, L., Vaalasti, A., Vaalasti, T., and Tuohimaa, P. (1989). Localization of lactoferrin in the male reproductive tract. Int. J. Androl. 12:179-186.
221. Xiao, Y., Monitto, C. L., Minhas, K. M., and Sidransky, D. (2004). Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells. Clin. Cancer Res. 10:8683-8686.
222. Yamauchi, K., Hiruma, M., Yamazaki, N., Wakabayashi, H., Kuwata, H., Teraguchi, S., Hayasawa, H., Suegara, N., and Yamguchi, H. (2000c). Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebocontrolled, double-blind study. Mycoses 43:197-202.
223. Yamauchi, K., Toida, T.,Kawai, A., Nishimura, S., Teraguchi, S., and Hayasawa, H. (2000)b. Mutagenicity of bovine lactoferrin in reverse mutation test. J. Toxicol. Sci. 25:63-66.
224. Yamauchi, K., Toida, T., Nishimura, S., Nagano, E., Kusuoka, O. Teraguchi, S., Hayasawa, H., Shimamura, S., and Tomita, M. (2000)a. 13-week oral repeated administration toxicity study of bovine lactoferrin in rats. Food Chem. Toxicol. 38:503-512.
225. Yamauchi, K., Tomita, M., Giehl, T. J., and Ellison, R. T. (1993). Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect. Immun. 61:719-728.
226. Yamauchi, K.,Wakabayashi, H., Shin, K., and Takase, M. (2006). Bovine lactoferrin: benefits and mechanism of action against infections. Biochem. Cell Biol. 84:291-296.
227. Yi, M., Kaneko, S., Yu, D. Y., and Murakami, S. (1997). Hepatitis C virus envelope proteins bind lactoferrin. J. Virol. 71:5997-6002.
228. Yoo, Y. C., Watanabe, R., Koike, Y., Mitobe, M., Shimazaki, K., Watanabe, S., and Azuma, I. (1997b). Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: involvement of reactive oxygen species. Biochem. Biophys. Res. Commun. 237:624-628.
229. Yoo, Y. C., Watanabe, S., Watanabe, R., Hata, K., Shimazaki, K., and Azuma I. (1997a). Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Jpn. J. Cancer Res. 88:184-190.
230. Yoshida, S. and Ye, X. (1991). Isolation of lactoperoxidase and lactoferrins from bovine milk acid whey by carboxymethyl cation exchange chromatography. J. Dairy Sci. 74:1439-1444.
231. Yu, R. H. and Schryvers, A. B. (1993). Regions located in both the N-lobe and C-lobe of human lactoferrin participate in the binding interactions with bacterial lactoferrin receptors. Microb. Pathog. 14:343-353.
232. Zakharova, E. T., Shavloski, M. M., Bass, M. G., Gridasova, A. A., Pulina, M. O., De Filippis, V., Beltramini, M., Di Muro, P., Salvato,B., Fontana, A., Vasilyev, V. B., and Gaitskhoki, V. S. (2000). Interaction of lactoferrin with ceruloplasmin. Arch. Biochem. Biophys. 374:222-228.
233. Zimecki, M., Mazurier, J., Machnicki, M.,Wieczorek, Z., Montreuil, J., and Spik, G. (1991). Immunostimulatory activity of lactotransferrin and maturation of CD4-CD8- murine thymocytes. Immunol. Lett. 30:119-123.
234. Zimecki, M., Mazurier, J., Spik, G., and Kapp, J. A. (1995). Human lactoferrin induces phenotypic and functional changes in murine splenic B cells. Immunology 86:122-127.
235. Zydney, A. L. (1998). Protein separations using membrane filtration:new opportunities for whey fractionation. Int. Dairy J. 8:243-250.