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Tumor Biology

, Volume 34, Issue 4, pp 2075–2091 | Cite as

Alpha-fetoprotein: a renaissance

  • A. A. Terentiev
  • N. T. Moldogazieva
Review

Abstract

Alpha-fetoprotein (AFP) is a major mammalian embryo-specific and tumor-associated protein that is also present in small quantities in adults at normal conditions. Discovery of the phenomenon of AFP biosynthesis in carcinogenesis by G. Abelev and Yu. Tatarinov 50 years ago, in 1963, provoked intensive studies of this protein. AFPs of some mammalian species were isolated, purified and physico-chemically and immunochemically characterized. Despite the significant success in study of AFP, its three-dimensional structure, mechanisms of receptor binding along with a structure of the receptor itself and, what is the most important, its biological role in embryo- and carcinogenesis remain still obscure. Due to difficulties linked with methodological limitations, research of AFP was to some extent extinguished by the 1990s. However, over the last decade a growing number of investigations of AFP and its usage as a tumor-specific biomarker have been observed. This was caused by the use of new technologies, primarily, computer-based and genetic engineering approaches in studying of this very important oncodevelopmental protein. Our review summarizes efforts of different scientific groups throughout the world in studying AFP for 50 years with emphasis on detailed description of recent achievements in this field.

Keywords

AFP Alpha-fetoprotein Structure and function Biologically active peptides Hepatocellular carcinoma Onco-biomarker 

References

  1. 1.
    Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonic alpha-globulin by the transplantable mouse hepatomas. Transplantation. 1963;1:174–80.PubMedCrossRefGoogle Scholar
  2. 2.
    Tatarinov YuS. Detection of embryospecific alpha-globulin in serum of patients with primary liver cancer . In I-st All-Union Biochem Cong Abstr Book. 1963;2:274. Moscow-Leningrad.Google Scholar
  3. 3.
    Bergstrand CG, Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scan J Clin Lab Invest. 1956;8:174–6.CrossRefGoogle Scholar
  4. 4.
    Debruyne EN, Delange JR. Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta. 2008;395:19–26.PubMedCrossRefGoogle Scholar
  5. 5.
    Tatarinov YS. Content of embryo-specific alpha-globulin in the blood serum of human fetus, newborns and adults. Vorp Med Khim. 1965;11:20–4.Google Scholar
  6. 6.
    Abelev GI. Alpha-fetoprotein in ontogenesis and its association with malignant tumors. Adv Cancer Res. 1971;14:295–358.PubMedCrossRefGoogle Scholar
  7. 7.
    Ruoslahti E, Seppala M. Alpha-fetoprotein in cancer and fetal development. Adv Cancer Res. 1979;29:275–346.PubMedCrossRefGoogle Scholar
  8. 8.
    Gitlin D, Boesman M. Sites of serum alpha-fetoprotein synthesis in the human and in the rat. J Clin Invest. 1967;46:1010–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Terentiev AA. Comparative studies of physico-chemical properties of human, bovine and sheep embryo-specific alpha-globulins. Proc ASMU 1968; XVI:336–41. Astrakhan.Google Scholar
  10. 10.
    Terentiev AA. Comparative study of fetuin and bovine embryo-specific alpha-globulin. Bull Exp Biol Med. 1969;7:42–5.Google Scholar
  11. 11.
    Kithier K, Masopust J, Rádl J. Fetal alpha-globulin of bone serum differing from fetuin. Biochim Biophys Acta. 1968;160:135–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Nishi S, Watabe H, Hirai H. Production of antibody to homologous alpha-fetoprotein in rabbits, rats and horses by immunization with human alpha-fetoprotein. J Immunol. 1967;109:957–60.Google Scholar
  13. 13.
    Nishi S, Watabe H, Hirai H. Species cross-reaction of alpha-fetoprotein and break down of the tolerance to alpha-fetoprotein by immunization with heterologous alpha-fetoprotein. Tumor Res. 1973;8:17–22.PubMedGoogle Scholar
  14. 14.
    Ruoslahti E, Seppala M. Studies of carcino-fetal proteinsIII. Development of radio-immunoassay for alpha-fetoprotein. Demonstration of alpha-fetoprotein in serum of healthy human adults. Intern J Cancer. 1971;8:374–83.CrossRefGoogle Scholar
  15. 15.
    Ruoslahti E, Seppala M. α-Foetoprotein in normal human serum. Nature. 1972;235:161–2.PubMedCrossRefGoogle Scholar
  16. 16.
    Deutsch HF. Chemistry and biology of alpha-fetoprotein. Adv Cancer Res. 1991;56:253–312.PubMedCrossRefGoogle Scholar
  17. 17.
    Mizejewski GJ. The phylogeny of alpha-fetoprotein in vertebrates: survey of biochemical and physiological data. Crit Rev Eucaryot Gene Expr. 1995;5:281–316.CrossRefGoogle Scholar
  18. 18.
    Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes and conformational variants. Exp Biol Med. 2001;226:377–408.Google Scholar
  19. 19.
    Terentiev AA, Moldogazieva NT. Structural and functional mapping of alpha-fetoprotein. Biochemistry (Mosc). 2006;71:120–32.CrossRefGoogle Scholar
  20. 20.
    Lutsenko SV, Feldman NB, Finakova GV, Gukasova NV, Petukhov SV, Posypanova GA, et al. Study of antitumor activity of alpha-fetoprotein and epidermal growth factor conjugates in vitro and in vivo. Tumor Biol. 2000;21:367–74.CrossRefGoogle Scholar
  21. 21.
    Godovannyi AV, Vorontsov EA, Gukasova NV, Pozdnyakova NV, Vasilenko EA, Yabbarov NG, et al. Targeted delivery of paclitaxel-loaded recombinant alpha-fetoprotein fragment-conjugated nanoparticles to tumor cells. Dokl Biochem Biophys. 2011;439:158–60.PubMedCrossRefGoogle Scholar
  22. 22.
    Morinaga T, Sakai M, Wegmann TG, Namaoki T. Primary structure of human alpha-fetoprotein and its mRNA. Proc Natl Acad Sci U S A. 1983;80:4604–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Pucci P, Siliciano R, Malorni A, Marino G, Tecce MF, Ceccarini C, et al. Human alpha-fetoprotein primary structure: a mass spectrometric study. Biochemistry. 1991;30:5061–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Dudich I, Tokhtamysheva N, Semenkova L, Dudich E, Hellman Y, Korpela T. Isolation and structural and functional characterization of two stable peptic fragments of human alpha-fetoprotein. Biochemistry. 1999;38:10406–14.PubMedCrossRefGoogle Scholar
  25. 25.
    Song Y-H, Naumova AK, Liebhaber SA, Cooke NE. Physical and meiotic mapping of the region of human chromosome 4q11-q13 encompassing the vitamin D-binding protein DBP/Gc-globulin and albumin multigene cluster. Genome Res. 1999;9:581–7.PubMedGoogle Scholar
  26. 26.
    Beatie WG, Dugaiczyk A. Structure and evolution of human alpha-fetoprotein deduced from partial sequence of cloned cDNA. Gene. 1982;20:415–22.CrossRefGoogle Scholar
  27. 27.
    Ruoslahti E, Terry WD. Alpha-fetoprotein and serum albumin show sequence homology. Nature. 1976;260:804–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Cooke NE, David EV. Serum vitamin-D-binding protein is a third member of the albumin and alpha-fetoprotein gene family. J Clin Invest. 1985;76:2420–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Lichtenstein HS, Lyons DE, Wurfer MM, Johnson DA, MacGinley MD, Leidli JC, et al. Afamin is a new member of the albumin, alpha-fetoprotein and vitamin D-binding protein gene family. J Biol Chem. 1994;269:18149–54.Google Scholar
  30. 30.
    Terentiev AA. Structural prerequisition for participation of alpha-fetoprotein and transforming growth factor (TGF-beta) in cell cycle regulation. Med Immunol. 2004;6:256.Google Scholar
  31. 31.
    Luft AJ, Loscheider FL. Structural analysis of human and bovine α-fetoprotein by electron microscopy, image processing and circular dichroism. Biochemistry. 1983;22:5971–8.CrossRefGoogle Scholar
  32. 32.
    He X-M, Carter D. Atomic structure and chemistry of human serum albumin. Nature. 1992;358:209–15.PubMedCrossRefGoogle Scholar
  33. 33.
    Zizkovsky V, Strop P, Korcakova J, Havranova M, Mikes F. Fluorescence spectroscopy, fluorescence polarization and circular dichroism in studies of pH-dependent changes in the alpha-fetoprotein molecule. Ann N Y Acad Sci. 1983;417:49–56.PubMedCrossRefGoogle Scholar
  34. 34.
    Barker ME. Evolution of alpha-fetoprotein: sequence comparisons among AFP species and with albumin species. Tumor Biol. 1988;9:123–36.CrossRefGoogle Scholar
  35. 35.
    Gorin MB, Cooper DL, Eiferman F, van de Rijn P, Tilghman SM. The evolution of alpha-fetoprotein and albumin: 1 a comparison of the primary amino acid sequences of mammalian alpha-fetoprotein and albumin. J Biol Chem. 1981;256:1954–9.PubMedGoogle Scholar
  36. 36.
    Valette G, Vranckx R, Martin M-E, Benassayag C, Nunez EA. Conformational changes in rodent and human alpha-fetoprotein: influence of fatty acids. Biochim Biophys Acta. 1989;997:302–12.CrossRefGoogle Scholar
  37. 37.
    Haourigui M, Thobie N, Martin M-E, Benassayag C, Nunez EA. In vivo transient rise in plasma free acids alters the functional properties of alpha-fetoprotein. Biochim Biophys Acta. 1992;1125:157–65.PubMedCrossRefGoogle Scholar
  38. 38.
    Festin SM, Bennett JA, Fletcher PW, Jacobson HI, Shaye DD, Andersen TT. The recombinant third domain of human alpha-fetoprotein retains the antiestrothophic activity found in the full-length molecule. Biochim Biophys Acta. 1999;1427:307–14.PubMedCrossRefGoogle Scholar
  39. 39.
    Carreres G, Dauphinee MJ, Eisele LE, MacColl R, Mizejewski GJ. Anti-prostate cancer and anti-breast cancer activities of two peptides derived from alpha-fetoprotein. Anticancer Res. 2002;22:2817–20.Google Scholar
  40. 40.
    Uversky VN, Kirkitadze MD, Narizhneva NV, Potekhin SA, Tomashevsky AY. Structural properties of alpha-fetoprotein from human cord serum: the protein molecule at low pH possesses all the properties of the molten globule. FEBS Letts. 1995;364:165–7.CrossRefGoogle Scholar
  41. 41.
    Uversky VN, Narizhneva NV, Ivanova TV, Tomashevski AY. Rigidity of human alpha-fetoprotein tertiary structure is under ligand control. Biochemistry. 1997;36:13638–45.PubMedCrossRefGoogle Scholar
  42. 42.
    Uversky VN, Narizhneva NV, Ivanova TV, Kirkitadze MD, Tomashevsky AY. Ligand-free form of human alpha-fetoprotein: evidence for the molten globule state. FEBS Letts. 1997;410:280–4.CrossRefGoogle Scholar
  43. 43.
    Taketa K. Characterization of sugar chain structures of human AFP by lectin affinity electrophoresis. Electrophoresis. 1998;19:1774–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Breborowich J. Microheterogeneity of human alpha-fetoprotein. Tumor Biol. 1988;9:3–14.CrossRefGoogle Scholar
  45. 45.
    Krivonosov SK, Zorin NA, Ionova NK, Terentiev AA, Tatarinov YS. Interaction of pregnancy-associated proteins with hemagglutinin and concanavalin A. Byul Eksp Biol Med. 1985;5:568–71.Google Scholar
  46. 46.
    Zorin NA, Krivonosov SK, Zorina RM, Terentiev AA, Ionova NK. Competitive inhibition of interactions between phytohemaglutinin A and blood serum glycoproteins by carbohydrates. Vopr Med Khim. 1986;32:96–8.PubMedGoogle Scholar
  47. 47.
    Aoyagi Y, Saitoh A, Suzuki Y, Igarashi K, Oguro M, Yokota T, et al. Fucosylation index of alpha-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis. Hepatology. 1993;17:50–2.PubMedCrossRefGoogle Scholar
  48. 48.
    Seta N, Gayno S, Jezequel-Guer M, Toueg ML, Erlinger S, Durand G. Sequential study of serum glycoprotein fucosylation in acute hepatitis. J Hepatol. 1997;26:265–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Taketa K, Ichikawa E, Sakuda H, Iwamasa T, Hayakawa M, Taga H, et al. Lectin reactivity of alpha-fetoprotein in a case of renal cell carcinoma. Tumor Biol. 1989;10:275–80.CrossRefGoogle Scholar
  50. 50.
    Taketa K, Fujii Y, Taga H. Characterization of E-PHA-reactive alpha-fetoprotein isoforms by two-dimensional lectin affinity electrophoresis. Electrophoresis. 1993;14:1333–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Shimizu K, Katoh H, Yamashita F, Tanaka M, Tanikawa K, Taketa K, et al. Comparison of carbohydrate structures of serum alpha-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis. Clin Chim Acta. 1996;254:23–40.PubMedCrossRefGoogle Scholar
  52. 52.
    Taketa K. Multimodal application of lectin affinity electrophoresis of alpha-fetoprotein. Electrophoresis. 1998;19:1774–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Parmelee DC, Evenson MA, Deutsch HF. The presence of fatty acids in human alpha-fetoprotein. J Biol Chem. 1978;253:2114–9.PubMedGoogle Scholar
  54. 54.
    Berde CB, Nagai M, Deutsch HF. Human alpha-fetoprotein. Fluorescence studies on binding and proximity relationships for fatty acids and bilirubin. J Biol Chem. 1979;254:12609–14.PubMedGoogle Scholar
  55. 55.
    Hsia JC, Er JS, Tan CT, Ester T, Ruoslahti E. α-Fetoprotein binding specificity for arachidonate, bilirubin, docosahexaenoate and palmitate. J Biol Chem. 1980;255:4224–7.PubMedGoogle Scholar
  56. 56.
    Nagai M, Becker JD, Deutsch HF. The fatty acid levels in rat alpha-fetoprotein derived from fetuses, pregnancy and hepatoma sera. Oncodev Biol Med. 1982;3:343–50.PubMedGoogle Scholar
  57. 57.
    Iturralde M, Alava MA, Gonzalez B, Anel A, Pineiro A. Effect of AFP and albumin on the uptake of polyunsaturated fatty acids by rat hepatoma cells and fetal rat hepatocytes. Biochim Biophys Acta. 1991;1086:81–8.PubMedCrossRefGoogle Scholar
  58. 58.
    Aussel C, Negrel L. Effect of AFP on arachidonic acid metabolism in the preadipocyte cell line OB-17. Prostaglandins Leukotriene Med. 1986;21:69–76.CrossRefGoogle Scholar
  59. 59.
    Ruoslahti E, Ester T, Seppala M. Binding of bilirubin by bovine and human alpha-fetoprotein. Biochim Biophys Acta. 1979;578:511–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Aoyagi Y, Ikenaka T, Ichida F. Alpha-fetoprotein as a carrier protein in plasma and its bilirubin-binding ability. Cancer Res. 1979;39:3571–4.PubMedGoogle Scholar
  61. 61.
    Aoyagi Y, Ikenaka T, Ishida F. Copper (II)-binding ability of human alpha-fetoprotein. Cancer Res. 1978;38:3483–6.PubMedGoogle Scholar
  62. 62.
    Birkenmeier G, Usbeck E, Saro L, Kopperschlager G. Triazine dye binding of human alpha-fetoprotein and albumin. J Chromatogr. 1983;265:27–35.PubMedCrossRefGoogle Scholar
  63. 63.
    Ruiz-Gutierrez V, Moreno R, Moreda W, Copado MA, Rodriguez-Burgoz A. Detection of squalene in alpha-fetoprotein and fetal serum albumin from bovine. J Prot Chem. 2001;20:19–23.CrossRefGoogle Scholar
  64. 64.
    Soloff MS, Swartz SK, Pearlmutter F, Kithier K. Binding of 17-β-estradiol by variants of alpha-fetoprotein in rat amniotic fluid. Biochim Biophys Acta. 1972;427:644–51.Google Scholar
  65. 65.
    Uriel J, de Nechaut B, Dupiers M. Estrogen-binding properties of rat, mouse and man fetospecific serum protein. Demonstration by immuno-autoradiographic methods. Biochem Biophys Res Commun. 1972;46:1175–80.PubMedCrossRefGoogle Scholar
  66. 66.
    Uriel J, Bouillon D, Dupiers M. Affinity chromatography of human, rat and mouse alpha-fetoprotein on estradiol-sepharose adsorbents. FEBS Lett. 1975;53:305–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Uriel J, Bouillon D, Aussel C, Dupiers M. Alpha-fetoprotein: the major high affinity estrogen binder in rat uterine cytosols. Proc Natl Acad Sci USA. 1976;75:1452–6.CrossRefGoogle Scholar
  68. 68.
    Nishi S, Matsue H, Yoshida H, Yamamoto R, Sakai M. Localization of estrogen-binding site of alpha-fetoprotein in chimeric human-rat proteins. Proc Natl Acad Sci USA. 1991;88:3102–5.PubMedCrossRefGoogle Scholar
  69. 69.
    Milligan SR, Khan O, Nash M. Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss) plasma. J Comp Endocrinol. 1998;112:89–95.CrossRefGoogle Scholar
  70. 70.
    Terentiev AA, Moldogazieva NT, Tagirova AK, Tatarinov YS. Affinity chromatography of human alpha-fetoprotein on immobilized estrogens. Byul Eksp Biol Med. 1988;4:422–4.Google Scholar
  71. 71.
    Terentiev AA, Moldogazieva NT, Tagirova AK, Tatarinov YS. Competitive affinity chromatography of human alpha-fetoprotein on immobilized diethylstilbestrol. Byul Eksp Biol Med. 1990;5:438–40.Google Scholar
  72. 72.
    Tatarinov YS, Terentiev AA, Moldogazieva NT, Tagirova AK. Human alpha-fetoprotein and its purification by chromatography on immobilized estrogens. Tumor Biol. 1991;12:125–30.CrossRefGoogle Scholar
  73. 73.
    Terentiev AA, Moldogazieva NT, Tagirova AK, Tatarinov YS. Affinity chromatography of rodent alpha-fetoprotein on immobilized diethylstilbestrol. Byul Eksp Biol Med. 1992;6:588–90.Google Scholar
  74. 74.
    Terentiev AA, Moldogazieva NT, Levtsova OV, Maximenko D, Borozdenko D, Shaitan KV. Modeling of three-dimensional structure of human alpha-fetoprotein complexed with diethylstilbestrol: docking and molecular dynamics simulation study. J Bioinform Comput Biol. 2012;10:1241012.PubMedCrossRefGoogle Scholar
  75. 75.
    Lu CY, Changelian PS, Unanue ER. Alpha-fetoprotein inhibits macrophage expression of Ia antigens. J Immunol. 1984;132:1722–7.PubMedGoogle Scholar
  76. 76.
    Atemezem A, Mbemba E, Marfaing R, Vaysse J, Pontet M, Saffar L, et al. Human alpha-fetoprotein binds to primary macrophages. Biochem Biophys Res Commun. 2002;296:507.PubMedCrossRefGoogle Scholar
  77. 77.
    Peck AB, Murgita RA, Wigzell H. Cellular and genetic restrictions in the immunoregulatory activity of α-fetoprotein. III. Role of the MLC-stimulating cell of α-fetoprotein induced suppression of T cell-mediated cytotoxicity. J Immunol. 1982;128:1134–40.PubMedGoogle Scholar
  78. 78.
    Cohen BL, Orn A, Gronvik K-O, Gidlund M, Wigzell H, Murgita RA. Suppression by alpha-fetoprotein of murine natural killer cell activity stimulated in vitro and in vivo by interferon and interleukin 2. Scand J Immunol. 1986;23:211–23.PubMedCrossRefGoogle Scholar
  79. 79.
    Yachnin S. Demonstration of the inhibitory effect of human AFP on in vitro transformation of human lymphocytes. Proc Nat Acad Sci U S A. 1976;73:2857–60.CrossRefGoogle Scholar
  80. 80.
    Yachnin S. The immunosuppressive properties of α-fetoprotein: a brief overview. Ann N Y Acad Sci. 1983;417:105–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Matsuura E, Kang Y, Katikawa H, Ogata P, Kotani T, Ohtaki S, et al. Modulation of T-cell function by alpha-fetoprotein. An in vivo study on porcine thyroid peroxidase induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein. Tumor Biol. 1999;20:162–71.CrossRefGoogle Scholar
  82. 82.
    Alpert E, Dienstag JL, Sepersky S, Littman B, Rocklin R. Immunosupressive characteristic of human AFP: effect on tests of cell mediated immunity and induction of human suppressor cell. Immunol Commun. 1978;7:163–85.PubMedGoogle Scholar
  83. 83.
    Van Oers NS, Cohen BL, Murgita RA. Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus. J Exp Med. 1989;170:811–25.PubMedCrossRefGoogle Scholar
  84. 84.
    Semeniuk DJ, Boismenu R, Tam J, Weissenhofer W, Murgita RA. Evidence that immunosuppression is an intrinsic property of the alpha-fetoprotein molecule. Adv Exp Mol Biol. 1995;383:255–69.CrossRefGoogle Scholar
  85. 85.
    Irony-Tur-Sinai M, Grigoriadis N, Tsiantoulas D, Touloumi O, Abramsky O, Brenner T. Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell apoptosis markers and the transcription factor FoxP3. J Neurol Sci. 2009;279:80–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Kang G, Matsuura E, Sakamoto T, Sakai M, Nishi B. Analysis of epitopes of mouse monoclonal antibodies against human alpha-fetoprotein. Tumor Biol. 2001;22:254–61.CrossRefGoogle Scholar
  87. 87.
    Butterfield LH, Koh A, Meng W, Volhmer CM, Ribas A, Dissette V, et al. Generation of human T-cell responses to an HLA-A2.1-restricted peptide epitope derived from alpha-fetoprotein. Cancer Res. 1999;59:3134–42.PubMedGoogle Scholar
  88. 88.
    Butterfield LH, Meng WS, Koh A, Vollmer CM, Ribas A, Dissette VB, et al. T cell responses to HLA-A*0201-restricted peptides derived from human alpha fetoprotein. J Immunol. 2001;166:5300–8.PubMedGoogle Scholar
  89. 89.
    Butterfield LH, Ribas A, Mena WS, Dissette VB, Amarnami S, Vu HT, et al. T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha-fetoprotein in patients with hepatocellular cancer. Clin Cancer Res. 2003;9:5902–8.PubMedGoogle Scholar
  90. 90.
    Butterfield LH, Ribas A, Dissette VB, Lee Y, Yang JQ, De la Rocha P, et al. A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin Cancer Res. 2006;12:2817–25.PubMedCrossRefGoogle Scholar
  91. 91.
    Liu Y, Daley S, Evdokimova VN, Zdobinski DD, Potter DM, Butterfield LH. Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer. J Immunol. 2006;177:712–21.PubMedGoogle Scholar
  92. 92.
    Butterfield LH. Recent advances in immunotherapy for hepatocellular cancer. Swiss Med WKLY. 2007;137:83–90.PubMedGoogle Scholar
  93. 93.
    Pardee AD, Butterfield LH. Immunotherapy of hepatocellular carcinoma: unique challenges and clinical opportunities. Oncoimmunol. 2012;1:48–50.CrossRefGoogle Scholar
  94. 94.
    Thimme R, Neagu M, Boettler T, Neumann-Haefelin C, Kersting N, Geissler M, et al. Comprehensive analysis of the alpha-fetoprotein-specific CD8+ T-cell responses in patients with hepatocellular carcinoma. Hepatology. 2008;48:1821–33.PubMedCrossRefGoogle Scholar
  95. 95.
    Alisa A, Ives A, Pathan AA, Navarrete CV, Williams R, Bertoletti A, et al. Analysis of CD4+ T-сell responses to a novel alpha-fetoprotein-derived epitope in hepatocellular carcinoma patients. Clin Cancer Res. 2005;11:6686–94.PubMedCrossRefGoogle Scholar
  96. 96.
    Ayaru L, Pereira SP, Alisa A, Pathan AA, Williams R, Davidson B, et al. Unmasking of alpha-fetoprotein-specific CD4+ T-cell responses in hepatocellular carcinoma patients undergoing embolization. J Immunol. 2007;178:1914–22.PubMedGoogle Scholar
  97. 97.
    Alisa A, Bouswell S, Pathan AA, Ayaru L, Williams R, Behboudi S. Human CD4+ T-cells recognize an epitope within alpha-fetoprotein sequence and develop into TGF-producing CD4+ T- cells. J Immunol. 2008;180:5109–17.PubMedGoogle Scholar
  98. 98.
    Behboudi S, Alisa A, Boswell S, Anastassiou J, Pathan AA, Williams R. Expansion of anti-AFP Th1 and Tc1 responses in hepatocellular carcinoma occur in different stages of disease. Br J Cancer. 2010;102:748–53.PubMedCrossRefGoogle Scholar
  99. 99.
    Terentiev AA, Kazimirski AN, Salmasi JM. AFP and apoptosis: synthetic oligopeptide LDSYQCT (AFP13-19) induced expression of CD-95 (FAS, Apo-1). Tumor Biol. 2000;21(Suppl1):110.Google Scholar
  100. 100.
    Terentiev AA, Simonova AV, Arshinova SS, Kulakov VV, Bahus GO, Kudryavtseva EV, et al. Influence of peptide LDSYQCT (sequence 14–20 of human AFP) on proliferative activity of human lymphocytes. Tumor Biol. 2003;24 Suppl 1:54.Google Scholar
  101. 101.
    Terentiev AA, Simonova AV, Arshinova SS, Kulakov VV, Bahus GO, Pavlichenkov AV, et al. Influence of the human AFP-derived peptide LDSYQC(acm)T on proliferative and cytotoxic activity of peripheral blood lymphocytes. Immunologiya. 2004;5:279–81.Google Scholar
  102. 102.
    Salmasi JM, Kazimirski AN, Terentiev AA, Poryadin GV, Kudryavtseva EV, Tatarinov YS. LDSYQCT-peptide synthetic analogue of human alpha-fetoprotein (13–19) increases anti-proliferative effect of cytozar on the lymphocytes of chronic leukemia patients. Tumor Biol. 1999;20 Suppl 2:43.Google Scholar
  103. 103.
    Moldogazieva NT, Terentiev AA, Kazimirsky AN, Antonov MY, Shaitan KV. Conformational dynamics of human alpha-fetoprotein-derived heptapeptide LDSYQCT analogs. Biochemistry (Mosc). 2007;72:529–39.CrossRefGoogle Scholar
  104. 104.
    Moldogazieva NT, Shaitan KV, Antonov MY, Vinogradova IK, Terentiev AA. Influence of intramolecular interactions on conformational and dynamic properties of analogs of heptapeptide AFP14-20. Biochemistry (Mosc). 2011;76:1321–36.CrossRefGoogle Scholar
  105. 105.
    Moldogazieva NT, Terentiev AA, Antonov MY, Kazimirsky AN, Shaitan KV. Correlation between biological activity and conformational and dynamic properties of tetra- and pentapeptide fragments of fetoplacental proteins. Biochemistry (Mosc). 2012;77:469–84.CrossRefGoogle Scholar
  106. 106.
    Leffert HI, Sell S. Alpha-fetoprotein biosynthesis during the growth cycle of differentiated fetal rat hepatocytes to primary monolayer culture. J Cell Biol. 1974;61:823–9.PubMedCrossRefGoogle Scholar
  107. 107.
    Toder V, Bland M, Gold-Gefter L, Nebel J. The effect of alpha-fetoprotein on the growth of placental cells in vitro. Placenta. 1983;4:79–86.PubMedCrossRefGoogle Scholar
  108. 108.
    Hamel S, Hoskin DW, Hooper DC, Murgita RA. Phenotype and function of bone marrow-derived T and non-T cells activated in vitro by alpha-fetoprotein. In: Mizejewski GJ, Jacobson HI, editors. Biological activities of alpha-fetoprotein. Florida: CRC; 1987. p. 167–77.Google Scholar
  109. 109.
    Wang XW, Xu B. Stimulation of tumor-cell growth by alpha-fetoprotein. Int J Cancer. 1998;75:596–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Wang XW, Xie H. Alpha-fetoprotein enhances the proliferation of human hepatoma cells in vitro. Life Sci. 1999;64:17–23.PubMedCrossRefGoogle Scholar
  111. 111.
    Laderoute MP, Pilarski LM. Inhibition of apoptosis by alpha-fetoprotein (AFP) and role of AFP receptors in anti-cellular senescence. Anticancer Res. 1974;14:2429–38.Google Scholar
  112. 112.
    Shehata MA, Nosseir HR, Nagy HM, Farouk G. Cyclin dependent kinase inhibitor p27(kip1) expression and subcellular localization in relation to cell proliferation in heap to cellular carcinoma. Egypt J Immunol. 2006;13:115–30.PubMedGoogle Scholar
  113. 113.
    Mizejewski GJ, Vonnegut M, Jacobson HI. Estradiol-activated alpha-fetoprotein suppresses the uteroptropic response to estrogens. Proc Natl Acad Sci U S A. 1983;80:2733–7.PubMedCrossRefGoogle Scholar
  114. 114.
    Allen SHG, Bennett JA, Mizejewski GJ, Andersen TT, Ferraris S, Jacobson HI. Purification of human alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity. Biochim Biophys Acta. 1993;1202:135–42.PubMedCrossRefGoogle Scholar
  115. 115.
    Jacobson HI, Thompson VD, Janerich DT. Multiple births and maternal risk of breast cancer. Amer J Epidemiol. 1989;129:865–73.Google Scholar
  116. 116.
    Jacobson HI, Bennett JA, Mizejewski GJ. Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol. Cancer Res. 1990;50:415–20.PubMedGoogle Scholar
  117. 117.
    Boismenn R, Semeniuk D, Murgita RA. Purification and characterization of human and mouse recombinant alpha-fetoprotein expressed in Echerichia coli. Protein Expres Purif. 1997;10:10–26.CrossRefGoogle Scholar
  118. 118.
    Bennett JA, Semeniuk DJ, Jaсobson HI, Murgita RA. Similarity between natural and recombinant human alpha-fetoprotein as inhibitors of estrogen-dependent breast cancer growth. Breast Cancer Res Treat. 1997;45:169–79.PubMedCrossRefGoogle Scholar
  119. 119.
    Bennett JA, Zhu S, Pagano-Mirarchi A, Kellom TA, Jacobson HI. Alpha-fetoprotein derived from a human hepatoma prevents growth of estrogen-dependent human breast cancer xenografts. Clin Cancer Res. 1998;4:2877–84.PubMedGoogle Scholar
  120. 120.
    Mizejewski GJ, Dias JA, Hauer CR, Henrikson KP, Gierthy I. Alpha-fetoprotein derived synthetic peptides: assay from an estrogen-modifying regulatory segment. Mol Cell Endocrinol. 1996;118:15–33.PubMedCrossRefGoogle Scholar
  121. 121.
    Vakharia D, Mizejewski GJ. Human alpha-fetoprotein peptides bind estrogen receptor and estradiol and suppress breast cancer. Breast Cancer Res Treat. 2000;63:41–52.PubMedCrossRefGoogle Scholar
  122. 122.
    Eisele LE, Mesfin FB, Bennett JA, Andersen TT, Jacobson HI, Soldwedel H, et al. Studies of a growth inhibitory peptide derived from alpha-fetoprotein and some analogs. J Peptide Res. 2001;57:29–38.CrossRefGoogle Scholar
  123. 123.
    Eisele LE, Mesfin FB, Bennett JA, Andersen TT, Jacobson HI, Soldwedel H, et al. Studies on analogs of a peptide derived from alpha-fetoprotein having antigrowth properties. J Peptide Res. 2001;57:539–46.CrossRefGoogle Scholar
  124. 124.
    MacColl R, Eisele LE, Stack RF, Hauer C, Vakharia DD, Benno A, et al. Interrelationship among biological activity, disulphide bonds, secondary structure and metal ion binding for a chemically synthesized 34-amino-acid peptide derived from α-fetoprotein. Biochim Biophys Acta. 2001;1528:127–34.PubMedCrossRefGoogle Scholar
  125. 125.
    Butterstein G, Morrison J, Mizejewski GJ. Effect of alpha-fetoprotein and derived peptides on insulin and estrogen-induced fetotoxicity. Fetal Diagn Ther. 2003;18:360–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Carerres G, Dauphinee MJ, Eisele LE, MacColl R, Mizejewski GJ. Anti-prostate cancer and anti-breast cancer activities of two peptides derived from alpha-fetoprotein. Anticancer Res. 2002;22:2817–20.Google Scholar
  127. 127.
    Mesfin FB, Bennett GA, Jacobson HI, Zhu S, Andersen TT. Alpha-fetoprotein-derived antiestrotrophic octapeptide. Biochim Biophys Actа. 2000;1501:33–43.CrossRefGoogle Scholar
  128. 128.
    Mesfin FB, Andersen TT, Jacobson HI, Zhu S, Bennett GA. Development of a synthetic cyclized peptide derived from alpha-fetoprotein that prevents the growth of human breast cancer. J Peptide Res. 2001;58:246–56.CrossRefGoogle Scholar
  129. 129.
    Hamsa A, Sarma MH, Sarma RH. Plausible interaction of an alpha-fetoprotein cyclopeptide with the G-protein coupled receptor model GPR30: docking study by molecular dynamics simulated annealing. J Biomol Struct Dyn. 2003;20:751–8.CrossRefGoogle Scholar
  130. 130.
    Sierralta WD, Epunan MJ, Reyes JM, Valladares LE, Andersen TT, Bennett JA, et al. A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture. Oncol Rev. 2008;19:229–35.Google Scholar
  131. 131.
    Bennett JA, DeFreest L, Anaka I, Saadati H, Balulad S, Jacobson HI, et al. AFPep: an anti-breast cancer peptide that is orally active. Breast Cancer Res Treat. 2006;98:133–41.PubMedCrossRefGoogle Scholar
  132. 132.
    Mizejewski GJ, MacColl R. Alpha-fetoprotein growth inhibitory peptides: potential leads for cancer therapeutics. Mol Cancer Ther. 2003;2:1243–55.PubMedGoogle Scholar
  133. 133.
    Mizejewski GJ. Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary. Cancer Immunol Immunother. 2009;58:159–70.PubMedCrossRefGoogle Scholar
  134. 134.
    Mizejewski GJ. Mapping of structure-function peptide sites on the human alpha-fetoprotein amino acid sequence. Atlas Genet Cytogenet Oncol Hematol. 2010;2:331–82.Google Scholar
  135. 135.
    Gabant P, Forrester L, Nicols J, Van Reeth T, De Mees C, Bajac B, et al. Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility. Proc Natl Acad Sci U S A. 2002;99:12865–70.PubMedCrossRefGoogle Scholar
  136. 136.
    Dohler KD. The pre- and postnatal influence of hormones and neurotransmitters on sexual differentiation of the mammalian hypothalamus. Int Rev Cytol. 1991;131:1–57.PubMedCrossRefGoogle Scholar
  137. 137.
    De Mees C, Laes JF, Bakker J, Smitz J, Hennuy B, Van Vooren P, et al. Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action. Mol Cell Biol. 2006;26:2012–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Uriel J, Trojan J, Moro R, Pineiro A. Intracellular uptake of α-fetoprotein: a marker of neural differentiation. Ann N Y Acad Sci. 1983;417:321–9.PubMedCrossRefGoogle Scholar
  139. 139.
    Villacampa MJ, Moro R, Naval J, Failly-Crepin C, Lampreave F, Uriel J. Alpha-fetoprotein receptors in a human breast cancer cell line. Biochem Biophys Res Commun. 1984;122:1322–7.PubMedCrossRefGoogle Scholar
  140. 140.
    Naval J, Villacampa MJ, Goguel AF, Uriel J. Cell-type-specific receptors for alpha-fetoprotein in a mouse T-lymphoma cell line. Proc Natl Acad Sci U S A. 1986;82:3301–4.CrossRefGoogle Scholar
  141. 141.
    Uriel J, Naval J, Laborda J. Alpha-Fetoprotein-mediated transfer of arachidonic acid into cultured cloned cells derived from a rat rhabdomyosarcoma. J Biol Chem. 1987;262:3579–85.PubMedGoogle Scholar
  142. 142.
    Torres JM, Laborda J, Naval J, Darracq N, Calvo M, Mishal Z, et al. Expression of alpha-fetoprotein receptors by human T-lymphocytes during blastic transformation. Mol Immunol. 1989;26:851–7.PubMedCrossRefGoogle Scholar
  143. 143.
    Torres JM, Geuskens M, Uriel J. Activated human T lymphocytes express albumin binding proteins which cross-react with alpha-fetoprotein. Eur J Cell Biol. 1992;57:222–8.PubMedGoogle Scholar
  144. 144.
    Suzuki Y, Zeng CQY, Alpert E. Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes. J Clin Invest. 1992;90:1530–6.PubMedCrossRefGoogle Scholar
  145. 145.
    Alava MA, Iturralde M, Lampreave F, Pineiro A. Specific uptake of alpha-fetoprotein and albumin by rat Morris 7777 hepatoma cells. Tumor Biol. 1999;20:52–64.CrossRefGoogle Scholar
  146. 146.
    Moro R, Tamaoki T, Wegmann TJ, Longnecker BM, Laderoute MP. Monoclonal antibodies directed against a widespread oncofetal antigen: the alpha-fetoprotein receptor. Tumor Biol. 1993;14:116–30.CrossRefGoogle Scholar
  147. 147.
    Lorenzo HG, Geuskens M, Macho A, Lachkar S, Verdiere-Sahuque M, Pineiro A, et al. Alpha-fetoprotein binding and uptake by primary cultures of human skeletal muscle. Tumour Biol. 1996;17:251–60.PubMedCrossRefGoogle Scholar
  148. 148.
    Li MS, Li PF, Yang FY, He SP, Du GG, Li G. The intracellular mechanism of AFP promoting the proliferation of NIH 393 cells. Cell Res. 2002;12:151–6.PubMedCrossRefGoogle Scholar
  149. 149.
    Newby D, Dalgliesh G, Lyall F, Aitken DA. Alpha-fetoprotein and alpha-fetoprotein receptor expression in the normal human placenta at term. Placenta. 2005;26:190–200.PubMedCrossRefGoogle Scholar
  150. 150.
    Mizejewski GJ. Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family. Tumor Biol. 2011;32:241–58.CrossRefGoogle Scholar
  151. 151.
    Mizejewski GJ. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor. Tumor Biol. 2013;34:1317–36.CrossRefGoogle Scholar
  152. 152.
    Li MS, Li PF, Du GG, Li G. The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line. World J Gastroenterol. 2002;8:469–75.PubMedGoogle Scholar
  153. 153.
    Li MS, Li PF, Chen Q, Du GG, Li G. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel7402 cells. World J Gastroenterol. 2004;10:819–24.PubMedGoogle Scholar
  154. 154.
    Li M-S, Ma Q-L, Chen Q, Liu X-H, Li P-F, Du G-G, et al. Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells. World J Gastroenterol. 2005;11:2564–9.PubMedGoogle Scholar
  155. 155.
    Li M-S, Li H, Li C, Zhou S, Guo L, Liu H, et al. Alpha fetoprotein is a novel protein-binding partner for caspase-3 and blocks the apoptotic signaling pathway in human hepatoma cells. Int J Cancer. 2009;124:2845–54.PubMedCrossRefGoogle Scholar
  156. 156.
    Li M-S, Li H, Li C, Guo L, Liu H, Zhou S, et al. Cytoplasmic alpha-fetoprotein functions as a co-repressor in RA-RAR signaling to promote the growth of human hepatoma Bel 7402 cells. Cancer Lett. 2009;285:190–9.PubMedCrossRefGoogle Scholar
  157. 157.
    Li M-S, Li H, Li C, Wang S, Wei J, Liu Z, et al. Alpha-fetoprotein: a new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines. Int J Cancer. 2011;128:524–32.PubMedCrossRefGoogle Scholar
  158. 158.
    Goldstein NS, Blue DE, Hankin R, Hunter S, Bayati N, Silverman AL, et al. Serum alpha-fetoprotein levels in patients with chronic hepatitis C: relationships with serum alanine aminotransferase values, histologic activity index and hepatocyte MIB-I scores. Am J Clin Pathol. 1999;111:811–6.PubMedGoogle Scholar
  159. 159.
    Semenkova LN, Dudich EI, Dudich IV, Shingarova LN, Korobko VG. α-Fetoprotein as a TNF-resistance factor for human hepatocarcinoma cell line HepG2. Tumor Biol. 1997;18:30–40.CrossRefGoogle Scholar
  160. 160.
    Dudich E, Semenkova L, Dudich I, Gorbatova E, Tokhtamisheva N, Tatulov E, et al. Alpha-fetoprotein causes apoptosis in tumor cells via a pathway independent of CD95, TNFR1 and TNFR2 through activation of caspase-3-like proteases. Eur J Biochem. 1999;266:750–61.PubMedCrossRefGoogle Scholar
  161. 161.
    Semenkova L, Dudich E, Dudich I, Tokhtamisheva N, Tatulov E, Okruzhnov Y, et al. Alpha-fetoprotein positively regulates cytochrome c-mediated caspase activation and apoptosome complex formation. Eur J Biochem. 2003;270:4388–99.PubMedCrossRefGoogle Scholar
  162. 162.
    Dudich E. MM-093, a recombinant human alpha-fetoprotein for the potential treatment of rheumatoid arthritis and other autoimmune diseases. Curr Opin Mol Ther. 2007;9:603–10.PubMedGoogle Scholar
  163. 163.
    Seppala M. Fetal pathophysiology of human alpha-fetoprotein. Ann NY Acad Sci. 1975;259:59–73.PubMedCrossRefGoogle Scholar
  164. 164.
    Brock DJ, Scrimgeour JB, Nelson MM. Amniotic fluid alpha-fetoprotein measurements in the prenatal diagnosis of central nervous system disorders. Genetics. 1975;7:163–9.Google Scholar
  165. 165.
    Petropoulos C, Andrews G, Tamaoki T, Fausto N. Alpha-fetoprotein and albumin mRNA levels in liver regeneration and carcinogenesis. J Biol Chem. 1983;258:4901–6.PubMedGoogle Scholar
  166. 166.
    Won YS, Lee SW. Targeted retardation of hepatocarcinoma cells by specific replacement of alpha-fetoprotein RNA. J Biotechnol. 2007;129:614–9.PubMedCrossRefGoogle Scholar
  167. 167.
    Zhang H, Bai ZL, Chen J, Wang Z, Li J. Alpha-fetoprotein-specific transfer factors downregulate alpha-fetoprotein expression and specifically induce apoptosis in Bel7402 alpha-fetoprotein-positive hepatocarcinoma cells. Hepatol Res. 2007;37:557–67.PubMedCrossRefGoogle Scholar
  168. 168.
    Lee NP, Chen L, Lin MC, Tsang FH, Yeung C, Poon RT, et al. Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. J Proteome Res. 2009;8:1293–303.PubMedCrossRefGoogle Scholar
  169. 169.
    Saito S, Ojima H, Ichikawa H, Hirohashi S, Kondo T. Molecular background of alpha-fetoprotein in liver cancer cells as revealed by global RNA expression analysis. Cancer Sci. 2008;99:2402–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Wang XY, Degos F, Dubois S. Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Hum Pathol. 2006;37:1435–41.PubMedCrossRefGoogle Scholar
  171. 171.
    Spangenberg HC, Thimme R, Blum HE. Serum markers of hepatocellular carcinoma. Semin Lver Dis. 2006;26:385–90.CrossRefGoogle Scholar
  172. 172.
    Durazo FA, Blatt LM, Corey WG, Lin JH, Han S, Saab S, et al. Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23:1541–8.PubMedCrossRefGoogle Scholar
  173. 173.
    Bertino G, Neri S, Bruno CM, Ardini AM, Calvagno GS, Malaguarnera M, et al. Diagnostic and prognostic value of alpha-fetoprotein, des-γ-carboxy prothrombin and squamous cell carcinoma antigen immunoglobulin M complexes in hepatocellular carcinoma. Minerva Med. 2011;102:363–71.PubMedGoogle Scholar
  174. 174.
    Bertino G, Ardini A, Malaguarnera M, Malaguarnera G, Bertino N, Calvagno GS. Hepatocellualar carcinoma serum markers. Semin Oncol. 2012;39:410–33.PubMedCrossRefGoogle Scholar
  175. 175.
    Sharapova OA, Pozdniakova NV, Laurinavichiute DK, Iurkova MS, Posypanova GA, Andronova SM, et al. Purification and characterization of recombinant human alpha-fetoprotein fragment, corresponding to the C-terminal structural domain. Bioorg Khim. 2010;36:760–8.PubMedGoogle Scholar
  176. 176.
    Sharapova OA, Yurkova MS, Laurinavichyute DK, Andronova SM, Fedorov AN, Severin SE, et al. Efficient refolding of a hydrophobic protein with multiple S–S bonds by on-resin immobilized metal affinity chromatography. J Chromat A. 2011;1218:5115–9.CrossRefGoogle Scholar
  177. 177.
    Mizejewski GJ, Mirowski M, Garnuszek P, Maurin M, Cohen BD, Poiesz BJ, et al. Targeted delivery of anti-cancer growth inhibitory peptides derived from human α-fetoprotein: review of an International Multi-Center Collaborative Study. J Drug Target. 2010;18:575–88.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.N. I. Pirogov Russian National Research Medical UniversityMoscowRussia

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